Cardiology

TOPLINE:

A new study finds SARS-CoV-2 directly infects the coronary vasculature and causes plaque inflammation, which could help explain why people with COVID-19 have an increased risk for ischemic cardiovascular complications up to 1 year after infection.

METHODOLOGY:

• Researchers obtained 27 coronary autopsy specimens from eight patients who died from COVID-19, mean age 70 years and 75% male. All had coronary artery disease and most had cardiovascular risk factors such as hypertension, were overweight or obese, and had hyperlipidemia and type 2 diabetes.
• All but one patient, who was pronounced dead before hospital admission, were hospitalized for an average of 17.6 days.
• To identify SARS-CoV-2 viral RNA (vRNA) in the autoptic coronary vasculature, researchers performed RNA fluorescence in situ hybridization (RNA-FISH) analysis for the vRNA encoding the spike (S) protein; they also probed the antisense strand of the S gene (S antisense), which is only produced during viral replication.

TAKEAWAY:

• The study found evidence of SARS-CoV-2 replication in all analyzed human autopsy coronaries regardless of their pathological classification, although viral replication was highest in early-stage lesions that progress to more advanced atherosclerotic plaques.
• Findings indicated that more than 79% of macrophages (white blood cells that help remove lipids) and more than 90% of foam cells (lipid-laden macrophages that are a hallmark of atherosclerosis at all stages of the disease) are S+, and more than 40% of both cell types are S antisense+, indicating SARS-CoV-2 can infect macrophages at a high rate.
• SARS-CoV-2 induced a strong inflammatory response as evidenced by release of cytokines (including interleukin-1 beta and interluekin-6 that are linked to myocardial infarction) in both macrophages and foam cells, which may contribute to the ischemic cardiovascular complications in patients with COVID-19.

IN PRACTICE:

“Our data conclusively demonstrate that SARS-CoV-2 is capable of infecting and replicating in macrophages within the coronary vasculature of patients with COVID-19,” write the authors, adding that SARS-CoV-2 preferentially replicates in foam cells, compared with other macrophages, suggesting these cells “might act as a reservoir of SARS-CoV-2 viral debris in the atherosclerotic plaque.”

SOURCE:

The study was led by Natalia Eberhardt, PhD, postdoctoral fellow, department of medicine, division of cardiology, New York University, and colleagues. It was published online in Nature Cardiovascular Research.

LIMITATIONS:

Findings are relevant only to the original strains of SARS-CoV-2 that circulated in New York between May 2020 and May 2021, and are not generalizable to patients younger and healthier than those from whom samples were obtained for the study.

DISCLOSURES:

The study received support from the National Institutes of Health. The authors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A new study finds SARS-CoV-2 directly infects the coronary vasculature and causes plaque inflammation, which could help explain why people with COVID-19 have an increased risk for ischemic cardiovascular complications up to 1 year after infection.

METHODOLOGY:

• Researchers obtained 27 coronary autopsy specimens from eight patients who died from COVID-19, mean age 70 years and 75% male. All had coronary artery disease and most had cardiovascular risk factors such as hypertension, were overweight or obese, and had hyperlipidemia and type 2 diabetes.
• All but one patient, who was pronounced dead before hospital admission, were hospitalized for an average of 17.6 days.
• To identify SARS-CoV-2 viral RNA (vRNA) in the autoptic coronary vasculature, researchers performed RNA fluorescence in situ hybridization (RNA-FISH) analysis for the vRNA encoding the spike (S) protein; they also probed the antisense strand of the S gene (S antisense), which is only produced during viral replication.

TAKEAWAY:

• The study found evidence of SARS-CoV-2 replication in all analyzed human autopsy coronaries regardless of their pathological classification, although viral replication was highest in early-stage lesions that progress to more advanced atherosclerotic plaques.
• Findings indicated that more than 79% of macrophages (white blood cells that help remove lipids) and more than 90% of foam cells (lipid-laden macrophages that are a hallmark of atherosclerosis at all stages of the disease) are S+, and more than 40% of both cell types are S antisense+, indicating SARS-CoV-2 can infect macrophages at a high rate.
• SARS-CoV-2 induced a strong inflammatory response as evidenced by release of cytokines (including interleukin-1 beta and interluekin-6 that are linked to myocardial infarction) in both macrophages and foam cells, which may contribute to the ischemic cardiovascular complications in patients with COVID-19.

IN PRACTICE:

“Our data conclusively demonstrate that SARS-CoV-2 is capable of infecting and replicating in macrophages within the coronary vasculature of patients with COVID-19,” write the authors, adding that SARS-CoV-2 preferentially replicates in foam cells, compared with other macrophages, suggesting these cells “might act as a reservoir of SARS-CoV-2 viral debris in the atherosclerotic plaque.”

SOURCE:

The study was led by Natalia Eberhardt, PhD, postdoctoral fellow, department of medicine, division of cardiology, New York University, and colleagues. It was published online in Nature Cardiovascular Research.

LIMITATIONS:

Findings are relevant only to the original strains of SARS-CoV-2 that circulated in New York between May 2020 and May 2021, and are not generalizable to patients younger and healthier than those from whom samples were obtained for the study.

DISCLOSURES:

The study received support from the National Institutes of Health. The authors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A new study finds SARS-CoV-2 directly infects the coronary vasculature and causes plaque inflammation, which could help explain why people with COVID-19 have an increased risk for ischemic cardiovascular complications up to 1 year after infection.

METHODOLOGY:

• Researchers obtained 27 coronary autopsy specimens from eight patients who died from COVID-19, mean age 70 years and 75% male. All had coronary artery disease and most had cardiovascular risk factors such as hypertension, were overweight or obese, and had hyperlipidemia and type 2 diabetes.
• All but one patient, who was pronounced dead before hospital admission, were hospitalized for an average of 17.6 days.
• To identify SARS-CoV-2 viral RNA (vRNA) in the autoptic coronary vasculature, researchers performed RNA fluorescence in situ hybridization (RNA-FISH) analysis for the vRNA encoding the spike (S) protein; they also probed the antisense strand of the S gene (S antisense), which is only produced during viral replication.

TAKEAWAY:

• The study found evidence of SARS-CoV-2 replication in all analyzed human autopsy coronaries regardless of their pathological classification, although viral replication was highest in early-stage lesions that progress to more advanced atherosclerotic plaques.
• Findings indicated that more than 79% of macrophages (white blood cells that help remove lipids) and more than 90% of foam cells (lipid-laden macrophages that are a hallmark of atherosclerosis at all stages of the disease) are S+, and more than 40% of both cell types are S antisense+, indicating SARS-CoV-2 can infect macrophages at a high rate.
• SARS-CoV-2 induced a strong inflammatory response as evidenced by release of cytokines (including interleukin-1 beta and interluekin-6 that are linked to myocardial infarction) in both macrophages and foam cells, which may contribute to the ischemic cardiovascular complications in patients with COVID-19.

IN PRACTICE:

“Our data conclusively demonstrate that SARS-CoV-2 is capable of infecting and replicating in macrophages within the coronary vasculature of patients with COVID-19,” write the authors, adding that SARS-CoV-2 preferentially replicates in foam cells, compared with other macrophages, suggesting these cells “might act as a reservoir of SARS-CoV-2 viral debris in the atherosclerotic plaque.”

SOURCE:

The study was led by Natalia Eberhardt, PhD, postdoctoral fellow, department of medicine, division of cardiology, New York University, and colleagues. It was published online in Nature Cardiovascular Research.

LIMITATIONS:

Findings are relevant only to the original strains of SARS-CoV-2 that circulated in New York between May 2020 and May 2021, and are not generalizable to patients younger and healthier than those from whom samples were obtained for the study.

DISCLOSURES:

The study received support from the National Institutes of Health. The authors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

The quest to find an anticoagulant that can prevent strokes, cardiovascular events, and venous thrombosis without significantly increasing risk of bleeding is something of a holy grail in cardiovascular medicine. Could the latest focus of interest in this field – the factor XI inhibitors – be the long–sought-after answer?

Topline results from the largest study so far of a factor XI inhibitor – released on Sep. 18 – are indeed very encouraging. The phase 2 AZALEA-TIMI 71 study was stopped early because of an “overwhelming” reduction in major and clinically relevant nonmajor bleeding shown with the factor XI inhibitor abelacimab (Anthos), compared with apixaban for patients with atrial fibrillation (AFib).

Very few other data from this study have yet been released. Full results are due to be presented at the scientific sessions of the American Heart Association in November. Researchers in the field are optimistic that this new class of drugs may allow millions more patients who are at risk of thrombotic events but are concerned about bleeding risk to be treated, with a consequent reduction in strokes and possibly cardiovascular events as well.
 

Why factor XI?

The hope that factor XI inhibitors will prevent pathologic thrombosis with a lower bleeding risk, compared with other anticoagulants, comes down to the role of factor XI in the coagulation cascade.

In natural physiology, there are two ongoing processes: hemostasis – a set of actions that cause bleeding to stop after an injury – and thrombosis – a pathologic clotting process in which thrombus is formed and causes a stroke, MI, or deep venous thrombosis (DVT).

In patients prone to pathologic clotting, such as those with AFib, the balance of these two processes has shifted toward thrombosis, so anticoagulants are used to reduce the thrombotic risks. For many years, the only available oral anticoagulant was warfarin, a vitamin K antagonist that was very effective at preventing strokes but that comes with a high risk for bleeding, including intracranial hemorrhage (ICH) and fatal bleeding.

The introduction of the direct-acting anticoagulants (DOACs) a few years ago was a step forward in that these drugs have been shown to be as effective as warfarin but are associated with a lower risk of bleeding, particularly of ICH and fatal bleeding. But they still cause bleeding, and concerns over that risk of bleeding prevent millions of patients from taking these drugs and receiving protection against stroke.

John Alexander, MD, professor of medicine at Duke University Medical Center, Durham, N.C., a researcher active in this area, notes that “while the DOACs cause less bleeding than warfarin, they still cause two or three times more bleeding than placebo, and there is a huge, unmet need for safer anticoagulants that don’t cause as much bleeding. We are hopeful that factor XI inhibitors might be those anticoagulants.”

The lead investigator the AZALEA study, Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, explained why it is thought that factor XI inhibitors may be different.

“There’s a lot of different clotting factors, and most of them converge in a central pathway. The problem, therefore, with anticoagulants used to date that block one of these factors is that they prevent clotting but also cause bleeding.

“It has been discovered that factor XI has a really unique position in the cascade of how our body forms clots in that it seems to be important in clot formation, but it doesn’t seem to play a major role in our ability to heal and repair blood vessels.”

Another doctor involved in the field, Manesh Patel, MD, chief of cardiology at Duke University Medical Center, added, “We think that factor XI inhibitors may prevent the pathologic formation of thrombosis while allowing formation of thrombus for natural hemostasis to prevent bleeding. That is why they are so promising.”

This correlates with epidemiologic data suggesting that patients with a genetic factor XI deficiency have low rates of stroke and MI but don’t appear to bleed spontaneously, Dr. Patel notes.
 

Candidates in development

The pharmaceutical industry is on the case with several factor XI inhibitors now in clinical development. At present, three main candidates lead the field. These are abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and two small molecules, milvexian (BMS/Janssen) and asundexian (Bayer), which are both given orally.

Phase 3 trials of these three factor XI inhibitors have recently started for a variety of thrombotic indications, including the prevention of stroke in patients with AFib, prevention of recurrent stroke in patients with ischemic stroke, and prevention of future cardiovascular events in patients with acute coronary syndrome (ACS).

Dr. Alexander, who has been involved in clinical trials of both milvexian and asundexian, commented: “We have pretty good data from a number of phase 2 trials now that these factor XI inhibitors at the doses used in these studies cause a lot less bleeding than therapeutic doses of DOACs and low-molecular-weight heparins.”

He pointed out that, in addition to the AZALEA trial with abelacimab, the phase 2 PACIFIC program of studies has shown less bleeding with asundexian than with apixaban in patients with AFib and a similar amount of bleeding as placebo in ACS/stroke patients on top of antiplatelet therapy. Milvexian has also shown similar results in the AXIOMATIC program of studies.

Dr. Ruff noted that the biggest need for new anticoagulants in general is in the AFib population. “Atrial fibrillation is one of the most common medical conditions in the world. Approximately one in every three people will develop AFib in their lifetime, and it is associated with more than a fivefold increased risk of stroke. But up to half of patients with AFib currently do not take anticoagulants because of concerns about bleeding risks, so these patients are being left unprotected from stroke risk.”

Dr. Ruff pointed out that the AZALEA study was the largest and longest study of a factor XI inhibitor to date; 1,287 patients were followed for a median of 2 years.

“This was the first trial of long-term administration of factor XI inhibitor against a full-dose DOAC, and it was stopped because of an overwhelming reduction in a major bleeding with abelacimab, compared with rivaroxaban,” he noted. “That is very encouraging. It looks like our quest to develop a safe anticoagulant with much lower rates of bleeding, compared with standard of care, seems to have been borne out. I think the field is very excited that we may finally have something that protects patients from thrombosis whilst being much safer than current agents.”

While all this sounds very promising, for these drugs to be successful, in addition to reducing bleeding risk, they will also have to be effective at preventing strokes and other thrombotic events.

“While we are pretty sure that factor XI inhibitors will cause less bleeding than current anticoagulants, what is unknown still is how effective they will be at preventing pathologic blood clots,” Dr. Alexander points out.

“We have some data from studies of these drugs in DVT prophylaxis after orthopedic surgery which suggest that they are effective in preventing blood clots in that scenario. But we don’t know yet about whether they can prevent pathologic blood clots that occur in AFib patients or in poststroke or post-ACS patients. Phase 3 studies are now underway with these three leading drug candidates which will answer some of these questions.”

Dr. Patel agrees that the efficacy data in the phase 3 trials will be key to the success of these drugs. “That is a very important part of the puzzle that is still missing,” he says.

Dr. Ruff notes that the AZALEA study will provide some data on efficacy. “But we already know that in the orthopedic surgery trials there was a 70%-80% reduction in VTE with abelacimab (at the 150-mg dose going forward) vs. prophylactic doses of low-molecular-weight heparin. And we know from the DOACs that the doses preventing clots on the venous side also translated into preventing strokes on the [AFib] side. So that is very encouraging,” Dr. Ruff adds.
 

Potential indications

The three leading factor XI inhibitors have slightly different phase 3 development programs.

Dr. Ruff notes that not every agent is being investigated in phase 3 trials for all the potential indications, but all three are going for the AFib indication. “This is by far the biggest population, the biggest market, and the biggest clinical need for these agents,” he says.

While the milvexian and asundexian trials are using an active comparator – pitting the factor XI inhibitors against apixaban in AFib patients – the Anthos LILAC trial is taking a slightly different approach and is comparing abelacimab with placebo in patients with AFib who are not currently taking an anticoagulant because of concerns about bleeding risk.

Janssen/BMS is conducting two other phase 3 trials of milvexian in their LIBREXIA phase 3 program. Those trials involve poststroke patients and ACS patients. Bayer is also involved in a poststroke trial of asundexian as part of its OCEANIC phase 3 program.

Dr. Ruff points out that anticoagulants currently do not have a large role in the poststroke or post-ACS population. “But the hope is that, if factor XI inhibitors are so safe, then there will be more enthusiasm about using an anticoagulant on top of antiplatelet therapy, which is the cornerstone of therapy in atherosclerotic cardiovascular disease.”

In addition to its phase 3 LILAC study in patients with AFib, Anthos is conducting two major phase 3 trials with abelacimab for the treatment of cancer-associated venous thromboembolism.

Dr. Ruff notes that the indication of postsurgery or general prevention of VTE is not being pursued at present.

“The orthopedic surgery studies were done mainly for dose finding and proof of principle reasons,” he explains. “In orthopedic surgery the window for anticoagulation is quite short – a few weeks or months. And for the prevention of recurrent VTE in general in the community, those people are at a relatively low risk of bleeding, so there may not be much advantage of the factor XI inhibitors, whereas AFib patients and those with stroke or ACS are usually older and have a much higher bleeding risk. I think this is where the advantages of an anticoagulant with a lower bleeding risk are most needed.”

Dr. Alexander points out that to date anticoagulants have shown more efficacy in venous clotting, which appears to be more dependent on coagulation factors and less dependent on platelets. “Atrial fibrillation is a mix between venous and arterial clotting, but it has more similarities to venous, so I think AFib is a place where new anticoagulants such as the factor XI inhibitors are more likely to have success,” he suggests.

“So far, anticoagulants have had a less clear long-term role in the poststroke and post-ACS populations, so these indications may be a more difficult goal,” he added.

The phase 3 studies are just starting and will take a few years before results are known.
 

Differences between the agents

The three factor XI inhibitors also have some differences. Dr. Ruff points out that most important will be the safety and efficacy of the drugs in phase 3 trials.

“Early data suggest that the various agents being developed may not have equal inhibition of factor XI. The monoclonal antibody abelacimab may produce a higher degree of inhibition than the small molecules. But we don’t know if that matters or not – whether we need to achieve a certain threshold to prevent stroke. The efficacy and safety data from the phase 3 trials are what will primarily guide use.”

There are also differences in formulations and dosage. Abelacimab is administered by subcutaneous injection once a month and has a long duration of activity, whereas the small molecules are taken orally and their duration of action is much shorter.

Dr. Ruff notes: “If these drugs cause bleeding, having a long-acting drug like abelacimab could be a disadvantage because we wouldn’t be able to stop it. But if they are very safe with regard to bleeding, then having the drug hang around for a long time is not necessarily a disadvantage, and it may improve compliance. These older patients often miss doses, and with a shorter-acting drug, that will mean they will be unprotected from stroke risk for a period of time, so there is a trade-off here.”

Dr. Ruff says that the AZALEA phase 2 study will provide some data on patients being managed around procedures. “The hope is that these drugs are so safe that they will not have to be stopped for procedures. And then the compliance issue of a once-a-month dosing would be an advantage.”

Dr. Patel says he believes there is a place for different formations. “Some patients may prefer a once-monthly injection; others will prefer a daily tablet. It may come down to patient preference, but a lot will depend on the study results with the different agents,” he commented.
 

What effect could these drugs have?

If these drugs do show efficacy in these phase 3 trials, what difference will they make to clinical practice? The potential appears to be very large.

“If these drugs are as effective at preventing strokes as DOACs, they will be a huge breakthrough, and there is good reason to think they would replace the DOACs,” Dr. Alexander says. “It would be a really big deal to have an anticoagulant that causes almost no bleeding and could prevent clots as well as the DOACs. This would enable a lot more patients to receive protection against stroke.”

Dr. Alexander believes the surgery studies are hopeful. “They show that the factor XI inhibitors are doing something to prevent blood clots. The big question is whether they are as effective as what we already have for the prevention of stroke and if not, what is the trade-off with bleeding?”

He points out that, even if the factor XI inhibitors are not as effective as DOACs but are found to be much safer, they might still have a potential clinical role, especially for those patients who currently do not take an anticoagulant because of concerns regarding bleeding.

But Dr. Patel points out that there is always the issue of costs with new drugs. “New drugs are always expensive. The DOACS are just about to become generic, and there will inevitably be concerns about access to an expensive new therapy.”

Dr. Alexander adds: “Yes, costs could be an issue, but a safer drug will definitely help to get more patients treated and in preventing more strokes, which would be a great thing.”

Dr. Patel has received grants from and acts as an adviser to Bayer (asundexian) and Janssen (milvexian). Dr. Alexander receives research funding from Bayer. Dr. Ruff receives research funding from Anthos for abelacimab trials, is on an AFib executive committee for BMS/Janssen, and has been on an advisory board for Bayer.

A version of this article first appeared on Medscape.com.

The quest to find an anticoagulant that can prevent strokes, cardiovascular events, and venous thrombosis without significantly increasing risk of bleeding is something of a holy grail in cardiovascular medicine. Could the latest focus of interest in this field – the factor XI inhibitors – be the long–sought-after answer?

Topline results from the largest study so far of a factor XI inhibitor – released on Sep. 18 – are indeed very encouraging. The phase 2 AZALEA-TIMI 71 study was stopped early because of an “overwhelming” reduction in major and clinically relevant nonmajor bleeding shown with the factor XI inhibitor abelacimab (Anthos), compared with apixaban for patients with atrial fibrillation (AFib).

Very few other data from this study have yet been released. Full results are due to be presented at the scientific sessions of the American Heart Association in November. Researchers in the field are optimistic that this new class of drugs may allow millions more patients who are at risk of thrombotic events but are concerned about bleeding risk to be treated, with a consequent reduction in strokes and possibly cardiovascular events as well.
 

Why factor XI?

The hope that factor XI inhibitors will prevent pathologic thrombosis with a lower bleeding risk, compared with other anticoagulants, comes down to the role of factor XI in the coagulation cascade.

In natural physiology, there are two ongoing processes: hemostasis – a set of actions that cause bleeding to stop after an injury – and thrombosis – a pathologic clotting process in which thrombus is formed and causes a stroke, MI, or deep venous thrombosis (DVT).

In patients prone to pathologic clotting, such as those with AFib, the balance of these two processes has shifted toward thrombosis, so anticoagulants are used to reduce the thrombotic risks. For many years, the only available oral anticoagulant was warfarin, a vitamin K antagonist that was very effective at preventing strokes but that comes with a high risk for bleeding, including intracranial hemorrhage (ICH) and fatal bleeding.

The introduction of the direct-acting anticoagulants (DOACs) a few years ago was a step forward in that these drugs have been shown to be as effective as warfarin but are associated with a lower risk of bleeding, particularly of ICH and fatal bleeding. But they still cause bleeding, and concerns over that risk of bleeding prevent millions of patients from taking these drugs and receiving protection against stroke.

John Alexander, MD, professor of medicine at Duke University Medical Center, Durham, N.C., a researcher active in this area, notes that “while the DOACs cause less bleeding than warfarin, they still cause two or three times more bleeding than placebo, and there is a huge, unmet need for safer anticoagulants that don’t cause as much bleeding. We are hopeful that factor XI inhibitors might be those anticoagulants.”

The lead investigator the AZALEA study, Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, explained why it is thought that factor XI inhibitors may be different.

“There’s a lot of different clotting factors, and most of them converge in a central pathway. The problem, therefore, with anticoagulants used to date that block one of these factors is that they prevent clotting but also cause bleeding.

“It has been discovered that factor XI has a really unique position in the cascade of how our body forms clots in that it seems to be important in clot formation, but it doesn’t seem to play a major role in our ability to heal and repair blood vessels.”

Another doctor involved in the field, Manesh Patel, MD, chief of cardiology at Duke University Medical Center, added, “We think that factor XI inhibitors may prevent the pathologic formation of thrombosis while allowing formation of thrombus for natural hemostasis to prevent bleeding. That is why they are so promising.”

This correlates with epidemiologic data suggesting that patients with a genetic factor XI deficiency have low rates of stroke and MI but don’t appear to bleed spontaneously, Dr. Patel notes.
 

Candidates in development

The pharmaceutical industry is on the case with several factor XI inhibitors now in clinical development. At present, three main candidates lead the field. These are abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and two small molecules, milvexian (BMS/Janssen) and asundexian (Bayer), which are both given orally.

Phase 3 trials of these three factor XI inhibitors have recently started for a variety of thrombotic indications, including the prevention of stroke in patients with AFib, prevention of recurrent stroke in patients with ischemic stroke, and prevention of future cardiovascular events in patients with acute coronary syndrome (ACS).

Dr. Alexander, who has been involved in clinical trials of both milvexian and asundexian, commented: “We have pretty good data from a number of phase 2 trials now that these factor XI inhibitors at the doses used in these studies cause a lot less bleeding than therapeutic doses of DOACs and low-molecular-weight heparins.”

He pointed out that, in addition to the AZALEA trial with abelacimab, the phase 2 PACIFIC program of studies has shown less bleeding with asundexian than with apixaban in patients with AFib and a similar amount of bleeding as placebo in ACS/stroke patients on top of antiplatelet therapy. Milvexian has also shown similar results in the AXIOMATIC program of studies.

Dr. Ruff noted that the biggest need for new anticoagulants in general is in the AFib population. “Atrial fibrillation is one of the most common medical conditions in the world. Approximately one in every three people will develop AFib in their lifetime, and it is associated with more than a fivefold increased risk of stroke. But up to half of patients with AFib currently do not take anticoagulants because of concerns about bleeding risks, so these patients are being left unprotected from stroke risk.”

Dr. Ruff pointed out that the AZALEA study was the largest and longest study of a factor XI inhibitor to date; 1,287 patients were followed for a median of 2 years.

“This was the first trial of long-term administration of factor XI inhibitor against a full-dose DOAC, and it was stopped because of an overwhelming reduction in a major bleeding with abelacimab, compared with rivaroxaban,” he noted. “That is very encouraging. It looks like our quest to develop a safe anticoagulant with much lower rates of bleeding, compared with standard of care, seems to have been borne out. I think the field is very excited that we may finally have something that protects patients from thrombosis whilst being much safer than current agents.”

While all this sounds very promising, for these drugs to be successful, in addition to reducing bleeding risk, they will also have to be effective at preventing strokes and other thrombotic events.

“While we are pretty sure that factor XI inhibitors will cause less bleeding than current anticoagulants, what is unknown still is how effective they will be at preventing pathologic blood clots,” Dr. Alexander points out.

“We have some data from studies of these drugs in DVT prophylaxis after orthopedic surgery which suggest that they are effective in preventing blood clots in that scenario. But we don’t know yet about whether they can prevent pathologic blood clots that occur in AFib patients or in poststroke or post-ACS patients. Phase 3 studies are now underway with these three leading drug candidates which will answer some of these questions.”

Dr. Patel agrees that the efficacy data in the phase 3 trials will be key to the success of these drugs. “That is a very important part of the puzzle that is still missing,” he says.

Dr. Ruff notes that the AZALEA study will provide some data on efficacy. “But we already know that in the orthopedic surgery trials there was a 70%-80% reduction in VTE with abelacimab (at the 150-mg dose going forward) vs. prophylactic doses of low-molecular-weight heparin. And we know from the DOACs that the doses preventing clots on the venous side also translated into preventing strokes on the [AFib] side. So that is very encouraging,” Dr. Ruff adds.
 

Potential indications

The three leading factor XI inhibitors have slightly different phase 3 development programs.

Dr. Ruff notes that not every agent is being investigated in phase 3 trials for all the potential indications, but all three are going for the AFib indication. “This is by far the biggest population, the biggest market, and the biggest clinical need for these agents,” he says.

While the milvexian and asundexian trials are using an active comparator – pitting the factor XI inhibitors against apixaban in AFib patients – the Anthos LILAC trial is taking a slightly different approach and is comparing abelacimab with placebo in patients with AFib who are not currently taking an anticoagulant because of concerns about bleeding risk.

Janssen/BMS is conducting two other phase 3 trials of milvexian in their LIBREXIA phase 3 program. Those trials involve poststroke patients and ACS patients. Bayer is also involved in a poststroke trial of asundexian as part of its OCEANIC phase 3 program.

Dr. Ruff points out that anticoagulants currently do not have a large role in the poststroke or post-ACS population. “But the hope is that, if factor XI inhibitors are so safe, then there will be more enthusiasm about using an anticoagulant on top of antiplatelet therapy, which is the cornerstone of therapy in atherosclerotic cardiovascular disease.”

In addition to its phase 3 LILAC study in patients with AFib, Anthos is conducting two major phase 3 trials with abelacimab for the treatment of cancer-associated venous thromboembolism.

Dr. Ruff notes that the indication of postsurgery or general prevention of VTE is not being pursued at present.

“The orthopedic surgery studies were done mainly for dose finding and proof of principle reasons,” he explains. “In orthopedic surgery the window for anticoagulation is quite short – a few weeks or months. And for the prevention of recurrent VTE in general in the community, those people are at a relatively low risk of bleeding, so there may not be much advantage of the factor XI inhibitors, whereas AFib patients and those with stroke or ACS are usually older and have a much higher bleeding risk. I think this is where the advantages of an anticoagulant with a lower bleeding risk are most needed.”

Dr. Alexander points out that to date anticoagulants have shown more efficacy in venous clotting, which appears to be more dependent on coagulation factors and less dependent on platelets. “Atrial fibrillation is a mix between venous and arterial clotting, but it has more similarities to venous, so I think AFib is a place where new anticoagulants such as the factor XI inhibitors are more likely to have success,” he suggests.

“So far, anticoagulants have had a less clear long-term role in the poststroke and post-ACS populations, so these indications may be a more difficult goal,” he added.

The phase 3 studies are just starting and will take a few years before results are known.
 

Differences between the agents

The three factor XI inhibitors also have some differences. Dr. Ruff points out that most important will be the safety and efficacy of the drugs in phase 3 trials.

“Early data suggest that the various agents being developed may not have equal inhibition of factor XI. The monoclonal antibody abelacimab may produce a higher degree of inhibition than the small molecules. But we don’t know if that matters or not – whether we need to achieve a certain threshold to prevent stroke. The efficacy and safety data from the phase 3 trials are what will primarily guide use.”

There are also differences in formulations and dosage. Abelacimab is administered by subcutaneous injection once a month and has a long duration of activity, whereas the small molecules are taken orally and their duration of action is much shorter.

Dr. Ruff notes: “If these drugs cause bleeding, having a long-acting drug like abelacimab could be a disadvantage because we wouldn’t be able to stop it. But if they are very safe with regard to bleeding, then having the drug hang around for a long time is not necessarily a disadvantage, and it may improve compliance. These older patients often miss doses, and with a shorter-acting drug, that will mean they will be unprotected from stroke risk for a period of time, so there is a trade-off here.”

Dr. Ruff says that the AZALEA phase 2 study will provide some data on patients being managed around procedures. “The hope is that these drugs are so safe that they will not have to be stopped for procedures. And then the compliance issue of a once-a-month dosing would be an advantage.”

Dr. Patel says he believes there is a place for different formations. “Some patients may prefer a once-monthly injection; others will prefer a daily tablet. It may come down to patient preference, but a lot will depend on the study results with the different agents,” he commented.
 

What effect could these drugs have?

If these drugs do show efficacy in these phase 3 trials, what difference will they make to clinical practice? The potential appears to be very large.

“If these drugs are as effective at preventing strokes as DOACs, they will be a huge breakthrough, and there is good reason to think they would replace the DOACs,” Dr. Alexander says. “It would be a really big deal to have an anticoagulant that causes almost no bleeding and could prevent clots as well as the DOACs. This would enable a lot more patients to receive protection against stroke.”

Dr. Alexander believes the surgery studies are hopeful. “They show that the factor XI inhibitors are doing something to prevent blood clots. The big question is whether they are as effective as what we already have for the prevention of stroke and if not, what is the trade-off with bleeding?”

He points out that, even if the factor XI inhibitors are not as effective as DOACs but are found to be much safer, they might still have a potential clinical role, especially for those patients who currently do not take an anticoagulant because of concerns regarding bleeding.

But Dr. Patel points out that there is always the issue of costs with new drugs. “New drugs are always expensive. The DOACS are just about to become generic, and there will inevitably be concerns about access to an expensive new therapy.”

Dr. Alexander adds: “Yes, costs could be an issue, but a safer drug will definitely help to get more patients treated and in preventing more strokes, which would be a great thing.”

Dr. Patel has received grants from and acts as an adviser to Bayer (asundexian) and Janssen (milvexian). Dr. Alexander receives research funding from Bayer. Dr. Ruff receives research funding from Anthos for abelacimab trials, is on an AFib executive committee for BMS/Janssen, and has been on an advisory board for Bayer.

A version of this article first appeared on Medscape.com.

The quest to find an anticoagulant that can prevent strokes, cardiovascular events, and venous thrombosis without significantly increasing risk of bleeding is something of a holy grail in cardiovascular medicine. Could the latest focus of interest in this field – the factor XI inhibitors – be the long–sought-after answer?

Topline results from the largest study so far of a factor XI inhibitor – released on Sep. 18 – are indeed very encouraging. The phase 2 AZALEA-TIMI 71 study was stopped early because of an “overwhelming” reduction in major and clinically relevant nonmajor bleeding shown with the factor XI inhibitor abelacimab (Anthos), compared with apixaban for patients with atrial fibrillation (AFib).

Very few other data from this study have yet been released. Full results are due to be presented at the scientific sessions of the American Heart Association in November. Researchers in the field are optimistic that this new class of drugs may allow millions more patients who are at risk of thrombotic events but are concerned about bleeding risk to be treated, with a consequent reduction in strokes and possibly cardiovascular events as well.
 

Why factor XI?

The hope that factor XI inhibitors will prevent pathologic thrombosis with a lower bleeding risk, compared with other anticoagulants, comes down to the role of factor XI in the coagulation cascade.

In natural physiology, there are two ongoing processes: hemostasis – a set of actions that cause bleeding to stop after an injury – and thrombosis – a pathologic clotting process in which thrombus is formed and causes a stroke, MI, or deep venous thrombosis (DVT).

In patients prone to pathologic clotting, such as those with AFib, the balance of these two processes has shifted toward thrombosis, so anticoagulants are used to reduce the thrombotic risks. For many years, the only available oral anticoagulant was warfarin, a vitamin K antagonist that was very effective at preventing strokes but that comes with a high risk for bleeding, including intracranial hemorrhage (ICH) and fatal bleeding.

The introduction of the direct-acting anticoagulants (DOACs) a few years ago was a step forward in that these drugs have been shown to be as effective as warfarin but are associated with a lower risk of bleeding, particularly of ICH and fatal bleeding. But they still cause bleeding, and concerns over that risk of bleeding prevent millions of patients from taking these drugs and receiving protection against stroke.

John Alexander, MD, professor of medicine at Duke University Medical Center, Durham, N.C., a researcher active in this area, notes that “while the DOACs cause less bleeding than warfarin, they still cause two or three times more bleeding than placebo, and there is a huge, unmet need for safer anticoagulants that don’t cause as much bleeding. We are hopeful that factor XI inhibitors might be those anticoagulants.”

The lead investigator the AZALEA study, Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, explained why it is thought that factor XI inhibitors may be different.

“There’s a lot of different clotting factors, and most of them converge in a central pathway. The problem, therefore, with anticoagulants used to date that block one of these factors is that they prevent clotting but also cause bleeding.

“It has been discovered that factor XI has a really unique position in the cascade of how our body forms clots in that it seems to be important in clot formation, but it doesn’t seem to play a major role in our ability to heal and repair blood vessels.”

Another doctor involved in the field, Manesh Patel, MD, chief of cardiology at Duke University Medical Center, added, “We think that factor XI inhibitors may prevent the pathologic formation of thrombosis while allowing formation of thrombus for natural hemostasis to prevent bleeding. That is why they are so promising.”

This correlates with epidemiologic data suggesting that patients with a genetic factor XI deficiency have low rates of stroke and MI but don’t appear to bleed spontaneously, Dr. Patel notes.
 

Candidates in development

The pharmaceutical industry is on the case with several factor XI inhibitors now in clinical development. At present, three main candidates lead the field. These are abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and two small molecules, milvexian (BMS/Janssen) and asundexian (Bayer), which are both given orally.

Phase 3 trials of these three factor XI inhibitors have recently started for a variety of thrombotic indications, including the prevention of stroke in patients with AFib, prevention of recurrent stroke in patients with ischemic stroke, and prevention of future cardiovascular events in patients with acute coronary syndrome (ACS).

Dr. Alexander, who has been involved in clinical trials of both milvexian and asundexian, commented: “We have pretty good data from a number of phase 2 trials now that these factor XI inhibitors at the doses used in these studies cause a lot less bleeding than therapeutic doses of DOACs and low-molecular-weight heparins.”

He pointed out that, in addition to the AZALEA trial with abelacimab, the phase 2 PACIFIC program of studies has shown less bleeding with asundexian than with apixaban in patients with AFib and a similar amount of bleeding as placebo in ACS/stroke patients on top of antiplatelet therapy. Milvexian has also shown similar results in the AXIOMATIC program of studies.

Dr. Ruff noted that the biggest need for new anticoagulants in general is in the AFib population. “Atrial fibrillation is one of the most common medical conditions in the world. Approximately one in every three people will develop AFib in their lifetime, and it is associated with more than a fivefold increased risk of stroke. But up to half of patients with AFib currently do not take anticoagulants because of concerns about bleeding risks, so these patients are being left unprotected from stroke risk.”

Dr. Ruff pointed out that the AZALEA study was the largest and longest study of a factor XI inhibitor to date; 1,287 patients were followed for a median of 2 years.

“This was the first trial of long-term administration of factor XI inhibitor against a full-dose DOAC, and it was stopped because of an overwhelming reduction in a major bleeding with abelacimab, compared with rivaroxaban,” he noted. “That is very encouraging. It looks like our quest to develop a safe anticoagulant with much lower rates of bleeding, compared with standard of care, seems to have been borne out. I think the field is very excited that we may finally have something that protects patients from thrombosis whilst being much safer than current agents.”

While all this sounds very promising, for these drugs to be successful, in addition to reducing bleeding risk, they will also have to be effective at preventing strokes and other thrombotic events.

“While we are pretty sure that factor XI inhibitors will cause less bleeding than current anticoagulants, what is unknown still is how effective they will be at preventing pathologic blood clots,” Dr. Alexander points out.

“We have some data from studies of these drugs in DVT prophylaxis after orthopedic surgery which suggest that they are effective in preventing blood clots in that scenario. But we don’t know yet about whether they can prevent pathologic blood clots that occur in AFib patients or in poststroke or post-ACS patients. Phase 3 studies are now underway with these three leading drug candidates which will answer some of these questions.”

Dr. Patel agrees that the efficacy data in the phase 3 trials will be key to the success of these drugs. “That is a very important part of the puzzle that is still missing,” he says.

Dr. Ruff notes that the AZALEA study will provide some data on efficacy. “But we already know that in the orthopedic surgery trials there was a 70%-80% reduction in VTE with abelacimab (at the 150-mg dose going forward) vs. prophylactic doses of low-molecular-weight heparin. And we know from the DOACs that the doses preventing clots on the venous side also translated into preventing strokes on the [AFib] side. So that is very encouraging,” Dr. Ruff adds.
 

Potential indications

The three leading factor XI inhibitors have slightly different phase 3 development programs.

Dr. Ruff notes that not every agent is being investigated in phase 3 trials for all the potential indications, but all three are going for the AFib indication. “This is by far the biggest population, the biggest market, and the biggest clinical need for these agents,” he says.

While the milvexian and asundexian trials are using an active comparator – pitting the factor XI inhibitors against apixaban in AFib patients – the Anthos LILAC trial is taking a slightly different approach and is comparing abelacimab with placebo in patients with AFib who are not currently taking an anticoagulant because of concerns about bleeding risk.

Janssen/BMS is conducting two other phase 3 trials of milvexian in their LIBREXIA phase 3 program. Those trials involve poststroke patients and ACS patients. Bayer is also involved in a poststroke trial of asundexian as part of its OCEANIC phase 3 program.

Dr. Ruff points out that anticoagulants currently do not have a large role in the poststroke or post-ACS population. “But the hope is that, if factor XI inhibitors are so safe, then there will be more enthusiasm about using an anticoagulant on top of antiplatelet therapy, which is the cornerstone of therapy in atherosclerotic cardiovascular disease.”

In addition to its phase 3 LILAC study in patients with AFib, Anthos is conducting two major phase 3 trials with abelacimab for the treatment of cancer-associated venous thromboembolism.

Dr. Ruff notes that the indication of postsurgery or general prevention of VTE is not being pursued at present.

“The orthopedic surgery studies were done mainly for dose finding and proof of principle reasons,” he explains. “In orthopedic surgery the window for anticoagulation is quite short – a few weeks or months. And for the prevention of recurrent VTE in general in the community, those people are at a relatively low risk of bleeding, so there may not be much advantage of the factor XI inhibitors, whereas AFib patients and those with stroke or ACS are usually older and have a much higher bleeding risk. I think this is where the advantages of an anticoagulant with a lower bleeding risk are most needed.”

Dr. Alexander points out that to date anticoagulants have shown more efficacy in venous clotting, which appears to be more dependent on coagulation factors and less dependent on platelets. “Atrial fibrillation is a mix between venous and arterial clotting, but it has more similarities to venous, so I think AFib is a place where new anticoagulants such as the factor XI inhibitors are more likely to have success,” he suggests.

“So far, anticoagulants have had a less clear long-term role in the poststroke and post-ACS populations, so these indications may be a more difficult goal,” he added.

The phase 3 studies are just starting and will take a few years before results are known.
 

Differences between the agents

The three factor XI inhibitors also have some differences. Dr. Ruff points out that most important will be the safety and efficacy of the drugs in phase 3 trials.

“Early data suggest that the various agents being developed may not have equal inhibition of factor XI. The monoclonal antibody abelacimab may produce a higher degree of inhibition than the small molecules. But we don’t know if that matters or not – whether we need to achieve a certain threshold to prevent stroke. The efficacy and safety data from the phase 3 trials are what will primarily guide use.”

There are also differences in formulations and dosage. Abelacimab is administered by subcutaneous injection once a month and has a long duration of activity, whereas the small molecules are taken orally and their duration of action is much shorter.

Dr. Ruff notes: “If these drugs cause bleeding, having a long-acting drug like abelacimab could be a disadvantage because we wouldn’t be able to stop it. But if they are very safe with regard to bleeding, then having the drug hang around for a long time is not necessarily a disadvantage, and it may improve compliance. These older patients often miss doses, and with a shorter-acting drug, that will mean they will be unprotected from stroke risk for a period of time, so there is a trade-off here.”

Dr. Ruff says that the AZALEA phase 2 study will provide some data on patients being managed around procedures. “The hope is that these drugs are so safe that they will not have to be stopped for procedures. And then the compliance issue of a once-a-month dosing would be an advantage.”

Dr. Patel says he believes there is a place for different formations. “Some patients may prefer a once-monthly injection; others will prefer a daily tablet. It may come down to patient preference, but a lot will depend on the study results with the different agents,” he commented.
 

What effect could these drugs have?

If these drugs do show efficacy in these phase 3 trials, what difference will they make to clinical practice? The potential appears to be very large.

“If these drugs are as effective at preventing strokes as DOACs, they will be a huge breakthrough, and there is good reason to think they would replace the DOACs,” Dr. Alexander says. “It would be a really big deal to have an anticoagulant that causes almost no bleeding and could prevent clots as well as the DOACs. This would enable a lot more patients to receive protection against stroke.”

Dr. Alexander believes the surgery studies are hopeful. “They show that the factor XI inhibitors are doing something to prevent blood clots. The big question is whether they are as effective as what we already have for the prevention of stroke and if not, what is the trade-off with bleeding?”

He points out that, even if the factor XI inhibitors are not as effective as DOACs but are found to be much safer, they might still have a potential clinical role, especially for those patients who currently do not take an anticoagulant because of concerns regarding bleeding.

But Dr. Patel points out that there is always the issue of costs with new drugs. “New drugs are always expensive. The DOACS are just about to become generic, and there will inevitably be concerns about access to an expensive new therapy.”

Dr. Alexander adds: “Yes, costs could be an issue, but a safer drug will definitely help to get more patients treated and in preventing more strokes, which would be a great thing.”

Dr. Patel has received grants from and acts as an adviser to Bayer (asundexian) and Janssen (milvexian). Dr. Alexander receives research funding from Bayer. Dr. Ruff receives research funding from Anthos for abelacimab trials, is on an AFib executive committee for BMS/Janssen, and has been on an advisory board for Bayer.

A version of this article first appeared on Medscape.com.

Moving from one residence to another after an acute myocardial infarction (AMI) significantly increases the risk for death or transition to a long-term care facility as an end-of-life measure, data suggest.

In a prospective study that followed more than 3,000 patients with AMI over 2 decades, each residential move was associated with a 12% higher rate of death.

“This study determined that residential mobility was more important than any other social factor that we studied,” investigator David Alter, MD, PhD, chair of cardiovascular and metabolic research at the University Health Network–Toronto Rehabilitation Institute and associate professor of medicine at the University of Toronto, said in an interview.

The results were published online in the Canadian Journal of Cardiology.
 

Moving and mortality

“There’s been very little work, surprisingly, on what happens when individuals move from community to community,” said Dr. Alter. “It is that movement from community to community that is a factor within the social context that needs to be explored better. To the best of our knowledge, up until our study, it has been studied very briefly in the literature.”

The prospective cohort study sample included 3,369 patients who had an AMI between Dec. 1, 1999, and March 30, 2023. The investigators followed participants until death or the last available follow-up date of March 30, 2020. They defined a residential move as a relocation from one postal code region to another.

The investigators drew data from multiple sources, including the prospective, observational Socio-Economic Status and Acute Myocardial Infarction study, which encompassed more than 35,000 patient life-years following hospitalization for a first heart attack in Ontario. Mortality data were collected from the Ontario Registered Persons Data Base. Other sources included Statistics Canada for information on neighborhood income, the Canadian Institutes for Health Information for patients’ clinical factors and comorbidities, and the Ontario Health Insurance Plan (OHIP) database for physician visits. Information on long-term care admissions came from the Continuous Care Reporting System-Long Term Care, OHIP, and the Ontario Drugs Benefit databases, the latter of which also provided information on medication prescriptions for individuals aged 65 years and older.

Patients’ ages ranged from 19 to 101 years (median age, 65 years). About 69% of patients were men. Of the study population, 1,828 patients (54.3%) had at least one residential move during the study period. Approximately 87% died in the community or moved from home into a long-term care facility as an end-of-life destination. Overall, 84.8% of patients who were admitted to long-term care facilities died.

The study also tracked the socioeconomic status of persons living in the postal code regions from and to which patients moved. About 32% of patients moved to a neighborhood with a lower socioeconomic status, and 30.5% moved to an area with a higher socioeconomic status.

Each residential move was associated with a 12% higher rate of death and a 26% higher rate of long-term institutionalization for end-of-life care. In unadjusted analyses, the rate of death was almost double for those who moved more frequently: 44.3% for those who moved two or more times versus 24.8% for those who moved once in 10 years.

Accounting for a multitude of variables, such as the socioeconomic status of areas that patients moved between, is a strength of the study, said Dr. Alter. But the study lacked information about why people moved.

“Where this study has a huge amount of strength is that it was designed specifically to really understand a patient’s clinical and psychosocial profile at the start of their journey, their first AMI. But the fact that we took it from heart attack onward is also a strength because it characterizes and anchors a clinical context in which we were following patients out,” said Dr. Alter.
 

‘An important marker’

In a comment, Paul Oh, MD, medical director of the cardiovascular disease prevention and rehabilitation program at University Health Network, said: “This is a very well-designed study and analysis from a cohort that has provided important insights about the role of socioeconomic factors and long-term outcomes post MI over many years.” Dr. Oh did not participate in the study.

“A few covariates that could impact on outcomes, like institutionalization, were not available to include in adjusted analyses – e.g., functional status, frailty, mild cognitive changes, and availability of social supports in the home,” he said.

The findings add another variable that cardiologists who care for post-MI patients need to be aware of, Dr. Oh added. “Clinicians need better awareness that the need to change residence is an important marker of changing health status and may portend end-of-life events in the near future. The need to change residence can signal an important change in physical, cognitive, and social circumstances that needs to be further explored during clinical encounters, with the goal of identifying and addressing any potentially reversible issues and identifying additional supports that may help that individual continue to live independently in their own home.”

The study was supported by ICES, which receives funding from the Ontario Ministry of Health. The investigators disclosed no relevant financial relationships. Dr. Oh serves on research boards for Lilly and Novartis and receives research funding from Apple.

A version of this article first appeared on Medscape.com.

Moving from one residence to another after an acute myocardial infarction (AMI) significantly increases the risk for death or transition to a long-term care facility as an end-of-life measure, data suggest.

In a prospective study that followed more than 3,000 patients with AMI over 2 decades, each residential move was associated with a 12% higher rate of death.

“This study determined that residential mobility was more important than any other social factor that we studied,” investigator David Alter, MD, PhD, chair of cardiovascular and metabolic research at the University Health Network–Toronto Rehabilitation Institute and associate professor of medicine at the University of Toronto, said in an interview.

The results were published online in the Canadian Journal of Cardiology.
 

Moving and mortality

“There’s been very little work, surprisingly, on what happens when individuals move from community to community,” said Dr. Alter. “It is that movement from community to community that is a factor within the social context that needs to be explored better. To the best of our knowledge, up until our study, it has been studied very briefly in the literature.”

The prospective cohort study sample included 3,369 patients who had an AMI between Dec. 1, 1999, and March 30, 2023. The investigators followed participants until death or the last available follow-up date of March 30, 2020. They defined a residential move as a relocation from one postal code region to another.

The investigators drew data from multiple sources, including the prospective, observational Socio-Economic Status and Acute Myocardial Infarction study, which encompassed more than 35,000 patient life-years following hospitalization for a first heart attack in Ontario. Mortality data were collected from the Ontario Registered Persons Data Base. Other sources included Statistics Canada for information on neighborhood income, the Canadian Institutes for Health Information for patients’ clinical factors and comorbidities, and the Ontario Health Insurance Plan (OHIP) database for physician visits. Information on long-term care admissions came from the Continuous Care Reporting System-Long Term Care, OHIP, and the Ontario Drugs Benefit databases, the latter of which also provided information on medication prescriptions for individuals aged 65 years and older.

Patients’ ages ranged from 19 to 101 years (median age, 65 years). About 69% of patients were men. Of the study population, 1,828 patients (54.3%) had at least one residential move during the study period. Approximately 87% died in the community or moved from home into a long-term care facility as an end-of-life destination. Overall, 84.8% of patients who were admitted to long-term care facilities died.

The study also tracked the socioeconomic status of persons living in the postal code regions from and to which patients moved. About 32% of patients moved to a neighborhood with a lower socioeconomic status, and 30.5% moved to an area with a higher socioeconomic status.

Each residential move was associated with a 12% higher rate of death and a 26% higher rate of long-term institutionalization for end-of-life care. In unadjusted analyses, the rate of death was almost double for those who moved more frequently: 44.3% for those who moved two or more times versus 24.8% for those who moved once in 10 years.

Accounting for a multitude of variables, such as the socioeconomic status of areas that patients moved between, is a strength of the study, said Dr. Alter. But the study lacked information about why people moved.

“Where this study has a huge amount of strength is that it was designed specifically to really understand a patient’s clinical and psychosocial profile at the start of their journey, their first AMI. But the fact that we took it from heart attack onward is also a strength because it characterizes and anchors a clinical context in which we were following patients out,” said Dr. Alter.
 

‘An important marker’

In a comment, Paul Oh, MD, medical director of the cardiovascular disease prevention and rehabilitation program at University Health Network, said: “This is a very well-designed study and analysis from a cohort that has provided important insights about the role of socioeconomic factors and long-term outcomes post MI over many years.” Dr. Oh did not participate in the study.

“A few covariates that could impact on outcomes, like institutionalization, were not available to include in adjusted analyses – e.g., functional status, frailty, mild cognitive changes, and availability of social supports in the home,” he said.

The findings add another variable that cardiologists who care for post-MI patients need to be aware of, Dr. Oh added. “Clinicians need better awareness that the need to change residence is an important marker of changing health status and may portend end-of-life events in the near future. The need to change residence can signal an important change in physical, cognitive, and social circumstances that needs to be further explored during clinical encounters, with the goal of identifying and addressing any potentially reversible issues and identifying additional supports that may help that individual continue to live independently in their own home.”

The study was supported by ICES, which receives funding from the Ontario Ministry of Health. The investigators disclosed no relevant financial relationships. Dr. Oh serves on research boards for Lilly and Novartis and receives research funding from Apple.

A version of this article first appeared on Medscape.com.

Moving from one residence to another after an acute myocardial infarction (AMI) significantly increases the risk for death or transition to a long-term care facility as an end-of-life measure, data suggest.

In a prospective study that followed more than 3,000 patients with AMI over 2 decades, each residential move was associated with a 12% higher rate of death.

“This study determined that residential mobility was more important than any other social factor that we studied,” investigator David Alter, MD, PhD, chair of cardiovascular and metabolic research at the University Health Network–Toronto Rehabilitation Institute and associate professor of medicine at the University of Toronto, said in an interview.

The results were published online in the Canadian Journal of Cardiology.
 

Moving and mortality

“There’s been very little work, surprisingly, on what happens when individuals move from community to community,” said Dr. Alter. “It is that movement from community to community that is a factor within the social context that needs to be explored better. To the best of our knowledge, up until our study, it has been studied very briefly in the literature.”

The prospective cohort study sample included 3,369 patients who had an AMI between Dec. 1, 1999, and March 30, 2023. The investigators followed participants until death or the last available follow-up date of March 30, 2020. They defined a residential move as a relocation from one postal code region to another.

The investigators drew data from multiple sources, including the prospective, observational Socio-Economic Status and Acute Myocardial Infarction study, which encompassed more than 35,000 patient life-years following hospitalization for a first heart attack in Ontario. Mortality data were collected from the Ontario Registered Persons Data Base. Other sources included Statistics Canada for information on neighborhood income, the Canadian Institutes for Health Information for patients’ clinical factors and comorbidities, and the Ontario Health Insurance Plan (OHIP) database for physician visits. Information on long-term care admissions came from the Continuous Care Reporting System-Long Term Care, OHIP, and the Ontario Drugs Benefit databases, the latter of which also provided information on medication prescriptions for individuals aged 65 years and older.

Patients’ ages ranged from 19 to 101 years (median age, 65 years). About 69% of patients were men. Of the study population, 1,828 patients (54.3%) had at least one residential move during the study period. Approximately 87% died in the community or moved from home into a long-term care facility as an end-of-life destination. Overall, 84.8% of patients who were admitted to long-term care facilities died.

The study also tracked the socioeconomic status of persons living in the postal code regions from and to which patients moved. About 32% of patients moved to a neighborhood with a lower socioeconomic status, and 30.5% moved to an area with a higher socioeconomic status.

Each residential move was associated with a 12% higher rate of death and a 26% higher rate of long-term institutionalization for end-of-life care. In unadjusted analyses, the rate of death was almost double for those who moved more frequently: 44.3% for those who moved two or more times versus 24.8% for those who moved once in 10 years.

Accounting for a multitude of variables, such as the socioeconomic status of areas that patients moved between, is a strength of the study, said Dr. Alter. But the study lacked information about why people moved.

“Where this study has a huge amount of strength is that it was designed specifically to really understand a patient’s clinical and psychosocial profile at the start of their journey, their first AMI. But the fact that we took it from heart attack onward is also a strength because it characterizes and anchors a clinical context in which we were following patients out,” said Dr. Alter.
 

‘An important marker’

In a comment, Paul Oh, MD, medical director of the cardiovascular disease prevention and rehabilitation program at University Health Network, said: “This is a very well-designed study and analysis from a cohort that has provided important insights about the role of socioeconomic factors and long-term outcomes post MI over many years.” Dr. Oh did not participate in the study.

“A few covariates that could impact on outcomes, like institutionalization, were not available to include in adjusted analyses – e.g., functional status, frailty, mild cognitive changes, and availability of social supports in the home,” he said.

The findings add another variable that cardiologists who care for post-MI patients need to be aware of, Dr. Oh added. “Clinicians need better awareness that the need to change residence is an important marker of changing health status and may portend end-of-life events in the near future. The need to change residence can signal an important change in physical, cognitive, and social circumstances that needs to be further explored during clinical encounters, with the goal of identifying and addressing any potentially reversible issues and identifying additional supports that may help that individual continue to live independently in their own home.”

The study was supported by ICES, which receives funding from the Ontario Ministry of Health. The investigators disclosed no relevant financial relationships. Dr. Oh serves on research boards for Lilly and Novartis and receives research funding from Apple.

A version of this article first appeared on Medscape.com.

A lack of standardized blood pressure training among doctors, physician assistants, nurses, and other health care professionals is preventing the country’s medical community from curbing hypertension, according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.

First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.

The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.

The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.

The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.

In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.

Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.

The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.

Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.

Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.

Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.

Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.

Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.

A version of this article first appeared on Medscape.com.

A lack of standardized blood pressure training among doctors, physician assistants, nurses, and other health care professionals is preventing the country’s medical community from curbing hypertension, according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.

First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.

The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.

The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.

The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.

In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.

Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.

The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.

Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.

Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.

Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.

Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.

Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.

A version of this article first appeared on Medscape.com.

A lack of standardized blood pressure training among doctors, physician assistants, nurses, and other health care professionals is preventing the country’s medical community from curbing hypertension, according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.

First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.

The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.

The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.

The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.

In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.

Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.

The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.

Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.

Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.

Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.

Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.

Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.

A version of this article first appeared on Medscape.com.

Some physicians are frustrated that key information about implantable medical devices rarely makes it into electronic health records, despite a 10-year mandate on manufacturers to label these products with identifiers.

As a result of this siloing of information, patients are not getting the expected benefits of a regulation finalized over a decade ago by the U.S. Food and Drug Administration.

In 2013, the agency ordered companies to include unique device identifiers (UDIs) in plain-text and barcode format on some device labels, starting with implanted devices that are considered life-sustaining. The FDA said that tracking of UDI information would speed detection of complications linked to devices.

But identifiers are rarely on devices. At the time of the regulation creation, the FDA also said it expected this data would be integrated into EHRs. But only a few pioneer organizations such as Duke University and Mercy Health have so far attempted to track any UDI data in an organized way, researchers say.

Richard J. Kovacs, MD, the chief medical officer of the American College of Cardiology, contrasted the lack of useful implementation of UDI data with the speedy transfers of information that happen routinely in other industries. For example, employees of car rental agencies use handheld devices to gather detailed information about the vehicles being returned.

“But if you go to an emergency room with a medical device in your body, no one knows what it is or where it came from or anything about it,” Dr. Kovacs said in an interview.

Many physicians with expertise in device research have pushed for years to have insurers like Medicare require identification information on medical claims.

Even researchers face multiple obstacles in trying to investigate how well UDIs have been incorporated into EHRs and outcomes tied to certain devices.

In August, a Harvard team published a study in JAMA Internal Medicine, attempting to analyze the risks of endovascular aortic repair (EVAR) devices. They reported an 11.6% risk for serious blood leaks with AFX Endovascular AAA System aneurysm devices, more than double the 5.7% risk estimated for competing products. The team selected EVAR devices for the study due in part to their known safety concerns. Endologix, the maker of the devices, declined to comment for this story.

The Harvard team used data from the Veterans Affairs health system, which is considered more well organized than most other health systems. But UDI information was found for only 19 of the 13,941 patients whose records were studied. In those cases, only partial information was included.

The researchers developed natural language processing tools, which they used to scrounge clinical notes for information about which devices patients received.

Using this method isn’t feasible for most clinicians, given that records from independent hospitals might not provide this kind of data and descriptions to search, according to the authors of an editorial accompanying the paper. Those researchers urged Congress to pass a law mandating inclusion of UDIs for all devices on claims forms as a condition for reimbursement by federal health care programs.

Setback for advocates

The movement toward UDI suffered a setback in June.

An influential, but little known federal advisory panel, the National Committee on Vital Health Statistics (NCVHS), opted to not recommend use of this information in claims, saying the FDA should consider the matter further.

Gaining an NCVHS recommendation would have been a win, said Sen. Elizabeth Warren (D-MA), Sen. Charles E. Grassley (R-IA), and Rep. Bill Pascrell Jr. (D-NJ), in a December 2022 letter to the panel.

Including UDI data would let researchers track patients’ interactions with a health system and could be used to establish population-level correlations between a particular device and a long-term outcome or side effect, the lawmakers said.

That view had the support of at least one major maker of devices, Cook Group, which sells products for a variety of specialties, including cardiology.

In a comment to NCVHS, Cook urged for the inclusion identifiers in Medicare claims.

“While some have argued that the UDI is better suited for inclusion in the electronic health records, Cook believes this argument sets up a false choice between the two,” wrote Stephen L. Ferguson, JD, the chairman of Cook’s board. “Inclusion of the UDI in both electronic health records and claims forms will lead to a more robust system of real-world data.”

In contrast, AdvaMed, the trade group for device makers, told the NCVHS that it did not support adding the information to payment claims submissions, instead just supporting the inclusion in EHRs.

Dr. Kovacs of the ACC said one potential drawback to more transparency could be challenges in interpreting reports of complications in certain cases, at least initially. Reports about a flaw or even a suspected flaw in a device might lead patients to become concerned about their implanted devices, potentially registering unfounded complaints.

But this concern can be addressed through using “scientific rigor and safeguards” and is outweighed by the potential safety benefits for patients, Dr. Kovacs said.

Patients should ask health care systems to track and share information about their implanted devices, Dr. Kovacs suggested.

“I feel it would be my right to demand that that device information follows my electronic medical record, so that it’s readily available to anyone who’s taking care of me,” Dr. Kovacs said. “They would know what it is that’s in me, whether it’s a lens in my eye or a prosthesis in my hip or a highly complicated implantable cardiac electronic device.”

The Harvard study was supported by the FDA and National Institutes of Health. Authors of the study reported receiving fees from the FDA, Burroughs Wellcome Fund, and Harvard-MIT Center for Regulatory Science outside the submitted work. No other disclosures were reported. Authors of the editorial reported past and present connections with F-Prime Capital, FDA, Johnson & Johnson, the Medical Devices Innovation Consortium; the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and Arnold Ventures, as well being an expert witness at in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen. Authors of the Viewpoint reported past and present connections with the National Evaluation System for Health Technology Coordinating Center (NESTcc), which is part of the Medical Device Innovation Consortium (MDIC); AIM North America UDI Advisory Committee, Mass General Brigham, Arnold Ventures; the Institute for Clinical and Economic Review California Technology Assessment Forum; Yale University, Johnson & Johnson, FD, Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute of the National Institutes of Health; as well as having been an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against.

A version of this article first appeared on Medscape.com.

Some physicians are frustrated that key information about implantable medical devices rarely makes it into electronic health records, despite a 10-year mandate on manufacturers to label these products with identifiers.

As a result of this siloing of information, patients are not getting the expected benefits of a regulation finalized over a decade ago by the U.S. Food and Drug Administration.

In 2013, the agency ordered companies to include unique device identifiers (UDIs) in plain-text and barcode format on some device labels, starting with implanted devices that are considered life-sustaining. The FDA said that tracking of UDI information would speed detection of complications linked to devices.

But identifiers are rarely on devices. At the time of the regulation creation, the FDA also said it expected this data would be integrated into EHRs. But only a few pioneer organizations such as Duke University and Mercy Health have so far attempted to track any UDI data in an organized way, researchers say.

Richard J. Kovacs, MD, the chief medical officer of the American College of Cardiology, contrasted the lack of useful implementation of UDI data with the speedy transfers of information that happen routinely in other industries. For example, employees of car rental agencies use handheld devices to gather detailed information about the vehicles being returned.

“But if you go to an emergency room with a medical device in your body, no one knows what it is or where it came from or anything about it,” Dr. Kovacs said in an interview.

Many physicians with expertise in device research have pushed for years to have insurers like Medicare require identification information on medical claims.

Even researchers face multiple obstacles in trying to investigate how well UDIs have been incorporated into EHRs and outcomes tied to certain devices.

In August, a Harvard team published a study in JAMA Internal Medicine, attempting to analyze the risks of endovascular aortic repair (EVAR) devices. They reported an 11.6% risk for serious blood leaks with AFX Endovascular AAA System aneurysm devices, more than double the 5.7% risk estimated for competing products. The team selected EVAR devices for the study due in part to their known safety concerns. Endologix, the maker of the devices, declined to comment for this story.

The Harvard team used data from the Veterans Affairs health system, which is considered more well organized than most other health systems. But UDI information was found for only 19 of the 13,941 patients whose records were studied. In those cases, only partial information was included.

The researchers developed natural language processing tools, which they used to scrounge clinical notes for information about which devices patients received.

Using this method isn’t feasible for most clinicians, given that records from independent hospitals might not provide this kind of data and descriptions to search, according to the authors of an editorial accompanying the paper. Those researchers urged Congress to pass a law mandating inclusion of UDIs for all devices on claims forms as a condition for reimbursement by federal health care programs.

Setback for advocates

The movement toward UDI suffered a setback in June.

An influential, but little known federal advisory panel, the National Committee on Vital Health Statistics (NCVHS), opted to not recommend use of this information in claims, saying the FDA should consider the matter further.

Gaining an NCVHS recommendation would have been a win, said Sen. Elizabeth Warren (D-MA), Sen. Charles E. Grassley (R-IA), and Rep. Bill Pascrell Jr. (D-NJ), in a December 2022 letter to the panel.

Including UDI data would let researchers track patients’ interactions with a health system and could be used to establish population-level correlations between a particular device and a long-term outcome or side effect, the lawmakers said.

That view had the support of at least one major maker of devices, Cook Group, which sells products for a variety of specialties, including cardiology.

In a comment to NCVHS, Cook urged for the inclusion identifiers in Medicare claims.

“While some have argued that the UDI is better suited for inclusion in the electronic health records, Cook believes this argument sets up a false choice between the two,” wrote Stephen L. Ferguson, JD, the chairman of Cook’s board. “Inclusion of the UDI in both electronic health records and claims forms will lead to a more robust system of real-world data.”

In contrast, AdvaMed, the trade group for device makers, told the NCVHS that it did not support adding the information to payment claims submissions, instead just supporting the inclusion in EHRs.

Dr. Kovacs of the ACC said one potential drawback to more transparency could be challenges in interpreting reports of complications in certain cases, at least initially. Reports about a flaw or even a suspected flaw in a device might lead patients to become concerned about their implanted devices, potentially registering unfounded complaints.

But this concern can be addressed through using “scientific rigor and safeguards” and is outweighed by the potential safety benefits for patients, Dr. Kovacs said.

Patients should ask health care systems to track and share information about their implanted devices, Dr. Kovacs suggested.

“I feel it would be my right to demand that that device information follows my electronic medical record, so that it’s readily available to anyone who’s taking care of me,” Dr. Kovacs said. “They would know what it is that’s in me, whether it’s a lens in my eye or a prosthesis in my hip or a highly complicated implantable cardiac electronic device.”

The Harvard study was supported by the FDA and National Institutes of Health. Authors of the study reported receiving fees from the FDA, Burroughs Wellcome Fund, and Harvard-MIT Center for Regulatory Science outside the submitted work. No other disclosures were reported. Authors of the editorial reported past and present connections with F-Prime Capital, FDA, Johnson & Johnson, the Medical Devices Innovation Consortium; the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and Arnold Ventures, as well being an expert witness at in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen. Authors of the Viewpoint reported past and present connections with the National Evaluation System for Health Technology Coordinating Center (NESTcc), which is part of the Medical Device Innovation Consortium (MDIC); AIM North America UDI Advisory Committee, Mass General Brigham, Arnold Ventures; the Institute for Clinical and Economic Review California Technology Assessment Forum; Yale University, Johnson & Johnson, FD, Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute of the National Institutes of Health; as well as having been an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against.

A version of this article first appeared on Medscape.com.

Some physicians are frustrated that key information about implantable medical devices rarely makes it into electronic health records, despite a 10-year mandate on manufacturers to label these products with identifiers.

As a result of this siloing of information, patients are not getting the expected benefits of a regulation finalized over a decade ago by the U.S. Food and Drug Administration.

In 2013, the agency ordered companies to include unique device identifiers (UDIs) in plain-text and barcode format on some device labels, starting with implanted devices that are considered life-sustaining. The FDA said that tracking of UDI information would speed detection of complications linked to devices.

But identifiers are rarely on devices. At the time of the regulation creation, the FDA also said it expected this data would be integrated into EHRs. But only a few pioneer organizations such as Duke University and Mercy Health have so far attempted to track any UDI data in an organized way, researchers say.

Richard J. Kovacs, MD, the chief medical officer of the American College of Cardiology, contrasted the lack of useful implementation of UDI data with the speedy transfers of information that happen routinely in other industries. For example, employees of car rental agencies use handheld devices to gather detailed information about the vehicles being returned.

“But if you go to an emergency room with a medical device in your body, no one knows what it is or where it came from or anything about it,” Dr. Kovacs said in an interview.

Many physicians with expertise in device research have pushed for years to have insurers like Medicare require identification information on medical claims.

Even researchers face multiple obstacles in trying to investigate how well UDIs have been incorporated into EHRs and outcomes tied to certain devices.

In August, a Harvard team published a study in JAMA Internal Medicine, attempting to analyze the risks of endovascular aortic repair (EVAR) devices. They reported an 11.6% risk for serious blood leaks with AFX Endovascular AAA System aneurysm devices, more than double the 5.7% risk estimated for competing products. The team selected EVAR devices for the study due in part to their known safety concerns. Endologix, the maker of the devices, declined to comment for this story.

The Harvard team used data from the Veterans Affairs health system, which is considered more well organized than most other health systems. But UDI information was found for only 19 of the 13,941 patients whose records were studied. In those cases, only partial information was included.

The researchers developed natural language processing tools, which they used to scrounge clinical notes for information about which devices patients received.

Using this method isn’t feasible for most clinicians, given that records from independent hospitals might not provide this kind of data and descriptions to search, according to the authors of an editorial accompanying the paper. Those researchers urged Congress to pass a law mandating inclusion of UDIs for all devices on claims forms as a condition for reimbursement by federal health care programs.

Setback for advocates

The movement toward UDI suffered a setback in June.

An influential, but little known federal advisory panel, the National Committee on Vital Health Statistics (NCVHS), opted to not recommend use of this information in claims, saying the FDA should consider the matter further.

Gaining an NCVHS recommendation would have been a win, said Sen. Elizabeth Warren (D-MA), Sen. Charles E. Grassley (R-IA), and Rep. Bill Pascrell Jr. (D-NJ), in a December 2022 letter to the panel.

Including UDI data would let researchers track patients’ interactions with a health system and could be used to establish population-level correlations between a particular device and a long-term outcome or side effect, the lawmakers said.

That view had the support of at least one major maker of devices, Cook Group, which sells products for a variety of specialties, including cardiology.

In a comment to NCVHS, Cook urged for the inclusion identifiers in Medicare claims.

“While some have argued that the UDI is better suited for inclusion in the electronic health records, Cook believes this argument sets up a false choice between the two,” wrote Stephen L. Ferguson, JD, the chairman of Cook’s board. “Inclusion of the UDI in both electronic health records and claims forms will lead to a more robust system of real-world data.”

In contrast, AdvaMed, the trade group for device makers, told the NCVHS that it did not support adding the information to payment claims submissions, instead just supporting the inclusion in EHRs.

Dr. Kovacs of the ACC said one potential drawback to more transparency could be challenges in interpreting reports of complications in certain cases, at least initially. Reports about a flaw or even a suspected flaw in a device might lead patients to become concerned about their implanted devices, potentially registering unfounded complaints.

But this concern can be addressed through using “scientific rigor and safeguards” and is outweighed by the potential safety benefits for patients, Dr. Kovacs said.

Patients should ask health care systems to track and share information about their implanted devices, Dr. Kovacs suggested.

“I feel it would be my right to demand that that device information follows my electronic medical record, so that it’s readily available to anyone who’s taking care of me,” Dr. Kovacs said. “They would know what it is that’s in me, whether it’s a lens in my eye or a prosthesis in my hip or a highly complicated implantable cardiac electronic device.”

The Harvard study was supported by the FDA and National Institutes of Health. Authors of the study reported receiving fees from the FDA, Burroughs Wellcome Fund, and Harvard-MIT Center for Regulatory Science outside the submitted work. No other disclosures were reported. Authors of the editorial reported past and present connections with F-Prime Capital, FDA, Johnson & Johnson, the Medical Devices Innovation Consortium; the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and Arnold Ventures, as well being an expert witness at in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen. Authors of the Viewpoint reported past and present connections with the National Evaluation System for Health Technology Coordinating Center (NESTcc), which is part of the Medical Device Innovation Consortium (MDIC); AIM North America UDI Advisory Committee, Mass General Brigham, Arnold Ventures; the Institute for Clinical and Economic Review California Technology Assessment Forum; Yale University, Johnson & Johnson, FD, Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute of the National Institutes of Health; as well as having been an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients older than age 70 years have a 23% lower risk of a first major vascular events with each 1 mmol/L lowering of low-density lipoprotein (LDL) cholesterol, which is similar to the benefit seen among younger patients in primary prevention, new research shows.

METHODOLOGY:

• Using various cross-linked Danish registries, researchers analyzed 65,190 participants aged 50 years and older (49,155 aged 50-69 and 16,035 aged 70+) without a history of atherosclerotic cardiovascular disease (ASCVD) who initiated new lipid-lowering treatment and had a baseline LDL cholesterol measurement and a subsequent measurement within a year.
• The primary outcome was hospitalization for a major vascular event, defined as a composite of acute coronary syndrome, nonhemorrhagic stroke, and coronary revascularization. Secondary outcomes included individual cardiovascular components of the primary outcome and all-cause mortality.

TAKEAWAY:

• During a median follow-up of 2.5 years, 626 older (70 years and over) and 1,123 younger (aged 50-69) participants had a major vascular event, with crude incidence rates of 13.4 and 7.1 per 1000 person-years, respectively.
• After adjustment for potential confounders, each 1-mmol/L reduction in LDL cholesterol in people aged 70 and older was associated with a significant 23% lower risk for major vascular events (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.83), similar to results for those younger than 70 (HR, 0.76; 95% CI, 0.71-0.80; P value for the difference between the age groups, 0.79).
• Results across all cardiovascular secondary analyses supported the main findings, and there was no significant difference between older and younger participants across all subgroup analyses, including using 75 years as the age cutoff.
• There was no association with all-cause mortality for either the older (HR, 1.03; 95% CI, 0.98-1.09) or younger (HR, 1.00; 95% CI, 0.95-1.06) groups.

IN PRACTICE:

“Our results, based on a substantial sample size representative of a contemporary general population, may contribute to informing future guideline recommendations,” and to discussions with older patients about the benefits of LDL lowering therapy, the authors wrote. They stressed that any potential benefits should be balanced against potential harms in this population, as these individuals may have comorbidities and may be taking multiple medications.

In an accompanying editorial, Safi U. Khan, MD, from the department of cardiology at Houston Methodist DeBakey Heart and Vascular Center, said the study “contributes valuable insights regarding the effects of LDL-C-lowering therapy, especially as the burgeoning aging population faces escalating burden of ASCVD,” and added future research “should focus on corroborating these findings and addressing the safety of lipid-lowering treatments in older individuals.”
 

SOURCE:

The study was conducted by Niklas Worm Andersson, MD, department of epidemiology research, Statens Serum Institut, Copenhagen, and colleagues. It was published online Journal of the American College of Cardiology.

LIMITATIONS:

The results may not apply to individuals without LDL monitoring when receiving lipid-lowering treatment. Outcomes relied on the validity of recorded diagnostic codes in the registries, and medical record review of cases was not done. Residual confounding can’t be ruled out, in part because data on potentially important risk factors such as smoking, blood pressure, and body mass index weren’t available. The results may not generalize to clinical scenarios or subpopulations not directly studied.

DISCLOSURES:

Dr. Andersson has no relevant conflicts of interest. Author Tine Lovsø Dohlmann, PhD, was employed by Statens Serum Institut during the study, but has been employed by Novo Nordisk since January 2023. All other study authors and the editorialist Dr. Khan have no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients older than age 70 years have a 23% lower risk of a first major vascular events with each 1 mmol/L lowering of low-density lipoprotein (LDL) cholesterol, which is similar to the benefit seen among younger patients in primary prevention, new research shows.

METHODOLOGY:

• Using various cross-linked Danish registries, researchers analyzed 65,190 participants aged 50 years and older (49,155 aged 50-69 and 16,035 aged 70+) without a history of atherosclerotic cardiovascular disease (ASCVD) who initiated new lipid-lowering treatment and had a baseline LDL cholesterol measurement and a subsequent measurement within a year.
• The primary outcome was hospitalization for a major vascular event, defined as a composite of acute coronary syndrome, nonhemorrhagic stroke, and coronary revascularization. Secondary outcomes included individual cardiovascular components of the primary outcome and all-cause mortality.

TAKEAWAY:

• During a median follow-up of 2.5 years, 626 older (70 years and over) and 1,123 younger (aged 50-69) participants had a major vascular event, with crude incidence rates of 13.4 and 7.1 per 1000 person-years, respectively.
• After adjustment for potential confounders, each 1-mmol/L reduction in LDL cholesterol in people aged 70 and older was associated with a significant 23% lower risk for major vascular events (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.83), similar to results for those younger than 70 (HR, 0.76; 95% CI, 0.71-0.80; P value for the difference between the age groups, 0.79).
• Results across all cardiovascular secondary analyses supported the main findings, and there was no significant difference between older and younger participants across all subgroup analyses, including using 75 years as the age cutoff.
• There was no association with all-cause mortality for either the older (HR, 1.03; 95% CI, 0.98-1.09) or younger (HR, 1.00; 95% CI, 0.95-1.06) groups.

IN PRACTICE:

“Our results, based on a substantial sample size representative of a contemporary general population, may contribute to informing future guideline recommendations,” and to discussions with older patients about the benefits of LDL lowering therapy, the authors wrote. They stressed that any potential benefits should be balanced against potential harms in this population, as these individuals may have comorbidities and may be taking multiple medications.

In an accompanying editorial, Safi U. Khan, MD, from the department of cardiology at Houston Methodist DeBakey Heart and Vascular Center, said the study “contributes valuable insights regarding the effects of LDL-C-lowering therapy, especially as the burgeoning aging population faces escalating burden of ASCVD,” and added future research “should focus on corroborating these findings and addressing the safety of lipid-lowering treatments in older individuals.”
 

SOURCE:

The study was conducted by Niklas Worm Andersson, MD, department of epidemiology research, Statens Serum Institut, Copenhagen, and colleagues. It was published online Journal of the American College of Cardiology.

LIMITATIONS:

The results may not apply to individuals without LDL monitoring when receiving lipid-lowering treatment. Outcomes relied on the validity of recorded diagnostic codes in the registries, and medical record review of cases was not done. Residual confounding can’t be ruled out, in part because data on potentially important risk factors such as smoking, blood pressure, and body mass index weren’t available. The results may not generalize to clinical scenarios or subpopulations not directly studied.

DISCLOSURES:

Dr. Andersson has no relevant conflicts of interest. Author Tine Lovsø Dohlmann, PhD, was employed by Statens Serum Institut during the study, but has been employed by Novo Nordisk since January 2023. All other study authors and the editorialist Dr. Khan have no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients older than age 70 years have a 23% lower risk of a first major vascular events with each 1 mmol/L lowering of low-density lipoprotein (LDL) cholesterol, which is similar to the benefit seen among younger patients in primary prevention, new research shows.

METHODOLOGY:

• Using various cross-linked Danish registries, researchers analyzed 65,190 participants aged 50 years and older (49,155 aged 50-69 and 16,035 aged 70+) without a history of atherosclerotic cardiovascular disease (ASCVD) who initiated new lipid-lowering treatment and had a baseline LDL cholesterol measurement and a subsequent measurement within a year.
• The primary outcome was hospitalization for a major vascular event, defined as a composite of acute coronary syndrome, nonhemorrhagic stroke, and coronary revascularization. Secondary outcomes included individual cardiovascular components of the primary outcome and all-cause mortality.

TAKEAWAY:

• During a median follow-up of 2.5 years, 626 older (70 years and over) and 1,123 younger (aged 50-69) participants had a major vascular event, with crude incidence rates of 13.4 and 7.1 per 1000 person-years, respectively.
• After adjustment for potential confounders, each 1-mmol/L reduction in LDL cholesterol in people aged 70 and older was associated with a significant 23% lower risk for major vascular events (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.83), similar to results for those younger than 70 (HR, 0.76; 95% CI, 0.71-0.80; P value for the difference between the age groups, 0.79).
• Results across all cardiovascular secondary analyses supported the main findings, and there was no significant difference between older and younger participants across all subgroup analyses, including using 75 years as the age cutoff.
• There was no association with all-cause mortality for either the older (HR, 1.03; 95% CI, 0.98-1.09) or younger (HR, 1.00; 95% CI, 0.95-1.06) groups.

IN PRACTICE:

“Our results, based on a substantial sample size representative of a contemporary general population, may contribute to informing future guideline recommendations,” and to discussions with older patients about the benefits of LDL lowering therapy, the authors wrote. They stressed that any potential benefits should be balanced against potential harms in this population, as these individuals may have comorbidities and may be taking multiple medications.

In an accompanying editorial, Safi U. Khan, MD, from the department of cardiology at Houston Methodist DeBakey Heart and Vascular Center, said the study “contributes valuable insights regarding the effects of LDL-C-lowering therapy, especially as the burgeoning aging population faces escalating burden of ASCVD,” and added future research “should focus on corroborating these findings and addressing the safety of lipid-lowering treatments in older individuals.”
 

SOURCE:

The study was conducted by Niklas Worm Andersson, MD, department of epidemiology research, Statens Serum Institut, Copenhagen, and colleagues. It was published online Journal of the American College of Cardiology.

LIMITATIONS:

The results may not apply to individuals without LDL monitoring when receiving lipid-lowering treatment. Outcomes relied on the validity of recorded diagnostic codes in the registries, and medical record review of cases was not done. Residual confounding can’t be ruled out, in part because data on potentially important risk factors such as smoking, blood pressure, and body mass index weren’t available. The results may not generalize to clinical scenarios or subpopulations not directly studied.

DISCLOSURES:

Dr. Andersson has no relevant conflicts of interest. Author Tine Lovsø Dohlmann, PhD, was employed by Statens Serum Institut during the study, but has been employed by Novo Nordisk since January 2023. All other study authors and the editorialist Dr. Khan have no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

All pregnant women should undergo screening for hypertensive disorders, with evidence-based management for those screening positive, according to a new recommendation from the U.S. Preventive Services Task Force.

Hypertensive disorders of pregnancy in the United States increased from approximately 500 cases per 10,000 deliveries to 1,021 cases per 10,000 deliveries from 1993 to 2016-2017, and remain a leading cause of maternal morbidity and mortality, wrote Task Force Chair Michael J. Barry, MD, of Massachusetts General Hospital, Boston, and colleagues in the final recommendation statement published in JAMA.

The USPSTF commissioned a systematic review to assess the risks and benefits of hypertensive screening for asymptomatic pregnant women. The resulting grade B recommendation indicates that screening for hypertensive disorders in pregnancy using blood pressure measurements yields a substantial net benefit.

The recommendation applies to “all pregnant women and pregnant persons of all genders without a known diagnosis of a hypertensive disorder of pregnancy or chronic hypertension,” the authors said.

The recommendation calls for the use of blood pressure measurements to evaluate hypertensive disorders, with measurements taken at each prenatal visit. A positive result for new-onset hypertension was defined as systolic blood pressure of 140 mm Hg or diastolic blood pressure 90 mm Hg in the absence of chronic hypertension, based on two measurements at least 4 hours apart. Regular review of blood pressure can help identify and manage potentially fatal conditions.

However, screening alone is insufficient to improve inequities in health outcomes associated with hypertensive disorders of pregnancy, the authors emphasized. Data from previous studies have shown that Black patients are at increased risk for hypertensive disorders of pregnancy and severe complications, and that Black and Hispanic patients have twice the risk of stroke with hypertensive disorders of pregnancy as White patients.

In the evidence report that supported the recommendation, Jillian T. Henderson, PhD, of Kaiser Permanente in Portland, Ore., and colleagues reviewed six studies including 10,165 individuals. The studies (five clinical trials and one nonrandomized study) compared changes in prenatal screening with usual care.

Overall, the review yielded no evidence that any other screening strategies were more useful than routine blood pressure measurement to identify hypertensive disorders of pregnancy in asymptomatic women.

The findings cited to support the recommendation were limited by several factors, including the lack of power to detect pregnancy health outcomes and potential harms of different screening programs, and the lack of power to evaluate outcomes for American Indian, Alaska Native, or Black individuals, who have disproportionately high rates of hypertensive disorders of pregnancy, the authors said.

More research is needed to identify which screening approaches may lead to improved disease detection and better health outcomes, but the results of the review support the grade B recommendation for hypertensive screening of all pregnant women, they concluded.
 

Early identification makes a difference

The new recommendation is important because it can help all moms and babies to be healthier, said Wanda Nicholson, MD, vice chair of the task force, in an interview.

“We are recommending that all pregnant persons have a blood pressure check at every visit throughout pregnancy,” said Dr. Nicholson, an ob.gyn. by training who also serves as professor of prevention and community health at George Washington University in Washington. “We know that there is a maternal health crisis in this country, and we know that hypertensive disorders of pregnancy are one of the key factors related to that,” she said.

Unfortunately, barriers to routine screening for hypertensive disorders of pregnancy persist, said Dr. Nicholson. The incidence of hypertensive disorders of pregnancy is higher in many of the same populations who also have challenges in accessing regular prenatal care, notably those who are Black, Native American, or Alaska Native, she noted.

The new recommendation also serves as an opportunity to call attention to the health care disparities for these populations, not only during pregnancy, but in general, she emphasized.

In clinical practice, the definition of hypertensive disorders of pregnancy involves three different diagnoses – gestational hypertension, preeclampsia, and eclampsia – that can be seen as points on a continuum, said Dr. Nicholson. The sooner patients are identified with hypertensive disorders of pregnancy, the sooner intervention and treatment can begin, she said. To that end, she added the clinical pearl of using a properly sized blood pressure cuff to obtain an accurate reading and avoid missed diagnoses.

The task force also outlined several key areas for additional research, said Dr. Nicholson. First, more research is needed on alternative screening strategies, such as at-home blood pressure monitoring for patients, as well as teleheath visits. Second, more studies are needed to address the disparities in prenatal care and include more diverse populations in clinical research. Third, future studies need to consider social determinants of health and other factors that might impact maternal health outcomes. “These steps will help achieve the larger goal of healthier mothers and babies,” Dr. Nicholson said.
 

Back to basics to improve women’s health

Some clinicians may be disappointed by the Evidence Report’s primary finding that no alternative screening strategies outperformed routine blood pressure measurement, wrote Anne E. Denoble, MD, and Christian M. Pettker, MD, both of Yale University, New Haven, Conn., in an accompanying editorial.

While potentially frustrating at first glance, the findings of the Evidence Report provide a foundation for improvement and reassurance that the best existing screening methods are basic and fundamental: regular prenatal visits with routine, in-office blood pressure measurements, and urine protein screening when clinically indicated, they said.

However, the USPSTF review also noted persistent research gaps that must be addressed to significantly improve maternal health outcomes, they said. Notable gaps include the disproportionately low numbers of Black patients in current studies, and the need for studies of alternate models of prenatal care, including the use of remote blood pressure monitoring, and the use of biomarkers to screen for and predict hypertensive disorders of pregnancy.

The most striking limitation may be the focus on prenatal care, with lack of attention to postpartum mortality risk, given that more than half of pregnancy-related deaths occur postpartum, the authors noted.

Although current screening tools may be used in practice “with skill and might,” more effort at multiple levels is needed to address the larger maternal health crisis in the United States, they said.
 

Expand screening, engage primary care for long-term benefits

Screening for hypertensive disorders of pregnancy “can and should be within the purview of internists,” wrote Srilakshmi Mitta, MD; Cary P. Gross, MD; Melissa A. Simon, MD, of Brown University, Yale University, and Northwestern University, respectively, in a separate editorial. The recommendation to extend screening beyond preeclampsia is timely, given the consistent increase in all hypertensive disorders of pregnancy since 1990, the authors said.

Pregnancy is not the only time for screening, counseling, and management of hypertensive disorders, they emphasized. “All persons who have reproductive capacity and/or are planning pregnancy, along with those who are post partum, should be screened for hypertensive disorders, aligning the USPSTF with guidelines from the American College of Obstetricians and Gynecologists, the American College of Cardiology, and the American Heart Association,” they said, and all clinicians should be on board to identify and treat hypertensive disorders of pregnancy, especially in underserved racial and ethnic minorities for whom primary care may be their only source of health care.

“Pregnancy is a window of opportunity to influence current and future life course, not just of the individual, but also of the fetus(es),other children, and family,” and timely intervention has the potential for great public health impact, they said.

Dr. Denoble disclosed grants from the HealthPartners Institute for Education and Research and from the Patient-Centered Outcomes Research Institute. Dr. Simon serves on the Advisory Committee for Research on Women’s Health for the National Institutes of Health Office of Research on Women’s Health and serves as a member of the Centers for Disease Control and Prevention Community Preventive Services Task Force; she was a member of the USPSTF from 2017 to 2020. Dr. Gross disclosed grants from Johnson and Johnson and the National Comprehensive Cancer Network (through a grant to the NCCN from AstraZeneca) and personal fees from Genentech.

All pregnant women should undergo screening for hypertensive disorders, with evidence-based management for those screening positive, according to a new recommendation from the U.S. Preventive Services Task Force.

Hypertensive disorders of pregnancy in the United States increased from approximately 500 cases per 10,000 deliveries to 1,021 cases per 10,000 deliveries from 1993 to 2016-2017, and remain a leading cause of maternal morbidity and mortality, wrote Task Force Chair Michael J. Barry, MD, of Massachusetts General Hospital, Boston, and colleagues in the final recommendation statement published in JAMA.

The USPSTF commissioned a systematic review to assess the risks and benefits of hypertensive screening for asymptomatic pregnant women. The resulting grade B recommendation indicates that screening for hypertensive disorders in pregnancy using blood pressure measurements yields a substantial net benefit.

The recommendation applies to “all pregnant women and pregnant persons of all genders without a known diagnosis of a hypertensive disorder of pregnancy or chronic hypertension,” the authors said.

The recommendation calls for the use of blood pressure measurements to evaluate hypertensive disorders, with measurements taken at each prenatal visit. A positive result for new-onset hypertension was defined as systolic blood pressure of 140 mm Hg or diastolic blood pressure 90 mm Hg in the absence of chronic hypertension, based on two measurements at least 4 hours apart. Regular review of blood pressure can help identify and manage potentially fatal conditions.

However, screening alone is insufficient to improve inequities in health outcomes associated with hypertensive disorders of pregnancy, the authors emphasized. Data from previous studies have shown that Black patients are at increased risk for hypertensive disorders of pregnancy and severe complications, and that Black and Hispanic patients have twice the risk of stroke with hypertensive disorders of pregnancy as White patients.

In the evidence report that supported the recommendation, Jillian T. Henderson, PhD, of Kaiser Permanente in Portland, Ore., and colleagues reviewed six studies including 10,165 individuals. The studies (five clinical trials and one nonrandomized study) compared changes in prenatal screening with usual care.

Overall, the review yielded no evidence that any other screening strategies were more useful than routine blood pressure measurement to identify hypertensive disorders of pregnancy in asymptomatic women.

The findings cited to support the recommendation were limited by several factors, including the lack of power to detect pregnancy health outcomes and potential harms of different screening programs, and the lack of power to evaluate outcomes for American Indian, Alaska Native, or Black individuals, who have disproportionately high rates of hypertensive disorders of pregnancy, the authors said.

More research is needed to identify which screening approaches may lead to improved disease detection and better health outcomes, but the results of the review support the grade B recommendation for hypertensive screening of all pregnant women, they concluded.
 

Early identification makes a difference

The new recommendation is important because it can help all moms and babies to be healthier, said Wanda Nicholson, MD, vice chair of the task force, in an interview.

“We are recommending that all pregnant persons have a blood pressure check at every visit throughout pregnancy,” said Dr. Nicholson, an ob.gyn. by training who also serves as professor of prevention and community health at George Washington University in Washington. “We know that there is a maternal health crisis in this country, and we know that hypertensive disorders of pregnancy are one of the key factors related to that,” she said.

Unfortunately, barriers to routine screening for hypertensive disorders of pregnancy persist, said Dr. Nicholson. The incidence of hypertensive disorders of pregnancy is higher in many of the same populations who also have challenges in accessing regular prenatal care, notably those who are Black, Native American, or Alaska Native, she noted.

The new recommendation also serves as an opportunity to call attention to the health care disparities for these populations, not only during pregnancy, but in general, she emphasized.

In clinical practice, the definition of hypertensive disorders of pregnancy involves three different diagnoses – gestational hypertension, preeclampsia, and eclampsia – that can be seen as points on a continuum, said Dr. Nicholson. The sooner patients are identified with hypertensive disorders of pregnancy, the sooner intervention and treatment can begin, she said. To that end, she added the clinical pearl of using a properly sized blood pressure cuff to obtain an accurate reading and avoid missed diagnoses.

The task force also outlined several key areas for additional research, said Dr. Nicholson. First, more research is needed on alternative screening strategies, such as at-home blood pressure monitoring for patients, as well as teleheath visits. Second, more studies are needed to address the disparities in prenatal care and include more diverse populations in clinical research. Third, future studies need to consider social determinants of health and other factors that might impact maternal health outcomes. “These steps will help achieve the larger goal of healthier mothers and babies,” Dr. Nicholson said.
 

Back to basics to improve women’s health

Some clinicians may be disappointed by the Evidence Report’s primary finding that no alternative screening strategies outperformed routine blood pressure measurement, wrote Anne E. Denoble, MD, and Christian M. Pettker, MD, both of Yale University, New Haven, Conn., in an accompanying editorial.

While potentially frustrating at first glance, the findings of the Evidence Report provide a foundation for improvement and reassurance that the best existing screening methods are basic and fundamental: regular prenatal visits with routine, in-office blood pressure measurements, and urine protein screening when clinically indicated, they said.

However, the USPSTF review also noted persistent research gaps that must be addressed to significantly improve maternal health outcomes, they said. Notable gaps include the disproportionately low numbers of Black patients in current studies, and the need for studies of alternate models of prenatal care, including the use of remote blood pressure monitoring, and the use of biomarkers to screen for and predict hypertensive disorders of pregnancy.

The most striking limitation may be the focus on prenatal care, with lack of attention to postpartum mortality risk, given that more than half of pregnancy-related deaths occur postpartum, the authors noted.

Although current screening tools may be used in practice “with skill and might,” more effort at multiple levels is needed to address the larger maternal health crisis in the United States, they said.
 

Expand screening, engage primary care for long-term benefits

Screening for hypertensive disorders of pregnancy “can and should be within the purview of internists,” wrote Srilakshmi Mitta, MD; Cary P. Gross, MD; Melissa A. Simon, MD, of Brown University, Yale University, and Northwestern University, respectively, in a separate editorial. The recommendation to extend screening beyond preeclampsia is timely, given the consistent increase in all hypertensive disorders of pregnancy since 1990, the authors said.

Pregnancy is not the only time for screening, counseling, and management of hypertensive disorders, they emphasized. “All persons who have reproductive capacity and/or are planning pregnancy, along with those who are post partum, should be screened for hypertensive disorders, aligning the USPSTF with guidelines from the American College of Obstetricians and Gynecologists, the American College of Cardiology, and the American Heart Association,” they said, and all clinicians should be on board to identify and treat hypertensive disorders of pregnancy, especially in underserved racial and ethnic minorities for whom primary care may be their only source of health care.

“Pregnancy is a window of opportunity to influence current and future life course, not just of the individual, but also of the fetus(es),other children, and family,” and timely intervention has the potential for great public health impact, they said.

Dr. Denoble disclosed grants from the HealthPartners Institute for Education and Research and from the Patient-Centered Outcomes Research Institute. Dr. Simon serves on the Advisory Committee for Research on Women’s Health for the National Institutes of Health Office of Research on Women’s Health and serves as a member of the Centers for Disease Control and Prevention Community Preventive Services Task Force; she was a member of the USPSTF from 2017 to 2020. Dr. Gross disclosed grants from Johnson and Johnson and the National Comprehensive Cancer Network (through a grant to the NCCN from AstraZeneca) and personal fees from Genentech.

All pregnant women should undergo screening for hypertensive disorders, with evidence-based management for those screening positive, according to a new recommendation from the U.S. Preventive Services Task Force.

Hypertensive disorders of pregnancy in the United States increased from approximately 500 cases per 10,000 deliveries to 1,021 cases per 10,000 deliveries from 1993 to 2016-2017, and remain a leading cause of maternal morbidity and mortality, wrote Task Force Chair Michael J. Barry, MD, of Massachusetts General Hospital, Boston, and colleagues in the final recommendation statement published in JAMA.

The USPSTF commissioned a systematic review to assess the risks and benefits of hypertensive screening for asymptomatic pregnant women. The resulting grade B recommendation indicates that screening for hypertensive disorders in pregnancy using blood pressure measurements yields a substantial net benefit.

The recommendation applies to “all pregnant women and pregnant persons of all genders without a known diagnosis of a hypertensive disorder of pregnancy or chronic hypertension,” the authors said.

The recommendation calls for the use of blood pressure measurements to evaluate hypertensive disorders, with measurements taken at each prenatal visit. A positive result for new-onset hypertension was defined as systolic blood pressure of 140 mm Hg or diastolic blood pressure 90 mm Hg in the absence of chronic hypertension, based on two measurements at least 4 hours apart. Regular review of blood pressure can help identify and manage potentially fatal conditions.

However, screening alone is insufficient to improve inequities in health outcomes associated with hypertensive disorders of pregnancy, the authors emphasized. Data from previous studies have shown that Black patients are at increased risk for hypertensive disorders of pregnancy and severe complications, and that Black and Hispanic patients have twice the risk of stroke with hypertensive disorders of pregnancy as White patients.

In the evidence report that supported the recommendation, Jillian T. Henderson, PhD, of Kaiser Permanente in Portland, Ore., and colleagues reviewed six studies including 10,165 individuals. The studies (five clinical trials and one nonrandomized study) compared changes in prenatal screening with usual care.

Overall, the review yielded no evidence that any other screening strategies were more useful than routine blood pressure measurement to identify hypertensive disorders of pregnancy in asymptomatic women.

The findings cited to support the recommendation were limited by several factors, including the lack of power to detect pregnancy health outcomes and potential harms of different screening programs, and the lack of power to evaluate outcomes for American Indian, Alaska Native, or Black individuals, who have disproportionately high rates of hypertensive disorders of pregnancy, the authors said.

More research is needed to identify which screening approaches may lead to improved disease detection and better health outcomes, but the results of the review support the grade B recommendation for hypertensive screening of all pregnant women, they concluded.
 

Early identification makes a difference

The new recommendation is important because it can help all moms and babies to be healthier, said Wanda Nicholson, MD, vice chair of the task force, in an interview.

“We are recommending that all pregnant persons have a blood pressure check at every visit throughout pregnancy,” said Dr. Nicholson, an ob.gyn. by training who also serves as professor of prevention and community health at George Washington University in Washington. “We know that there is a maternal health crisis in this country, and we know that hypertensive disorders of pregnancy are one of the key factors related to that,” she said.

Unfortunately, barriers to routine screening for hypertensive disorders of pregnancy persist, said Dr. Nicholson. The incidence of hypertensive disorders of pregnancy is higher in many of the same populations who also have challenges in accessing regular prenatal care, notably those who are Black, Native American, or Alaska Native, she noted.

The new recommendation also serves as an opportunity to call attention to the health care disparities for these populations, not only during pregnancy, but in general, she emphasized.

In clinical practice, the definition of hypertensive disorders of pregnancy involves three different diagnoses – gestational hypertension, preeclampsia, and eclampsia – that can be seen as points on a continuum, said Dr. Nicholson. The sooner patients are identified with hypertensive disorders of pregnancy, the sooner intervention and treatment can begin, she said. To that end, she added the clinical pearl of using a properly sized blood pressure cuff to obtain an accurate reading and avoid missed diagnoses.

The task force also outlined several key areas for additional research, said Dr. Nicholson. First, more research is needed on alternative screening strategies, such as at-home blood pressure monitoring for patients, as well as teleheath visits. Second, more studies are needed to address the disparities in prenatal care and include more diverse populations in clinical research. Third, future studies need to consider social determinants of health and other factors that might impact maternal health outcomes. “These steps will help achieve the larger goal of healthier mothers and babies,” Dr. Nicholson said.
 

Back to basics to improve women’s health

Some clinicians may be disappointed by the Evidence Report’s primary finding that no alternative screening strategies outperformed routine blood pressure measurement, wrote Anne E. Denoble, MD, and Christian M. Pettker, MD, both of Yale University, New Haven, Conn., in an accompanying editorial.

While potentially frustrating at first glance, the findings of the Evidence Report provide a foundation for improvement and reassurance that the best existing screening methods are basic and fundamental: regular prenatal visits with routine, in-office blood pressure measurements, and urine protein screening when clinically indicated, they said.

However, the USPSTF review also noted persistent research gaps that must be addressed to significantly improve maternal health outcomes, they said. Notable gaps include the disproportionately low numbers of Black patients in current studies, and the need for studies of alternate models of prenatal care, including the use of remote blood pressure monitoring, and the use of biomarkers to screen for and predict hypertensive disorders of pregnancy.

The most striking limitation may be the focus on prenatal care, with lack of attention to postpartum mortality risk, given that more than half of pregnancy-related deaths occur postpartum, the authors noted.

Although current screening tools may be used in practice “with skill and might,” more effort at multiple levels is needed to address the larger maternal health crisis in the United States, they said.
 

Expand screening, engage primary care for long-term benefits

Screening for hypertensive disorders of pregnancy “can and should be within the purview of internists,” wrote Srilakshmi Mitta, MD; Cary P. Gross, MD; Melissa A. Simon, MD, of Brown University, Yale University, and Northwestern University, respectively, in a separate editorial. The recommendation to extend screening beyond preeclampsia is timely, given the consistent increase in all hypertensive disorders of pregnancy since 1990, the authors said.

Pregnancy is not the only time for screening, counseling, and management of hypertensive disorders, they emphasized. “All persons who have reproductive capacity and/or are planning pregnancy, along with those who are post partum, should be screened for hypertensive disorders, aligning the USPSTF with guidelines from the American College of Obstetricians and Gynecologists, the American College of Cardiology, and the American Heart Association,” they said, and all clinicians should be on board to identify and treat hypertensive disorders of pregnancy, especially in underserved racial and ethnic minorities for whom primary care may be their only source of health care.

“Pregnancy is a window of opportunity to influence current and future life course, not just of the individual, but also of the fetus(es),other children, and family,” and timely intervention has the potential for great public health impact, they said.

Dr. Denoble disclosed grants from the HealthPartners Institute for Education and Research and from the Patient-Centered Outcomes Research Institute. Dr. Simon serves on the Advisory Committee for Research on Women’s Health for the National Institutes of Health Office of Research on Women’s Health and serves as a member of the Centers for Disease Control and Prevention Community Preventive Services Task Force; she was a member of the USPSTF from 2017 to 2020. Dr. Gross disclosed grants from Johnson and Johnson and the National Comprehensive Cancer Network (through a grant to the NCCN from AstraZeneca) and personal fees from Genentech.

TOPLINE:

Men exposed to either job-related stress or an imbalance between the effort they put in and the rewards they reap at work have a 50% increased risk for coronary heart disease (CHD), and those facing both stressors have double the risk compared with colleagues not suffering from these stressors, new research shows. Results in women were inconclusive, suggesting a more complex relationship of these factors, the researchers noted.

METHODOLOGY:

• Evidence suggests psychosocial stressors at work, from job strain related to level of demand and control in workload and decision-making responsibilities, and an effort-reward imbalance (ERI) in areas such as salary, promotion, and job stability, increase CHD risk, with the effect of both types of stressors together possibly being especially harmful.
• The study, which included 6,465 participants in the cardiovascular component of PROQ, a Canadian prospective cohort of white-collar workers initially free of cardiovascular disease, mean age 45 years, estimated that the separate and combined effect of job strain and ERI on CHD incidence.
• Researchers used the Job Content Questionnaire to assess psychological demands and job control; various measures; scales to determine job strain, reward, and effort at work; and the sum of both effort and reward to calculate the ERI ratio.
• They assessed CHD using medico-administrative databases and an algorithm validated by medical records.

TAKEAWAY:

• After a median follow-up of 18.7 years, there were 571 and 265 incident CHD cases among men and women, respectively.
• Men with either job strain or ERI had a 49% increased risk for CHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.07-2.09), an estimate comparable to that of several lifestyle risk factors for CHD.
• Male workers facing both job strain and ERI had a 103% increased risk for CHD (HR, 2.03; 95% CI, 1.38-2.97), which is comparable to the increased risk associated with obesity.
• Associations were robust to adjustments for demographic, socioeconomic, psychosocial, personality, stressful life events, and biomedical and lifestyle factors.
• Among women, results were inconclusive because the CIs were wide enough to encompass both protective and detrimental effects, suggesting more research is needed into the complex interplay of various stressors and women’s heart health.

IN PRACTICE:

“Integrative and interdisciplinary approaches should be used to tackle psychosocial stressors at work,” the authors wrote, adding this involves “going beyond traditional modifiable individual behaviors” and should include “population-based prevention strategies taking into consideration both the individual and their work environment.” 

SOURCE:

The study was conducted by Mathilde Lavigne-Robichaud, Population Health and Optimal Health Practices Research Unit, CHU de Québec-Laval University, Quebec City, Canada. It was published online in Circulation: Cardiovascular Quality and Outcomes. 

LIMITATIONS:

There was a risk for chance associations due to multiple testing. The exposure may have changed over the course of the study. Using medical databases for CHD event definition may have led to misclassification and underestimation of outcomes. The study population is limited to white-collar workers.

DISCLOSURES:

The study received funding from the Canadian Institute of Health Research. Lavigne-Robichaud was supported by a PhD grant from les Fonds de Recherche du Québec-Santé. See paper for disclosures of other authors.

A version of this article first appeared on Medscape.com.

TOPLINE:

Men exposed to either job-related stress or an imbalance between the effort they put in and the rewards they reap at work have a 50% increased risk for coronary heart disease (CHD), and those facing both stressors have double the risk compared with colleagues not suffering from these stressors, new research shows. Results in women were inconclusive, suggesting a more complex relationship of these factors, the researchers noted.

METHODOLOGY:

• Evidence suggests psychosocial stressors at work, from job strain related to level of demand and control in workload and decision-making responsibilities, and an effort-reward imbalance (ERI) in areas such as salary, promotion, and job stability, increase CHD risk, with the effect of both types of stressors together possibly being especially harmful.
• The study, which included 6,465 participants in the cardiovascular component of PROQ, a Canadian prospective cohort of white-collar workers initially free of cardiovascular disease, mean age 45 years, estimated that the separate and combined effect of job strain and ERI on CHD incidence.
• Researchers used the Job Content Questionnaire to assess psychological demands and job control; various measures; scales to determine job strain, reward, and effort at work; and the sum of both effort and reward to calculate the ERI ratio.
• They assessed CHD using medico-administrative databases and an algorithm validated by medical records.

TAKEAWAY:

• After a median follow-up of 18.7 years, there were 571 and 265 incident CHD cases among men and women, respectively.
• Men with either job strain or ERI had a 49% increased risk for CHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.07-2.09), an estimate comparable to that of several lifestyle risk factors for CHD.
• Male workers facing both job strain and ERI had a 103% increased risk for CHD (HR, 2.03; 95% CI, 1.38-2.97), which is comparable to the increased risk associated with obesity.
• Associations were robust to adjustments for demographic, socioeconomic, psychosocial, personality, stressful life events, and biomedical and lifestyle factors.
• Among women, results were inconclusive because the CIs were wide enough to encompass both protective and detrimental effects, suggesting more research is needed into the complex interplay of various stressors and women’s heart health.

IN PRACTICE:

“Integrative and interdisciplinary approaches should be used to tackle psychosocial stressors at work,” the authors wrote, adding this involves “going beyond traditional modifiable individual behaviors” and should include “population-based prevention strategies taking into consideration both the individual and their work environment.” 

SOURCE:

The study was conducted by Mathilde Lavigne-Robichaud, Population Health and Optimal Health Practices Research Unit, CHU de Québec-Laval University, Quebec City, Canada. It was published online in Circulation: Cardiovascular Quality and Outcomes. 

LIMITATIONS:

There was a risk for chance associations due to multiple testing. The exposure may have changed over the course of the study. Using medical databases for CHD event definition may have led to misclassification and underestimation of outcomes. The study population is limited to white-collar workers.

DISCLOSURES:

The study received funding from the Canadian Institute of Health Research. Lavigne-Robichaud was supported by a PhD grant from les Fonds de Recherche du Québec-Santé. See paper for disclosures of other authors.

A version of this article first appeared on Medscape.com.

TOPLINE:

Men exposed to either job-related stress or an imbalance between the effort they put in and the rewards they reap at work have a 50% increased risk for coronary heart disease (CHD), and those facing both stressors have double the risk compared with colleagues not suffering from these stressors, new research shows. Results in women were inconclusive, suggesting a more complex relationship of these factors, the researchers noted.

METHODOLOGY:

• Evidence suggests psychosocial stressors at work, from job strain related to level of demand and control in workload and decision-making responsibilities, and an effort-reward imbalance (ERI) in areas such as salary, promotion, and job stability, increase CHD risk, with the effect of both types of stressors together possibly being especially harmful.
• The study, which included 6,465 participants in the cardiovascular component of PROQ, a Canadian prospective cohort of white-collar workers initially free of cardiovascular disease, mean age 45 years, estimated that the separate and combined effect of job strain and ERI on CHD incidence.
• Researchers used the Job Content Questionnaire to assess psychological demands and job control; various measures; scales to determine job strain, reward, and effort at work; and the sum of both effort and reward to calculate the ERI ratio.
• They assessed CHD using medico-administrative databases and an algorithm validated by medical records.

TAKEAWAY:

• After a median follow-up of 18.7 years, there were 571 and 265 incident CHD cases among men and women, respectively.
• Men with either job strain or ERI had a 49% increased risk for CHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.07-2.09), an estimate comparable to that of several lifestyle risk factors for CHD.
• Male workers facing both job strain and ERI had a 103% increased risk for CHD (HR, 2.03; 95% CI, 1.38-2.97), which is comparable to the increased risk associated with obesity.
• Associations were robust to adjustments for demographic, socioeconomic, psychosocial, personality, stressful life events, and biomedical and lifestyle factors.
• Among women, results were inconclusive because the CIs were wide enough to encompass both protective and detrimental effects, suggesting more research is needed into the complex interplay of various stressors and women’s heart health.

IN PRACTICE:

“Integrative and interdisciplinary approaches should be used to tackle psychosocial stressors at work,” the authors wrote, adding this involves “going beyond traditional modifiable individual behaviors” and should include “population-based prevention strategies taking into consideration both the individual and their work environment.” 

SOURCE:

The study was conducted by Mathilde Lavigne-Robichaud, Population Health and Optimal Health Practices Research Unit, CHU de Québec-Laval University, Quebec City, Canada. It was published online in Circulation: Cardiovascular Quality and Outcomes. 

LIMITATIONS:

There was a risk for chance associations due to multiple testing. The exposure may have changed over the course of the study. Using medical databases for CHD event definition may have led to misclassification and underestimation of outcomes. The study population is limited to white-collar workers.

DISCLOSURES:

The study received funding from the Canadian Institute of Health Research. Lavigne-Robichaud was supported by a PhD grant from les Fonds de Recherche du Québec-Santé. See paper for disclosures of other authors.

A version of this article first appeared on Medscape.com.

Multiple emerging risk factors for cardiovascular disease in women must be recognized and assessed to provide timely diagnosis and treatment, according to Dipti N. Itchhaporia, MD, an interventional cardiologist in southern California. These risk factors include pregnancy complications, autoimmune diseases, depression, breast cancer, and breast arterial calcification.

During the session titled “Cardiac Care in Women: Emerging Risk Factors” at CardioAcademic 2023, the former president of the American College of Cardiology emphasized that gender equity in care for cardiovascular disease will be achieved only when risk factors are evaluated from a gender-dependent perspective and when assessments are broadened to include novel and unrecognized risk factors, not just traditional risk factors.

Dr. Itchhaporia also remarked that women and primary care clinicians must be educated on the symptoms of heart disease so that they can be on the alert and provide patients with comprehensive treatments when necessary.

“Cardiovascular disease remains the leading cause of death in women, at least in the United States, and globally the outlook is similar,” she explained. “That’s why we need to provide our patients with guidance and carefully investigate when they experience chest pain. We need to remember that smoking and obesity pose a higher risk for cardiovascular disease in women than in men. Taking these risk factors into account will really make a difference by allowing us to provide more timely and targeted care.”

In her presentation, Dr. Itchhaporia noted that cardiovascular disease accounts for 35% of deaths in women worldwide. She reminded her audience that, according to The Lancet Women and Cardiovascular Disease Commission, heart diseases in this population remain “understudied, underrecognized, underdiagnosed, and undertreated. Furthermore, women are underrepresented in cardiovascular [clinical practice].”

She mentioned this because, despite U.S. legislation enacted between 1980 and 1990 that mandated the inclusion of women in clinical trials, women accounted for less than 39% of participants in cardiovascular clinical trials between 2010 and 2017. According to Dr. Itchhaporia, this situation limits the potential for developing tailored strategies and recommendations to treat the cardiovascular diseases affecting women.
 

Emerging risk factors

Dr. Itchhaporia pointed out that traditional risk factors have been known for many years. For example, 80% of women aged 75 years or younger have arterial hypertension. Only 29% receive adequate blood pressure control, those living with diabetes have a 45% greater risk of suffering ischemic heart disease, and obesity confers a 64% higher risk of developing ischemic heart disease in women versus 46% in men.

In addition to these factors, she noted that emerging factors must be assessed carefully. For example, women who experience pregnancy complications like gestational diabetes have a higher risk for ischemic heart disease and type 2 diabetes. Women with hypertension and preeclampsia are at a threefold higher risk of developing ischemic heart disease.

“Pregnancy can really be a major stress test for the heart, and I believe that, as health care professionals, we should all be asking women if they have had pregnancy-related complications. I don’t think that’s something we’ve been doing on a regular basis. Statistically, we know that 10%-20% of pregnant women report complications during pregnancy, and strong associations have been shown between gestational hypertension [and] preeclampsia.”

Dr. Itchhaporia explained that depression, a condition that globally affects women twice as much as men, is another emerging factor (though it has received some increased recognition). She explained that, in women, depression is a significant risk factor for developing a major adverse cardiovascular event or a combined event of cardiac death and myocardial infarction related to the target lesion and revascularization of the target lesion because of ischemia. Furthermore, women who have experienced a cardiac-related event are more likely to have depression than men.

“If we look into it in more detail, depression leads to changes in behavioral habits and physiological mechanisms,” she said. “Women living with depression are at higher risk of smoking, not exercising as much, are perhaps less careful with their hygiene, are not likely to adhere to their medications, and don’t sleep as well. All this moves them in the direction of heart disease.”

Added to these factors are autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus, where the female-to-male ratio for rheumatoid arthritis is 2½:1 and for lupus it’s 9:1. Dr. Itchhaporia explained that patients with rheumatoid arthritis are at two- to threefold greater risk for myocardial infarction and have a 50% higher risk for stroke. In the case of systemic lupus, the risk of myocardial infarction is 7-50 times greater than in the general population. She noted that cardiovascular risk calculators underestimate the burden of risk in patients with these diseases.

Lastly, she brought up breast cancer and breast arterial calcification as additional emerging risk factors. She explained that women with breast cancer are more likely to develop hypertension and diabetes, compared with women without this diagnosis. Women with hypertension or diabetes before developing breast cancer have twice the risk for heart problems after cancer.

She added that 12.7% of women screened for breast cancer have some degree of breast calcification. She explained that this occurs when calcium accumulates in the middle layer of artery walls in the breast, which is linked to aging, type 2 diabetes, or arterial hypertension and may be a marker of arterial stiffening, which is a cardiovascular disease.

“It’s extremely important to take into consideration data suggesting a strong association between breast calcifications and cardiovascular disease, independent of other known risk factors of cardiovascular disease. We need to improve our tests for detecting cardiovascular disease in women and we need to ask specific questions and not overlook these emerging factors,” she noted.
 

Improving health outcomes

Panelist María Guadalupe Parra Machuca, MD, a cardiologist in Guadalajara, Mexico, specializing in women’s heart disease, agreed that it is high time that clinical practice reflect public health policies, so that efforts to diagnose and treat cardiovascular diseases in women more effectively can transition from theory to reality.

“As physicians, we cannot allow public policy to remain outside of the reality we face,” she stressed. “We need to let it impact the decisions we make. Everything we see day to day, the things we learn at these conferences – let’s put it into practice. Otherwise, all our discussions and all the steps taken to improve care, from primary to highly specialized care and to detect and treat cardiovascular disease in women, will be nothing but rhetoric.”

Clinical cardiology specialist Victor Leal, MD, noted that, according to preliminary results from the national survey of cardiovascular risk factors in Mexican women, Mexico is no exception to these emerging risk factors for cardiovascular disease in women. More than 50% of women in Mexico have traditional risk factors, most notably hypertension, obesity, and diabetes, while hypertensive disorders of pregnancy top the list of other sex-specific risk factors.

“Not only are these factors increasing, but also having them increases the risk of a worse prognosis, leaving us with a very challenging scenario,” said Dr. Leal. “Not only do we need to educate patients about the traditional risk factors, but also about factors that might not be on our radar. We need to get women to link these factors to cardiovascular disease and to the possibility of developing much more adverse outcomes. This will reinforce our diagnosis and treatment.”

In an interview, Dr. Itchhaporia emphasized the changing face of cardiovascular disease for women, who have worse short- and long-term outcomes than men because they are not asked sex-specific questions during initial encounters and they experience greater prehospital delays.

She noted that, while experts need to raise awareness of the emerging risk factors among health care professionals, they also need to use information campaigns to make women aware of what the risks are. Then, if they experience any of the emerging risk factors, they can discuss it with their treating physicians.

“We need to assess both the traditional risk factors and the novel ones, those that are underrecognized. We need to include the history of pregnancy and complications during this period and we need to educate women about symptoms of heart disease like chest pain, difficulty breathing, and increasing fatigue,” she emphasized. “We must also provide guidance as to lifestyle, diet, and levels of physical activity and be aware of stress and symptoms of depression. Only then will we bring greater awareness to the fact that cardiovascular disease is the leading cause of death among women, and then we can reverse these trends.”

Dr. Itchhaporia, Dr. Parra, and Dr. Leal reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Multiple emerging risk factors for cardiovascular disease in women must be recognized and assessed to provide timely diagnosis and treatment, according to Dipti N. Itchhaporia, MD, an interventional cardiologist in southern California. These risk factors include pregnancy complications, autoimmune diseases, depression, breast cancer, and breast arterial calcification.

During the session titled “Cardiac Care in Women: Emerging Risk Factors” at CardioAcademic 2023, the former president of the American College of Cardiology emphasized that gender equity in care for cardiovascular disease will be achieved only when risk factors are evaluated from a gender-dependent perspective and when assessments are broadened to include novel and unrecognized risk factors, not just traditional risk factors.

Dr. Itchhaporia also remarked that women and primary care clinicians must be educated on the symptoms of heart disease so that they can be on the alert and provide patients with comprehensive treatments when necessary.

“Cardiovascular disease remains the leading cause of death in women, at least in the United States, and globally the outlook is similar,” she explained. “That’s why we need to provide our patients with guidance and carefully investigate when they experience chest pain. We need to remember that smoking and obesity pose a higher risk for cardiovascular disease in women than in men. Taking these risk factors into account will really make a difference by allowing us to provide more timely and targeted care.”

In her presentation, Dr. Itchhaporia noted that cardiovascular disease accounts for 35% of deaths in women worldwide. She reminded her audience that, according to The Lancet Women and Cardiovascular Disease Commission, heart diseases in this population remain “understudied, underrecognized, underdiagnosed, and undertreated. Furthermore, women are underrepresented in cardiovascular [clinical practice].”

She mentioned this because, despite U.S. legislation enacted between 1980 and 1990 that mandated the inclusion of women in clinical trials, women accounted for less than 39% of participants in cardiovascular clinical trials between 2010 and 2017. According to Dr. Itchhaporia, this situation limits the potential for developing tailored strategies and recommendations to treat the cardiovascular diseases affecting women.
 

Emerging risk factors

Dr. Itchhaporia pointed out that traditional risk factors have been known for many years. For example, 80% of women aged 75 years or younger have arterial hypertension. Only 29% receive adequate blood pressure control, those living with diabetes have a 45% greater risk of suffering ischemic heart disease, and obesity confers a 64% higher risk of developing ischemic heart disease in women versus 46% in men.

In addition to these factors, she noted that emerging factors must be assessed carefully. For example, women who experience pregnancy complications like gestational diabetes have a higher risk for ischemic heart disease and type 2 diabetes. Women with hypertension and preeclampsia are at a threefold higher risk of developing ischemic heart disease.

“Pregnancy can really be a major stress test for the heart, and I believe that, as health care professionals, we should all be asking women if they have had pregnancy-related complications. I don’t think that’s something we’ve been doing on a regular basis. Statistically, we know that 10%-20% of pregnant women report complications during pregnancy, and strong associations have been shown between gestational hypertension [and] preeclampsia.”

Dr. Itchhaporia explained that depression, a condition that globally affects women twice as much as men, is another emerging factor (though it has received some increased recognition). She explained that, in women, depression is a significant risk factor for developing a major adverse cardiovascular event or a combined event of cardiac death and myocardial infarction related to the target lesion and revascularization of the target lesion because of ischemia. Furthermore, women who have experienced a cardiac-related event are more likely to have depression than men.

“If we look into it in more detail, depression leads to changes in behavioral habits and physiological mechanisms,” she said. “Women living with depression are at higher risk of smoking, not exercising as much, are perhaps less careful with their hygiene, are not likely to adhere to their medications, and don’t sleep as well. All this moves them in the direction of heart disease.”

Added to these factors are autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus, where the female-to-male ratio for rheumatoid arthritis is 2½:1 and for lupus it’s 9:1. Dr. Itchhaporia explained that patients with rheumatoid arthritis are at two- to threefold greater risk for myocardial infarction and have a 50% higher risk for stroke. In the case of systemic lupus, the risk of myocardial infarction is 7-50 times greater than in the general population. She noted that cardiovascular risk calculators underestimate the burden of risk in patients with these diseases.

Lastly, she brought up breast cancer and breast arterial calcification as additional emerging risk factors. She explained that women with breast cancer are more likely to develop hypertension and diabetes, compared with women without this diagnosis. Women with hypertension or diabetes before developing breast cancer have twice the risk for heart problems after cancer.

She added that 12.7% of women screened for breast cancer have some degree of breast calcification. She explained that this occurs when calcium accumulates in the middle layer of artery walls in the breast, which is linked to aging, type 2 diabetes, or arterial hypertension and may be a marker of arterial stiffening, which is a cardiovascular disease.

“It’s extremely important to take into consideration data suggesting a strong association between breast calcifications and cardiovascular disease, independent of other known risk factors of cardiovascular disease. We need to improve our tests for detecting cardiovascular disease in women and we need to ask specific questions and not overlook these emerging factors,” she noted.
 

Improving health outcomes

Panelist María Guadalupe Parra Machuca, MD, a cardiologist in Guadalajara, Mexico, specializing in women’s heart disease, agreed that it is high time that clinical practice reflect public health policies, so that efforts to diagnose and treat cardiovascular diseases in women more effectively can transition from theory to reality.

“As physicians, we cannot allow public policy to remain outside of the reality we face,” she stressed. “We need to let it impact the decisions we make. Everything we see day to day, the things we learn at these conferences – let’s put it into practice. Otherwise, all our discussions and all the steps taken to improve care, from primary to highly specialized care and to detect and treat cardiovascular disease in women, will be nothing but rhetoric.”

Clinical cardiology specialist Victor Leal, MD, noted that, according to preliminary results from the national survey of cardiovascular risk factors in Mexican women, Mexico is no exception to these emerging risk factors for cardiovascular disease in women. More than 50% of women in Mexico have traditional risk factors, most notably hypertension, obesity, and diabetes, while hypertensive disorders of pregnancy top the list of other sex-specific risk factors.

“Not only are these factors increasing, but also having them increases the risk of a worse prognosis, leaving us with a very challenging scenario,” said Dr. Leal. “Not only do we need to educate patients about the traditional risk factors, but also about factors that might not be on our radar. We need to get women to link these factors to cardiovascular disease and to the possibility of developing much more adverse outcomes. This will reinforce our diagnosis and treatment.”

In an interview, Dr. Itchhaporia emphasized the changing face of cardiovascular disease for women, who have worse short- and long-term outcomes than men because they are not asked sex-specific questions during initial encounters and they experience greater prehospital delays.

She noted that, while experts need to raise awareness of the emerging risk factors among health care professionals, they also need to use information campaigns to make women aware of what the risks are. Then, if they experience any of the emerging risk factors, they can discuss it with their treating physicians.

“We need to assess both the traditional risk factors and the novel ones, those that are underrecognized. We need to include the history of pregnancy and complications during this period and we need to educate women about symptoms of heart disease like chest pain, difficulty breathing, and increasing fatigue,” she emphasized. “We must also provide guidance as to lifestyle, diet, and levels of physical activity and be aware of stress and symptoms of depression. Only then will we bring greater awareness to the fact that cardiovascular disease is the leading cause of death among women, and then we can reverse these trends.”

Dr. Itchhaporia, Dr. Parra, and Dr. Leal reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Multiple emerging risk factors for cardiovascular disease in women must be recognized and assessed to provide timely diagnosis and treatment, according to Dipti N. Itchhaporia, MD, an interventional cardiologist in southern California. These risk factors include pregnancy complications, autoimmune diseases, depression, breast cancer, and breast arterial calcification.

During the session titled “Cardiac Care in Women: Emerging Risk Factors” at CardioAcademic 2023, the former president of the American College of Cardiology emphasized that gender equity in care for cardiovascular disease will be achieved only when risk factors are evaluated from a gender-dependent perspective and when assessments are broadened to include novel and unrecognized risk factors, not just traditional risk factors.

Dr. Itchhaporia also remarked that women and primary care clinicians must be educated on the symptoms of heart disease so that they can be on the alert and provide patients with comprehensive treatments when necessary.

“Cardiovascular disease remains the leading cause of death in women, at least in the United States, and globally the outlook is similar,” she explained. “That’s why we need to provide our patients with guidance and carefully investigate when they experience chest pain. We need to remember that smoking and obesity pose a higher risk for cardiovascular disease in women than in men. Taking these risk factors into account will really make a difference by allowing us to provide more timely and targeted care.”

In her presentation, Dr. Itchhaporia noted that cardiovascular disease accounts for 35% of deaths in women worldwide. She reminded her audience that, according to The Lancet Women and Cardiovascular Disease Commission, heart diseases in this population remain “understudied, underrecognized, underdiagnosed, and undertreated. Furthermore, women are underrepresented in cardiovascular [clinical practice].”

She mentioned this because, despite U.S. legislation enacted between 1980 and 1990 that mandated the inclusion of women in clinical trials, women accounted for less than 39% of participants in cardiovascular clinical trials between 2010 and 2017. According to Dr. Itchhaporia, this situation limits the potential for developing tailored strategies and recommendations to treat the cardiovascular diseases affecting women.
 

Emerging risk factors

Dr. Itchhaporia pointed out that traditional risk factors have been known for many years. For example, 80% of women aged 75 years or younger have arterial hypertension. Only 29% receive adequate blood pressure control, those living with diabetes have a 45% greater risk of suffering ischemic heart disease, and obesity confers a 64% higher risk of developing ischemic heart disease in women versus 46% in men.

In addition to these factors, she noted that emerging factors must be assessed carefully. For example, women who experience pregnancy complications like gestational diabetes have a higher risk for ischemic heart disease and type 2 diabetes. Women with hypertension and preeclampsia are at a threefold higher risk of developing ischemic heart disease.

“Pregnancy can really be a major stress test for the heart, and I believe that, as health care professionals, we should all be asking women if they have had pregnancy-related complications. I don’t think that’s something we’ve been doing on a regular basis. Statistically, we know that 10%-20% of pregnant women report complications during pregnancy, and strong associations have been shown between gestational hypertension [and] preeclampsia.”

Dr. Itchhaporia explained that depression, a condition that globally affects women twice as much as men, is another emerging factor (though it has received some increased recognition). She explained that, in women, depression is a significant risk factor for developing a major adverse cardiovascular event or a combined event of cardiac death and myocardial infarction related to the target lesion and revascularization of the target lesion because of ischemia. Furthermore, women who have experienced a cardiac-related event are more likely to have depression than men.

“If we look into it in more detail, depression leads to changes in behavioral habits and physiological mechanisms,” she said. “Women living with depression are at higher risk of smoking, not exercising as much, are perhaps less careful with their hygiene, are not likely to adhere to their medications, and don’t sleep as well. All this moves them in the direction of heart disease.”

Added to these factors are autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus, where the female-to-male ratio for rheumatoid arthritis is 2½:1 and for lupus it’s 9:1. Dr. Itchhaporia explained that patients with rheumatoid arthritis are at two- to threefold greater risk for myocardial infarction and have a 50% higher risk for stroke. In the case of systemic lupus, the risk of myocardial infarction is 7-50 times greater than in the general population. She noted that cardiovascular risk calculators underestimate the burden of risk in patients with these diseases.

Lastly, she brought up breast cancer and breast arterial calcification as additional emerging risk factors. She explained that women with breast cancer are more likely to develop hypertension and diabetes, compared with women without this diagnosis. Women with hypertension or diabetes before developing breast cancer have twice the risk for heart problems after cancer.

She added that 12.7% of women screened for breast cancer have some degree of breast calcification. She explained that this occurs when calcium accumulates in the middle layer of artery walls in the breast, which is linked to aging, type 2 diabetes, or arterial hypertension and may be a marker of arterial stiffening, which is a cardiovascular disease.

“It’s extremely important to take into consideration data suggesting a strong association between breast calcifications and cardiovascular disease, independent of other known risk factors of cardiovascular disease. We need to improve our tests for detecting cardiovascular disease in women and we need to ask specific questions and not overlook these emerging factors,” she noted.
 

Improving health outcomes

Panelist María Guadalupe Parra Machuca, MD, a cardiologist in Guadalajara, Mexico, specializing in women’s heart disease, agreed that it is high time that clinical practice reflect public health policies, so that efforts to diagnose and treat cardiovascular diseases in women more effectively can transition from theory to reality.

“As physicians, we cannot allow public policy to remain outside of the reality we face,” she stressed. “We need to let it impact the decisions we make. Everything we see day to day, the things we learn at these conferences – let’s put it into practice. Otherwise, all our discussions and all the steps taken to improve care, from primary to highly specialized care and to detect and treat cardiovascular disease in women, will be nothing but rhetoric.”

Clinical cardiology specialist Victor Leal, MD, noted that, according to preliminary results from the national survey of cardiovascular risk factors in Mexican women, Mexico is no exception to these emerging risk factors for cardiovascular disease in women. More than 50% of women in Mexico have traditional risk factors, most notably hypertension, obesity, and diabetes, while hypertensive disorders of pregnancy top the list of other sex-specific risk factors.

“Not only are these factors increasing, but also having them increases the risk of a worse prognosis, leaving us with a very challenging scenario,” said Dr. Leal. “Not only do we need to educate patients about the traditional risk factors, but also about factors that might not be on our radar. We need to get women to link these factors to cardiovascular disease and to the possibility of developing much more adverse outcomes. This will reinforce our diagnosis and treatment.”

In an interview, Dr. Itchhaporia emphasized the changing face of cardiovascular disease for women, who have worse short- and long-term outcomes than men because they are not asked sex-specific questions during initial encounters and they experience greater prehospital delays.

She noted that, while experts need to raise awareness of the emerging risk factors among health care professionals, they also need to use information campaigns to make women aware of what the risks are. Then, if they experience any of the emerging risk factors, they can discuss it with their treating physicians.

“We need to assess both the traditional risk factors and the novel ones, those that are underrecognized. We need to include the history of pregnancy and complications during this period and we need to educate women about symptoms of heart disease like chest pain, difficulty breathing, and increasing fatigue,” she emphasized. “We must also provide guidance as to lifestyle, diet, and levels of physical activity and be aware of stress and symptoms of depression. Only then will we bring greater awareness to the fact that cardiovascular disease is the leading cause of death among women, and then we can reverse these trends.”

Dr. Itchhaporia, Dr. Parra, and Dr. Leal reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Recorded Aug. 26, 2023. This transcript has been edited for clarity.

Robert A. Harrington, MD: I’m here with my good friend, Manesh Patel, from Duke University. We’re at the European Society of Cardiology (ESC) congress in Amsterdam, and I pulled Manesh into the studio for a conversation about something that’s really topical right now: sudden cardiac death in athletes.

What I hope to do [in this interview] is really pick Manesh’s brain on how we are thinking about this. Are we going to think about treatment issues? Are we going to think about prevention issues? Are we thinking about screening? We’ll try to make it practical.

Dr. Manesh Patel is chief of cardiovascular medicine at Duke University and also the director of the Duke Heart Center. Manesh, thanks for joining me here.
 

Bronny James and Damar Hamlin

Manesh R. Patel, MD: Excited to be here, Bob. Always.

Harrington: [Recently,] a news article comes out about the cause of Bronny James’ sudden cardiac death. Let me put this into a bigger societal context.

Last winter, Damar Hamlin, from the Buffalo Bills, suffered a traumatic injury on the field, and with that, had cardiac arrest. He’s back playing football – great to see. You and I are involved with the American Heart Association. He’s been very supportive of our efforts around things like CPR. He’s been terrific. It’s great to see him playing.

We know a little less about Bronny James. The news articles say the cause is both functional and anatomical, and it seems to be congenital, but we don’t have any details beyond this. Let’s not focus on the people; let’s focus on the topic.

Patel: I’m excited that we’re having the conversation. First and foremost, we’re excited that, with what we’ve seen on a national stage, these two individuals are doing well. They survived sudden cardiac death, which is a testament to all the things that we’ll talk about.

There are many important questions, like, is this increasing? Is this something we can prevent? And what are those things that might be happening to athletes?

Harrington: Can we predict it?

Patel: Right. I think the idea of sudden cardiac death in athletes is really a critical one for us to think about because it does concern participation and what we think about that. There are many experts who’ve been studying this for years that I now get to work with.

Harrington: Tell us a little bit about the kind of things you’ve been doing in this area.

Patel: Even before these events in the COVID era, we were wondering about athletes getting myocarditis, just in general, what do we know about that? People like Aaron Baggish, Kim Harmon, Jonathan Drezner, and others have been studying this.

Harrington: You and I did a show on athletes and COVID-19.

Patel: With the American Heart Association (AHA), the Cornell Foundation, and others, we started the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA). This registry is across the United States, and athletes can sign up.

Harrington: Is it voluntary? Do the schools sign them up?

Patel: The athletes sign up. Team trainers and doctors talk to the athletes. We don’t really know the risks of some of these conditions. There’s a lot of gray area – people with certain conditions that were really interesting; aortas that are dilated in tall people.

Harrington: Long QT.

Patel: Long QT. There are certainly things that we know we should be intervening on and others where participation is a question. All of these we are trying to longitudinally put into the registry and follow them over time.

The second thing is understanding from the last Bethesda Conference that we want shared decision-making. There are going to be conditions where you say, “Look, I think your risk is high. You’ve a family history of sudden cardiac death. You have arrhythmias while you’re exercising.”

Harrington: You have a big, thick heart.

Patel: If you have hypertrophic cardiomyopathy, whether you’re an athlete or a 40-year-old adult, we’re going to have the same conversation. I think that holds. There’s a variety or a spectrum where we don’t know. I think the registry is one big step.

Thinking back to when somebody has an event, I would say take the teachable moment with the AHA and others to make sure your communities and your areas have automated external defibrillators (AEDs) and CPR training, and that we get to 100%: 100% response, 100% CPR, 100% defibrillation. I think that’s the first step.
 

Chain of survival

Harrington: Let’s really focus on the chain of survival. It is a chain: If any link is broken, your chance of survival really drops. We’ve had some well-known cases within our AHA community, including somebody who talks about it regularly: Kevin Volpp, from the University of Pennsylvania, a health economist. He had almost the perfect chain of survival. He had sudden cardiac death in a restaurant that was immediately observed, CPR started, EMTs called, and AED on the scene. Impressive.

Patel: That was in Cincinnati, where there are communities that have really worked on these things. I think you’re right. The chain of survival with rapid CPR to build a nation of survivors is key. The people at the AHA are helping us do this; there is a national call to make sure CPR is something that people feel comfortable doing. That they do it in men and women. They do it for anyone that goes down. And realize that it’s CPR that is hands-only. I think that’s an important lesson from Damar’s work, Nancy Brown’s, and AHA’s. Actually, schools in many countries require that to get through primary school.

Harrington: CPR training is a requirement to graduate from high school in some states.

Patel: My son just graduated from high school, and we spent time at his school making sure that everybody had access to CPR training. I think the way to do this is to start with that. Now, getting more specific about teams and athletes, I think most have emergency action plans, but it’s having action plans that work because of where you are and where the AED locations might be, or what the sport is. Having a plan on how you’re going to get that athlete to a place where you can help them recover is an important piece.

From there, I think the conversation for us is about what can we do as a society and as a country to answer some critical questions, including some real-world questions that people are asking: We had COVID-19 and we’re hearing these cases. Is this going up or down, and are these related?

Soon, hopefully the same group I talked about and others will have a publication, working with the NCAA to look at all of the deaths that they observed in NCAA Division I athletes over 20 years, including the sudden cardiac deaths. I won’t share the results because the publication isn’t out, but I think that’s the kind of important information that will help us understand if these rates are going up or down.

Harrington: What’s associated with that risk? Then we can start getting at whether it is something that, when we’re doing assessment for suitability for sports, has risk factors that should warrant more investigation.

Patel: Much like the field of cardiology, we haven’t enough of an evidence base, the right technologies, or the studies to determine how we should do screening, or not screening, across the board. Again, there is variation. There are some countries where anyone participating is going to get an ECG and an echocardiogram. There are other countries, like the United States, where it’s going to be a bit dependent on athlete risk.

Harrington: And where you live.

Patel: And where you live. Unfortunately, again, that brings in the idea that it might not be equitable in how we’re evaluating these individuals. I do think the opportunity to start to standardize that evaluation exists, and it likely comes from the ability to look back and say, “Here are some higher-risk individuals or some higher-risk scenarios.”

Harrington: Isn’t this what we do all the time in clinical medicine?

Patel: It’s going to be applied to a population that maybe is not as studied. I said this to you before we came on. The other thing is to make sure that the shared decision-making allows athletes who feel like they have a chance or want to play. During COVID, we had many college athletes, high school athletes, and kids not able to participate in sports. There was significant depression, feeling of loneliness, and even physical loss. People were actually getting less conditioned quickly. There’s a great benefit to sports participation.

Harrington: We were extrapolating from older data. If I’ve just had this new infection, COVID, and I’ve maybe got some signs of it in my heart, why can’t I exercise? That’s extrapolating from old myocarditis data.

Patel: We’re having to learn and follow it. I think there’s value in following that and getting those data. The second thing I think is really valuable is that we’ve shown that these individuals, if you do have these conversations and follow them, can participate and can be part of understanding the risk just like anything else.

Harrington: Is it sport specific? Are there some sports where maybe the conversation should be a little more intense than in other sports?

Patel: I think what we’ll see is that the conversations may be sport specific, and some may concern the number of athletes tested. At times, it’s pretty complicated. It does look like there are, as you know, different weight-bearing performance athletes, endurance athletes, or what I’ll call burst sports. There will probably be data that will identify certain sports where we may need to pay a bit more attention.

Harrington: What about the contact issues? Damar had a very specific thing, we think, happen to him. Football is a violent, contact-oriented sport, but fortunately we don’t regularly see what happened to Damar.

Patel: We’re talking about sudden cardiac death, but obviously, contact issues and neurologic evaluation is a whole other topic. That’s another big issue that I know many are following, and the NCAA is carefully, too. For Damar, I think we know that it was commotio cordis. At least when that happens, when there’s a ball or a trauma to the chest, those things have to be timed just so to actually lead to this event. Thankfully, it’s not very frequent, but it can happen.

Harrington: Hockey pucks, baseballs, soccer balls, a helmet to the chest ...

Patel: You have to be in a specific cycle of the squeeze. We don’t see that very frequently. I do think the evaluation and treatment, hopefully, makes a difference. One thing that we’re evolving in the screening world is our imaging; it’s getting better. We are not just doing echocardiograms; we are able to do other studies. There’s a mix of imaging and other technologies.

Is screening the answer?

Harrington: Let’s talk about that because screening is the area, I would say, with the most controversy – and a large amount of emotional controversy. Some argue that the data are not good enough to screen, or doctors are saying, “Wait a minute, why are we screening all these kids?” You said you were at your son’s high school doing CPR training. How many athletes are at his high school? There are many, and that’s a pretty small high school. Big communities, big universities, and the professional sports can afford it. Should we be doing this at the community level?

Patel: There have been some data. The Italians have done standard screening for some time, and it’s shown us that if you did echocardiograms in many individuals, you do find some cases that are hypertrophic cardiomyopathy in pathology. The issue is just how much you have to do and the resource utilization. I think as we get to a world where screening studies can happen with smaller technology and AI, that can be democratizing in how we get to athletes.

Harrington: Give an example of that. We were talking outside, you and I, about some of the new stethoscope technology.

Patel: Yes, stethoscopes are going to be one of the examples. We have stethoscopes that have the ability to get sounds and ECG signals, or at least some lead signals.

Harrington: Yes.

Patel: Potentially you can imagine that sound and ECG tracing in an AI environment, at least getting you from “everyone gets a listen with one stethoscope in their gym from their coach,” and it goes to the cloud. When there are enough questions, these are the ones that have to go further. Now, that’s a big study that has to be carried out; I’m not in any way saying we should do that.

Harrington: The technology is coming.

Patel: We start to see that our ability to rapidly do something to meet our athletes or our patients where they are will happen soon. Remember that the performance curve can vary, but once you have a sound where you can start to say that this is a regular flow murmur vs. “I’m worried about this,” especially as you mark it with ECG – that’s one example.

Smaller imaging is another example. For many years, ECGs have been talked about. There are entire courses that we run looking at ECGs in athletes. Remembering that Aaron Baggish and others are publishing that these individuals are large. When we look at their hearts, we see that they’re large, but when you adjust for size, often you can identify that many of them are within what we think are normal. Structurally, there are still many cases where you look at hearts and you’re asking, “Is this a thick heart? Is this noncompaction? Is this some pathology?”

That’s where you need imaging expertise. I think you have to have those individuals. I’m not advocating screening. I’m advocating studying it and that we should be thinking about the population. I don’t see a world where we don’t eventually start to really look to prevent those.

Harrington: Right. Whether it’s understanding that there are certain risk factors associated with this and we have to dedicate screening resources to those individuals, or if we want to do it more broadly on the population level to understand this with deeper dives into certain individuals, we’ve got to study it.

Patel: Some of the experts in sports medicine and sports cardiology have been collecting these data for a while. It’s time that we are there, because with these events we have the opportunity to share more of these data and maybe raise awareness – not in the teachable moment only – to get others to contribute.

I do believe that long term there’s an opportunity. We’ve seen that. We see that the rates, unfortunately, for marathon runners, where people unfortunately have events, seem to be higher. And we’ve seen the studies on troponin leaks in these individuals or evidence that there’s some effect on the heart from these events. We want people to be able to be long-term healthy.
 

Early defibrillation

Harrington: A large amount of work needs to be done. We talked with regard to screening, we’ve talked about CPR. We really need to have a nation of people who can do hands-only CPR. Let’s talk about AEDs, another key part of the chain of survival.

Patel: We have another important study going on, but an important message first: AEDs are critical to survival. We know that CPR is critical, but so is getting people to a defibrillator.

Harrington: Early defibrillation.

Patel: Early defibrillation. Early CPR is one of the biggest markers of making sure we perfuse people to get to early defibrillation, but then you have to get early defibrillation. There’s been a huge push in many communities, again, along with AHA and others, to make sure that AEDs are available not only in the U.S. but around the world. We’re at ESC and we see the push around the world to get AEDs available. They’ve come down in size and come down in cost, and that’s made it much more accessible. That’s really good. They’re still not always there.

We’ve seen really interesting randomized studies with people in some European countries where they have certain areas, just because of the locations, where bystanders will help get an AED  vs. randomizing to the EMS truck. They seem better in some of those variations. Chris Granger, at our institution, with Monique Starks, Dan Mark, and others, is doing a study in North Carolina where we’re testing different ways to potentially get AEDs in communities. We’re randomizing counties to one or two ways of getting AEDs to those individuals.

Harrington: Can you have an app where you just click “Find me an AED”?

Patel: Is there a world where the AED is found or is something bringing you the AED? Are there drones? Are there people driving? Are there ways that an AED is brought to the scene? All of those are going to be critical. It starts with continuing to figure out ways to support the costs of getting AEDs in places. The technology is continuing to evolve.

Harrington: It really is the premedical system stuff that makes the difference. Once EMS arrives with trained individuals who can defibrillate, they can transport you to a medical facility where trained physicians are at. It’s that pre-EMS thing that is so critical.

Patel: We talk often about athletes, but cardiac arrest care in general, and the chain of survival with CPR and AEDs, is critical. I still see patients in the CICU at Duke where, unfortunately, the biggest driver, as you just highlighted in that chain of survival, is how rapid we were in that golden hour. In the first 15 minutes, are you getting CPR, are you getting AED? Are you getting to a system?

Harrington: Are you getting a rapid transport?

Patel: Are you getting a neurologic assessment? Are you getting cooled or not? Those are important things.

Harrington: All right. Let’s try to wrap this up. Teachable moments, we talked about. One of the things about cases in prominent athletes is that it makes it to the newspaper and then it raises awareness. There is a drawing inference from a small group of cases to the broader societal issues. That’s an important topic.

We’ve talked about possible screening options, identifying at-risk individuals and high-risk individuals. A large amount of data has already been accumulated, but there is more work to be done. We focused on how to use those teachable moments to really influence the chain of survival, not just for athletes but for society at large.

I love your point about the Bethesda Conference on shared decision-making. Like with everything else, we have to have that two-way conversation: What are the athlete’s goals, hopes, and aspirations?

Patel: That group of experts, in addition to shared decision-making, gave us a whole list of conditions that we should be aware of and the cutpoints of where we think normal and not normal live for athletes. I think that’s used by many.

Can we build our systems to make research happen faster for the individuals? These athletes are at colleges that are obviously doing so much to make sure they’re okay. The people who are helping with this registry, and others, are going to continue to work to ask whether we can engage them as citizen participants and scientists. I think athletes are going to become some of our best advocates for why you’d want to know about yourself and how to perform CPR.

Harrington: I love the concept of citizen scientists, that we all have an obligation to contribute to the evidence base because we all want to use that evidence.

This has been a terrific conversation. I’ve been joined by my good friend, Dr. Manesh Patel from Duke University. I hope you’ve enjoyed our discussion here at the ESC. We have been taking a little break from the science going on around us to talk about sudden cardiac death in athletes. It really does have implications for broader societal concepts.

Dr. Harrington is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, New York, as well as a former president of the American Heart Association. He has disclosed the following relevant financial relationships: Research relationships with Baim Institute (DSMB); CSL (RCT executive committee); Janssen (RCT chair); National Heart, Lung, and Blood Institute (RCT executive committee, DSMB chair); Patient-Centered Outcomes Research Institute (RCT co-chair); Duke Clinical Research Institute. Consulting relationships with Atropos Health; Bitterroot Bio; Bristol Myers Squibb; BridgeBio; Element Science; Edwards Lifesciences; Foresite Labs; Medscape/WebMD Board of Directors for: American Heart Association; College of the Holy Cross; Cytokinetics. Dr. Patel is professor of medicine, Duke University; chief, division of cardiology; director, Duke Heart Center, Duke University Medical Center, Durham, N.C. He has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bayer; Janssen; Novartis (consultant). Received research grant from Bayer; Janssen.

A version of this article appeared on Medscape.com.

Recorded Aug. 26, 2023. This transcript has been edited for clarity.

Robert A. Harrington, MD: I’m here with my good friend, Manesh Patel, from Duke University. We’re at the European Society of Cardiology (ESC) congress in Amsterdam, and I pulled Manesh into the studio for a conversation about something that’s really topical right now: sudden cardiac death in athletes.

What I hope to do [in this interview] is really pick Manesh’s brain on how we are thinking about this. Are we going to think about treatment issues? Are we going to think about prevention issues? Are we thinking about screening? We’ll try to make it practical.

Dr. Manesh Patel is chief of cardiovascular medicine at Duke University and also the director of the Duke Heart Center. Manesh, thanks for joining me here.
 

Bronny James and Damar Hamlin

Manesh R. Patel, MD: Excited to be here, Bob. Always.

Harrington: [Recently,] a news article comes out about the cause of Bronny James’ sudden cardiac death. Let me put this into a bigger societal context.

Last winter, Damar Hamlin, from the Buffalo Bills, suffered a traumatic injury on the field, and with that, had cardiac arrest. He’s back playing football – great to see. You and I are involved with the American Heart Association. He’s been very supportive of our efforts around things like CPR. He’s been terrific. It’s great to see him playing.

We know a little less about Bronny James. The news articles say the cause is both functional and anatomical, and it seems to be congenital, but we don’t have any details beyond this. Let’s not focus on the people; let’s focus on the topic.

Patel: I’m excited that we’re having the conversation. First and foremost, we’re excited that, with what we’ve seen on a national stage, these two individuals are doing well. They survived sudden cardiac death, which is a testament to all the things that we’ll talk about.

There are many important questions, like, is this increasing? Is this something we can prevent? And what are those things that might be happening to athletes?

Harrington: Can we predict it?

Patel: Right. I think the idea of sudden cardiac death in athletes is really a critical one for us to think about because it does concern participation and what we think about that. There are many experts who’ve been studying this for years that I now get to work with.

Harrington: Tell us a little bit about the kind of things you’ve been doing in this area.

Patel: Even before these events in the COVID era, we were wondering about athletes getting myocarditis, just in general, what do we know about that? People like Aaron Baggish, Kim Harmon, Jonathan Drezner, and others have been studying this.

Harrington: You and I did a show on athletes and COVID-19.

Patel: With the American Heart Association (AHA), the Cornell Foundation, and others, we started the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA). This registry is across the United States, and athletes can sign up.

Harrington: Is it voluntary? Do the schools sign them up?

Patel: The athletes sign up. Team trainers and doctors talk to the athletes. We don’t really know the risks of some of these conditions. There’s a lot of gray area – people with certain conditions that were really interesting; aortas that are dilated in tall people.

Harrington: Long QT.

Patel: Long QT. There are certainly things that we know we should be intervening on and others where participation is a question. All of these we are trying to longitudinally put into the registry and follow them over time.

The second thing is understanding from the last Bethesda Conference that we want shared decision-making. There are going to be conditions where you say, “Look, I think your risk is high. You’ve a family history of sudden cardiac death. You have arrhythmias while you’re exercising.”

Harrington: You have a big, thick heart.

Patel: If you have hypertrophic cardiomyopathy, whether you’re an athlete or a 40-year-old adult, we’re going to have the same conversation. I think that holds. There’s a variety or a spectrum where we don’t know. I think the registry is one big step.

Thinking back to when somebody has an event, I would say take the teachable moment with the AHA and others to make sure your communities and your areas have automated external defibrillators (AEDs) and CPR training, and that we get to 100%: 100% response, 100% CPR, 100% defibrillation. I think that’s the first step.
 

Chain of survival

Harrington: Let’s really focus on the chain of survival. It is a chain: If any link is broken, your chance of survival really drops. We’ve had some well-known cases within our AHA community, including somebody who talks about it regularly: Kevin Volpp, from the University of Pennsylvania, a health economist. He had almost the perfect chain of survival. He had sudden cardiac death in a restaurant that was immediately observed, CPR started, EMTs called, and AED on the scene. Impressive.

Patel: That was in Cincinnati, where there are communities that have really worked on these things. I think you’re right. The chain of survival with rapid CPR to build a nation of survivors is key. The people at the AHA are helping us do this; there is a national call to make sure CPR is something that people feel comfortable doing. That they do it in men and women. They do it for anyone that goes down. And realize that it’s CPR that is hands-only. I think that’s an important lesson from Damar’s work, Nancy Brown’s, and AHA’s. Actually, schools in many countries require that to get through primary school.

Harrington: CPR training is a requirement to graduate from high school in some states.

Patel: My son just graduated from high school, and we spent time at his school making sure that everybody had access to CPR training. I think the way to do this is to start with that. Now, getting more specific about teams and athletes, I think most have emergency action plans, but it’s having action plans that work because of where you are and where the AED locations might be, or what the sport is. Having a plan on how you’re going to get that athlete to a place where you can help them recover is an important piece.

From there, I think the conversation for us is about what can we do as a society and as a country to answer some critical questions, including some real-world questions that people are asking: We had COVID-19 and we’re hearing these cases. Is this going up or down, and are these related?

Soon, hopefully the same group I talked about and others will have a publication, working with the NCAA to look at all of the deaths that they observed in NCAA Division I athletes over 20 years, including the sudden cardiac deaths. I won’t share the results because the publication isn’t out, but I think that’s the kind of important information that will help us understand if these rates are going up or down.

Harrington: What’s associated with that risk? Then we can start getting at whether it is something that, when we’re doing assessment for suitability for sports, has risk factors that should warrant more investigation.

Patel: Much like the field of cardiology, we haven’t enough of an evidence base, the right technologies, or the studies to determine how we should do screening, or not screening, across the board. Again, there is variation. There are some countries where anyone participating is going to get an ECG and an echocardiogram. There are other countries, like the United States, where it’s going to be a bit dependent on athlete risk.

Harrington: And where you live.

Patel: And where you live. Unfortunately, again, that brings in the idea that it might not be equitable in how we’re evaluating these individuals. I do think the opportunity to start to standardize that evaluation exists, and it likely comes from the ability to look back and say, “Here are some higher-risk individuals or some higher-risk scenarios.”

Harrington: Isn’t this what we do all the time in clinical medicine?

Patel: It’s going to be applied to a population that maybe is not as studied. I said this to you before we came on. The other thing is to make sure that the shared decision-making allows athletes who feel like they have a chance or want to play. During COVID, we had many college athletes, high school athletes, and kids not able to participate in sports. There was significant depression, feeling of loneliness, and even physical loss. People were actually getting less conditioned quickly. There’s a great benefit to sports participation.

Harrington: We were extrapolating from older data. If I’ve just had this new infection, COVID, and I’ve maybe got some signs of it in my heart, why can’t I exercise? That’s extrapolating from old myocarditis data.

Patel: We’re having to learn and follow it. I think there’s value in following that and getting those data. The second thing I think is really valuable is that we’ve shown that these individuals, if you do have these conversations and follow them, can participate and can be part of understanding the risk just like anything else.

Harrington: Is it sport specific? Are there some sports where maybe the conversation should be a little more intense than in other sports?

Patel: I think what we’ll see is that the conversations may be sport specific, and some may concern the number of athletes tested. At times, it’s pretty complicated. It does look like there are, as you know, different weight-bearing performance athletes, endurance athletes, or what I’ll call burst sports. There will probably be data that will identify certain sports where we may need to pay a bit more attention.

Harrington: What about the contact issues? Damar had a very specific thing, we think, happen to him. Football is a violent, contact-oriented sport, but fortunately we don’t regularly see what happened to Damar.

Patel: We’re talking about sudden cardiac death, but obviously, contact issues and neurologic evaluation is a whole other topic. That’s another big issue that I know many are following, and the NCAA is carefully, too. For Damar, I think we know that it was commotio cordis. At least when that happens, when there’s a ball or a trauma to the chest, those things have to be timed just so to actually lead to this event. Thankfully, it’s not very frequent, but it can happen.

Harrington: Hockey pucks, baseballs, soccer balls, a helmet to the chest ...

Patel: You have to be in a specific cycle of the squeeze. We don’t see that very frequently. I do think the evaluation and treatment, hopefully, makes a difference. One thing that we’re evolving in the screening world is our imaging; it’s getting better. We are not just doing echocardiograms; we are able to do other studies. There’s a mix of imaging and other technologies.

Is screening the answer?

Harrington: Let’s talk about that because screening is the area, I would say, with the most controversy – and a large amount of emotional controversy. Some argue that the data are not good enough to screen, or doctors are saying, “Wait a minute, why are we screening all these kids?” You said you were at your son’s high school doing CPR training. How many athletes are at his high school? There are many, and that’s a pretty small high school. Big communities, big universities, and the professional sports can afford it. Should we be doing this at the community level?

Patel: There have been some data. The Italians have done standard screening for some time, and it’s shown us that if you did echocardiograms in many individuals, you do find some cases that are hypertrophic cardiomyopathy in pathology. The issue is just how much you have to do and the resource utilization. I think as we get to a world where screening studies can happen with smaller technology and AI, that can be democratizing in how we get to athletes.

Harrington: Give an example of that. We were talking outside, you and I, about some of the new stethoscope technology.

Patel: Yes, stethoscopes are going to be one of the examples. We have stethoscopes that have the ability to get sounds and ECG signals, or at least some lead signals.

Harrington: Yes.

Patel: Potentially you can imagine that sound and ECG tracing in an AI environment, at least getting you from “everyone gets a listen with one stethoscope in their gym from their coach,” and it goes to the cloud. When there are enough questions, these are the ones that have to go further. Now, that’s a big study that has to be carried out; I’m not in any way saying we should do that.

Harrington: The technology is coming.

Patel: We start to see that our ability to rapidly do something to meet our athletes or our patients where they are will happen soon. Remember that the performance curve can vary, but once you have a sound where you can start to say that this is a regular flow murmur vs. “I’m worried about this,” especially as you mark it with ECG – that’s one example.

Smaller imaging is another example. For many years, ECGs have been talked about. There are entire courses that we run looking at ECGs in athletes. Remembering that Aaron Baggish and others are publishing that these individuals are large. When we look at their hearts, we see that they’re large, but when you adjust for size, often you can identify that many of them are within what we think are normal. Structurally, there are still many cases where you look at hearts and you’re asking, “Is this a thick heart? Is this noncompaction? Is this some pathology?”

That’s where you need imaging expertise. I think you have to have those individuals. I’m not advocating screening. I’m advocating studying it and that we should be thinking about the population. I don’t see a world where we don’t eventually start to really look to prevent those.

Harrington: Right. Whether it’s understanding that there are certain risk factors associated with this and we have to dedicate screening resources to those individuals, or if we want to do it more broadly on the population level to understand this with deeper dives into certain individuals, we’ve got to study it.

Patel: Some of the experts in sports medicine and sports cardiology have been collecting these data for a while. It’s time that we are there, because with these events we have the opportunity to share more of these data and maybe raise awareness – not in the teachable moment only – to get others to contribute.

I do believe that long term there’s an opportunity. We’ve seen that. We see that the rates, unfortunately, for marathon runners, where people unfortunately have events, seem to be higher. And we’ve seen the studies on troponin leaks in these individuals or evidence that there’s some effect on the heart from these events. We want people to be able to be long-term healthy.
 

Early defibrillation

Harrington: A large amount of work needs to be done. We talked with regard to screening, we’ve talked about CPR. We really need to have a nation of people who can do hands-only CPR. Let’s talk about AEDs, another key part of the chain of survival.

Patel: We have another important study going on, but an important message first: AEDs are critical to survival. We know that CPR is critical, but so is getting people to a defibrillator.

Harrington: Early defibrillation.

Patel: Early defibrillation. Early CPR is one of the biggest markers of making sure we perfuse people to get to early defibrillation, but then you have to get early defibrillation. There’s been a huge push in many communities, again, along with AHA and others, to make sure that AEDs are available not only in the U.S. but around the world. We’re at ESC and we see the push around the world to get AEDs available. They’ve come down in size and come down in cost, and that’s made it much more accessible. That’s really good. They’re still not always there.

We’ve seen really interesting randomized studies with people in some European countries where they have certain areas, just because of the locations, where bystanders will help get an AED  vs. randomizing to the EMS truck. They seem better in some of those variations. Chris Granger, at our institution, with Monique Starks, Dan Mark, and others, is doing a study in North Carolina where we’re testing different ways to potentially get AEDs in communities. We’re randomizing counties to one or two ways of getting AEDs to those individuals.

Harrington: Can you have an app where you just click “Find me an AED”?

Patel: Is there a world where the AED is found or is something bringing you the AED? Are there drones? Are there people driving? Are there ways that an AED is brought to the scene? All of those are going to be critical. It starts with continuing to figure out ways to support the costs of getting AEDs in places. The technology is continuing to evolve.

Harrington: It really is the premedical system stuff that makes the difference. Once EMS arrives with trained individuals who can defibrillate, they can transport you to a medical facility where trained physicians are at. It’s that pre-EMS thing that is so critical.

Patel: We talk often about athletes, but cardiac arrest care in general, and the chain of survival with CPR and AEDs, is critical. I still see patients in the CICU at Duke where, unfortunately, the biggest driver, as you just highlighted in that chain of survival, is how rapid we were in that golden hour. In the first 15 minutes, are you getting CPR, are you getting AED? Are you getting to a system?

Harrington: Are you getting a rapid transport?

Patel: Are you getting a neurologic assessment? Are you getting cooled or not? Those are important things.

Harrington: All right. Let’s try to wrap this up. Teachable moments, we talked about. One of the things about cases in prominent athletes is that it makes it to the newspaper and then it raises awareness. There is a drawing inference from a small group of cases to the broader societal issues. That’s an important topic.

We’ve talked about possible screening options, identifying at-risk individuals and high-risk individuals. A large amount of data has already been accumulated, but there is more work to be done. We focused on how to use those teachable moments to really influence the chain of survival, not just for athletes but for society at large.

I love your point about the Bethesda Conference on shared decision-making. Like with everything else, we have to have that two-way conversation: What are the athlete’s goals, hopes, and aspirations?

Patel: That group of experts, in addition to shared decision-making, gave us a whole list of conditions that we should be aware of and the cutpoints of where we think normal and not normal live for athletes. I think that’s used by many.

Can we build our systems to make research happen faster for the individuals? These athletes are at colleges that are obviously doing so much to make sure they’re okay. The people who are helping with this registry, and others, are going to continue to work to ask whether we can engage them as citizen participants and scientists. I think athletes are going to become some of our best advocates for why you’d want to know about yourself and how to perform CPR.

Harrington: I love the concept of citizen scientists, that we all have an obligation to contribute to the evidence base because we all want to use that evidence.

This has been a terrific conversation. I’ve been joined by my good friend, Dr. Manesh Patel from Duke University. I hope you’ve enjoyed our discussion here at the ESC. We have been taking a little break from the science going on around us to talk about sudden cardiac death in athletes. It really does have implications for broader societal concepts.

Dr. Harrington is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, New York, as well as a former president of the American Heart Association. He has disclosed the following relevant financial relationships: Research relationships with Baim Institute (DSMB); CSL (RCT executive committee); Janssen (RCT chair); National Heart, Lung, and Blood Institute (RCT executive committee, DSMB chair); Patient-Centered Outcomes Research Institute (RCT co-chair); Duke Clinical Research Institute. Consulting relationships with Atropos Health; Bitterroot Bio; Bristol Myers Squibb; BridgeBio; Element Science; Edwards Lifesciences; Foresite Labs; Medscape/WebMD Board of Directors for: American Heart Association; College of the Holy Cross; Cytokinetics. Dr. Patel is professor of medicine, Duke University; chief, division of cardiology; director, Duke Heart Center, Duke University Medical Center, Durham, N.C. He has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bayer; Janssen; Novartis (consultant). Received research grant from Bayer; Janssen.

A version of this article appeared on Medscape.com.

Recorded Aug. 26, 2023. This transcript has been edited for clarity.

Robert A. Harrington, MD: I’m here with my good friend, Manesh Patel, from Duke University. We’re at the European Society of Cardiology (ESC) congress in Amsterdam, and I pulled Manesh into the studio for a conversation about something that’s really topical right now: sudden cardiac death in athletes.

What I hope to do [in this interview] is really pick Manesh’s brain on how we are thinking about this. Are we going to think about treatment issues? Are we going to think about prevention issues? Are we thinking about screening? We’ll try to make it practical.

Dr. Manesh Patel is chief of cardiovascular medicine at Duke University and also the director of the Duke Heart Center. Manesh, thanks for joining me here.
 

Bronny James and Damar Hamlin

Manesh R. Patel, MD: Excited to be here, Bob. Always.

Harrington: [Recently,] a news article comes out about the cause of Bronny James’ sudden cardiac death. Let me put this into a bigger societal context.

Last winter, Damar Hamlin, from the Buffalo Bills, suffered a traumatic injury on the field, and with that, had cardiac arrest. He’s back playing football – great to see. You and I are involved with the American Heart Association. He’s been very supportive of our efforts around things like CPR. He’s been terrific. It’s great to see him playing.

We know a little less about Bronny James. The news articles say the cause is both functional and anatomical, and it seems to be congenital, but we don’t have any details beyond this. Let’s not focus on the people; let’s focus on the topic.

Patel: I’m excited that we’re having the conversation. First and foremost, we’re excited that, with what we’ve seen on a national stage, these two individuals are doing well. They survived sudden cardiac death, which is a testament to all the things that we’ll talk about.

There are many important questions, like, is this increasing? Is this something we can prevent? And what are those things that might be happening to athletes?

Harrington: Can we predict it?

Patel: Right. I think the idea of sudden cardiac death in athletes is really a critical one for us to think about because it does concern participation and what we think about that. There are many experts who’ve been studying this for years that I now get to work with.

Harrington: Tell us a little bit about the kind of things you’ve been doing in this area.

Patel: Even before these events in the COVID era, we were wondering about athletes getting myocarditis, just in general, what do we know about that? People like Aaron Baggish, Kim Harmon, Jonathan Drezner, and others have been studying this.

Harrington: You and I did a show on athletes and COVID-19.

Patel: With the American Heart Association (AHA), the Cornell Foundation, and others, we started the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA). This registry is across the United States, and athletes can sign up.

Harrington: Is it voluntary? Do the schools sign them up?

Patel: The athletes sign up. Team trainers and doctors talk to the athletes. We don’t really know the risks of some of these conditions. There’s a lot of gray area – people with certain conditions that were really interesting; aortas that are dilated in tall people.

Harrington: Long QT.

Patel: Long QT. There are certainly things that we know we should be intervening on and others where participation is a question. All of these we are trying to longitudinally put into the registry and follow them over time.

The second thing is understanding from the last Bethesda Conference that we want shared decision-making. There are going to be conditions where you say, “Look, I think your risk is high. You’ve a family history of sudden cardiac death. You have arrhythmias while you’re exercising.”

Harrington: You have a big, thick heart.

Patel: If you have hypertrophic cardiomyopathy, whether you’re an athlete or a 40-year-old adult, we’re going to have the same conversation. I think that holds. There’s a variety or a spectrum where we don’t know. I think the registry is one big step.

Thinking back to when somebody has an event, I would say take the teachable moment with the AHA and others to make sure your communities and your areas have automated external defibrillators (AEDs) and CPR training, and that we get to 100%: 100% response, 100% CPR, 100% defibrillation. I think that’s the first step.
 

Chain of survival

Harrington: Let’s really focus on the chain of survival. It is a chain: If any link is broken, your chance of survival really drops. We’ve had some well-known cases within our AHA community, including somebody who talks about it regularly: Kevin Volpp, from the University of Pennsylvania, a health economist. He had almost the perfect chain of survival. He had sudden cardiac death in a restaurant that was immediately observed, CPR started, EMTs called, and AED on the scene. Impressive.

Patel: That was in Cincinnati, where there are communities that have really worked on these things. I think you’re right. The chain of survival with rapid CPR to build a nation of survivors is key. The people at the AHA are helping us do this; there is a national call to make sure CPR is something that people feel comfortable doing. That they do it in men and women. They do it for anyone that goes down. And realize that it’s CPR that is hands-only. I think that’s an important lesson from Damar’s work, Nancy Brown’s, and AHA’s. Actually, schools in many countries require that to get through primary school.

Harrington: CPR training is a requirement to graduate from high school in some states.

Patel: My son just graduated from high school, and we spent time at his school making sure that everybody had access to CPR training. I think the way to do this is to start with that. Now, getting more specific about teams and athletes, I think most have emergency action plans, but it’s having action plans that work because of where you are and where the AED locations might be, or what the sport is. Having a plan on how you’re going to get that athlete to a place where you can help them recover is an important piece.

From there, I think the conversation for us is about what can we do as a society and as a country to answer some critical questions, including some real-world questions that people are asking: We had COVID-19 and we’re hearing these cases. Is this going up or down, and are these related?

Soon, hopefully the same group I talked about and others will have a publication, working with the NCAA to look at all of the deaths that they observed in NCAA Division I athletes over 20 years, including the sudden cardiac deaths. I won’t share the results because the publication isn’t out, but I think that’s the kind of important information that will help us understand if these rates are going up or down.

Harrington: What’s associated with that risk? Then we can start getting at whether it is something that, when we’re doing assessment for suitability for sports, has risk factors that should warrant more investigation.

Patel: Much like the field of cardiology, we haven’t enough of an evidence base, the right technologies, or the studies to determine how we should do screening, or not screening, across the board. Again, there is variation. There are some countries where anyone participating is going to get an ECG and an echocardiogram. There are other countries, like the United States, where it’s going to be a bit dependent on athlete risk.

Harrington: And where you live.

Patel: And where you live. Unfortunately, again, that brings in the idea that it might not be equitable in how we’re evaluating these individuals. I do think the opportunity to start to standardize that evaluation exists, and it likely comes from the ability to look back and say, “Here are some higher-risk individuals or some higher-risk scenarios.”

Harrington: Isn’t this what we do all the time in clinical medicine?

Patel: It’s going to be applied to a population that maybe is not as studied. I said this to you before we came on. The other thing is to make sure that the shared decision-making allows athletes who feel like they have a chance or want to play. During COVID, we had many college athletes, high school athletes, and kids not able to participate in sports. There was significant depression, feeling of loneliness, and even physical loss. People were actually getting less conditioned quickly. There’s a great benefit to sports participation.

Harrington: We were extrapolating from older data. If I’ve just had this new infection, COVID, and I’ve maybe got some signs of it in my heart, why can’t I exercise? That’s extrapolating from old myocarditis data.

Patel: We’re having to learn and follow it. I think there’s value in following that and getting those data. The second thing I think is really valuable is that we’ve shown that these individuals, if you do have these conversations and follow them, can participate and can be part of understanding the risk just like anything else.

Harrington: Is it sport specific? Are there some sports where maybe the conversation should be a little more intense than in other sports?

Patel: I think what we’ll see is that the conversations may be sport specific, and some may concern the number of athletes tested. At times, it’s pretty complicated. It does look like there are, as you know, different weight-bearing performance athletes, endurance athletes, or what I’ll call burst sports. There will probably be data that will identify certain sports where we may need to pay a bit more attention.

Harrington: What about the contact issues? Damar had a very specific thing, we think, happen to him. Football is a violent, contact-oriented sport, but fortunately we don’t regularly see what happened to Damar.

Patel: We’re talking about sudden cardiac death, but obviously, contact issues and neurologic evaluation is a whole other topic. That’s another big issue that I know many are following, and the NCAA is carefully, too. For Damar, I think we know that it was commotio cordis. At least when that happens, when there’s a ball or a trauma to the chest, those things have to be timed just so to actually lead to this event. Thankfully, it’s not very frequent, but it can happen.

Harrington: Hockey pucks, baseballs, soccer balls, a helmet to the chest ...

Patel: You have to be in a specific cycle of the squeeze. We don’t see that very frequently. I do think the evaluation and treatment, hopefully, makes a difference. One thing that we’re evolving in the screening world is our imaging; it’s getting better. We are not just doing echocardiograms; we are able to do other studies. There’s a mix of imaging and other technologies.

Is screening the answer?

Harrington: Let’s talk about that because screening is the area, I would say, with the most controversy – and a large amount of emotional controversy. Some argue that the data are not good enough to screen, or doctors are saying, “Wait a minute, why are we screening all these kids?” You said you were at your son’s high school doing CPR training. How many athletes are at his high school? There are many, and that’s a pretty small high school. Big communities, big universities, and the professional sports can afford it. Should we be doing this at the community level?

Patel: There have been some data. The Italians have done standard screening for some time, and it’s shown us that if you did echocardiograms in many individuals, you do find some cases that are hypertrophic cardiomyopathy in pathology. The issue is just how much you have to do and the resource utilization. I think as we get to a world where screening studies can happen with smaller technology and AI, that can be democratizing in how we get to athletes.

Harrington: Give an example of that. We were talking outside, you and I, about some of the new stethoscope technology.

Patel: Yes, stethoscopes are going to be one of the examples. We have stethoscopes that have the ability to get sounds and ECG signals, or at least some lead signals.

Harrington: Yes.

Patel: Potentially you can imagine that sound and ECG tracing in an AI environment, at least getting you from “everyone gets a listen with one stethoscope in their gym from their coach,” and it goes to the cloud. When there are enough questions, these are the ones that have to go further. Now, that’s a big study that has to be carried out; I’m not in any way saying we should do that.

Harrington: The technology is coming.

Patel: We start to see that our ability to rapidly do something to meet our athletes or our patients where they are will happen soon. Remember that the performance curve can vary, but once you have a sound where you can start to say that this is a regular flow murmur vs. “I’m worried about this,” especially as you mark it with ECG – that’s one example.

Smaller imaging is another example. For many years, ECGs have been talked about. There are entire courses that we run looking at ECGs in athletes. Remembering that Aaron Baggish and others are publishing that these individuals are large. When we look at their hearts, we see that they’re large, but when you adjust for size, often you can identify that many of them are within what we think are normal. Structurally, there are still many cases where you look at hearts and you’re asking, “Is this a thick heart? Is this noncompaction? Is this some pathology?”

That’s where you need imaging expertise. I think you have to have those individuals. I’m not advocating screening. I’m advocating studying it and that we should be thinking about the population. I don’t see a world where we don’t eventually start to really look to prevent those.

Harrington: Right. Whether it’s understanding that there are certain risk factors associated with this and we have to dedicate screening resources to those individuals, or if we want to do it more broadly on the population level to understand this with deeper dives into certain individuals, we’ve got to study it.

Patel: Some of the experts in sports medicine and sports cardiology have been collecting these data for a while. It’s time that we are there, because with these events we have the opportunity to share more of these data and maybe raise awareness – not in the teachable moment only – to get others to contribute.

I do believe that long term there’s an opportunity. We’ve seen that. We see that the rates, unfortunately, for marathon runners, where people unfortunately have events, seem to be higher. And we’ve seen the studies on troponin leaks in these individuals or evidence that there’s some effect on the heart from these events. We want people to be able to be long-term healthy.
 

Early defibrillation

Harrington: A large amount of work needs to be done. We talked with regard to screening, we’ve talked about CPR. We really need to have a nation of people who can do hands-only CPR. Let’s talk about AEDs, another key part of the chain of survival.

Patel: We have another important study going on, but an important message first: AEDs are critical to survival. We know that CPR is critical, but so is getting people to a defibrillator.

Harrington: Early defibrillation.

Patel: Early defibrillation. Early CPR is one of the biggest markers of making sure we perfuse people to get to early defibrillation, but then you have to get early defibrillation. There’s been a huge push in many communities, again, along with AHA and others, to make sure that AEDs are available not only in the U.S. but around the world. We’re at ESC and we see the push around the world to get AEDs available. They’ve come down in size and come down in cost, and that’s made it much more accessible. That’s really good. They’re still not always there.

We’ve seen really interesting randomized studies with people in some European countries where they have certain areas, just because of the locations, where bystanders will help get an AED  vs. randomizing to the EMS truck. They seem better in some of those variations. Chris Granger, at our institution, with Monique Starks, Dan Mark, and others, is doing a study in North Carolina where we’re testing different ways to potentially get AEDs in communities. We’re randomizing counties to one or two ways of getting AEDs to those individuals.

Harrington: Can you have an app where you just click “Find me an AED”?

Patel: Is there a world where the AED is found or is something bringing you the AED? Are there drones? Are there people driving? Are there ways that an AED is brought to the scene? All of those are going to be critical. It starts with continuing to figure out ways to support the costs of getting AEDs in places. The technology is continuing to evolve.

Harrington: It really is the premedical system stuff that makes the difference. Once EMS arrives with trained individuals who can defibrillate, they can transport you to a medical facility where trained physicians are at. It’s that pre-EMS thing that is so critical.

Patel: We talk often about athletes, but cardiac arrest care in general, and the chain of survival with CPR and AEDs, is critical. I still see patients in the CICU at Duke where, unfortunately, the biggest driver, as you just highlighted in that chain of survival, is how rapid we were in that golden hour. In the first 15 minutes, are you getting CPR, are you getting AED? Are you getting to a system?

Harrington: Are you getting a rapid transport?

Patel: Are you getting a neurologic assessment? Are you getting cooled or not? Those are important things.

Harrington: All right. Let’s try to wrap this up. Teachable moments, we talked about. One of the things about cases in prominent athletes is that it makes it to the newspaper and then it raises awareness. There is a drawing inference from a small group of cases to the broader societal issues. That’s an important topic.

We’ve talked about possible screening options, identifying at-risk individuals and high-risk individuals. A large amount of data has already been accumulated, but there is more work to be done. We focused on how to use those teachable moments to really influence the chain of survival, not just for athletes but for society at large.

I love your point about the Bethesda Conference on shared decision-making. Like with everything else, we have to have that two-way conversation: What are the athlete’s goals, hopes, and aspirations?

Patel: That group of experts, in addition to shared decision-making, gave us a whole list of conditions that we should be aware of and the cutpoints of where we think normal and not normal live for athletes. I think that’s used by many.

Can we build our systems to make research happen faster for the individuals? These athletes are at colleges that are obviously doing so much to make sure they’re okay. The people who are helping with this registry, and others, are going to continue to work to ask whether we can engage them as citizen participants and scientists. I think athletes are going to become some of our best advocates for why you’d want to know about yourself and how to perform CPR.

Harrington: I love the concept of citizen scientists, that we all have an obligation to contribute to the evidence base because we all want to use that evidence.

This has been a terrific conversation. I’ve been joined by my good friend, Dr. Manesh Patel from Duke University. I hope you’ve enjoyed our discussion here at the ESC. We have been taking a little break from the science going on around us to talk about sudden cardiac death in athletes. It really does have implications for broader societal concepts.

Dr. Harrington is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, New York, as well as a former president of the American Heart Association. He has disclosed the following relevant financial relationships: Research relationships with Baim Institute (DSMB); CSL (RCT executive committee); Janssen (RCT chair); National Heart, Lung, and Blood Institute (RCT executive committee, DSMB chair); Patient-Centered Outcomes Research Institute (RCT co-chair); Duke Clinical Research Institute. Consulting relationships with Atropos Health; Bitterroot Bio; Bristol Myers Squibb; BridgeBio; Element Science; Edwards Lifesciences; Foresite Labs; Medscape/WebMD Board of Directors for: American Heart Association; College of the Holy Cross; Cytokinetics. Dr. Patel is professor of medicine, Duke University; chief, division of cardiology; director, Duke Heart Center, Duke University Medical Center, Durham, N.C. He has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bayer; Janssen; Novartis (consultant). Received research grant from Bayer; Janssen.

A version of this article appeared on Medscape.com.