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Finerenone benefits T2D across spectrum of renal function
Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.
The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.
Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m2 despite also having albuminuria with a UACR of at least 30 mg/g, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.
“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.
The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.
The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.
A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
A new reason to screen for albuminuria
“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.
“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.
The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m2 in FIDELIO-DKD, and as high as 90 mL/min/1.73m2 in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.
In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.
The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m2. The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
Finerenone favors patients with less advanced CKD
In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”
Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.
“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.
The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”
The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.
Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.
The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.
Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m2 despite also having albuminuria with a UACR of at least 30 mg/g, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.
“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.
The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.
The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.
A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
A new reason to screen for albuminuria
“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.
“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.
The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m2 in FIDELIO-DKD, and as high as 90 mL/min/1.73m2 in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.
In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.
The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m2. The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
Finerenone favors patients with less advanced CKD
In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”
Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.
“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.
The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”
The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.
Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.
The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.
Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m2 despite also having albuminuria with a UACR of at least 30 mg/g, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.
“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.
The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.
The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.
A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
A new reason to screen for albuminuria
“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.
“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.
The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m2 in FIDELIO-DKD, and as high as 90 mL/min/1.73m2 in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.
In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.
The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m2. The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
Finerenone favors patients with less advanced CKD
In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”
Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.
“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.
The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”
The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.
FROM JACC: HEART FAILURE
Most pediatric myocarditis caused by viruses
ANAHEIM – A wide range of factors can cause myocarditis; most often viral infections cause myocarditis in children and teens, according to Ryan Butts, MD, medical director of the pediatric advanced cardiac care program at the University of Texas Southwestern Medical Center and Children’s Health of Texas.
Dr. Butts provided an overview of what pediatricians and other clinicians caring for children and teens should know about myocarditis at the annual meeting of the American Academy of Pediatrics.
The important new things that attendees may want to take away from this for their practice are improved recognition and diagnostic workup for acute viral myocarditis, making sure cardiology follow-up occurs after an admission for the condition, enhanced evaluation of the child before they return to competitive sports, and the availability of written or verbal education for patients relating to COVID vaccine–associated myocarditis, Dr. Butts said.
He also provided a set of key takeaways:
- Myocarditis is rare.
- The most common viruses causing myocarditis are always changing.
- Myocarditis is most common in infants and teenagers but it has different clinical patterns in each population.
- MRI is becoming the diagnostic tool of choice.
- IVIG frequently is used but good evidence for the therapy is lacking.
- Patients may go home on cardiac medications but have good long-term outcomes.
- Patients must have a 6-month restriction on competitive sports after diagnosis.
Frank Han, MD, a pediatric cardiologist at OSF Medical Center and Children’s Hospital of Illinois in Peoria, said he found the most helpful parts of Dr. Butts’ presentation to be the diagnosis and triage of myocarditis in the major age groups.
“Myocarditis can have variable presentations, and its cause may influence how the myocarditis behaves,” Dr. Han said. Pediatric cardiologists, he said, are uniquely positioned to triage and diagnose myocarditis.
Epidemiology and presentation
Just 0.05% of admissions from 28.6 million U.S. pediatric ED visits every year are for myocarditis, Dr. Butts said. While viruses are the most common cause of myocarditis, bacterial infections and noninfectious causes, including hypersensitivity reactions, systemic disorders, and toxic substances, can also cause the condition. The dominant viruses causing myocarditis have shifted over the years as well. Coxsackie B was the most common cause in the 1980s, but adenovirus became more common in the 1990s and parvovirus B19 in the 2000s. Why some kids develop myocarditis while others don’t is unclear, but the host-immune response to the virus likely plays an important role.
Research has shown two substantial spikes in the incidence of myocarditis children: infants under 2 years old and teens aged 14-19. Although myocarditis refers to any inflammation of myocardium not caused by ischemia, the signs, symptoms, and lab results vary according to patient’s age group. The only constant is that diaphoresis is rare across all ages.
Infants are more likely to show respiratory distress (68%) and an enlarged liver (40%) but can also present with gastrointestinal symptoms (24%). Vomiting without fever or diarrhea should arouse clinical suspicion of myocarditis in infants, although fever and diarrhea can occur.
In young children, who have the lowest incidence, fatigue presents in about one-third, with 20% presenting with chest pain and 20% with hepatomegaly. The most common symptom in teens by far (80%) is chest pain. About one-third also have respiratory distress but gastrointestinal symptoms are less common (20%).
When should a clinician suspect myocarditis in a teen presenting with chest pain? “If the chest pain is reproducible and if you can localize it, they don’t need further evaluation,” Dr. Butts said. “After that, it’s a lot about the history.”
In terms of lab results, ventricular function measured by brain natriuretic peptide is significantly depressed in infants and young children but often near normal in teens. Inflammatory markers (C-reactive protein) tend to be low in infants but elevated in young children and teens. And troponin levels, denoting myocardial injury, are minimal in infants and young children but elevated in teens. Median ejection fraction on echocardiograms, about 55% in normal hearts, will often be low in infants and young children, around 30%-33%, but is near normal (54%) in teens.
Diagnosis and management
Cardiac MRI increasingly has been replacing endomyocardial biopsy for diagnosis, with MRI exceeding biopsy use between 2009 and 2010, Dr. Butts said. The advantage of endomyocardial biopsy is that it’s specific, if not very sensitive. The test is invasive, however, requiring sedation and carrying the risk of tricuspid injury. The most common finding on cardiac MRI is late gadolinium enhancement (80%) while early gadolinium enhancement is less common (55%).
Although Dr. Butts mentioned the Dallas diagnostic criteria from 1987, he advocated for the more recent Lake Louise Criteria, which require clinical suspicion of myocarditis and at least two of three findings on MRI: T2-weighted myocardial abnormalities, T1 early or late gadolinium enhancement, or regional wall motion abnormalities or evidence of pericarditis
Point-of-care ultrasound can be useful for detecting myocarditis, but its success depends on whether the user can pick up on the subtle changes in ventricular function. “Just because someone has a point-of-care ultrasound that’s normal or thought to be normal, it shouldn’t rule out the diagnosis,” he said.
Learning the etiology of viral myocarditis often is difficult, and etiology doesn’t affect management of the condition, Dr. Butts said. Even in cases of myocarditis confirmed by biopsy, the virus may be identified in only about 60%-70% of cases with myocardial polymerase chain reaction. In clinical cases, the virus can be determined only about 25%-30% of the time with serum PCR.
Prognosis is usually good, with 80%-90% of children and teens going home transplant free despite most arriving critically ill and 50%-80% initially being admitted to ICU. Two-thirds of those discharged go home with heart failure medications, but only one in six are readmitted within a year.
The strongest risk factors for poor prognosis are younger age and being critically ill at presentation but other risk factors include female sex, poor ventricular function, poor perfusion on exam, increased dilation on echocardiogram, and a need for ECMO or inotropes or mechanical ventilation.
That said, Dr. Butts cautioned attendees not to ignore normal function. In one study of 171 patients, among 75 who presented with normal function, 15% went home with inotropes, 12% required mechanical ventilation, 9% had arrhythmia, and 5% needed extracorporeal membrane oxygenation.
A big question in treatment is whether to give IVIG or not and the evidence is murky, Dr. Butts said. He reviewed a couple studies on IVIG, including one that suggested better ventricular functional recovery with the treatment but those who received IVIG were also more likely to be on an ACE inhibitor.
“Was it the ACE inhibitor or was it IVIG? We don’t know,” he said. Different cardiologists may give different opinions on IVIG. “It has nothing to do with the actual evidence behind it.”
IVIG has drawbacks: It’s very expensive and it involves risks that include serum sickness and interstitial nephritis.
“Pediatricians typically aren’t going to directly decide on giving or not giving IVIG,” Dr. Han said. “Typically, the ultimate choice comes from a group discussion between the hospital cardiologist – perhaps the hospitalist pediatrician if they are involved – and the family. We acknowledge the ambiguity of the evidence and decide based upon the severity of the initial disease process.”
Return to competitive sports; Follow-up critical
Experts are much more confident, however, about when teens admitted with viral myocarditis can return to competitive sports. But Dr. Butts said he suspects the guidelines for these children aren’t followed as closely as they should be. The American Heart Association recommends waiting 6 months after discharge and ensuring the athlete has a normal echocardiogram, Holter monitoring, and stress test.
“It’s incredibly important to have them come back and see the cardiologist 6 months after admission,” Dr. Butts said. “The only patient I’ve ever had who died 6-7 months post myocarditis is somebody who, during their stress test, had increasing ventricular ectopy. I told him not to do sports. He didn’t listen to me and unfortunately passed away – I’m assuming from arrhythmia.”
COVID and vaccine-associated myocarditis
Vaccine-associated myocarditis is substantially milder than viral myocarditis, Dr. Butts said. A small study from a single center in Atlanta found that ejection fraction at admission was normal, around 56%, in those with vaccine-associated myocarditis, compared with 45% with non-COVID viral myocarditis and 50% with multisystem inflammatory syndrome in children or myocarditis from COVID-19. All patients with vaccine-associated myocarditis had normal function at discharge, compared with 73% of those with viral myocarditis and 93% with COVID-associated myocarditis.
While 22% of those with vaccine-associated myocarditis were admitted to the ICU, twice as many (40%) with viral myocarditis were, and three times as many (68%) with COVID-associated myocarditis ended up in intensive care.
Dr. Butts also noted a Morbidity and Mortality Weekly Report from the Centers of Disease Control and Prevention that found teen boys had two to six times greater risk of heart complications after COVID-19 infection than after COVID vaccination.
In terms of direct comparisons, vaccine-related myocarditis occurred about 12-18 times per 100,000 doses for boys ages 5-11 years, compared with cardiac involvement in 93-133 cases out of 100,000 COVID-19 infections. Boys aged 12-17 years experienced 12-21 cases of myocarditis per 100,000 doses of the vaccine, compared with cardiac involvement in 50-64 out of 100,000 infections.
The bottom line, Dr. Butts said, is that cardiac involvement in MIS-C is common, but typically improves by discharge. “Vaccine-associated myocarditis is a mild clinical syndrome that has a very short duration, and, in my opinion, should never lead us to ever advise anybody not to get the vaccine. I’ve had many patients, even patients in their first year post transplant, who have gotten the COVID-19 vaccine and were just fine.”
Dr. Butts acknowledged that talking with families about the risk of myocarditis with the vaccine is challenging. He often starts these conversations by sharing the statistics, but he said relatable stories are the key. He will also relate the statistics to something the parents and teen will understand, whether it’s sports or another comparison. He does recommend that teens who develop vaccine-associated myocarditis complete the series and get the booster. Their chances of developing myocarditis again are extremely low, whereas “the likelihood of them being really ill from COVID-19 is much, much higher.”
Dr. Butts and Dr. Han had no disclosures. The presentation involved no external funding.
ANAHEIM – A wide range of factors can cause myocarditis; most often viral infections cause myocarditis in children and teens, according to Ryan Butts, MD, medical director of the pediatric advanced cardiac care program at the University of Texas Southwestern Medical Center and Children’s Health of Texas.
Dr. Butts provided an overview of what pediatricians and other clinicians caring for children and teens should know about myocarditis at the annual meeting of the American Academy of Pediatrics.
The important new things that attendees may want to take away from this for their practice are improved recognition and diagnostic workup for acute viral myocarditis, making sure cardiology follow-up occurs after an admission for the condition, enhanced evaluation of the child before they return to competitive sports, and the availability of written or verbal education for patients relating to COVID vaccine–associated myocarditis, Dr. Butts said.
He also provided a set of key takeaways:
- Myocarditis is rare.
- The most common viruses causing myocarditis are always changing.
- Myocarditis is most common in infants and teenagers but it has different clinical patterns in each population.
- MRI is becoming the diagnostic tool of choice.
- IVIG frequently is used but good evidence for the therapy is lacking.
- Patients may go home on cardiac medications but have good long-term outcomes.
- Patients must have a 6-month restriction on competitive sports after diagnosis.
Frank Han, MD, a pediatric cardiologist at OSF Medical Center and Children’s Hospital of Illinois in Peoria, said he found the most helpful parts of Dr. Butts’ presentation to be the diagnosis and triage of myocarditis in the major age groups.
“Myocarditis can have variable presentations, and its cause may influence how the myocarditis behaves,” Dr. Han said. Pediatric cardiologists, he said, are uniquely positioned to triage and diagnose myocarditis.
Epidemiology and presentation
Just 0.05% of admissions from 28.6 million U.S. pediatric ED visits every year are for myocarditis, Dr. Butts said. While viruses are the most common cause of myocarditis, bacterial infections and noninfectious causes, including hypersensitivity reactions, systemic disorders, and toxic substances, can also cause the condition. The dominant viruses causing myocarditis have shifted over the years as well. Coxsackie B was the most common cause in the 1980s, but adenovirus became more common in the 1990s and parvovirus B19 in the 2000s. Why some kids develop myocarditis while others don’t is unclear, but the host-immune response to the virus likely plays an important role.
Research has shown two substantial spikes in the incidence of myocarditis children: infants under 2 years old and teens aged 14-19. Although myocarditis refers to any inflammation of myocardium not caused by ischemia, the signs, symptoms, and lab results vary according to patient’s age group. The only constant is that diaphoresis is rare across all ages.
Infants are more likely to show respiratory distress (68%) and an enlarged liver (40%) but can also present with gastrointestinal symptoms (24%). Vomiting without fever or diarrhea should arouse clinical suspicion of myocarditis in infants, although fever and diarrhea can occur.
In young children, who have the lowest incidence, fatigue presents in about one-third, with 20% presenting with chest pain and 20% with hepatomegaly. The most common symptom in teens by far (80%) is chest pain. About one-third also have respiratory distress but gastrointestinal symptoms are less common (20%).
When should a clinician suspect myocarditis in a teen presenting with chest pain? “If the chest pain is reproducible and if you can localize it, they don’t need further evaluation,” Dr. Butts said. “After that, it’s a lot about the history.”
In terms of lab results, ventricular function measured by brain natriuretic peptide is significantly depressed in infants and young children but often near normal in teens. Inflammatory markers (C-reactive protein) tend to be low in infants but elevated in young children and teens. And troponin levels, denoting myocardial injury, are minimal in infants and young children but elevated in teens. Median ejection fraction on echocardiograms, about 55% in normal hearts, will often be low in infants and young children, around 30%-33%, but is near normal (54%) in teens.
Diagnosis and management
Cardiac MRI increasingly has been replacing endomyocardial biopsy for diagnosis, with MRI exceeding biopsy use between 2009 and 2010, Dr. Butts said. The advantage of endomyocardial biopsy is that it’s specific, if not very sensitive. The test is invasive, however, requiring sedation and carrying the risk of tricuspid injury. The most common finding on cardiac MRI is late gadolinium enhancement (80%) while early gadolinium enhancement is less common (55%).
Although Dr. Butts mentioned the Dallas diagnostic criteria from 1987, he advocated for the more recent Lake Louise Criteria, which require clinical suspicion of myocarditis and at least two of three findings on MRI: T2-weighted myocardial abnormalities, T1 early or late gadolinium enhancement, or regional wall motion abnormalities or evidence of pericarditis
Point-of-care ultrasound can be useful for detecting myocarditis, but its success depends on whether the user can pick up on the subtle changes in ventricular function. “Just because someone has a point-of-care ultrasound that’s normal or thought to be normal, it shouldn’t rule out the diagnosis,” he said.
Learning the etiology of viral myocarditis often is difficult, and etiology doesn’t affect management of the condition, Dr. Butts said. Even in cases of myocarditis confirmed by biopsy, the virus may be identified in only about 60%-70% of cases with myocardial polymerase chain reaction. In clinical cases, the virus can be determined only about 25%-30% of the time with serum PCR.
Prognosis is usually good, with 80%-90% of children and teens going home transplant free despite most arriving critically ill and 50%-80% initially being admitted to ICU. Two-thirds of those discharged go home with heart failure medications, but only one in six are readmitted within a year.
The strongest risk factors for poor prognosis are younger age and being critically ill at presentation but other risk factors include female sex, poor ventricular function, poor perfusion on exam, increased dilation on echocardiogram, and a need for ECMO or inotropes or mechanical ventilation.
That said, Dr. Butts cautioned attendees not to ignore normal function. In one study of 171 patients, among 75 who presented with normal function, 15% went home with inotropes, 12% required mechanical ventilation, 9% had arrhythmia, and 5% needed extracorporeal membrane oxygenation.
A big question in treatment is whether to give IVIG or not and the evidence is murky, Dr. Butts said. He reviewed a couple studies on IVIG, including one that suggested better ventricular functional recovery with the treatment but those who received IVIG were also more likely to be on an ACE inhibitor.
“Was it the ACE inhibitor or was it IVIG? We don’t know,” he said. Different cardiologists may give different opinions on IVIG. “It has nothing to do with the actual evidence behind it.”
IVIG has drawbacks: It’s very expensive and it involves risks that include serum sickness and interstitial nephritis.
“Pediatricians typically aren’t going to directly decide on giving or not giving IVIG,” Dr. Han said. “Typically, the ultimate choice comes from a group discussion between the hospital cardiologist – perhaps the hospitalist pediatrician if they are involved – and the family. We acknowledge the ambiguity of the evidence and decide based upon the severity of the initial disease process.”
Return to competitive sports; Follow-up critical
Experts are much more confident, however, about when teens admitted with viral myocarditis can return to competitive sports. But Dr. Butts said he suspects the guidelines for these children aren’t followed as closely as they should be. The American Heart Association recommends waiting 6 months after discharge and ensuring the athlete has a normal echocardiogram, Holter monitoring, and stress test.
“It’s incredibly important to have them come back and see the cardiologist 6 months after admission,” Dr. Butts said. “The only patient I’ve ever had who died 6-7 months post myocarditis is somebody who, during their stress test, had increasing ventricular ectopy. I told him not to do sports. He didn’t listen to me and unfortunately passed away – I’m assuming from arrhythmia.”
COVID and vaccine-associated myocarditis
Vaccine-associated myocarditis is substantially milder than viral myocarditis, Dr. Butts said. A small study from a single center in Atlanta found that ejection fraction at admission was normal, around 56%, in those with vaccine-associated myocarditis, compared with 45% with non-COVID viral myocarditis and 50% with multisystem inflammatory syndrome in children or myocarditis from COVID-19. All patients with vaccine-associated myocarditis had normal function at discharge, compared with 73% of those with viral myocarditis and 93% with COVID-associated myocarditis.
While 22% of those with vaccine-associated myocarditis were admitted to the ICU, twice as many (40%) with viral myocarditis were, and three times as many (68%) with COVID-associated myocarditis ended up in intensive care.
Dr. Butts also noted a Morbidity and Mortality Weekly Report from the Centers of Disease Control and Prevention that found teen boys had two to six times greater risk of heart complications after COVID-19 infection than after COVID vaccination.
In terms of direct comparisons, vaccine-related myocarditis occurred about 12-18 times per 100,000 doses for boys ages 5-11 years, compared with cardiac involvement in 93-133 cases out of 100,000 COVID-19 infections. Boys aged 12-17 years experienced 12-21 cases of myocarditis per 100,000 doses of the vaccine, compared with cardiac involvement in 50-64 out of 100,000 infections.
The bottom line, Dr. Butts said, is that cardiac involvement in MIS-C is common, but typically improves by discharge. “Vaccine-associated myocarditis is a mild clinical syndrome that has a very short duration, and, in my opinion, should never lead us to ever advise anybody not to get the vaccine. I’ve had many patients, even patients in their first year post transplant, who have gotten the COVID-19 vaccine and were just fine.”
Dr. Butts acknowledged that talking with families about the risk of myocarditis with the vaccine is challenging. He often starts these conversations by sharing the statistics, but he said relatable stories are the key. He will also relate the statistics to something the parents and teen will understand, whether it’s sports or another comparison. He does recommend that teens who develop vaccine-associated myocarditis complete the series and get the booster. Their chances of developing myocarditis again are extremely low, whereas “the likelihood of them being really ill from COVID-19 is much, much higher.”
Dr. Butts and Dr. Han had no disclosures. The presentation involved no external funding.
ANAHEIM – A wide range of factors can cause myocarditis; most often viral infections cause myocarditis in children and teens, according to Ryan Butts, MD, medical director of the pediatric advanced cardiac care program at the University of Texas Southwestern Medical Center and Children’s Health of Texas.
Dr. Butts provided an overview of what pediatricians and other clinicians caring for children and teens should know about myocarditis at the annual meeting of the American Academy of Pediatrics.
The important new things that attendees may want to take away from this for their practice are improved recognition and diagnostic workup for acute viral myocarditis, making sure cardiology follow-up occurs after an admission for the condition, enhanced evaluation of the child before they return to competitive sports, and the availability of written or verbal education for patients relating to COVID vaccine–associated myocarditis, Dr. Butts said.
He also provided a set of key takeaways:
- Myocarditis is rare.
- The most common viruses causing myocarditis are always changing.
- Myocarditis is most common in infants and teenagers but it has different clinical patterns in each population.
- MRI is becoming the diagnostic tool of choice.
- IVIG frequently is used but good evidence for the therapy is lacking.
- Patients may go home on cardiac medications but have good long-term outcomes.
- Patients must have a 6-month restriction on competitive sports after diagnosis.
Frank Han, MD, a pediatric cardiologist at OSF Medical Center and Children’s Hospital of Illinois in Peoria, said he found the most helpful parts of Dr. Butts’ presentation to be the diagnosis and triage of myocarditis in the major age groups.
“Myocarditis can have variable presentations, and its cause may influence how the myocarditis behaves,” Dr. Han said. Pediatric cardiologists, he said, are uniquely positioned to triage and diagnose myocarditis.
Epidemiology and presentation
Just 0.05% of admissions from 28.6 million U.S. pediatric ED visits every year are for myocarditis, Dr. Butts said. While viruses are the most common cause of myocarditis, bacterial infections and noninfectious causes, including hypersensitivity reactions, systemic disorders, and toxic substances, can also cause the condition. The dominant viruses causing myocarditis have shifted over the years as well. Coxsackie B was the most common cause in the 1980s, but adenovirus became more common in the 1990s and parvovirus B19 in the 2000s. Why some kids develop myocarditis while others don’t is unclear, but the host-immune response to the virus likely plays an important role.
Research has shown two substantial spikes in the incidence of myocarditis children: infants under 2 years old and teens aged 14-19. Although myocarditis refers to any inflammation of myocardium not caused by ischemia, the signs, symptoms, and lab results vary according to patient’s age group. The only constant is that diaphoresis is rare across all ages.
Infants are more likely to show respiratory distress (68%) and an enlarged liver (40%) but can also present with gastrointestinal symptoms (24%). Vomiting without fever or diarrhea should arouse clinical suspicion of myocarditis in infants, although fever and diarrhea can occur.
In young children, who have the lowest incidence, fatigue presents in about one-third, with 20% presenting with chest pain and 20% with hepatomegaly. The most common symptom in teens by far (80%) is chest pain. About one-third also have respiratory distress but gastrointestinal symptoms are less common (20%).
When should a clinician suspect myocarditis in a teen presenting with chest pain? “If the chest pain is reproducible and if you can localize it, they don’t need further evaluation,” Dr. Butts said. “After that, it’s a lot about the history.”
In terms of lab results, ventricular function measured by brain natriuretic peptide is significantly depressed in infants and young children but often near normal in teens. Inflammatory markers (C-reactive protein) tend to be low in infants but elevated in young children and teens. And troponin levels, denoting myocardial injury, are minimal in infants and young children but elevated in teens. Median ejection fraction on echocardiograms, about 55% in normal hearts, will often be low in infants and young children, around 30%-33%, but is near normal (54%) in teens.
Diagnosis and management
Cardiac MRI increasingly has been replacing endomyocardial biopsy for diagnosis, with MRI exceeding biopsy use between 2009 and 2010, Dr. Butts said. The advantage of endomyocardial biopsy is that it’s specific, if not very sensitive. The test is invasive, however, requiring sedation and carrying the risk of tricuspid injury. The most common finding on cardiac MRI is late gadolinium enhancement (80%) while early gadolinium enhancement is less common (55%).
Although Dr. Butts mentioned the Dallas diagnostic criteria from 1987, he advocated for the more recent Lake Louise Criteria, which require clinical suspicion of myocarditis and at least two of three findings on MRI: T2-weighted myocardial abnormalities, T1 early or late gadolinium enhancement, or regional wall motion abnormalities or evidence of pericarditis
Point-of-care ultrasound can be useful for detecting myocarditis, but its success depends on whether the user can pick up on the subtle changes in ventricular function. “Just because someone has a point-of-care ultrasound that’s normal or thought to be normal, it shouldn’t rule out the diagnosis,” he said.
Learning the etiology of viral myocarditis often is difficult, and etiology doesn’t affect management of the condition, Dr. Butts said. Even in cases of myocarditis confirmed by biopsy, the virus may be identified in only about 60%-70% of cases with myocardial polymerase chain reaction. In clinical cases, the virus can be determined only about 25%-30% of the time with serum PCR.
Prognosis is usually good, with 80%-90% of children and teens going home transplant free despite most arriving critically ill and 50%-80% initially being admitted to ICU. Two-thirds of those discharged go home with heart failure medications, but only one in six are readmitted within a year.
The strongest risk factors for poor prognosis are younger age and being critically ill at presentation but other risk factors include female sex, poor ventricular function, poor perfusion on exam, increased dilation on echocardiogram, and a need for ECMO or inotropes or mechanical ventilation.
That said, Dr. Butts cautioned attendees not to ignore normal function. In one study of 171 patients, among 75 who presented with normal function, 15% went home with inotropes, 12% required mechanical ventilation, 9% had arrhythmia, and 5% needed extracorporeal membrane oxygenation.
A big question in treatment is whether to give IVIG or not and the evidence is murky, Dr. Butts said. He reviewed a couple studies on IVIG, including one that suggested better ventricular functional recovery with the treatment but those who received IVIG were also more likely to be on an ACE inhibitor.
“Was it the ACE inhibitor or was it IVIG? We don’t know,” he said. Different cardiologists may give different opinions on IVIG. “It has nothing to do with the actual evidence behind it.”
IVIG has drawbacks: It’s very expensive and it involves risks that include serum sickness and interstitial nephritis.
“Pediatricians typically aren’t going to directly decide on giving or not giving IVIG,” Dr. Han said. “Typically, the ultimate choice comes from a group discussion between the hospital cardiologist – perhaps the hospitalist pediatrician if they are involved – and the family. We acknowledge the ambiguity of the evidence and decide based upon the severity of the initial disease process.”
Return to competitive sports; Follow-up critical
Experts are much more confident, however, about when teens admitted with viral myocarditis can return to competitive sports. But Dr. Butts said he suspects the guidelines for these children aren’t followed as closely as they should be. The American Heart Association recommends waiting 6 months after discharge and ensuring the athlete has a normal echocardiogram, Holter monitoring, and stress test.
“It’s incredibly important to have them come back and see the cardiologist 6 months after admission,” Dr. Butts said. “The only patient I’ve ever had who died 6-7 months post myocarditis is somebody who, during their stress test, had increasing ventricular ectopy. I told him not to do sports. He didn’t listen to me and unfortunately passed away – I’m assuming from arrhythmia.”
COVID and vaccine-associated myocarditis
Vaccine-associated myocarditis is substantially milder than viral myocarditis, Dr. Butts said. A small study from a single center in Atlanta found that ejection fraction at admission was normal, around 56%, in those with vaccine-associated myocarditis, compared with 45% with non-COVID viral myocarditis and 50% with multisystem inflammatory syndrome in children or myocarditis from COVID-19. All patients with vaccine-associated myocarditis had normal function at discharge, compared with 73% of those with viral myocarditis and 93% with COVID-associated myocarditis.
While 22% of those with vaccine-associated myocarditis were admitted to the ICU, twice as many (40%) with viral myocarditis were, and three times as many (68%) with COVID-associated myocarditis ended up in intensive care.
Dr. Butts also noted a Morbidity and Mortality Weekly Report from the Centers of Disease Control and Prevention that found teen boys had two to six times greater risk of heart complications after COVID-19 infection than after COVID vaccination.
In terms of direct comparisons, vaccine-related myocarditis occurred about 12-18 times per 100,000 doses for boys ages 5-11 years, compared with cardiac involvement in 93-133 cases out of 100,000 COVID-19 infections. Boys aged 12-17 years experienced 12-21 cases of myocarditis per 100,000 doses of the vaccine, compared with cardiac involvement in 50-64 out of 100,000 infections.
The bottom line, Dr. Butts said, is that cardiac involvement in MIS-C is common, but typically improves by discharge. “Vaccine-associated myocarditis is a mild clinical syndrome that has a very short duration, and, in my opinion, should never lead us to ever advise anybody not to get the vaccine. I’ve had many patients, even patients in their first year post transplant, who have gotten the COVID-19 vaccine and were just fine.”
Dr. Butts acknowledged that talking with families about the risk of myocarditis with the vaccine is challenging. He often starts these conversations by sharing the statistics, but he said relatable stories are the key. He will also relate the statistics to something the parents and teen will understand, whether it’s sports or another comparison. He does recommend that teens who develop vaccine-associated myocarditis complete the series and get the booster. Their chances of developing myocarditis again are extremely low, whereas “the likelihood of them being really ill from COVID-19 is much, much higher.”
Dr. Butts and Dr. Han had no disclosures. The presentation involved no external funding.
AT AAP 2022
AFib detection by smartwatch challenging in some patients
The ability of an Apple Watch to detect atrial fibrillation (AFib) is significantly affected by underlying ECG abnormalities such as sinus node dysfunction, atrioventricular (AV) block, or intraventricular conduction delay (IVCD), a single-center study suggests.
“We were surprised to find that in one in every five patients, the smartwatch ECG failed to produce an automatic diagnosis,” study author Marc Strik, MD, PhD, a clinician at Bordeaux University Hospital in Pessac, France, told this news organization. “This [failure] was mostly due to insufficient quality of the tracing [60%], but in a third of cases, [34%], it was due to bradycardia, and in some cases, tachycardia [6%].
“We were also surprised to find that the existence of ventricular conduction disease was associated with a higher likelihood of missing AFib,” he said.
The study was published in the Canadian Journal of Cardiology.
Abnormalities affected detection
The investigators tested the accuracy of the Apple Watch (Apple, Cupertino, California) in detecting AFib in patients with various ECG anomalies. All participants underwent 12-lead ECG, followed by a 30-second ECG tracing with an Apple Watch Series 5. The smartwatch’s automated AFib detection algorithm gave a result of “no signs of AFib,” “AFib,” or “not checked for AFib (unclassified).”
Unclassified recordings resulted from “low heart rate” (below 50 beats/min), “high heart rate” (above 150 beats/min), “poor recording,” or “inconclusive recording.”
The smartwatch recordings were reviewed by a blinded electrophysiologist who interpreted each tracing and assigned a diagnosis of “AFib,” “absence of AFib,” or “diagnosis unclear.” To assess interobserver agreement, a second blinded electrophysiologist interpreted 100 randomly selected tracings.
Among the 734 patients (mean age, 66; 58% men) enrolled, 539 (73%) were in normal sinus rhythm (SR), 154 (21%) in AFib, 33 in atrial flutter or atrial tachycardia, 3 in ventricular tachycardia, and 5 in junctional tachycardia.
Furthermore, 65 (8.9%) had sinus node dysfunction, 21 (2.9%) had second- or third-degree AV block, 39 (5.3%) had a ventricular paced rhythm, 54 (7.4%) had premature ventricular contractions (PVCs), and 132 (18%) had IVCD (right or left bundle branch block or nonspecific IVCD).
Of the 539 patients in normal SR, 437 recordings were correctly diagnosed by the smartwatch, 7 were diagnosed incorrectly as AFib, and 95 were not classified.
Of the 187 patients in AFib, 129 were correctly diagnosed, 17 were incorrectly diagnosed as SR, and 41 were not classified.
When unclassified ECGs were considered false results, the smartwatch had a sensitivity of 69% and specificity of 81% for AFib detection. When unclassified ECGs were excluded from the analysis, sensitivity was 88%, and specificity was 98%.
Compared with patients without the abnormality, the relative risk of having false positive tracings was higher for patients with premature atrial contractions (PACs) or PVCs (risk ratio, 2.9), sinus node dysfunction (RR, 3.71), and AV block (RR, 7.8).
Fifty-eight patients with AFib were classified as SR or inconclusive by the smartwatch. Among them, 21 (36%) had an IVCD, 7 (12%) had a ventricular paced rhythm, and 5 (9%) had PACs or PVCs.
The risk of having false negative tracings (missed AF) was higher for patients with IVCD (RR, 2.6) and pacing (RR, 2.47), compared with those without the abnormality.
‘A powerful tool’
Overall, cardiac electrophysiologists showed high agreement in differentiating between AFib and non-AFib, with high interobserver reproducibility. A manual diagnosis was not possible for 10% of tracings because of either poor ECG quality (3%) or unclear P-waves (7%).
Fifty-nine of the 580 patients in SR were misclassified as AFib by the experts, and 5 of the 154 patients in AFib were misclassified as SR.
“Our results show that the presence of sinus node dysfunction, second- or third-degree AV block, ventricular paced rhythm, PVCs, and IVCD were more frequently represented in smartwatch misdiagnoses,” wrote the authors. “Patients with PVCs were three times as likely to have false positive AFib diagnoses.”
Study limitations included the single-center nature of the study and the fact that patients were recruited in a cardiology office. The latter factor may have influenced the incidence of ECG abnormalities, which was much higher than for the average smartwatch user.
“Even with its limitations, the smartwatch remains a powerful tool that is able to detect AFib and multiple other abnormalities,” said Dr. Strik. “Missed diagnosis of AFib may be less important in real life because of repeated measurements, and algorithms will continue to improve.”
Technology improving
Richard C. Becker, MD, director and physician in chief of the University of Cincinnati Heart, Lung, and Vascular Institute, said, “This is exactly the kind of investigation required to improve upon existing detection algorithms that will someday facilitate routine use in patient care. An ability to detect AFib in a large proportion of those with the heart rhythm abnormality is encouraging.”
The findings should not detract from well-conducted studies in otherwise healthy individuals of varied age in whom AFib was accurately detected, he added. “Similarly, an automatic diagnosis algorithm for AF, pending optimization and validation in a large and diverse cohort, should be viewed as a communication tool between patients and health care providers.”
Patients at risk for developing AFib could benefit from continuous monitoring using a smartwatch, said Dr. Becker. “Pre-existing heart rhythm abnormalities must be taken into consideration. Optimal utilization of emerging technology to include wearables requires an understanding of performance and limitations. It is best undertaken in coordination with a health care provider.”
Andrés F. Miranda-Arboleda, MD, and Adrian Baranchuk, MD, of Kingston Health Sciences Center, Canada, conclude in an accompanying editorial, “In a certain manner, the smartwatch algorithms for the detection of AFib in patients with cardiovascular conditions are not yet smart enough ... but they may soon be.”
The study was supported by the French government. Dr. Strik, Dr. Miranda-Arboleda, Dr. Baranchuk, and Dr. Becker reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
The ability of an Apple Watch to detect atrial fibrillation (AFib) is significantly affected by underlying ECG abnormalities such as sinus node dysfunction, atrioventricular (AV) block, or intraventricular conduction delay (IVCD), a single-center study suggests.
“We were surprised to find that in one in every five patients, the smartwatch ECG failed to produce an automatic diagnosis,” study author Marc Strik, MD, PhD, a clinician at Bordeaux University Hospital in Pessac, France, told this news organization. “This [failure] was mostly due to insufficient quality of the tracing [60%], but in a third of cases, [34%], it was due to bradycardia, and in some cases, tachycardia [6%].
“We were also surprised to find that the existence of ventricular conduction disease was associated with a higher likelihood of missing AFib,” he said.
The study was published in the Canadian Journal of Cardiology.
Abnormalities affected detection
The investigators tested the accuracy of the Apple Watch (Apple, Cupertino, California) in detecting AFib in patients with various ECG anomalies. All participants underwent 12-lead ECG, followed by a 30-second ECG tracing with an Apple Watch Series 5. The smartwatch’s automated AFib detection algorithm gave a result of “no signs of AFib,” “AFib,” or “not checked for AFib (unclassified).”
Unclassified recordings resulted from “low heart rate” (below 50 beats/min), “high heart rate” (above 150 beats/min), “poor recording,” or “inconclusive recording.”
The smartwatch recordings were reviewed by a blinded electrophysiologist who interpreted each tracing and assigned a diagnosis of “AFib,” “absence of AFib,” or “diagnosis unclear.” To assess interobserver agreement, a second blinded electrophysiologist interpreted 100 randomly selected tracings.
Among the 734 patients (mean age, 66; 58% men) enrolled, 539 (73%) were in normal sinus rhythm (SR), 154 (21%) in AFib, 33 in atrial flutter or atrial tachycardia, 3 in ventricular tachycardia, and 5 in junctional tachycardia.
Furthermore, 65 (8.9%) had sinus node dysfunction, 21 (2.9%) had second- or third-degree AV block, 39 (5.3%) had a ventricular paced rhythm, 54 (7.4%) had premature ventricular contractions (PVCs), and 132 (18%) had IVCD (right or left bundle branch block or nonspecific IVCD).
Of the 539 patients in normal SR, 437 recordings were correctly diagnosed by the smartwatch, 7 were diagnosed incorrectly as AFib, and 95 were not classified.
Of the 187 patients in AFib, 129 were correctly diagnosed, 17 were incorrectly diagnosed as SR, and 41 were not classified.
When unclassified ECGs were considered false results, the smartwatch had a sensitivity of 69% and specificity of 81% for AFib detection. When unclassified ECGs were excluded from the analysis, sensitivity was 88%, and specificity was 98%.
Compared with patients without the abnormality, the relative risk of having false positive tracings was higher for patients with premature atrial contractions (PACs) or PVCs (risk ratio, 2.9), sinus node dysfunction (RR, 3.71), and AV block (RR, 7.8).
Fifty-eight patients with AFib were classified as SR or inconclusive by the smartwatch. Among them, 21 (36%) had an IVCD, 7 (12%) had a ventricular paced rhythm, and 5 (9%) had PACs or PVCs.
The risk of having false negative tracings (missed AF) was higher for patients with IVCD (RR, 2.6) and pacing (RR, 2.47), compared with those without the abnormality.
‘A powerful tool’
Overall, cardiac electrophysiologists showed high agreement in differentiating between AFib and non-AFib, with high interobserver reproducibility. A manual diagnosis was not possible for 10% of tracings because of either poor ECG quality (3%) or unclear P-waves (7%).
Fifty-nine of the 580 patients in SR were misclassified as AFib by the experts, and 5 of the 154 patients in AFib were misclassified as SR.
“Our results show that the presence of sinus node dysfunction, second- or third-degree AV block, ventricular paced rhythm, PVCs, and IVCD were more frequently represented in smartwatch misdiagnoses,” wrote the authors. “Patients with PVCs were three times as likely to have false positive AFib diagnoses.”
Study limitations included the single-center nature of the study and the fact that patients were recruited in a cardiology office. The latter factor may have influenced the incidence of ECG abnormalities, which was much higher than for the average smartwatch user.
“Even with its limitations, the smartwatch remains a powerful tool that is able to detect AFib and multiple other abnormalities,” said Dr. Strik. “Missed diagnosis of AFib may be less important in real life because of repeated measurements, and algorithms will continue to improve.”
Technology improving
Richard C. Becker, MD, director and physician in chief of the University of Cincinnati Heart, Lung, and Vascular Institute, said, “This is exactly the kind of investigation required to improve upon existing detection algorithms that will someday facilitate routine use in patient care. An ability to detect AFib in a large proportion of those with the heart rhythm abnormality is encouraging.”
The findings should not detract from well-conducted studies in otherwise healthy individuals of varied age in whom AFib was accurately detected, he added. “Similarly, an automatic diagnosis algorithm for AF, pending optimization and validation in a large and diverse cohort, should be viewed as a communication tool between patients and health care providers.”
Patients at risk for developing AFib could benefit from continuous monitoring using a smartwatch, said Dr. Becker. “Pre-existing heart rhythm abnormalities must be taken into consideration. Optimal utilization of emerging technology to include wearables requires an understanding of performance and limitations. It is best undertaken in coordination with a health care provider.”
Andrés F. Miranda-Arboleda, MD, and Adrian Baranchuk, MD, of Kingston Health Sciences Center, Canada, conclude in an accompanying editorial, “In a certain manner, the smartwatch algorithms for the detection of AFib in patients with cardiovascular conditions are not yet smart enough ... but they may soon be.”
The study was supported by the French government. Dr. Strik, Dr. Miranda-Arboleda, Dr. Baranchuk, and Dr. Becker reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
The ability of an Apple Watch to detect atrial fibrillation (AFib) is significantly affected by underlying ECG abnormalities such as sinus node dysfunction, atrioventricular (AV) block, or intraventricular conduction delay (IVCD), a single-center study suggests.
“We were surprised to find that in one in every five patients, the smartwatch ECG failed to produce an automatic diagnosis,” study author Marc Strik, MD, PhD, a clinician at Bordeaux University Hospital in Pessac, France, told this news organization. “This [failure] was mostly due to insufficient quality of the tracing [60%], but in a third of cases, [34%], it was due to bradycardia, and in some cases, tachycardia [6%].
“We were also surprised to find that the existence of ventricular conduction disease was associated with a higher likelihood of missing AFib,” he said.
The study was published in the Canadian Journal of Cardiology.
Abnormalities affected detection
The investigators tested the accuracy of the Apple Watch (Apple, Cupertino, California) in detecting AFib in patients with various ECG anomalies. All participants underwent 12-lead ECG, followed by a 30-second ECG tracing with an Apple Watch Series 5. The smartwatch’s automated AFib detection algorithm gave a result of “no signs of AFib,” “AFib,” or “not checked for AFib (unclassified).”
Unclassified recordings resulted from “low heart rate” (below 50 beats/min), “high heart rate” (above 150 beats/min), “poor recording,” or “inconclusive recording.”
The smartwatch recordings were reviewed by a blinded electrophysiologist who interpreted each tracing and assigned a diagnosis of “AFib,” “absence of AFib,” or “diagnosis unclear.” To assess interobserver agreement, a second blinded electrophysiologist interpreted 100 randomly selected tracings.
Among the 734 patients (mean age, 66; 58% men) enrolled, 539 (73%) were in normal sinus rhythm (SR), 154 (21%) in AFib, 33 in atrial flutter or atrial tachycardia, 3 in ventricular tachycardia, and 5 in junctional tachycardia.
Furthermore, 65 (8.9%) had sinus node dysfunction, 21 (2.9%) had second- or third-degree AV block, 39 (5.3%) had a ventricular paced rhythm, 54 (7.4%) had premature ventricular contractions (PVCs), and 132 (18%) had IVCD (right or left bundle branch block or nonspecific IVCD).
Of the 539 patients in normal SR, 437 recordings were correctly diagnosed by the smartwatch, 7 were diagnosed incorrectly as AFib, and 95 were not classified.
Of the 187 patients in AFib, 129 were correctly diagnosed, 17 were incorrectly diagnosed as SR, and 41 were not classified.
When unclassified ECGs were considered false results, the smartwatch had a sensitivity of 69% and specificity of 81% for AFib detection. When unclassified ECGs were excluded from the analysis, sensitivity was 88%, and specificity was 98%.
Compared with patients without the abnormality, the relative risk of having false positive tracings was higher for patients with premature atrial contractions (PACs) or PVCs (risk ratio, 2.9), sinus node dysfunction (RR, 3.71), and AV block (RR, 7.8).
Fifty-eight patients with AFib were classified as SR or inconclusive by the smartwatch. Among them, 21 (36%) had an IVCD, 7 (12%) had a ventricular paced rhythm, and 5 (9%) had PACs or PVCs.
The risk of having false negative tracings (missed AF) was higher for patients with IVCD (RR, 2.6) and pacing (RR, 2.47), compared with those without the abnormality.
‘A powerful tool’
Overall, cardiac electrophysiologists showed high agreement in differentiating between AFib and non-AFib, with high interobserver reproducibility. A manual diagnosis was not possible for 10% of tracings because of either poor ECG quality (3%) or unclear P-waves (7%).
Fifty-nine of the 580 patients in SR were misclassified as AFib by the experts, and 5 of the 154 patients in AFib were misclassified as SR.
“Our results show that the presence of sinus node dysfunction, second- or third-degree AV block, ventricular paced rhythm, PVCs, and IVCD were more frequently represented in smartwatch misdiagnoses,” wrote the authors. “Patients with PVCs were three times as likely to have false positive AFib diagnoses.”
Study limitations included the single-center nature of the study and the fact that patients were recruited in a cardiology office. The latter factor may have influenced the incidence of ECG abnormalities, which was much higher than for the average smartwatch user.
“Even with its limitations, the smartwatch remains a powerful tool that is able to detect AFib and multiple other abnormalities,” said Dr. Strik. “Missed diagnosis of AFib may be less important in real life because of repeated measurements, and algorithms will continue to improve.”
Technology improving
Richard C. Becker, MD, director and physician in chief of the University of Cincinnati Heart, Lung, and Vascular Institute, said, “This is exactly the kind of investigation required to improve upon existing detection algorithms that will someday facilitate routine use in patient care. An ability to detect AFib in a large proportion of those with the heart rhythm abnormality is encouraging.”
The findings should not detract from well-conducted studies in otherwise healthy individuals of varied age in whom AFib was accurately detected, he added. “Similarly, an automatic diagnosis algorithm for AF, pending optimization and validation in a large and diverse cohort, should be viewed as a communication tool between patients and health care providers.”
Patients at risk for developing AFib could benefit from continuous monitoring using a smartwatch, said Dr. Becker. “Pre-existing heart rhythm abnormalities must be taken into consideration. Optimal utilization of emerging technology to include wearables requires an understanding of performance and limitations. It is best undertaken in coordination with a health care provider.”
Andrés F. Miranda-Arboleda, MD, and Adrian Baranchuk, MD, of Kingston Health Sciences Center, Canada, conclude in an accompanying editorial, “In a certain manner, the smartwatch algorithms for the detection of AFib in patients with cardiovascular conditions are not yet smart enough ... but they may soon be.”
The study was supported by the French government. Dr. Strik, Dr. Miranda-Arboleda, Dr. Baranchuk, and Dr. Becker reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM CANADIAN JOURNAL OF CARDIOLOGY
New deep dive into Paxlovid interactions with CVD meds
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Cardiac biomarkers track with hormone therapy in transgender people
Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.
Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.
“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.
Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”
The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”
For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.
The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.
The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).
As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.
In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.
“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.
The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.
Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”
Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.
For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.
“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”
The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”
Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.
“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”
The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.
Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.
“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.
Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”
The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”
For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.
The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.
The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).
As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.
In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.
“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.
The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.
Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”
Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.
For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.
“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”
The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”
Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.
“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”
The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.
Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.
“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.
Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”
The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”
For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.
The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.
The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).
As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.
In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.
“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.
The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.
Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”
Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.
For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.
“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”
The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”
Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.
“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”
The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
FROM JAMA CARDIOLOGY
SPRINT’s intensive therapy benefit fades once BP creeps back up
The substantial reductions in cardiovascular disease (CVD) and all-cause mortality achieved with intensive blood pressure lowering in the landmark SPRINT trial were not sustained in a newly released long-term follow-up.
The loss of the mortality benefits corresponded with a steady climb in the average systolic blood pressures (SBP) in the intensive treatment group after the trial ended. The long-term benefit serves as a call to develop better strategies for sustained SBP control.
“We were disappointed but not surprised that the blood pressure levels in the intensive goal group were not sustained,” acknowledged William C. Cushman, MD, Medical Director, department of preventive medicine, University of Tennessee Health Science Center, Memphis. “There are many trials showing no residual or legacy effect once the intervention is stopped.”
Long-term results do not weaken SPRINT
One of the coinvestigators of this most recent analysis published in JAMA Cardiology and a member of the SPRINT writing committee at the time of its 2015 publication in the New England Journal of Medicine, Dr. Cushman pointed out that the long-term results do not weaken the main trial result. Long-term adherence was not part of the trial design.
“After the trial, we were no longer treating these participants, so it was up to them and their primary care providers to decide on blood pressure goals,” he noted in an interview. Based on the trajectory of benefit when the study was stopped, “it is possible longer intensive treatment may lead to more benefit and some long-term residual benefits.”
The senior author of this most recent analysis, Nicholas M. Pajewski, PhD, associate professor of biostatistics and data science, Wake Forest University, Winston-Salem, N.C., generally agreed. However, he pointed out that the most recent data do not rule out meaningful benefit after the study ended.
For one reason, the loss of the SBP advantage was gradual so that median SBP levels of the two groups did not meet for nearly 3 years. This likely explains why there was still an attenuation of CVD mortality for several years after the all-cause mortality benefit was lost, according to Dr. Pajewski.
“It is important to mention that we were not able to assess nonfatal cardiovascular events, so while the two groups do eventually come together, if one thinks about the distinction of healthspan versus lifespan, there was probably residual benefit in terms of delaying CVD morbidity and mortality,” Dr. Pajewski said.
In SPRINT, CVD mortality reduced 43%
In the 9,631-patient SPRINT trial, the intensive treatment group achieved a mean SBP of 121.4 mm Hg versus 136.2 mm Hg in the standard treatment group at the end of 1 year. The trial was stopped early after 3.26 years because of strength of the benefit in the intensive treatment arm. At that time, the reductions by hazard ratio were 25% (HR, 0.75; P < .001) for a composite major adverse cardiovascular event (MACE) endpoint, 43% for CVD mortality (P = .005), and 27% for all-cause mortality (P = .003).
In the new observational follow-up, mortality data were drawn from the National Death Index, and change in SBP from electronic health records in a subset of 2,944 SPRINT trial participants. Data were available and analyzed through 2020.
The newly published long-term observational analysis showed that the median SBP in the intensive treatment arm was already climbing by the end of the end of the trial. It reached 132.8 mm Hg at 5 years after randomization and then 140.4 mm Hg by 10 years.
This latter figure was essentially equivalent to the SBP among those who were initially randomized to the standard treatment arm.
Factors driving rising BP are unclear
There is limited information on what medications were taken by either group following the end of the trial, so the reason for the regression in the intensive treatment arm after leaving the trial is unknown. The authors speculated that this might have been due to therapeutic inertia among treating physicians, poor adherence among patients, the difficulty of keeping blood pressures low in patients with advancing pathology, or some combination of these.
“Perhaps the most important reason was that providers and patients were not aiming for the lower goals since guidelines did not recommend these targets until 2017,” Dr. Cushman pointed out. He noted that Healthcare Effectiveness Data and Information Set (HEDIS) “has still not adopted a performance measure goal of less than 140 mm Hg.”
In an accompanying editorial, the authors focused on what these data mean for population-based strategies to achieve sustained control of one of the most important risk factors for cardiovascular events. Led by Daniel W. Jones, MD, director of clinical and population science, University of Mississippi, Jackson, the authors of the editorial wrote that these data emphasized “the challenge of achieving sustained intensive BP reductions in the real-world setting.”
Basically, the editorial concluded that current approaches to achieving meaningful and sustained blood pressure control are not working.
This study “should be a wakeup call, but other previously published good data have also been ignored,” said Dr. Jones in an interview. Despite the compelling benefit from intensive blood pressure control the SPRINT trial, the observational follow-up emphasizes the difficulty of maintaining the rigorous reductions in blood pressure needed for sustained protection.
“Systemic change is necessary,” said Dr. Jones, reprising the major thrust of the editorial he wrote with Donald Clark III, MD, and Michael E. Hall, MD, who are both colleagues at the University of Mississippi.
“My view is that health care providers should be held responsible for motivating better compliance of their patients, just as a teacher is accountable for the outcomes of their students,” he said.
The solutions are not likely to be simple. Dr. Jones called for multiple strategies, such as employing telehealth and community health workers to monitor and reinforce blood pressure control, but he said that these and other data have convinced him that “simply trying harder at what we currently do” is not enough.
Dr. Pajewski and Dr. Jones report no potential conflicts of interest. Dr. Cushman reports a financial relationship with ReCor.
The substantial reductions in cardiovascular disease (CVD) and all-cause mortality achieved with intensive blood pressure lowering in the landmark SPRINT trial were not sustained in a newly released long-term follow-up.
The loss of the mortality benefits corresponded with a steady climb in the average systolic blood pressures (SBP) in the intensive treatment group after the trial ended. The long-term benefit serves as a call to develop better strategies for sustained SBP control.
“We were disappointed but not surprised that the blood pressure levels in the intensive goal group were not sustained,” acknowledged William C. Cushman, MD, Medical Director, department of preventive medicine, University of Tennessee Health Science Center, Memphis. “There are many trials showing no residual or legacy effect once the intervention is stopped.”
Long-term results do not weaken SPRINT
One of the coinvestigators of this most recent analysis published in JAMA Cardiology and a member of the SPRINT writing committee at the time of its 2015 publication in the New England Journal of Medicine, Dr. Cushman pointed out that the long-term results do not weaken the main trial result. Long-term adherence was not part of the trial design.
“After the trial, we were no longer treating these participants, so it was up to them and their primary care providers to decide on blood pressure goals,” he noted in an interview. Based on the trajectory of benefit when the study was stopped, “it is possible longer intensive treatment may lead to more benefit and some long-term residual benefits.”
The senior author of this most recent analysis, Nicholas M. Pajewski, PhD, associate professor of biostatistics and data science, Wake Forest University, Winston-Salem, N.C., generally agreed. However, he pointed out that the most recent data do not rule out meaningful benefit after the study ended.
For one reason, the loss of the SBP advantage was gradual so that median SBP levels of the two groups did not meet for nearly 3 years. This likely explains why there was still an attenuation of CVD mortality for several years after the all-cause mortality benefit was lost, according to Dr. Pajewski.
“It is important to mention that we were not able to assess nonfatal cardiovascular events, so while the two groups do eventually come together, if one thinks about the distinction of healthspan versus lifespan, there was probably residual benefit in terms of delaying CVD morbidity and mortality,” Dr. Pajewski said.
In SPRINT, CVD mortality reduced 43%
In the 9,631-patient SPRINT trial, the intensive treatment group achieved a mean SBP of 121.4 mm Hg versus 136.2 mm Hg in the standard treatment group at the end of 1 year. The trial was stopped early after 3.26 years because of strength of the benefit in the intensive treatment arm. At that time, the reductions by hazard ratio were 25% (HR, 0.75; P < .001) for a composite major adverse cardiovascular event (MACE) endpoint, 43% for CVD mortality (P = .005), and 27% for all-cause mortality (P = .003).
In the new observational follow-up, mortality data were drawn from the National Death Index, and change in SBP from electronic health records in a subset of 2,944 SPRINT trial participants. Data were available and analyzed through 2020.
The newly published long-term observational analysis showed that the median SBP in the intensive treatment arm was already climbing by the end of the end of the trial. It reached 132.8 mm Hg at 5 years after randomization and then 140.4 mm Hg by 10 years.
This latter figure was essentially equivalent to the SBP among those who were initially randomized to the standard treatment arm.
Factors driving rising BP are unclear
There is limited information on what medications were taken by either group following the end of the trial, so the reason for the regression in the intensive treatment arm after leaving the trial is unknown. The authors speculated that this might have been due to therapeutic inertia among treating physicians, poor adherence among patients, the difficulty of keeping blood pressures low in patients with advancing pathology, or some combination of these.
“Perhaps the most important reason was that providers and patients were not aiming for the lower goals since guidelines did not recommend these targets until 2017,” Dr. Cushman pointed out. He noted that Healthcare Effectiveness Data and Information Set (HEDIS) “has still not adopted a performance measure goal of less than 140 mm Hg.”
In an accompanying editorial, the authors focused on what these data mean for population-based strategies to achieve sustained control of one of the most important risk factors for cardiovascular events. Led by Daniel W. Jones, MD, director of clinical and population science, University of Mississippi, Jackson, the authors of the editorial wrote that these data emphasized “the challenge of achieving sustained intensive BP reductions in the real-world setting.”
Basically, the editorial concluded that current approaches to achieving meaningful and sustained blood pressure control are not working.
This study “should be a wakeup call, but other previously published good data have also been ignored,” said Dr. Jones in an interview. Despite the compelling benefit from intensive blood pressure control the SPRINT trial, the observational follow-up emphasizes the difficulty of maintaining the rigorous reductions in blood pressure needed for sustained protection.
“Systemic change is necessary,” said Dr. Jones, reprising the major thrust of the editorial he wrote with Donald Clark III, MD, and Michael E. Hall, MD, who are both colleagues at the University of Mississippi.
“My view is that health care providers should be held responsible for motivating better compliance of their patients, just as a teacher is accountable for the outcomes of their students,” he said.
The solutions are not likely to be simple. Dr. Jones called for multiple strategies, such as employing telehealth and community health workers to monitor and reinforce blood pressure control, but he said that these and other data have convinced him that “simply trying harder at what we currently do” is not enough.
Dr. Pajewski and Dr. Jones report no potential conflicts of interest. Dr. Cushman reports a financial relationship with ReCor.
The substantial reductions in cardiovascular disease (CVD) and all-cause mortality achieved with intensive blood pressure lowering in the landmark SPRINT trial were not sustained in a newly released long-term follow-up.
The loss of the mortality benefits corresponded with a steady climb in the average systolic blood pressures (SBP) in the intensive treatment group after the trial ended. The long-term benefit serves as a call to develop better strategies for sustained SBP control.
“We were disappointed but not surprised that the blood pressure levels in the intensive goal group were not sustained,” acknowledged William C. Cushman, MD, Medical Director, department of preventive medicine, University of Tennessee Health Science Center, Memphis. “There are many trials showing no residual or legacy effect once the intervention is stopped.”
Long-term results do not weaken SPRINT
One of the coinvestigators of this most recent analysis published in JAMA Cardiology and a member of the SPRINT writing committee at the time of its 2015 publication in the New England Journal of Medicine, Dr. Cushman pointed out that the long-term results do not weaken the main trial result. Long-term adherence was not part of the trial design.
“After the trial, we were no longer treating these participants, so it was up to them and their primary care providers to decide on blood pressure goals,” he noted in an interview. Based on the trajectory of benefit when the study was stopped, “it is possible longer intensive treatment may lead to more benefit and some long-term residual benefits.”
The senior author of this most recent analysis, Nicholas M. Pajewski, PhD, associate professor of biostatistics and data science, Wake Forest University, Winston-Salem, N.C., generally agreed. However, he pointed out that the most recent data do not rule out meaningful benefit after the study ended.
For one reason, the loss of the SBP advantage was gradual so that median SBP levels of the two groups did not meet for nearly 3 years. This likely explains why there was still an attenuation of CVD mortality for several years after the all-cause mortality benefit was lost, according to Dr. Pajewski.
“It is important to mention that we were not able to assess nonfatal cardiovascular events, so while the two groups do eventually come together, if one thinks about the distinction of healthspan versus lifespan, there was probably residual benefit in terms of delaying CVD morbidity and mortality,” Dr. Pajewski said.
In SPRINT, CVD mortality reduced 43%
In the 9,631-patient SPRINT trial, the intensive treatment group achieved a mean SBP of 121.4 mm Hg versus 136.2 mm Hg in the standard treatment group at the end of 1 year. The trial was stopped early after 3.26 years because of strength of the benefit in the intensive treatment arm. At that time, the reductions by hazard ratio were 25% (HR, 0.75; P < .001) for a composite major adverse cardiovascular event (MACE) endpoint, 43% for CVD mortality (P = .005), and 27% for all-cause mortality (P = .003).
In the new observational follow-up, mortality data were drawn from the National Death Index, and change in SBP from electronic health records in a subset of 2,944 SPRINT trial participants. Data were available and analyzed through 2020.
The newly published long-term observational analysis showed that the median SBP in the intensive treatment arm was already climbing by the end of the end of the trial. It reached 132.8 mm Hg at 5 years after randomization and then 140.4 mm Hg by 10 years.
This latter figure was essentially equivalent to the SBP among those who were initially randomized to the standard treatment arm.
Factors driving rising BP are unclear
There is limited information on what medications were taken by either group following the end of the trial, so the reason for the regression in the intensive treatment arm after leaving the trial is unknown. The authors speculated that this might have been due to therapeutic inertia among treating physicians, poor adherence among patients, the difficulty of keeping blood pressures low in patients with advancing pathology, or some combination of these.
“Perhaps the most important reason was that providers and patients were not aiming for the lower goals since guidelines did not recommend these targets until 2017,” Dr. Cushman pointed out. He noted that Healthcare Effectiveness Data and Information Set (HEDIS) “has still not adopted a performance measure goal of less than 140 mm Hg.”
In an accompanying editorial, the authors focused on what these data mean for population-based strategies to achieve sustained control of one of the most important risk factors for cardiovascular events. Led by Daniel W. Jones, MD, director of clinical and population science, University of Mississippi, Jackson, the authors of the editorial wrote that these data emphasized “the challenge of achieving sustained intensive BP reductions in the real-world setting.”
Basically, the editorial concluded that current approaches to achieving meaningful and sustained blood pressure control are not working.
This study “should be a wakeup call, but other previously published good data have also been ignored,” said Dr. Jones in an interview. Despite the compelling benefit from intensive blood pressure control the SPRINT trial, the observational follow-up emphasizes the difficulty of maintaining the rigorous reductions in blood pressure needed for sustained protection.
“Systemic change is necessary,” said Dr. Jones, reprising the major thrust of the editorial he wrote with Donald Clark III, MD, and Michael E. Hall, MD, who are both colleagues at the University of Mississippi.
“My view is that health care providers should be held responsible for motivating better compliance of their patients, just as a teacher is accountable for the outcomes of their students,” he said.
The solutions are not likely to be simple. Dr. Jones called for multiple strategies, such as employing telehealth and community health workers to monitor and reinforce blood pressure control, but he said that these and other data have convinced him that “simply trying harder at what we currently do” is not enough.
Dr. Pajewski and Dr. Jones report no potential conflicts of interest. Dr. Cushman reports a financial relationship with ReCor.
FROM JAMA CARDIOLOGY
Trial of early intensive meds at HF discharge halted for benefit: STRONG-HF
A “high-intensity-care” strategy based on early and rapid uptitration of guideline-directed meds improves postdischarge clinical outcomes for patients hospitalized with decompensated heart failure (HF), suggest topline results from a randomized trial.
The STRONG-HF study was halted early on recommendation from its data safety monitoring board after an interim analysis suggested the high-intensity-care strategy significantly cut risk of death or HF readmission, compared with a standard-of-care approach.
The trial termination was announced in a press release from one of its sponsors, The Heart Initiative, a nonprofit organization. STRONG-HF was also supported by Roche Diagnostics.
The early termination was based on interim data from the approximately 1,000 patients, out of an estimated planned enrollment of 1,800, who had been followed for at least 90 days. The study’s actual primary endpoint had been defined by death or HF readmission at 6 months.
The announcement did not include outcomes data or P values, or any other indication of the magnitude of benefit from the high-intensity-care approach.
Patients in STRONG-HF who had been assigned to a high-intensity-care strategy had been started in-hospital on a beta blocker, a renin-angiotensin system inhibitor (RASi), and a mineralocorticoid receptor blocker (MRA) with dosages uptitrated at least halfway by the time of discharge.
The meds were uptitrated fully within 2 weeks of discharge guided by clinical and biomarker assessments, especially natriuretic peptides, at frequent postdischarge visits, the press release states.
Patients conducted “safety visits 1 week after any uptitration and follow-up visits at 6 weeks and 3 months,” the announcement notes. “At each visit, patients were assessed by physical examination for congestion and blood tests, including NT-proBNP measurements.”
The “full STRONG-HF trial results” are scheduled for presentation at the American Heart Association annual scientific sessions, the announcement states.
STRONG-HF is sponsored by The Heart Initiative and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
A “high-intensity-care” strategy based on early and rapid uptitration of guideline-directed meds improves postdischarge clinical outcomes for patients hospitalized with decompensated heart failure (HF), suggest topline results from a randomized trial.
The STRONG-HF study was halted early on recommendation from its data safety monitoring board after an interim analysis suggested the high-intensity-care strategy significantly cut risk of death or HF readmission, compared with a standard-of-care approach.
The trial termination was announced in a press release from one of its sponsors, The Heart Initiative, a nonprofit organization. STRONG-HF was also supported by Roche Diagnostics.
The early termination was based on interim data from the approximately 1,000 patients, out of an estimated planned enrollment of 1,800, who had been followed for at least 90 days. The study’s actual primary endpoint had been defined by death or HF readmission at 6 months.
The announcement did not include outcomes data or P values, or any other indication of the magnitude of benefit from the high-intensity-care approach.
Patients in STRONG-HF who had been assigned to a high-intensity-care strategy had been started in-hospital on a beta blocker, a renin-angiotensin system inhibitor (RASi), and a mineralocorticoid receptor blocker (MRA) with dosages uptitrated at least halfway by the time of discharge.
The meds were uptitrated fully within 2 weeks of discharge guided by clinical and biomarker assessments, especially natriuretic peptides, at frequent postdischarge visits, the press release states.
Patients conducted “safety visits 1 week after any uptitration and follow-up visits at 6 weeks and 3 months,” the announcement notes. “At each visit, patients were assessed by physical examination for congestion and blood tests, including NT-proBNP measurements.”
The “full STRONG-HF trial results” are scheduled for presentation at the American Heart Association annual scientific sessions, the announcement states.
STRONG-HF is sponsored by The Heart Initiative and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
A “high-intensity-care” strategy based on early and rapid uptitration of guideline-directed meds improves postdischarge clinical outcomes for patients hospitalized with decompensated heart failure (HF), suggest topline results from a randomized trial.
The STRONG-HF study was halted early on recommendation from its data safety monitoring board after an interim analysis suggested the high-intensity-care strategy significantly cut risk of death or HF readmission, compared with a standard-of-care approach.
The trial termination was announced in a press release from one of its sponsors, The Heart Initiative, a nonprofit organization. STRONG-HF was also supported by Roche Diagnostics.
The early termination was based on interim data from the approximately 1,000 patients, out of an estimated planned enrollment of 1,800, who had been followed for at least 90 days. The study’s actual primary endpoint had been defined by death or HF readmission at 6 months.
The announcement did not include outcomes data or P values, or any other indication of the magnitude of benefit from the high-intensity-care approach.
Patients in STRONG-HF who had been assigned to a high-intensity-care strategy had been started in-hospital on a beta blocker, a renin-angiotensin system inhibitor (RASi), and a mineralocorticoid receptor blocker (MRA) with dosages uptitrated at least halfway by the time of discharge.
The meds were uptitrated fully within 2 weeks of discharge guided by clinical and biomarker assessments, especially natriuretic peptides, at frequent postdischarge visits, the press release states.
Patients conducted “safety visits 1 week after any uptitration and follow-up visits at 6 weeks and 3 months,” the announcement notes. “At each visit, patients were assessed by physical examination for congestion and blood tests, including NT-proBNP measurements.”
The “full STRONG-HF trial results” are scheduled for presentation at the American Heart Association annual scientific sessions, the announcement states.
STRONG-HF is sponsored by The Heart Initiative and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
AHA pens roadmap to more patient-focused care for PAD
Patient-reported symptoms and quality of life should guide treatment for the roughly 8.5 million people in the United States living with peripheral artery disease (PAD), the American Heart Association said in a new scientific statement released Oct. 13.
“The person living with PAD is the authority on the impact it has on their daily life. Our treatment must be grounded in their lived experiences and go beyond the clinical measures of how well blood flows through the arteries,” Kim G. Smolderen, PhD, lead author of the statement writing group, says in a release.
“We have spent years developing and validating standardized instruments to capture people’s experiences in a reliable and sensitive way. We are now at a point where we can start integrating this information into real-world care, through pilot programs that can develop quality benchmarks for different phenotypes of patients with PAD and the types of treatments they undergo, as seen from their perspective,” adds Dr. Smolderen, co-director of the Vascular Medicine Outcomes Research (VAMOS) lab at Yale University, New Haven, Conn.
The statement, “Advancing Peripheral Artery Disease Quality of Care and Outcomes Through Patient-Reported Health Status Assessment,” is published online in Circulation.
It comes on the heels of a 2021 AHA statement urging greater attention to PAD, which is underdiagnosed and undertreated in the United States despite its high prevalence.
Fragmented care
Dr. Smolderen said that the multidisciplinary writing group was united in one overarching goal: “How can we disrupt the fragmented care model for PAD and make PAD care more accountable, value-based, and patient-centered?”
“True disruption is needed in a clinical space where the treatment of lower-extremity disease lies in the hands of many different specialties and variability in care and outcomes is a major concern,” Dr. Smolderen said.
The statement calls for improving and individualizing PAD care by gathering feedback from their experience through treatment using systematic and validated patient-reported outcome measures (PROMs).
PROMs for PAD include the Walking Impairment Questionnaire (WIQ), the Vascular Quality of Life Questionnaire (VascuQoL), and Peripheral Artery Questionnaire (PAQ).
Accountability tied to reimbursement
Dr. Smolderen noted that PROMs are increasingly being integrated into definitions of what it means to deliver high-quality, patient-centered care, and PROMs scores may directly impact reimbursement.
“Using a template that has been implemented in other medical conditions, we propose a shift in metrics that will tell us whether high-quality PAD care has been delivered from a patients’ perspective,” Dr. Smolderen told this news organization.
That is, “have we been able to improve the health status of that person’s life? We may have removed the blockage in the arteries, but will the patient feel that this intervention has addressed their PAD-specific health status goals?”
To facilitate accountability in quality PAD care, the writing group calls for developing, testing, and implementing PAD-specific patient-reported outcomes performance measures – or PRO-PMs.
Pilot efforts demonstrating feasibility of PRO-PMs in various practice settings are needed, as is implementation research evaluating the integration of PRO-PMs and pragmatic clinical trial evidence to demonstrate efficacy of the use of PROs in real world care settings to improve overall PAD outcomes, the writing group says.
“Following that experience and data, we believe value-based models can be proposed integrating PRO information that will affect accountability in PAD care and may ultimately affect reimbursement,” Dr. Smolderen said.
“Adoption of this new paradigm will further improve the quality of care for PAD and will put the patient front and center, as an agent in their care,” she added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Peripheral Vascular Disease and the Council on Lifestyle and Cardiometabolic Health. The writing group includes a patient advocate and experts in clinical psychology, outcomes research, nursing, cardiology, vascular surgery, and vascular medicine.
This research had no commercial funding. Dr. Smolderen has disclosed relationships with Optum, Abbott, Cook Medical, Happify, and Tegus.
A version of this article first appeared on Medscape.com.
Patient-reported symptoms and quality of life should guide treatment for the roughly 8.5 million people in the United States living with peripheral artery disease (PAD), the American Heart Association said in a new scientific statement released Oct. 13.
“The person living with PAD is the authority on the impact it has on their daily life. Our treatment must be grounded in their lived experiences and go beyond the clinical measures of how well blood flows through the arteries,” Kim G. Smolderen, PhD, lead author of the statement writing group, says in a release.
“We have spent years developing and validating standardized instruments to capture people’s experiences in a reliable and sensitive way. We are now at a point where we can start integrating this information into real-world care, through pilot programs that can develop quality benchmarks for different phenotypes of patients with PAD and the types of treatments they undergo, as seen from their perspective,” adds Dr. Smolderen, co-director of the Vascular Medicine Outcomes Research (VAMOS) lab at Yale University, New Haven, Conn.
The statement, “Advancing Peripheral Artery Disease Quality of Care and Outcomes Through Patient-Reported Health Status Assessment,” is published online in Circulation.
It comes on the heels of a 2021 AHA statement urging greater attention to PAD, which is underdiagnosed and undertreated in the United States despite its high prevalence.
Fragmented care
Dr. Smolderen said that the multidisciplinary writing group was united in one overarching goal: “How can we disrupt the fragmented care model for PAD and make PAD care more accountable, value-based, and patient-centered?”
“True disruption is needed in a clinical space where the treatment of lower-extremity disease lies in the hands of many different specialties and variability in care and outcomes is a major concern,” Dr. Smolderen said.
The statement calls for improving and individualizing PAD care by gathering feedback from their experience through treatment using systematic and validated patient-reported outcome measures (PROMs).
PROMs for PAD include the Walking Impairment Questionnaire (WIQ), the Vascular Quality of Life Questionnaire (VascuQoL), and Peripheral Artery Questionnaire (PAQ).
Accountability tied to reimbursement
Dr. Smolderen noted that PROMs are increasingly being integrated into definitions of what it means to deliver high-quality, patient-centered care, and PROMs scores may directly impact reimbursement.
“Using a template that has been implemented in other medical conditions, we propose a shift in metrics that will tell us whether high-quality PAD care has been delivered from a patients’ perspective,” Dr. Smolderen told this news organization.
That is, “have we been able to improve the health status of that person’s life? We may have removed the blockage in the arteries, but will the patient feel that this intervention has addressed their PAD-specific health status goals?”
To facilitate accountability in quality PAD care, the writing group calls for developing, testing, and implementing PAD-specific patient-reported outcomes performance measures – or PRO-PMs.
Pilot efforts demonstrating feasibility of PRO-PMs in various practice settings are needed, as is implementation research evaluating the integration of PRO-PMs and pragmatic clinical trial evidence to demonstrate efficacy of the use of PROs in real world care settings to improve overall PAD outcomes, the writing group says.
“Following that experience and data, we believe value-based models can be proposed integrating PRO information that will affect accountability in PAD care and may ultimately affect reimbursement,” Dr. Smolderen said.
“Adoption of this new paradigm will further improve the quality of care for PAD and will put the patient front and center, as an agent in their care,” she added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Peripheral Vascular Disease and the Council on Lifestyle and Cardiometabolic Health. The writing group includes a patient advocate and experts in clinical psychology, outcomes research, nursing, cardiology, vascular surgery, and vascular medicine.
This research had no commercial funding. Dr. Smolderen has disclosed relationships with Optum, Abbott, Cook Medical, Happify, and Tegus.
A version of this article first appeared on Medscape.com.
Patient-reported symptoms and quality of life should guide treatment for the roughly 8.5 million people in the United States living with peripheral artery disease (PAD), the American Heart Association said in a new scientific statement released Oct. 13.
“The person living with PAD is the authority on the impact it has on their daily life. Our treatment must be grounded in their lived experiences and go beyond the clinical measures of how well blood flows through the arteries,” Kim G. Smolderen, PhD, lead author of the statement writing group, says in a release.
“We have spent years developing and validating standardized instruments to capture people’s experiences in a reliable and sensitive way. We are now at a point where we can start integrating this information into real-world care, through pilot programs that can develop quality benchmarks for different phenotypes of patients with PAD and the types of treatments they undergo, as seen from their perspective,” adds Dr. Smolderen, co-director of the Vascular Medicine Outcomes Research (VAMOS) lab at Yale University, New Haven, Conn.
The statement, “Advancing Peripheral Artery Disease Quality of Care and Outcomes Through Patient-Reported Health Status Assessment,” is published online in Circulation.
It comes on the heels of a 2021 AHA statement urging greater attention to PAD, which is underdiagnosed and undertreated in the United States despite its high prevalence.
Fragmented care
Dr. Smolderen said that the multidisciplinary writing group was united in one overarching goal: “How can we disrupt the fragmented care model for PAD and make PAD care more accountable, value-based, and patient-centered?”
“True disruption is needed in a clinical space where the treatment of lower-extremity disease lies in the hands of many different specialties and variability in care and outcomes is a major concern,” Dr. Smolderen said.
The statement calls for improving and individualizing PAD care by gathering feedback from their experience through treatment using systematic and validated patient-reported outcome measures (PROMs).
PROMs for PAD include the Walking Impairment Questionnaire (WIQ), the Vascular Quality of Life Questionnaire (VascuQoL), and Peripheral Artery Questionnaire (PAQ).
Accountability tied to reimbursement
Dr. Smolderen noted that PROMs are increasingly being integrated into definitions of what it means to deliver high-quality, patient-centered care, and PROMs scores may directly impact reimbursement.
“Using a template that has been implemented in other medical conditions, we propose a shift in metrics that will tell us whether high-quality PAD care has been delivered from a patients’ perspective,” Dr. Smolderen told this news organization.
That is, “have we been able to improve the health status of that person’s life? We may have removed the blockage in the arteries, but will the patient feel that this intervention has addressed their PAD-specific health status goals?”
To facilitate accountability in quality PAD care, the writing group calls for developing, testing, and implementing PAD-specific patient-reported outcomes performance measures – or PRO-PMs.
Pilot efforts demonstrating feasibility of PRO-PMs in various practice settings are needed, as is implementation research evaluating the integration of PRO-PMs and pragmatic clinical trial evidence to demonstrate efficacy of the use of PROs in real world care settings to improve overall PAD outcomes, the writing group says.
“Following that experience and data, we believe value-based models can be proposed integrating PRO information that will affect accountability in PAD care and may ultimately affect reimbursement,” Dr. Smolderen said.
“Adoption of this new paradigm will further improve the quality of care for PAD and will put the patient front and center, as an agent in their care,” she added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Peripheral Vascular Disease and the Council on Lifestyle and Cardiometabolic Health. The writing group includes a patient advocate and experts in clinical psychology, outcomes research, nursing, cardiology, vascular surgery, and vascular medicine.
This research had no commercial funding. Dr. Smolderen has disclosed relationships with Optum, Abbott, Cook Medical, Happify, and Tegus.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
Athletes with mild HCM can likely continue competitive sports
Athletes with mild hypertrophic cardiomyopathy (HCM) at low risk of sudden cardiac death (SCD) can safely continue to exercise at competitive levels, a retrospective study suggests.
During a mean follow-up of 4.5 years, athletes who continued to engage in high-intensity competitive sports after a mild HCM diagnosis were free of cardiac symptoms, and there were no deaths, incidents of sustained ventricular tachycardia or syncope, or changes in cardiac electrical, structural, or functional phenotypes.
“This study supports emerging evidence that HCM individuals with a low-risk profile and mild hypertrophy may engage in vigorous exercise and competitive sport,” Sanjay Sharma, MD, of St. George’s University of London, said in an interview. Current guidelines from the European Society of Cardiology and the American College of Cardiology support a more liberal approach to exercise for these individuals.
That said, he added, “it is important to emphasize that our cohort consisted of a group of adult competitive athletes who had probably been competing for several years before the diagnosis was made and therefore represented a self-selected, low-risk cohort. It is difficult to extrapolate this data to adolescent athletes, who appear to be more vulnerable to exercise-related SCD from HCM.”
The study was published online in the Journal of the American College of Cardiology.
Vigorous exercise OK for some
Dr. Sharma and colleagues analyzed data from 53 athletes with HCM who continued to participate in competitive sports. The mean age was 39 years, 98% were men, and 72% were White. About half (53%) competed as professionals, and were most commonly engaged in cycling, football, running, and rugby.
Participants underwent 6-12 monthly assessments that included electrocardiograms, echocardiograms, cardiopulmonary exercise testing, Holter monitoring (≥ 24 hours), and cardiac magnetic resonance imaging. A majority (64.2%) were evaluated because of an abnormal electrocardiograms, and one presented with an incidental abnormal echocardiogram.
About a quarter (24.5%) were symptomatic and 5 (9.4%) were identified on family screening. Eight (15%) had a family history of HCM, and six (11.3%) of SCD.
At the baseline evaluation, all athletes had a “low” ESC 5-year SCD risk score for HCM (1.9% ± 0.9%). None had syncope. Mean peak VO2 was 40.7 ± 6.8 mL/kg per minute.
The mean left ventricular wall thickness was 14.6 ± 2.3 mm; all had normal LV systolic and diastolic function and no LV outflow tract obstruction at rest or on provocation testing. In addition, none had an LV apical aneurysm.
Twenty-two (41%) showed late gadolinium enhancement on baseline cardiac magnetic resonance imaging.
A total of 19 participants underwent genotyping; 4 (21.1%) had a pathogenic/likely pathogenic sarcomeric variant. None took cardiovascular medication or had an implantable cardioverter defibrillator (ICD).
During a mean follow-up of 4.5 years, all participants continued to exercise at the same level as before their diagnosis; none underwent detraining. All stayed free of cardiac symptoms, and there were no deaths, sustained ventricular tachycardia episodes, or syncope.
Four demonstrated new, nonsustained ventricular tachycardia (NSVT) during follow-up, one of whom underwent ICD implantation because of an increased risk score and subsequently moderated exercise levels.
One participant had a 30-second atrial fibrillation (AFib) episode lasting longer than 30 seconds, started on a beta-blocker and oral anticoagulation, and also moderated exercise levels.
The event rate was 2.1% per year for asymptomatic arrhythmias (NSVT and AFib). No changes were observed in the cardiac electrical, structural, or functional phenotype during follow-up.
Dr. Sharma and colleagues stated: “Our sample size is small; however, it is nearly double the size of a previously studied Italian athletic cohort, and one-half were professional athletes. Furthermore, 17% of our cohort comprised Black athletes who are perceived to be at higher risk of SCD than White athletes.”
Daniele Massera, MD, assistant professor in the HCM program, department of medicine, Charney Division of Cardiology, New York University Langone Health, said in an interview: “Of note, these were athletes/patients at the very low end of phenotypic severity of HCM. ... It is also notable that diastolic function was normal in all of them, an uncommon finding in patients with HCM.”
Like Dr. Sharma, he said the findings are in line with recent guidelines, and cautioned: “This small study applies only to a very small subset of patients who are being evaluated at specialized HCM programs: asymptomatic male individuals who have mild, low-risk HCM and are on no medicines.
“The findings cannot be generalized to the population of symptomatic individuals with (or without) outflow obstruction, more severe hypertrophy, and who have ICDs and/or take medication for symptoms, nor to younger patients or adolescents, who may be at higher risk for adverse outcomes,” he concluded.
Individualized approach urged
Dr. Sharma was a coauthor of the recent article challenging the traditional restrictive approach to exercise for athletes diagnosed with HCM and other inherited cardiovascular diseases. The article suggested that individualized recommendations, taking risks into consideration, can help guide those who want to exercise or participate in competitive sports.
Dr. Sharma also is a coauthor of a 6-month follow-up to the SAFE-HCM study, which compared the effects of a supervised 12-week high-intensity exercise program to usual care in low-risk individuals with HCM (mean age, 45.7).
In the 6-month follow-up study, published as an abstract in the European Journal of Preventive Cardiology 2021 supplement, “exercising individuals had improved functional capacity and atherosclerotic risk profile and there were no differences in the composite safety outcomes [cardiovascular death, cardiac arrest, device therapy, exercise-induced syncope, sustained VT, NSVT, or sustained atrial arrhythmias] between exercising individuals and usual care individuals,” Dr. Sharma said.
The full study will soon be ready to submit for publication, he added.
No commercial funding or relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
Athletes with mild hypertrophic cardiomyopathy (HCM) at low risk of sudden cardiac death (SCD) can safely continue to exercise at competitive levels, a retrospective study suggests.
During a mean follow-up of 4.5 years, athletes who continued to engage in high-intensity competitive sports after a mild HCM diagnosis were free of cardiac symptoms, and there were no deaths, incidents of sustained ventricular tachycardia or syncope, or changes in cardiac electrical, structural, or functional phenotypes.
“This study supports emerging evidence that HCM individuals with a low-risk profile and mild hypertrophy may engage in vigorous exercise and competitive sport,” Sanjay Sharma, MD, of St. George’s University of London, said in an interview. Current guidelines from the European Society of Cardiology and the American College of Cardiology support a more liberal approach to exercise for these individuals.
That said, he added, “it is important to emphasize that our cohort consisted of a group of adult competitive athletes who had probably been competing for several years before the diagnosis was made and therefore represented a self-selected, low-risk cohort. It is difficult to extrapolate this data to adolescent athletes, who appear to be more vulnerable to exercise-related SCD from HCM.”
The study was published online in the Journal of the American College of Cardiology.
Vigorous exercise OK for some
Dr. Sharma and colleagues analyzed data from 53 athletes with HCM who continued to participate in competitive sports. The mean age was 39 years, 98% were men, and 72% were White. About half (53%) competed as professionals, and were most commonly engaged in cycling, football, running, and rugby.
Participants underwent 6-12 monthly assessments that included electrocardiograms, echocardiograms, cardiopulmonary exercise testing, Holter monitoring (≥ 24 hours), and cardiac magnetic resonance imaging. A majority (64.2%) were evaluated because of an abnormal electrocardiograms, and one presented with an incidental abnormal echocardiogram.
About a quarter (24.5%) were symptomatic and 5 (9.4%) were identified on family screening. Eight (15%) had a family history of HCM, and six (11.3%) of SCD.
At the baseline evaluation, all athletes had a “low” ESC 5-year SCD risk score for HCM (1.9% ± 0.9%). None had syncope. Mean peak VO2 was 40.7 ± 6.8 mL/kg per minute.
The mean left ventricular wall thickness was 14.6 ± 2.3 mm; all had normal LV systolic and diastolic function and no LV outflow tract obstruction at rest or on provocation testing. In addition, none had an LV apical aneurysm.
Twenty-two (41%) showed late gadolinium enhancement on baseline cardiac magnetic resonance imaging.
A total of 19 participants underwent genotyping; 4 (21.1%) had a pathogenic/likely pathogenic sarcomeric variant. None took cardiovascular medication or had an implantable cardioverter defibrillator (ICD).
During a mean follow-up of 4.5 years, all participants continued to exercise at the same level as before their diagnosis; none underwent detraining. All stayed free of cardiac symptoms, and there were no deaths, sustained ventricular tachycardia episodes, or syncope.
Four demonstrated new, nonsustained ventricular tachycardia (NSVT) during follow-up, one of whom underwent ICD implantation because of an increased risk score and subsequently moderated exercise levels.
One participant had a 30-second atrial fibrillation (AFib) episode lasting longer than 30 seconds, started on a beta-blocker and oral anticoagulation, and also moderated exercise levels.
The event rate was 2.1% per year for asymptomatic arrhythmias (NSVT and AFib). No changes were observed in the cardiac electrical, structural, or functional phenotype during follow-up.
Dr. Sharma and colleagues stated: “Our sample size is small; however, it is nearly double the size of a previously studied Italian athletic cohort, and one-half were professional athletes. Furthermore, 17% of our cohort comprised Black athletes who are perceived to be at higher risk of SCD than White athletes.”
Daniele Massera, MD, assistant professor in the HCM program, department of medicine, Charney Division of Cardiology, New York University Langone Health, said in an interview: “Of note, these were athletes/patients at the very low end of phenotypic severity of HCM. ... It is also notable that diastolic function was normal in all of them, an uncommon finding in patients with HCM.”
Like Dr. Sharma, he said the findings are in line with recent guidelines, and cautioned: “This small study applies only to a very small subset of patients who are being evaluated at specialized HCM programs: asymptomatic male individuals who have mild, low-risk HCM and are on no medicines.
“The findings cannot be generalized to the population of symptomatic individuals with (or without) outflow obstruction, more severe hypertrophy, and who have ICDs and/or take medication for symptoms, nor to younger patients or adolescents, who may be at higher risk for adverse outcomes,” he concluded.
Individualized approach urged
Dr. Sharma was a coauthor of the recent article challenging the traditional restrictive approach to exercise for athletes diagnosed with HCM and other inherited cardiovascular diseases. The article suggested that individualized recommendations, taking risks into consideration, can help guide those who want to exercise or participate in competitive sports.
Dr. Sharma also is a coauthor of a 6-month follow-up to the SAFE-HCM study, which compared the effects of a supervised 12-week high-intensity exercise program to usual care in low-risk individuals with HCM (mean age, 45.7).
In the 6-month follow-up study, published as an abstract in the European Journal of Preventive Cardiology 2021 supplement, “exercising individuals had improved functional capacity and atherosclerotic risk profile and there were no differences in the composite safety outcomes [cardiovascular death, cardiac arrest, device therapy, exercise-induced syncope, sustained VT, NSVT, or sustained atrial arrhythmias] between exercising individuals and usual care individuals,” Dr. Sharma said.
The full study will soon be ready to submit for publication, he added.
No commercial funding or relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
Athletes with mild hypertrophic cardiomyopathy (HCM) at low risk of sudden cardiac death (SCD) can safely continue to exercise at competitive levels, a retrospective study suggests.
During a mean follow-up of 4.5 years, athletes who continued to engage in high-intensity competitive sports after a mild HCM diagnosis were free of cardiac symptoms, and there were no deaths, incidents of sustained ventricular tachycardia or syncope, or changes in cardiac electrical, structural, or functional phenotypes.
“This study supports emerging evidence that HCM individuals with a low-risk profile and mild hypertrophy may engage in vigorous exercise and competitive sport,” Sanjay Sharma, MD, of St. George’s University of London, said in an interview. Current guidelines from the European Society of Cardiology and the American College of Cardiology support a more liberal approach to exercise for these individuals.
That said, he added, “it is important to emphasize that our cohort consisted of a group of adult competitive athletes who had probably been competing for several years before the diagnosis was made and therefore represented a self-selected, low-risk cohort. It is difficult to extrapolate this data to adolescent athletes, who appear to be more vulnerable to exercise-related SCD from HCM.”
The study was published online in the Journal of the American College of Cardiology.
Vigorous exercise OK for some
Dr. Sharma and colleagues analyzed data from 53 athletes with HCM who continued to participate in competitive sports. The mean age was 39 years, 98% were men, and 72% were White. About half (53%) competed as professionals, and were most commonly engaged in cycling, football, running, and rugby.
Participants underwent 6-12 monthly assessments that included electrocardiograms, echocardiograms, cardiopulmonary exercise testing, Holter monitoring (≥ 24 hours), and cardiac magnetic resonance imaging. A majority (64.2%) were evaluated because of an abnormal electrocardiograms, and one presented with an incidental abnormal echocardiogram.
About a quarter (24.5%) were symptomatic and 5 (9.4%) were identified on family screening. Eight (15%) had a family history of HCM, and six (11.3%) of SCD.
At the baseline evaluation, all athletes had a “low” ESC 5-year SCD risk score for HCM (1.9% ± 0.9%). None had syncope. Mean peak VO2 was 40.7 ± 6.8 mL/kg per minute.
The mean left ventricular wall thickness was 14.6 ± 2.3 mm; all had normal LV systolic and diastolic function and no LV outflow tract obstruction at rest or on provocation testing. In addition, none had an LV apical aneurysm.
Twenty-two (41%) showed late gadolinium enhancement on baseline cardiac magnetic resonance imaging.
A total of 19 participants underwent genotyping; 4 (21.1%) had a pathogenic/likely pathogenic sarcomeric variant. None took cardiovascular medication or had an implantable cardioverter defibrillator (ICD).
During a mean follow-up of 4.5 years, all participants continued to exercise at the same level as before their diagnosis; none underwent detraining. All stayed free of cardiac symptoms, and there were no deaths, sustained ventricular tachycardia episodes, or syncope.
Four demonstrated new, nonsustained ventricular tachycardia (NSVT) during follow-up, one of whom underwent ICD implantation because of an increased risk score and subsequently moderated exercise levels.
One participant had a 30-second atrial fibrillation (AFib) episode lasting longer than 30 seconds, started on a beta-blocker and oral anticoagulation, and also moderated exercise levels.
The event rate was 2.1% per year for asymptomatic arrhythmias (NSVT and AFib). No changes were observed in the cardiac electrical, structural, or functional phenotype during follow-up.
Dr. Sharma and colleagues stated: “Our sample size is small; however, it is nearly double the size of a previously studied Italian athletic cohort, and one-half were professional athletes. Furthermore, 17% of our cohort comprised Black athletes who are perceived to be at higher risk of SCD than White athletes.”
Daniele Massera, MD, assistant professor in the HCM program, department of medicine, Charney Division of Cardiology, New York University Langone Health, said in an interview: “Of note, these were athletes/patients at the very low end of phenotypic severity of HCM. ... It is also notable that diastolic function was normal in all of them, an uncommon finding in patients with HCM.”
Like Dr. Sharma, he said the findings are in line with recent guidelines, and cautioned: “This small study applies only to a very small subset of patients who are being evaluated at specialized HCM programs: asymptomatic male individuals who have mild, low-risk HCM and are on no medicines.
“The findings cannot be generalized to the population of symptomatic individuals with (or without) outflow obstruction, more severe hypertrophy, and who have ICDs and/or take medication for symptoms, nor to younger patients or adolescents, who may be at higher risk for adverse outcomes,” he concluded.
Individualized approach urged
Dr. Sharma was a coauthor of the recent article challenging the traditional restrictive approach to exercise for athletes diagnosed with HCM and other inherited cardiovascular diseases. The article suggested that individualized recommendations, taking risks into consideration, can help guide those who want to exercise or participate in competitive sports.
Dr. Sharma also is a coauthor of a 6-month follow-up to the SAFE-HCM study, which compared the effects of a supervised 12-week high-intensity exercise program to usual care in low-risk individuals with HCM (mean age, 45.7).
In the 6-month follow-up study, published as an abstract in the European Journal of Preventive Cardiology 2021 supplement, “exercising individuals had improved functional capacity and atherosclerotic risk profile and there were no differences in the composite safety outcomes [cardiovascular death, cardiac arrest, device therapy, exercise-induced syncope, sustained VT, NSVT, or sustained atrial arrhythmias] between exercising individuals and usual care individuals,” Dr. Sharma said.
The full study will soon be ready to submit for publication, he added.
No commercial funding or relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Novel head-up CPR position raises odds of survival of out-of-hospital heart attacks
Individuals who experience out-of-hospital cardiac arrest (OHCA) with nonshockable presentations have a better chance of survival when first responders use a novel CPR approach that includes gradual head-up positioning combined with basic but effective circulation-enhancing adjuncts, as shown from data from more than 2,000 patients.
In a study presented at the annual meeting of the American College of Emergency Physicians, Paul Pepe, MD, medical director for Dallas County Emergency Medical Services, reviewed data from five EMS systems that had adopted the new approach. Data were collected prospectively over the past 2 years from a national registry of patients who had received what Dr. Pepe called a “neuroprotective CPR bundle” (NP-CPR).
The study compared 380 NP-CPR case patients to 1,852 control patients who had received conventional CPR. Control data came from high-performance EMS systems that had participated in well-monitored, published OHCA trials funded by the National Institutes of Health. The primary outcome that was used for comparison was successful survival to hospital discharge with neurologically intact status (SURV-NI).
Traditional CPR supine chest compression techniques, if performed early and properly, can be lifesaving, but they are suboptimal, Dr. Pepe said. “Current techniques create pressure waves that run up the arterial side, but they also create back-pressure on the venous side, increasing intracranial pressure (ICP), thus compromising optimal cerebral blood flow,” he told this news organization.
For that reason, a modified physiologic approach to CPR was designed. It involves an airway adjunct called an impedance threshold device (ITD) and active compression-decompression (ACD) with a device “resembling a toilet plunger,” Dr. Pepe said.
The devices draw more blood out of the brain and into the thorax in a complementary fashion. The combination of these two adjuncts had dramatically improved SURV-NI by 50% in a clinical trial, Dr. Pepe said.
The new technology uses automated gradual head-up/torso-up positioning (AHUP) after first “priming the pump” with ITD-ACD–enhanced circulation. It was found to markedly augment that effect even further. In the laboratory setting, this synergistic NP-CPR bundle has been shown to help normalize cerebral perfusion pressure, further promoting neuro-intact survival. Normalization of end-tidal CO2 is routinely observed, according to Dr. Pepe.
In contrast to patients who present with ventricular fibrillation (shockable cases), patients with nonshockable presentations always have had grim prognoses, Dr. Pepe said. Until now, lifesaving advances had not been found, despite the fact that nonshockable presentations (asystole or electrical activity with no pulse) constitute approximately 80% of OHCA cases, or about 250,000 to 300,00 cases a year in the United States, he said.
In the study, approximately 60% of both the NP-CPR patients and control patients had asystole (flatline) presentations. The NP-CPR group had a significant threefold improvement in SURV-NI, compared with patients treated with conventional CPR in the high-functioning systems (odds ratio, 3.09). In a propensity-scored analysis matching all variables known to affect outcome, the OR increased to nearly fourfold higher (OR, 3.87; 95% confidence interval, 1.27-11.78), Dr. Pepe said.
The researchers also found that the time from receipt of a 911 call to initiation of AHUP was associated with progressively higher chances of survival. The median time for application was 11 minutes; when the elapsed time was less than 11 minutes, the SURV-NI was nearly 11-fold higher for NP-CPR patients than for control patients (OR, 10.59), with survival chances of 6% versus 0.5%. ORs were even higher when the time to treatment was less than 16 minutes (OR, 13.58), with survival rates of 5% versus 0.4%.
The findings not only demonstrate proof of concept in these most futile cases but also that implementation is feasible for the majority of patients, considering that the median time to the start of any CPR by a first responder was 8 minutes for both NP-CPR patients and control patients, “let alone 11 minutes for the AHUP initiation,” Dr. Pepe said. “This finally gives some hope for these nonshockable cases,” he emphasized.
“All of these devices have now been cleared by the Food and Drug Administration and should be adopted by all first-in responders,” said Dr. Pepe. “But they should be implemented as a bundle and in the proper sequence and as soon as feasible.”
Training and implementation efforts continue to expand, and more lives can be saved as more firefighters and first-in response teams acquire equipment and training, which can cut the time to response, he said.
The registry will continue to monitor outcomes with NP-CPR – the term was suggested by a patient who survived through this new approach – and Dr. Pepe and colleagues expect the statistics to improve further with wider adoption and faster implementation with the fastest responders.
A recent study by Dr. Pepe’s team, published in Resuscitation, showed the effectiveness of the neuroprotective bundle in improving survival for OHCA patients overall. The current study confirmed its impact on neuro-intact survival for the subgroup of patients with nonshockable cases.
One other take-home message is that head-up CPR cannot yet be performed by lay bystanders. “Also, do not implement this unless you are going to do it right,” Dr. Pepe emphasized in an interview.
Advanced CPR Solutions provided some materials and research funding for an independent data collector. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
Individuals who experience out-of-hospital cardiac arrest (OHCA) with nonshockable presentations have a better chance of survival when first responders use a novel CPR approach that includes gradual head-up positioning combined with basic but effective circulation-enhancing adjuncts, as shown from data from more than 2,000 patients.
In a study presented at the annual meeting of the American College of Emergency Physicians, Paul Pepe, MD, medical director for Dallas County Emergency Medical Services, reviewed data from five EMS systems that had adopted the new approach. Data were collected prospectively over the past 2 years from a national registry of patients who had received what Dr. Pepe called a “neuroprotective CPR bundle” (NP-CPR).
The study compared 380 NP-CPR case patients to 1,852 control patients who had received conventional CPR. Control data came from high-performance EMS systems that had participated in well-monitored, published OHCA trials funded by the National Institutes of Health. The primary outcome that was used for comparison was successful survival to hospital discharge with neurologically intact status (SURV-NI).
Traditional CPR supine chest compression techniques, if performed early and properly, can be lifesaving, but they are suboptimal, Dr. Pepe said. “Current techniques create pressure waves that run up the arterial side, but they also create back-pressure on the venous side, increasing intracranial pressure (ICP), thus compromising optimal cerebral blood flow,” he told this news organization.
For that reason, a modified physiologic approach to CPR was designed. It involves an airway adjunct called an impedance threshold device (ITD) and active compression-decompression (ACD) with a device “resembling a toilet plunger,” Dr. Pepe said.
The devices draw more blood out of the brain and into the thorax in a complementary fashion. The combination of these two adjuncts had dramatically improved SURV-NI by 50% in a clinical trial, Dr. Pepe said.
The new technology uses automated gradual head-up/torso-up positioning (AHUP) after first “priming the pump” with ITD-ACD–enhanced circulation. It was found to markedly augment that effect even further. In the laboratory setting, this synergistic NP-CPR bundle has been shown to help normalize cerebral perfusion pressure, further promoting neuro-intact survival. Normalization of end-tidal CO2 is routinely observed, according to Dr. Pepe.
In contrast to patients who present with ventricular fibrillation (shockable cases), patients with nonshockable presentations always have had grim prognoses, Dr. Pepe said. Until now, lifesaving advances had not been found, despite the fact that nonshockable presentations (asystole or electrical activity with no pulse) constitute approximately 80% of OHCA cases, or about 250,000 to 300,00 cases a year in the United States, he said.
In the study, approximately 60% of both the NP-CPR patients and control patients had asystole (flatline) presentations. The NP-CPR group had a significant threefold improvement in SURV-NI, compared with patients treated with conventional CPR in the high-functioning systems (odds ratio, 3.09). In a propensity-scored analysis matching all variables known to affect outcome, the OR increased to nearly fourfold higher (OR, 3.87; 95% confidence interval, 1.27-11.78), Dr. Pepe said.
The researchers also found that the time from receipt of a 911 call to initiation of AHUP was associated with progressively higher chances of survival. The median time for application was 11 minutes; when the elapsed time was less than 11 minutes, the SURV-NI was nearly 11-fold higher for NP-CPR patients than for control patients (OR, 10.59), with survival chances of 6% versus 0.5%. ORs were even higher when the time to treatment was less than 16 minutes (OR, 13.58), with survival rates of 5% versus 0.4%.
The findings not only demonstrate proof of concept in these most futile cases but also that implementation is feasible for the majority of patients, considering that the median time to the start of any CPR by a first responder was 8 minutes for both NP-CPR patients and control patients, “let alone 11 minutes for the AHUP initiation,” Dr. Pepe said. “This finally gives some hope for these nonshockable cases,” he emphasized.
“All of these devices have now been cleared by the Food and Drug Administration and should be adopted by all first-in responders,” said Dr. Pepe. “But they should be implemented as a bundle and in the proper sequence and as soon as feasible.”
Training and implementation efforts continue to expand, and more lives can be saved as more firefighters and first-in response teams acquire equipment and training, which can cut the time to response, he said.
The registry will continue to monitor outcomes with NP-CPR – the term was suggested by a patient who survived through this new approach – and Dr. Pepe and colleagues expect the statistics to improve further with wider adoption and faster implementation with the fastest responders.
A recent study by Dr. Pepe’s team, published in Resuscitation, showed the effectiveness of the neuroprotective bundle in improving survival for OHCA patients overall. The current study confirmed its impact on neuro-intact survival for the subgroup of patients with nonshockable cases.
One other take-home message is that head-up CPR cannot yet be performed by lay bystanders. “Also, do not implement this unless you are going to do it right,” Dr. Pepe emphasized in an interview.
Advanced CPR Solutions provided some materials and research funding for an independent data collector. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
Individuals who experience out-of-hospital cardiac arrest (OHCA) with nonshockable presentations have a better chance of survival when first responders use a novel CPR approach that includes gradual head-up positioning combined with basic but effective circulation-enhancing adjuncts, as shown from data from more than 2,000 patients.
In a study presented at the annual meeting of the American College of Emergency Physicians, Paul Pepe, MD, medical director for Dallas County Emergency Medical Services, reviewed data from five EMS systems that had adopted the new approach. Data were collected prospectively over the past 2 years from a national registry of patients who had received what Dr. Pepe called a “neuroprotective CPR bundle” (NP-CPR).
The study compared 380 NP-CPR case patients to 1,852 control patients who had received conventional CPR. Control data came from high-performance EMS systems that had participated in well-monitored, published OHCA trials funded by the National Institutes of Health. The primary outcome that was used for comparison was successful survival to hospital discharge with neurologically intact status (SURV-NI).
Traditional CPR supine chest compression techniques, if performed early and properly, can be lifesaving, but they are suboptimal, Dr. Pepe said. “Current techniques create pressure waves that run up the arterial side, but they also create back-pressure on the venous side, increasing intracranial pressure (ICP), thus compromising optimal cerebral blood flow,” he told this news organization.
For that reason, a modified physiologic approach to CPR was designed. It involves an airway adjunct called an impedance threshold device (ITD) and active compression-decompression (ACD) with a device “resembling a toilet plunger,” Dr. Pepe said.
The devices draw more blood out of the brain and into the thorax in a complementary fashion. The combination of these two adjuncts had dramatically improved SURV-NI by 50% in a clinical trial, Dr. Pepe said.
The new technology uses automated gradual head-up/torso-up positioning (AHUP) after first “priming the pump” with ITD-ACD–enhanced circulation. It was found to markedly augment that effect even further. In the laboratory setting, this synergistic NP-CPR bundle has been shown to help normalize cerebral perfusion pressure, further promoting neuro-intact survival. Normalization of end-tidal CO2 is routinely observed, according to Dr. Pepe.
In contrast to patients who present with ventricular fibrillation (shockable cases), patients with nonshockable presentations always have had grim prognoses, Dr. Pepe said. Until now, lifesaving advances had not been found, despite the fact that nonshockable presentations (asystole or electrical activity with no pulse) constitute approximately 80% of OHCA cases, or about 250,000 to 300,00 cases a year in the United States, he said.
In the study, approximately 60% of both the NP-CPR patients and control patients had asystole (flatline) presentations. The NP-CPR group had a significant threefold improvement in SURV-NI, compared with patients treated with conventional CPR in the high-functioning systems (odds ratio, 3.09). In a propensity-scored analysis matching all variables known to affect outcome, the OR increased to nearly fourfold higher (OR, 3.87; 95% confidence interval, 1.27-11.78), Dr. Pepe said.
The researchers also found that the time from receipt of a 911 call to initiation of AHUP was associated with progressively higher chances of survival. The median time for application was 11 minutes; when the elapsed time was less than 11 minutes, the SURV-NI was nearly 11-fold higher for NP-CPR patients than for control patients (OR, 10.59), with survival chances of 6% versus 0.5%. ORs were even higher when the time to treatment was less than 16 minutes (OR, 13.58), with survival rates of 5% versus 0.4%.
The findings not only demonstrate proof of concept in these most futile cases but also that implementation is feasible for the majority of patients, considering that the median time to the start of any CPR by a first responder was 8 minutes for both NP-CPR patients and control patients, “let alone 11 minutes for the AHUP initiation,” Dr. Pepe said. “This finally gives some hope for these nonshockable cases,” he emphasized.
“All of these devices have now been cleared by the Food and Drug Administration and should be adopted by all first-in responders,” said Dr. Pepe. “But they should be implemented as a bundle and in the proper sequence and as soon as feasible.”
Training and implementation efforts continue to expand, and more lives can be saved as more firefighters and first-in response teams acquire equipment and training, which can cut the time to response, he said.
The registry will continue to monitor outcomes with NP-CPR – the term was suggested by a patient who survived through this new approach – and Dr. Pepe and colleagues expect the statistics to improve further with wider adoption and faster implementation with the fastest responders.
A recent study by Dr. Pepe’s team, published in Resuscitation, showed the effectiveness of the neuroprotective bundle in improving survival for OHCA patients overall. The current study confirmed its impact on neuro-intact survival for the subgroup of patients with nonshockable cases.
One other take-home message is that head-up CPR cannot yet be performed by lay bystanders. “Also, do not implement this unless you are going to do it right,” Dr. Pepe emphasized in an interview.
Advanced CPR Solutions provided some materials and research funding for an independent data collector. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
FROM ACEP 2022