Heart Failure

CHICAGO – Black patients with heart failure with reduced ejection fraction (HFrEF) may receive more benefit from treatment with a sodium-glucose cotransporter-2 (SGLT2) inhibitor than do White patients, according to a new report.

A secondary analysis of data collected from the pivotal trials that assessed the SGLT2 inhibitor empagliflozin in patients with HFrEF, EMPEROR-Reduced, and in patients with heart failure with preserved ejection fraction (HFpEF), EMPEROR-Preserved, was presented by Subodh Verma, MD, PhD, at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The “hypothesis-generating” analysis of data from EMPEROR-Reduced showed “a suggestion of a greater benefit of empagliflozin” in Black, compared with White patients, for the study’s primary endpoint (cardiovascular death or hospitalization for heart failure) as well as for first and total hospitalizations for heart failure, he reported.

However, a similar but separate analysis that compared Black and White patients with heart failure who received treatment with a second agent, dapagliflozin, from the same SGLT2-inhibitor class did not show any suggestion of heterogeneity in the drug’s effect based on race.
 

Race-linked heterogeneity in empagliflozin’s effect

In EMPEROR-Reduced, which randomized 3,730 patients with heart failure and a left ventricular ejection fraction of 40% or less, treatment of White patients with empagliflozin (Jardiance) produced a nonsignificant 16% relative reduction in the rate of the primary endpoint, compared with placebo, during a median 16-month follow-up.

By contrast, among Black patients, treatment with empagliflozin produced a significant 56% reduction in the primary endpoint, compared with placebo-treated patients, a significant heterogeneity (P = .02) in effect between the two race subgroups, said Dr. Verma, a cardiac surgeon and professor at the University of Toronto.

The analysis he reported used combined data from EMPEROR-Reduced and the companion trial EMPEROR-Preserved, which randomized 5,988 patients with heart failure and a left ventricular ejection fraction greater than 40% to treatment with either empagliflozin or placebo and followed them for a median of 26 months.

To assess the effects of the randomized treatments in the two racial subgroups, Dr. Verma and associates used pooled data from both trials, but only from the 3,502 patients enrolled in the Americas, which included 3,024 White patients and 478 Black patients. Analysis of the patients in this subgroup who were randomized to placebo showed a significantly excess rate of the primary outcome among Blacks, who tallied 49% more of the primary outcome events during follow-up than did White patients, Dr. Verma reported. The absolute rate of the primary outcome without empagliflozin treatment was 13.15 events/100 patient-years of follow-up in White patients and 20.83 events/100 patient-years in Black patients.

The impact of empagliflozin was not statistically heterogeneous in the total pool of patients that included both those with HFrEF and those with HFpEF. The drug reduced the primary outcome incidence by a significant 20% in White patients, and by a significant 44% among Black patients.

But this point-estimate difference in efficacy, when coupled with the underlying difference in risk for an event between the two racial groups, meant that the number-needed-to-treat to prevent one primary outcome event was 42 among White patients and 12 among Black patients.
 

Race-linked treatment responses only in HFrEF

This suggestion of an imbalance in treatment efficacy was especially apparent among patients with HFrEF. In addition to the heterogeneity for the primary outcome, the Black and White subgroups also showed significantly divergent results for the outcomes of first hospitalization for heart failure, with a nonsignificant 21% relative reduction with empagliflozin treatment in Whites but a significant 65% relative cut in this endpoint with empagliflozin in Blacks, and for total hospitalizations for heart failure, which showed a similar level of significant heterogeneity between the two race subgroups.

In contrast, the patients with HFpEF showed no signal at all for heterogeneous outcome rates between Black and White subgroups.

One other study outcome, change in symptom burden measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed suggestion of a race-based imbalance. The adjusted mean difference from baseline in the KCCQ clinical summary score was 1.50 points higher with empagliflozin treatment, compared with placebo among all White patients (those with HFrEF and those with HFpEF), and compared with a 5.25-point increase with empagliflozin over placebo among all Black patients with heart failure in the pooled American EMPEROR dataset, a difference between White and Black patients that just missed significance (P = .06). Again, this difference was especially notable and significant among the patients with HFrEF, where the adjusted mean difference in KCCQ was a 0.77-point increase in White patients and a 6.71-point increase among Black patients (P = .043),

These results also appeared in a report published simultaneously with Dr. Verma’s talk.

But two other analyses that assessed a possible race-based difference in empagliflozin’s effect on renal protection and on functional status showed no suggestion of heterogeneity.

Dr. Verma stressed caution about the limitations of these analyses because they involved a relatively small number of Black patients, and were possibly subject to unadjusted confounding from differences in baseline characteristics between the Black and White patients.

Black patients also had a number-needed-to-treat advantage with dapagliflozin

The finding that Black patients with heart failure potentially get more bang for the buck from treatment with an SGLT2 inhibitor by having a lower number needed to treat also showed up in a separate report at the meeting that assessed the treatment effect from dapagliflozin (Farxiga) in Black and White patients in a pooled analysis of the DAPA-HF pivotal trial of patients with HFrEF and the DELIVER pivotal trial of patients with HFpEF. The pooled cohort included a total of 11,007, but for the analysis by race the investigators also limited their focus to patients from the Americas with 2,626 White patients and 381 Black patients.

Mitchel L. Zoler/MDedge News

Assessment of the effect of dapagliflozin on the primary outcome of cardiovascular death or hospitalization for heart failure among all patients, both those with HFrEF and those with HFpEF, again showed that event rates among patients treated with placebo were significantly higher in Black, compared with White patients, and this led to a difference in the number needed to treat to prevent one primary outcome event of 12 in Blacks and 17 in Whites, Jawad H. Butt, MD said in a talk at the meeting.

Although treatment with dapagliflozin reduced the rate of the primary outcome in this subgroup of patients from the DAPA-HF trial and the DELIVER trial by similar rates in Black and White patients, event rates were higher in the Black patients resulting in “greater benefit in absolute terms” for Black patients, explained Dr. Butt, a cardiologist at Rigshospitalet in Copenhagen.

But in contrast to the empagliflozin findings reported by Dr. Verma, the combined data from the dapagliflozin trials showed no suggestion of heterogeneity in the beneficial effect of dapagliflozin based on left ventricular ejection fraction. In the Black patients, for example, the relative benefit from dapagliflozin on the primary outcome was consistent across the full spectrum of patients with HFrEF and HFpEF.

EMPEROR-Reduced and EMPEROR-Preserved were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). The DAPA-HF and DELIVER trials were sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Verma has received honoraria, research support, or both from AstraZeneca, Boehringer Ingelheim, and Lilly, and from numerous other companies. Dr. Butt has been a consultant to and received travel grants from AstraZeneca, honoraria from Novartis, and has been an adviser to Bayer.




 

CHICAGO – Black patients with heart failure with reduced ejection fraction (HFrEF) may receive more benefit from treatment with a sodium-glucose cotransporter-2 (SGLT2) inhibitor than do White patients, according to a new report.

A secondary analysis of data collected from the pivotal trials that assessed the SGLT2 inhibitor empagliflozin in patients with HFrEF, EMPEROR-Reduced, and in patients with heart failure with preserved ejection fraction (HFpEF), EMPEROR-Preserved, was presented by Subodh Verma, MD, PhD, at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The “hypothesis-generating” analysis of data from EMPEROR-Reduced showed “a suggestion of a greater benefit of empagliflozin” in Black, compared with White patients, for the study’s primary endpoint (cardiovascular death or hospitalization for heart failure) as well as for first and total hospitalizations for heart failure, he reported.

However, a similar but separate analysis that compared Black and White patients with heart failure who received treatment with a second agent, dapagliflozin, from the same SGLT2-inhibitor class did not show any suggestion of heterogeneity in the drug’s effect based on race.
 

Race-linked heterogeneity in empagliflozin’s effect

In EMPEROR-Reduced, which randomized 3,730 patients with heart failure and a left ventricular ejection fraction of 40% or less, treatment of White patients with empagliflozin (Jardiance) produced a nonsignificant 16% relative reduction in the rate of the primary endpoint, compared with placebo, during a median 16-month follow-up.

By contrast, among Black patients, treatment with empagliflozin produced a significant 56% reduction in the primary endpoint, compared with placebo-treated patients, a significant heterogeneity (P = .02) in effect between the two race subgroups, said Dr. Verma, a cardiac surgeon and professor at the University of Toronto.

The analysis he reported used combined data from EMPEROR-Reduced and the companion trial EMPEROR-Preserved, which randomized 5,988 patients with heart failure and a left ventricular ejection fraction greater than 40% to treatment with either empagliflozin or placebo and followed them for a median of 26 months.

To assess the effects of the randomized treatments in the two racial subgroups, Dr. Verma and associates used pooled data from both trials, but only from the 3,502 patients enrolled in the Americas, which included 3,024 White patients and 478 Black patients. Analysis of the patients in this subgroup who were randomized to placebo showed a significantly excess rate of the primary outcome among Blacks, who tallied 49% more of the primary outcome events during follow-up than did White patients, Dr. Verma reported. The absolute rate of the primary outcome without empagliflozin treatment was 13.15 events/100 patient-years of follow-up in White patients and 20.83 events/100 patient-years in Black patients.

The impact of empagliflozin was not statistically heterogeneous in the total pool of patients that included both those with HFrEF and those with HFpEF. The drug reduced the primary outcome incidence by a significant 20% in White patients, and by a significant 44% among Black patients.

But this point-estimate difference in efficacy, when coupled with the underlying difference in risk for an event between the two racial groups, meant that the number-needed-to-treat to prevent one primary outcome event was 42 among White patients and 12 among Black patients.
 

Race-linked treatment responses only in HFrEF

This suggestion of an imbalance in treatment efficacy was especially apparent among patients with HFrEF. In addition to the heterogeneity for the primary outcome, the Black and White subgroups also showed significantly divergent results for the outcomes of first hospitalization for heart failure, with a nonsignificant 21% relative reduction with empagliflozin treatment in Whites but a significant 65% relative cut in this endpoint with empagliflozin in Blacks, and for total hospitalizations for heart failure, which showed a similar level of significant heterogeneity between the two race subgroups.

In contrast, the patients with HFpEF showed no signal at all for heterogeneous outcome rates between Black and White subgroups.

One other study outcome, change in symptom burden measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed suggestion of a race-based imbalance. The adjusted mean difference from baseline in the KCCQ clinical summary score was 1.50 points higher with empagliflozin treatment, compared with placebo among all White patients (those with HFrEF and those with HFpEF), and compared with a 5.25-point increase with empagliflozin over placebo among all Black patients with heart failure in the pooled American EMPEROR dataset, a difference between White and Black patients that just missed significance (P = .06). Again, this difference was especially notable and significant among the patients with HFrEF, where the adjusted mean difference in KCCQ was a 0.77-point increase in White patients and a 6.71-point increase among Black patients (P = .043),

These results also appeared in a report published simultaneously with Dr. Verma’s talk.

But two other analyses that assessed a possible race-based difference in empagliflozin’s effect on renal protection and on functional status showed no suggestion of heterogeneity.

Dr. Verma stressed caution about the limitations of these analyses because they involved a relatively small number of Black patients, and were possibly subject to unadjusted confounding from differences in baseline characteristics between the Black and White patients.

Black patients also had a number-needed-to-treat advantage with dapagliflozin

The finding that Black patients with heart failure potentially get more bang for the buck from treatment with an SGLT2 inhibitor by having a lower number needed to treat also showed up in a separate report at the meeting that assessed the treatment effect from dapagliflozin (Farxiga) in Black and White patients in a pooled analysis of the DAPA-HF pivotal trial of patients with HFrEF and the DELIVER pivotal trial of patients with HFpEF. The pooled cohort included a total of 11,007, but for the analysis by race the investigators also limited their focus to patients from the Americas with 2,626 White patients and 381 Black patients.

Mitchel L. Zoler/MDedge News

Assessment of the effect of dapagliflozin on the primary outcome of cardiovascular death or hospitalization for heart failure among all patients, both those with HFrEF and those with HFpEF, again showed that event rates among patients treated with placebo were significantly higher in Black, compared with White patients, and this led to a difference in the number needed to treat to prevent one primary outcome event of 12 in Blacks and 17 in Whites, Jawad H. Butt, MD said in a talk at the meeting.

Although treatment with dapagliflozin reduced the rate of the primary outcome in this subgroup of patients from the DAPA-HF trial and the DELIVER trial by similar rates in Black and White patients, event rates were higher in the Black patients resulting in “greater benefit in absolute terms” for Black patients, explained Dr. Butt, a cardiologist at Rigshospitalet in Copenhagen.

But in contrast to the empagliflozin findings reported by Dr. Verma, the combined data from the dapagliflozin trials showed no suggestion of heterogeneity in the beneficial effect of dapagliflozin based on left ventricular ejection fraction. In the Black patients, for example, the relative benefit from dapagliflozin on the primary outcome was consistent across the full spectrum of patients with HFrEF and HFpEF.

EMPEROR-Reduced and EMPEROR-Preserved were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). The DAPA-HF and DELIVER trials were sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Verma has received honoraria, research support, or both from AstraZeneca, Boehringer Ingelheim, and Lilly, and from numerous other companies. Dr. Butt has been a consultant to and received travel grants from AstraZeneca, honoraria from Novartis, and has been an adviser to Bayer.




 

CHICAGO – Black patients with heart failure with reduced ejection fraction (HFrEF) may receive more benefit from treatment with a sodium-glucose cotransporter-2 (SGLT2) inhibitor than do White patients, according to a new report.

A secondary analysis of data collected from the pivotal trials that assessed the SGLT2 inhibitor empagliflozin in patients with HFrEF, EMPEROR-Reduced, and in patients with heart failure with preserved ejection fraction (HFpEF), EMPEROR-Preserved, was presented by Subodh Verma, MD, PhD, at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The “hypothesis-generating” analysis of data from EMPEROR-Reduced showed “a suggestion of a greater benefit of empagliflozin” in Black, compared with White patients, for the study’s primary endpoint (cardiovascular death or hospitalization for heart failure) as well as for first and total hospitalizations for heart failure, he reported.

However, a similar but separate analysis that compared Black and White patients with heart failure who received treatment with a second agent, dapagliflozin, from the same SGLT2-inhibitor class did not show any suggestion of heterogeneity in the drug’s effect based on race.
 

Race-linked heterogeneity in empagliflozin’s effect

In EMPEROR-Reduced, which randomized 3,730 patients with heart failure and a left ventricular ejection fraction of 40% or less, treatment of White patients with empagliflozin (Jardiance) produced a nonsignificant 16% relative reduction in the rate of the primary endpoint, compared with placebo, during a median 16-month follow-up.

By contrast, among Black patients, treatment with empagliflozin produced a significant 56% reduction in the primary endpoint, compared with placebo-treated patients, a significant heterogeneity (P = .02) in effect between the two race subgroups, said Dr. Verma, a cardiac surgeon and professor at the University of Toronto.

The analysis he reported used combined data from EMPEROR-Reduced and the companion trial EMPEROR-Preserved, which randomized 5,988 patients with heart failure and a left ventricular ejection fraction greater than 40% to treatment with either empagliflozin or placebo and followed them for a median of 26 months.

To assess the effects of the randomized treatments in the two racial subgroups, Dr. Verma and associates used pooled data from both trials, but only from the 3,502 patients enrolled in the Americas, which included 3,024 White patients and 478 Black patients. Analysis of the patients in this subgroup who were randomized to placebo showed a significantly excess rate of the primary outcome among Blacks, who tallied 49% more of the primary outcome events during follow-up than did White patients, Dr. Verma reported. The absolute rate of the primary outcome without empagliflozin treatment was 13.15 events/100 patient-years of follow-up in White patients and 20.83 events/100 patient-years in Black patients.

The impact of empagliflozin was not statistically heterogeneous in the total pool of patients that included both those with HFrEF and those with HFpEF. The drug reduced the primary outcome incidence by a significant 20% in White patients, and by a significant 44% among Black patients.

But this point-estimate difference in efficacy, when coupled with the underlying difference in risk for an event between the two racial groups, meant that the number-needed-to-treat to prevent one primary outcome event was 42 among White patients and 12 among Black patients.
 

Race-linked treatment responses only in HFrEF

This suggestion of an imbalance in treatment efficacy was especially apparent among patients with HFrEF. In addition to the heterogeneity for the primary outcome, the Black and White subgroups also showed significantly divergent results for the outcomes of first hospitalization for heart failure, with a nonsignificant 21% relative reduction with empagliflozin treatment in Whites but a significant 65% relative cut in this endpoint with empagliflozin in Blacks, and for total hospitalizations for heart failure, which showed a similar level of significant heterogeneity between the two race subgroups.

In contrast, the patients with HFpEF showed no signal at all for heterogeneous outcome rates between Black and White subgroups.

One other study outcome, change in symptom burden measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed suggestion of a race-based imbalance. The adjusted mean difference from baseline in the KCCQ clinical summary score was 1.50 points higher with empagliflozin treatment, compared with placebo among all White patients (those with HFrEF and those with HFpEF), and compared with a 5.25-point increase with empagliflozin over placebo among all Black patients with heart failure in the pooled American EMPEROR dataset, a difference between White and Black patients that just missed significance (P = .06). Again, this difference was especially notable and significant among the patients with HFrEF, where the adjusted mean difference in KCCQ was a 0.77-point increase in White patients and a 6.71-point increase among Black patients (P = .043),

These results also appeared in a report published simultaneously with Dr. Verma’s talk.

But two other analyses that assessed a possible race-based difference in empagliflozin’s effect on renal protection and on functional status showed no suggestion of heterogeneity.

Dr. Verma stressed caution about the limitations of these analyses because they involved a relatively small number of Black patients, and were possibly subject to unadjusted confounding from differences in baseline characteristics between the Black and White patients.

Black patients also had a number-needed-to-treat advantage with dapagliflozin

The finding that Black patients with heart failure potentially get more bang for the buck from treatment with an SGLT2 inhibitor by having a lower number needed to treat also showed up in a separate report at the meeting that assessed the treatment effect from dapagliflozin (Farxiga) in Black and White patients in a pooled analysis of the DAPA-HF pivotal trial of patients with HFrEF and the DELIVER pivotal trial of patients with HFpEF. The pooled cohort included a total of 11,007, but for the analysis by race the investigators also limited their focus to patients from the Americas with 2,626 White patients and 381 Black patients.

Mitchel L. Zoler/MDedge News

Assessment of the effect of dapagliflozin on the primary outcome of cardiovascular death or hospitalization for heart failure among all patients, both those with HFrEF and those with HFpEF, again showed that event rates among patients treated with placebo were significantly higher in Black, compared with White patients, and this led to a difference in the number needed to treat to prevent one primary outcome event of 12 in Blacks and 17 in Whites, Jawad H. Butt, MD said in a talk at the meeting.

Although treatment with dapagliflozin reduced the rate of the primary outcome in this subgroup of patients from the DAPA-HF trial and the DELIVER trial by similar rates in Black and White patients, event rates were higher in the Black patients resulting in “greater benefit in absolute terms” for Black patients, explained Dr. Butt, a cardiologist at Rigshospitalet in Copenhagen.

But in contrast to the empagliflozin findings reported by Dr. Verma, the combined data from the dapagliflozin trials showed no suggestion of heterogeneity in the beneficial effect of dapagliflozin based on left ventricular ejection fraction. In the Black patients, for example, the relative benefit from dapagliflozin on the primary outcome was consistent across the full spectrum of patients with HFrEF and HFpEF.

EMPEROR-Reduced and EMPEROR-Preserved were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). The DAPA-HF and DELIVER trials were sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Verma has received honoraria, research support, or both from AstraZeneca, Boehringer Ingelheim, and Lilly, and from numerous other companies. Dr. Butt has been a consultant to and received travel grants from AstraZeneca, honoraria from Novartis, and has been an adviser to Bayer.




 

“I could relate to many, many, many of the experiences and emotions that Charlie, which is Brendan Fraser’s character, was portraying,” Patricia Nece recalls after watching a preview copy of the new film “The Whale.”

A24

Much of the movie “rang true and hit home for me as things that I, too, had experienced,” Ms. Nece, the board of directors’ chair of the Obesity Action Coalition (OAC) and a person living with obesity, shares with this news organization.

In theaters as of December 9, The Whale chronicles the experience of a 600-lb, middle-aged man named Charlie. Throughout the film, Charlie seeks to rebuild his relationship with his estranged teenage daughter. Charlie had left his daughter and family to pursue a relationship with a man, who eventually died. As he navigates the pain surrounding his partner’s death and his lack of community, Charlie turns to food for comfort.

When the movie premiered at the Venice Film Festival, Mr. Fraser received a 6-minute standing ovation. However, activists criticized the movie for casting Fraser over an actor with obesity as well as its depiction of people with obesity.

Representatives from the National Association to Advance Fat Acceptance contend that casting an actor without obesity only contributes to ongoing bias against people of size. “Medical weight stigma and other socio-political determinants of health for people of all sizes cause far more harm to fat people than body fat does. Bias endangers fat people’s health. Anti-obesity organizations, such as those consulted with for this movie, contribute to stigma rather than reducing it as they claim,” NAAFA wrote in a statement to this news organization.

And they added that though the fat suit used in the movie may be superior to previous ones, it is still not an accurate depiction: “The creators of The Whale consider its CGI-generated fat suit to be superior to tactile fat suits, but we don’t. The issue with fat suits in Hollywood is not that they aren’t realistic enough. The issue is that they are used rather than using performers who actually live in bodies like the ones being depicted. If there is a 600-pound character in a movie, there should be a 600-pound human in that role. Rather than concentrate on the hype around the fake fat body created for The Whale, we want to see Hollywood create more opportunities for fat people across the size spectrum, both in front of the camera and behind the scenes.”
 

Prosthetics vs. reality?

Ms. Nece says she understands the controversy surrounding the use of fat suits but believes that it was not done in poor taste.

“OAC got involved with the movie after Brendan was already chosen for the part, and we never would have gotten involved with it had the prosthetics or fat suit been used to ridicule or make fun of people with obesity, which is usually the case,” she explains.

“But we knew from the start that that was never the intent of anyone involved with The Whale. And I think that’s shown by the fact that Brendan and Darren Aronofsky, the director, reached out to people who live with obesity on a daily basis to find out and learn more about it and to educate themselves about it,” Ms. Nece continues.

In a Daily Mail article, Mr. Fraser credited his son Griffin, who is autistic and obese, with helping him understand the struggles that people with obesity face.

Rachel Goldman, PhD, a clinical psychologist in private practice in New York and a professor in the psychology department at New York University, notes that there are other considerations that played into casting. “I know there was some pushback in terms of could, a say 600-lb individual, even be able to go to be on set every day and do this kind of work, and the answer is we don’t know.”

“I’m sure Darren chose Brendan for many reasons above and beyond just his body. I think that’s very important to keep in mind that just as much as representation is very important, I think it is also about finding the right person for the right role,” adds Dr. Goldman, who served as a consultant to the film.
 

Fat suits, extreme weight gains all to play a role

About 42% of adults in the United States have obesity, according to the 2017-2020 National Health and Nutrition Examination Survey, but that reality is not reflected in films or television.

A study of 1018 major television characters found that 24% of men and 14% of women had either overweight or obesity – far below the national average. And when characters with obesity are portrayed, actors often wear prosthetics, like Gwyneth Paltrow in Shallow Hal or Eddie Murphy in the Nutty Professor.

But unlike Mr. Fraser, some actors gain weight quickly instead.

This practice is unhealthy, says Jaime Almandoz, MD, an associate professor at the University of Texas Southwestern Medical Center, Dallas, and a nonsurgical weight management expert. In interviews, actors have shared how they increased calorie intake by drinking two milkshakes per day, going to fast food places regularly, or, in Mark Walhberg’s case, consuming 7,000 calories per day to gain 30 pounds for his role as boxer-turned-priest in the movie Father Stu.

This method provides their bodies with excess calories they are unable to burn off. “Then the amount of sugar and fat that streams into the blood as a result creates problems both directly and indirectly as your body tries to store it. It basically ends up using overflow warehouses for fat storage, like the liver for example, so we can create a condition called fatty liver, or in the muscle and other places, and this excess sugar and fat in the bloodstream cause several factors that are both insulin resistance causing,” Dr. Almandoz explains.

Though gaining weight helps the actor understand the character’s life experience, it may also be risky.

“To have an actor deliberately put his own health at risk and gain a certain amount of weight and whatever that might entail, one – that’s not necessarily the safest thing for that actor – but two, it’s also important to highlight the authentic experience of someone who has dealt with this chronic disease as well,” says Disha Narang, MD, a quadruple-board certified endocrinologist, obesity medicine, and culinary medicine specialist at Northwestern Medicine Lake Forest Hospital, Chicago.

These extreme fluctuations in weight may create problems. “It is typically not something we recommend because there could be metabolic damages as well as health concerns when patients are trying to gain weight quickly, just as we don’t want patients to lose weight quickly,” says Kurt Hong, MD, PhD, board-certified in internal medicine and clinical nutrition at the University of Southern California, Los Angeles.

Dr. Hong notes that it may be difficult for individuals to experience sudden weight gain because the body works hard to maintain a state of homeostasis.

“Similarly, to someone trying to gain weight you overeat, initially your body will try to again, maybe enhance its metabolic efficiency to hold the body stable,” Dr. Hong adds.

Dietary choices that may contribute to insulin resistance or promote high blood sugar can contribute to inflammation and a number of other adverse health outcomes, notes Dr. Almandoz. “The things that actors need to do in order to gain this magnitude of weight and they want to do it in the most time-effective manner is often not helpful for our bodies, it can be very problematic, the same thing goes for weight loss when actors need to lose significant amounts of weight for roles,” says Dr. Almandoz.

And Dr. Hong explained that for patients trying to lose weight, they may cut calories, but the body will try to compensate by slowing down the metabolism to keep their weight the same.
 

‘Your own worst bully’

In “The Whale,” Charlie appears to suffer from internalized weight bias, which is common to many people living with obesity, Ms. Nece says.

“Internalized weight bias is when the person of size takes all that negativity and turns it on themselves. The easiest way to describe that is to tell you that I became my own worst bully because I started believing all the negative things people said to me about my weight,” Ms. Nece adds.

Her hope is that the film will bring attention to the harm that this bias creates, especially when it derives from other people. “There’s no telling whether it will, but what Charlie experiences in bias and stigma from others clearly happens. It’s realistic. Those of us in large bodies have experienced what he is experiencing, so some people have said the movie is fat-phobic, but I see it as I can relate to those experiences because I have them too, so they are very realistic.”

Ms. Nece notes that it is important for clinicians to understand that obesity is a multifaceted and sensitive topic. “For those medical professionals who do not already know that obesity is complex, I hope the film will begin to open their eyes to the many different facets involved in obesity and their patients with obesity, I hope it will help them empathize and show compassion to their patients with obesity,” she concludes.

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

“I could relate to many, many, many of the experiences and emotions that Charlie, which is Brendan Fraser’s character, was portraying,” Patricia Nece recalls after watching a preview copy of the new film “The Whale.”

A24

Much of the movie “rang true and hit home for me as things that I, too, had experienced,” Ms. Nece, the board of directors’ chair of the Obesity Action Coalition (OAC) and a person living with obesity, shares with this news organization.

In theaters as of December 9, The Whale chronicles the experience of a 600-lb, middle-aged man named Charlie. Throughout the film, Charlie seeks to rebuild his relationship with his estranged teenage daughter. Charlie had left his daughter and family to pursue a relationship with a man, who eventually died. As he navigates the pain surrounding his partner’s death and his lack of community, Charlie turns to food for comfort.

When the movie premiered at the Venice Film Festival, Mr. Fraser received a 6-minute standing ovation. However, activists criticized the movie for casting Fraser over an actor with obesity as well as its depiction of people with obesity.

Representatives from the National Association to Advance Fat Acceptance contend that casting an actor without obesity only contributes to ongoing bias against people of size. “Medical weight stigma and other socio-political determinants of health for people of all sizes cause far more harm to fat people than body fat does. Bias endangers fat people’s health. Anti-obesity organizations, such as those consulted with for this movie, contribute to stigma rather than reducing it as they claim,” NAAFA wrote in a statement to this news organization.

And they added that though the fat suit used in the movie may be superior to previous ones, it is still not an accurate depiction: “The creators of The Whale consider its CGI-generated fat suit to be superior to tactile fat suits, but we don’t. The issue with fat suits in Hollywood is not that they aren’t realistic enough. The issue is that they are used rather than using performers who actually live in bodies like the ones being depicted. If there is a 600-pound character in a movie, there should be a 600-pound human in that role. Rather than concentrate on the hype around the fake fat body created for The Whale, we want to see Hollywood create more opportunities for fat people across the size spectrum, both in front of the camera and behind the scenes.”
 

Prosthetics vs. reality?

Ms. Nece says she understands the controversy surrounding the use of fat suits but believes that it was not done in poor taste.

“OAC got involved with the movie after Brendan was already chosen for the part, and we never would have gotten involved with it had the prosthetics or fat suit been used to ridicule or make fun of people with obesity, which is usually the case,” she explains.

“But we knew from the start that that was never the intent of anyone involved with The Whale. And I think that’s shown by the fact that Brendan and Darren Aronofsky, the director, reached out to people who live with obesity on a daily basis to find out and learn more about it and to educate themselves about it,” Ms. Nece continues.

In a Daily Mail article, Mr. Fraser credited his son Griffin, who is autistic and obese, with helping him understand the struggles that people with obesity face.

Rachel Goldman, PhD, a clinical psychologist in private practice in New York and a professor in the psychology department at New York University, notes that there are other considerations that played into casting. “I know there was some pushback in terms of could, a say 600-lb individual, even be able to go to be on set every day and do this kind of work, and the answer is we don’t know.”

“I’m sure Darren chose Brendan for many reasons above and beyond just his body. I think that’s very important to keep in mind that just as much as representation is very important, I think it is also about finding the right person for the right role,” adds Dr. Goldman, who served as a consultant to the film.
 

Fat suits, extreme weight gains all to play a role

About 42% of adults in the United States have obesity, according to the 2017-2020 National Health and Nutrition Examination Survey, but that reality is not reflected in films or television.

A study of 1018 major television characters found that 24% of men and 14% of women had either overweight or obesity – far below the national average. And when characters with obesity are portrayed, actors often wear prosthetics, like Gwyneth Paltrow in Shallow Hal or Eddie Murphy in the Nutty Professor.

But unlike Mr. Fraser, some actors gain weight quickly instead.

This practice is unhealthy, says Jaime Almandoz, MD, an associate professor at the University of Texas Southwestern Medical Center, Dallas, and a nonsurgical weight management expert. In interviews, actors have shared how they increased calorie intake by drinking two milkshakes per day, going to fast food places regularly, or, in Mark Walhberg’s case, consuming 7,000 calories per day to gain 30 pounds for his role as boxer-turned-priest in the movie Father Stu.

This method provides their bodies with excess calories they are unable to burn off. “Then the amount of sugar and fat that streams into the blood as a result creates problems both directly and indirectly as your body tries to store it. It basically ends up using overflow warehouses for fat storage, like the liver for example, so we can create a condition called fatty liver, or in the muscle and other places, and this excess sugar and fat in the bloodstream cause several factors that are both insulin resistance causing,” Dr. Almandoz explains.

Though gaining weight helps the actor understand the character’s life experience, it may also be risky.

“To have an actor deliberately put his own health at risk and gain a certain amount of weight and whatever that might entail, one – that’s not necessarily the safest thing for that actor – but two, it’s also important to highlight the authentic experience of someone who has dealt with this chronic disease as well,” says Disha Narang, MD, a quadruple-board certified endocrinologist, obesity medicine, and culinary medicine specialist at Northwestern Medicine Lake Forest Hospital, Chicago.

These extreme fluctuations in weight may create problems. “It is typically not something we recommend because there could be metabolic damages as well as health concerns when patients are trying to gain weight quickly, just as we don’t want patients to lose weight quickly,” says Kurt Hong, MD, PhD, board-certified in internal medicine and clinical nutrition at the University of Southern California, Los Angeles.

Dr. Hong notes that it may be difficult for individuals to experience sudden weight gain because the body works hard to maintain a state of homeostasis.

“Similarly, to someone trying to gain weight you overeat, initially your body will try to again, maybe enhance its metabolic efficiency to hold the body stable,” Dr. Hong adds.

Dietary choices that may contribute to insulin resistance or promote high blood sugar can contribute to inflammation and a number of other adverse health outcomes, notes Dr. Almandoz. “The things that actors need to do in order to gain this magnitude of weight and they want to do it in the most time-effective manner is often not helpful for our bodies, it can be very problematic, the same thing goes for weight loss when actors need to lose significant amounts of weight for roles,” says Dr. Almandoz.

And Dr. Hong explained that for patients trying to lose weight, they may cut calories, but the body will try to compensate by slowing down the metabolism to keep their weight the same.
 

‘Your own worst bully’

In “The Whale,” Charlie appears to suffer from internalized weight bias, which is common to many people living with obesity, Ms. Nece says.

“Internalized weight bias is when the person of size takes all that negativity and turns it on themselves. The easiest way to describe that is to tell you that I became my own worst bully because I started believing all the negative things people said to me about my weight,” Ms. Nece adds.

Her hope is that the film will bring attention to the harm that this bias creates, especially when it derives from other people. “There’s no telling whether it will, but what Charlie experiences in bias and stigma from others clearly happens. It’s realistic. Those of us in large bodies have experienced what he is experiencing, so some people have said the movie is fat-phobic, but I see it as I can relate to those experiences because I have them too, so they are very realistic.”

Ms. Nece notes that it is important for clinicians to understand that obesity is a multifaceted and sensitive topic. “For those medical professionals who do not already know that obesity is complex, I hope the film will begin to open their eyes to the many different facets involved in obesity and their patients with obesity, I hope it will help them empathize and show compassion to their patients with obesity,” she concludes.

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

“I could relate to many, many, many of the experiences and emotions that Charlie, which is Brendan Fraser’s character, was portraying,” Patricia Nece recalls after watching a preview copy of the new film “The Whale.”

A24

Much of the movie “rang true and hit home for me as things that I, too, had experienced,” Ms. Nece, the board of directors’ chair of the Obesity Action Coalition (OAC) and a person living with obesity, shares with this news organization.

In theaters as of December 9, The Whale chronicles the experience of a 600-lb, middle-aged man named Charlie. Throughout the film, Charlie seeks to rebuild his relationship with his estranged teenage daughter. Charlie had left his daughter and family to pursue a relationship with a man, who eventually died. As he navigates the pain surrounding his partner’s death and his lack of community, Charlie turns to food for comfort.

When the movie premiered at the Venice Film Festival, Mr. Fraser received a 6-minute standing ovation. However, activists criticized the movie for casting Fraser over an actor with obesity as well as its depiction of people with obesity.

Representatives from the National Association to Advance Fat Acceptance contend that casting an actor without obesity only contributes to ongoing bias against people of size. “Medical weight stigma and other socio-political determinants of health for people of all sizes cause far more harm to fat people than body fat does. Bias endangers fat people’s health. Anti-obesity organizations, such as those consulted with for this movie, contribute to stigma rather than reducing it as they claim,” NAAFA wrote in a statement to this news organization.

And they added that though the fat suit used in the movie may be superior to previous ones, it is still not an accurate depiction: “The creators of The Whale consider its CGI-generated fat suit to be superior to tactile fat suits, but we don’t. The issue with fat suits in Hollywood is not that they aren’t realistic enough. The issue is that they are used rather than using performers who actually live in bodies like the ones being depicted. If there is a 600-pound character in a movie, there should be a 600-pound human in that role. Rather than concentrate on the hype around the fake fat body created for The Whale, we want to see Hollywood create more opportunities for fat people across the size spectrum, both in front of the camera and behind the scenes.”
 

Prosthetics vs. reality?

Ms. Nece says she understands the controversy surrounding the use of fat suits but believes that it was not done in poor taste.

“OAC got involved with the movie after Brendan was already chosen for the part, and we never would have gotten involved with it had the prosthetics or fat suit been used to ridicule or make fun of people with obesity, which is usually the case,” she explains.

“But we knew from the start that that was never the intent of anyone involved with The Whale. And I think that’s shown by the fact that Brendan and Darren Aronofsky, the director, reached out to people who live with obesity on a daily basis to find out and learn more about it and to educate themselves about it,” Ms. Nece continues.

In a Daily Mail article, Mr. Fraser credited his son Griffin, who is autistic and obese, with helping him understand the struggles that people with obesity face.

Rachel Goldman, PhD, a clinical psychologist in private practice in New York and a professor in the psychology department at New York University, notes that there are other considerations that played into casting. “I know there was some pushback in terms of could, a say 600-lb individual, even be able to go to be on set every day and do this kind of work, and the answer is we don’t know.”

“I’m sure Darren chose Brendan for many reasons above and beyond just his body. I think that’s very important to keep in mind that just as much as representation is very important, I think it is also about finding the right person for the right role,” adds Dr. Goldman, who served as a consultant to the film.
 

Fat suits, extreme weight gains all to play a role

About 42% of adults in the United States have obesity, according to the 2017-2020 National Health and Nutrition Examination Survey, but that reality is not reflected in films or television.

A study of 1018 major television characters found that 24% of men and 14% of women had either overweight or obesity – far below the national average. And when characters with obesity are portrayed, actors often wear prosthetics, like Gwyneth Paltrow in Shallow Hal or Eddie Murphy in the Nutty Professor.

But unlike Mr. Fraser, some actors gain weight quickly instead.

This practice is unhealthy, says Jaime Almandoz, MD, an associate professor at the University of Texas Southwestern Medical Center, Dallas, and a nonsurgical weight management expert. In interviews, actors have shared how they increased calorie intake by drinking two milkshakes per day, going to fast food places regularly, or, in Mark Walhberg’s case, consuming 7,000 calories per day to gain 30 pounds for his role as boxer-turned-priest in the movie Father Stu.

This method provides their bodies with excess calories they are unable to burn off. “Then the amount of sugar and fat that streams into the blood as a result creates problems both directly and indirectly as your body tries to store it. It basically ends up using overflow warehouses for fat storage, like the liver for example, so we can create a condition called fatty liver, or in the muscle and other places, and this excess sugar and fat in the bloodstream cause several factors that are both insulin resistance causing,” Dr. Almandoz explains.

Though gaining weight helps the actor understand the character’s life experience, it may also be risky.

“To have an actor deliberately put his own health at risk and gain a certain amount of weight and whatever that might entail, one – that’s not necessarily the safest thing for that actor – but two, it’s also important to highlight the authentic experience of someone who has dealt with this chronic disease as well,” says Disha Narang, MD, a quadruple-board certified endocrinologist, obesity medicine, and culinary medicine specialist at Northwestern Medicine Lake Forest Hospital, Chicago.

These extreme fluctuations in weight may create problems. “It is typically not something we recommend because there could be metabolic damages as well as health concerns when patients are trying to gain weight quickly, just as we don’t want patients to lose weight quickly,” says Kurt Hong, MD, PhD, board-certified in internal medicine and clinical nutrition at the University of Southern California, Los Angeles.

Dr. Hong notes that it may be difficult for individuals to experience sudden weight gain because the body works hard to maintain a state of homeostasis.

“Similarly, to someone trying to gain weight you overeat, initially your body will try to again, maybe enhance its metabolic efficiency to hold the body stable,” Dr. Hong adds.

Dietary choices that may contribute to insulin resistance or promote high blood sugar can contribute to inflammation and a number of other adverse health outcomes, notes Dr. Almandoz. “The things that actors need to do in order to gain this magnitude of weight and they want to do it in the most time-effective manner is often not helpful for our bodies, it can be very problematic, the same thing goes for weight loss when actors need to lose significant amounts of weight for roles,” says Dr. Almandoz.

And Dr. Hong explained that for patients trying to lose weight, they may cut calories, but the body will try to compensate by slowing down the metabolism to keep their weight the same.
 

‘Your own worst bully’

In “The Whale,” Charlie appears to suffer from internalized weight bias, which is common to many people living with obesity, Ms. Nece says.

“Internalized weight bias is when the person of size takes all that negativity and turns it on themselves. The easiest way to describe that is to tell you that I became my own worst bully because I started believing all the negative things people said to me about my weight,” Ms. Nece adds.

Her hope is that the film will bring attention to the harm that this bias creates, especially when it derives from other people. “There’s no telling whether it will, but what Charlie experiences in bias and stigma from others clearly happens. It’s realistic. Those of us in large bodies have experienced what he is experiencing, so some people have said the movie is fat-phobic, but I see it as I can relate to those experiences because I have them too, so they are very realistic.”

Ms. Nece notes that it is important for clinicians to understand that obesity is a multifaceted and sensitive topic. “For those medical professionals who do not already know that obesity is complex, I hope the film will begin to open their eyes to the many different facets involved in obesity and their patients with obesity, I hope it will help them empathize and show compassion to their patients with obesity,” she concludes.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

A prespecified analysis of a large global trial of patients with symptomatic heart failure with mildly reduced and preserved ejection fraction “seals the deal” on the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to manage and improve their symptoms.

The prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial included 5,795 patients with mildly reduced and preserved ejection fraction who completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) after taking the SGLT2 inhibitor dapagliflozin or placebo. The results were published online in the Journal of the American College of Cardiology.

“We’ve known from studies prior to DELIVER that SGLT2 inhibitors have been shown to improve health status, patient symptoms and quality of life among those that are living with heart failure and mildly reduced [HFmrEF] and preserved [HFpEF] ejection fraction,” lead author Mikhail N. Kosiborod, MD, vice president for research at Saint Luke’s Health System, and codirector of the St. Luke’s Michael and Marly Haverty Cardiometabolic Center of Excellence at St. Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview. “But the picture was incomplete for a number of different reasons, partly because the previous studies were either relatively modest in size, geographically limited, or suggested potential attenuation of these benefits in patients with completely normal ejection fraction.”

Specifically, the study authors noted the EMPEROR-Preserved trial of the SGLT2 inhibitor empagliflozin showed improvement in health status vs. placebo across the range of EF except in those with normal EF of 65% or greater. The PRESERVED-HF trial of dapagliflozin demonstrated a more robust response than EMPEROR-Preserved or DELIVER, but PRESERVED-HF patients were recruited only in the United States and had more debilitating HF symptoms at baseline.

“Because of the results of the DELIVER trial and because of how large, extensive, and inclusive the trial was, it really seals the deal on the value of SGLT2 inhibitors in patients with heart failure,” said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri–Kansas City.

The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84.

Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62).

“The most important take home message is that the SGLT2 inhibitor dapagliflozin significantly improved patient symptoms as measured by the Kansas City Cardiomyopathy Questionnaire symptom score,” Dr. Kosiborod said. “It improved those symptoms within 1 month and those benefits were sustained out to 8 months.”

DELIVER patients also showed improvement in all other key KCCQ domains across the board, he added. “In addition, dapagliflozin also improved the proportion of patients who had small, moderate, and large improvements in a responder analysis. So really, by every measure that we had, dapagliflozin had a significant beneficial effect.”

The DELIVER results taken collectively with the EMPEROR-Preserved and PRESERVED-HF trials cinch the deal for SGLT2 inhibitors, Dr. Kosiborod said. “They deliver on the triple goal of care in patients with heart failure. They reduce the risk of cardiovascular death and worsening heart failure and they improve patient symptoms, function and quality of life – and they accomplish that across the entire continuum of heart failure regardless of ejection fraction, regardless of whether patients are hospitalized or in an ambulatory setting, regardless of age or background therapies or other comorbidities.”

He added: “It’s a pretty historic development because we haven’t had that before.”

AstraZeneca funded the DELIVER trial. Dr. Kosiborod disclosed financial relationships with Alnylam, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor Pharma.
 

A prespecified analysis of a large global trial of patients with symptomatic heart failure with mildly reduced and preserved ejection fraction “seals the deal” on the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to manage and improve their symptoms.

The prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial included 5,795 patients with mildly reduced and preserved ejection fraction who completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) after taking the SGLT2 inhibitor dapagliflozin or placebo. The results were published online in the Journal of the American College of Cardiology.

“We’ve known from studies prior to DELIVER that SGLT2 inhibitors have been shown to improve health status, patient symptoms and quality of life among those that are living with heart failure and mildly reduced [HFmrEF] and preserved [HFpEF] ejection fraction,” lead author Mikhail N. Kosiborod, MD, vice president for research at Saint Luke’s Health System, and codirector of the St. Luke’s Michael and Marly Haverty Cardiometabolic Center of Excellence at St. Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview. “But the picture was incomplete for a number of different reasons, partly because the previous studies were either relatively modest in size, geographically limited, or suggested potential attenuation of these benefits in patients with completely normal ejection fraction.”

Specifically, the study authors noted the EMPEROR-Preserved trial of the SGLT2 inhibitor empagliflozin showed improvement in health status vs. placebo across the range of EF except in those with normal EF of 65% or greater. The PRESERVED-HF trial of dapagliflozin demonstrated a more robust response than EMPEROR-Preserved or DELIVER, but PRESERVED-HF patients were recruited only in the United States and had more debilitating HF symptoms at baseline.

“Because of the results of the DELIVER trial and because of how large, extensive, and inclusive the trial was, it really seals the deal on the value of SGLT2 inhibitors in patients with heart failure,” said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri–Kansas City.

The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84.

Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62).

“The most important take home message is that the SGLT2 inhibitor dapagliflozin significantly improved patient symptoms as measured by the Kansas City Cardiomyopathy Questionnaire symptom score,” Dr. Kosiborod said. “It improved those symptoms within 1 month and those benefits were sustained out to 8 months.”

DELIVER patients also showed improvement in all other key KCCQ domains across the board, he added. “In addition, dapagliflozin also improved the proportion of patients who had small, moderate, and large improvements in a responder analysis. So really, by every measure that we had, dapagliflozin had a significant beneficial effect.”

The DELIVER results taken collectively with the EMPEROR-Preserved and PRESERVED-HF trials cinch the deal for SGLT2 inhibitors, Dr. Kosiborod said. “They deliver on the triple goal of care in patients with heart failure. They reduce the risk of cardiovascular death and worsening heart failure and they improve patient symptoms, function and quality of life – and they accomplish that across the entire continuum of heart failure regardless of ejection fraction, regardless of whether patients are hospitalized or in an ambulatory setting, regardless of age or background therapies or other comorbidities.”

He added: “It’s a pretty historic development because we haven’t had that before.”

AstraZeneca funded the DELIVER trial. Dr. Kosiborod disclosed financial relationships with Alnylam, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor Pharma.
 

A prespecified analysis of a large global trial of patients with symptomatic heart failure with mildly reduced and preserved ejection fraction “seals the deal” on the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to manage and improve their symptoms.

The prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial included 5,795 patients with mildly reduced and preserved ejection fraction who completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) after taking the SGLT2 inhibitor dapagliflozin or placebo. The results were published online in the Journal of the American College of Cardiology.

“We’ve known from studies prior to DELIVER that SGLT2 inhibitors have been shown to improve health status, patient symptoms and quality of life among those that are living with heart failure and mildly reduced [HFmrEF] and preserved [HFpEF] ejection fraction,” lead author Mikhail N. Kosiborod, MD, vice president for research at Saint Luke’s Health System, and codirector of the St. Luke’s Michael and Marly Haverty Cardiometabolic Center of Excellence at St. Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview. “But the picture was incomplete for a number of different reasons, partly because the previous studies were either relatively modest in size, geographically limited, or suggested potential attenuation of these benefits in patients with completely normal ejection fraction.”

Specifically, the study authors noted the EMPEROR-Preserved trial of the SGLT2 inhibitor empagliflozin showed improvement in health status vs. placebo across the range of EF except in those with normal EF of 65% or greater. The PRESERVED-HF trial of dapagliflozin demonstrated a more robust response than EMPEROR-Preserved or DELIVER, but PRESERVED-HF patients were recruited only in the United States and had more debilitating HF symptoms at baseline.

“Because of the results of the DELIVER trial and because of how large, extensive, and inclusive the trial was, it really seals the deal on the value of SGLT2 inhibitors in patients with heart failure,” said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri–Kansas City.

The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84.

Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62).

“The most important take home message is that the SGLT2 inhibitor dapagliflozin significantly improved patient symptoms as measured by the Kansas City Cardiomyopathy Questionnaire symptom score,” Dr. Kosiborod said. “It improved those symptoms within 1 month and those benefits were sustained out to 8 months.”

DELIVER patients also showed improvement in all other key KCCQ domains across the board, he added. “In addition, dapagliflozin also improved the proportion of patients who had small, moderate, and large improvements in a responder analysis. So really, by every measure that we had, dapagliflozin had a significant beneficial effect.”

The DELIVER results taken collectively with the EMPEROR-Preserved and PRESERVED-HF trials cinch the deal for SGLT2 inhibitors, Dr. Kosiborod said. “They deliver on the triple goal of care in patients with heart failure. They reduce the risk of cardiovascular death and worsening heart failure and they improve patient symptoms, function and quality of life – and they accomplish that across the entire continuum of heart failure regardless of ejection fraction, regardless of whether patients are hospitalized or in an ambulatory setting, regardless of age or background therapies or other comorbidities.”

He added: “It’s a pretty historic development because we haven’t had that before.”

AstraZeneca funded the DELIVER trial. Dr. Kosiborod disclosed financial relationships with Alnylam, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor Pharma.
 

A panel of advisers to the Food and Drug Administration has recommended against approval of omecamtiv mecarbil (Cytokinetics) for the treatment of heart failure with reduced ejection fraction (HFrEF).

Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA Cardiovascular and Renal Drugs Advisory Committee on Dec. 13 voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF.

Those who voted in favor of the drug cited the clinical benefit (albeit small) and good safety profile of the drug as well as the unmet need for new treatments.

C. Noel Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles, said she voted yes “on the basis of need,” and her personal experience, as well as the data presented, that “up to half of severe heart failure patients are intolerant of guidelines directed medical therapy.”

Christopher M. O’Connor, MD, with Inova Heart and Vascular Institute, Falls Church, Va., who also voted in favor of approval for the drug, cited the “important unmet need,” and said he believes “a path was constructed in which one could go forward safely and with enhanced efficacy.

“It may be a narrow path, but I think it’s a path that would afford a lot of benefit to this high-risk patient population,” said Dr. O’Connor.

Those who voted against approval generally felt the benefit was not large enough and that more data are needed, given this is a first-in-class agent.

Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who voted no, said she was concerned that, despite the large size of the trial, “a more positive effect could not have been found.” She was also concerned that there was no benefit on quality of life or any other secondary outcomes. 

David J. Moliterno, MD, University of Kentucky Medical Center, Lexington, who also voted no, felt the benefits were “more singular and that being a modest reduction primarily limited to fewer outpatient visits.” Dr. Moliterno, like many of the committee members who voted no, called for more study.

The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.

As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.

This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.

The results were presented at the American Heart Association 2020 scientific sessions and simultaneously published in the New England Journal of Medicine.

In a statement, Robert I. Blum, president and CEO of Cytokinetics, said, “We are disappointed there was not a greater consensus amongst committee members relating to the benefit-risk of omecamtiv mecarbil, and we maintain our conviction in the strength of evidence supporting its potential benefit for patients suffering from HFrEF.”

He added that the company plans to engage constructively with the FDA as it completes its review of the application for omecamtiv mecarbil. 

The drug has a Prescription Drug User Fee Act target date of Feb. 28, 2023.

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

A panel of advisers to the Food and Drug Administration has recommended against approval of omecamtiv mecarbil (Cytokinetics) for the treatment of heart failure with reduced ejection fraction (HFrEF).

Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA Cardiovascular and Renal Drugs Advisory Committee on Dec. 13 voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF.

Those who voted in favor of the drug cited the clinical benefit (albeit small) and good safety profile of the drug as well as the unmet need for new treatments.

C. Noel Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles, said she voted yes “on the basis of need,” and her personal experience, as well as the data presented, that “up to half of severe heart failure patients are intolerant of guidelines directed medical therapy.”

Christopher M. O’Connor, MD, with Inova Heart and Vascular Institute, Falls Church, Va., who also voted in favor of approval for the drug, cited the “important unmet need,” and said he believes “a path was constructed in which one could go forward safely and with enhanced efficacy.

“It may be a narrow path, but I think it’s a path that would afford a lot of benefit to this high-risk patient population,” said Dr. O’Connor.

Those who voted against approval generally felt the benefit was not large enough and that more data are needed, given this is a first-in-class agent.

Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who voted no, said she was concerned that, despite the large size of the trial, “a more positive effect could not have been found.” She was also concerned that there was no benefit on quality of life or any other secondary outcomes. 

David J. Moliterno, MD, University of Kentucky Medical Center, Lexington, who also voted no, felt the benefits were “more singular and that being a modest reduction primarily limited to fewer outpatient visits.” Dr. Moliterno, like many of the committee members who voted no, called for more study.

The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.

As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.

This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.

The results were presented at the American Heart Association 2020 scientific sessions and simultaneously published in the New England Journal of Medicine.

In a statement, Robert I. Blum, president and CEO of Cytokinetics, said, “We are disappointed there was not a greater consensus amongst committee members relating to the benefit-risk of omecamtiv mecarbil, and we maintain our conviction in the strength of evidence supporting its potential benefit for patients suffering from HFrEF.”

He added that the company plans to engage constructively with the FDA as it completes its review of the application for omecamtiv mecarbil. 

The drug has a Prescription Drug User Fee Act target date of Feb. 28, 2023.

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

A panel of advisers to the Food and Drug Administration has recommended against approval of omecamtiv mecarbil (Cytokinetics) for the treatment of heart failure with reduced ejection fraction (HFrEF).

Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA Cardiovascular and Renal Drugs Advisory Committee on Dec. 13 voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF.

Those who voted in favor of the drug cited the clinical benefit (albeit small) and good safety profile of the drug as well as the unmet need for new treatments.

C. Noel Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles, said she voted yes “on the basis of need,” and her personal experience, as well as the data presented, that “up to half of severe heart failure patients are intolerant of guidelines directed medical therapy.”

Christopher M. O’Connor, MD, with Inova Heart and Vascular Institute, Falls Church, Va., who also voted in favor of approval for the drug, cited the “important unmet need,” and said he believes “a path was constructed in which one could go forward safely and with enhanced efficacy.

“It may be a narrow path, but I think it’s a path that would afford a lot of benefit to this high-risk patient population,” said Dr. O’Connor.

Those who voted against approval generally felt the benefit was not large enough and that more data are needed, given this is a first-in-class agent.

Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who voted no, said she was concerned that, despite the large size of the trial, “a more positive effect could not have been found.” She was also concerned that there was no benefit on quality of life or any other secondary outcomes. 

David J. Moliterno, MD, University of Kentucky Medical Center, Lexington, who also voted no, felt the benefits were “more singular and that being a modest reduction primarily limited to fewer outpatient visits.” Dr. Moliterno, like many of the committee members who voted no, called for more study.

The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.

As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.

This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.

The results were presented at the American Heart Association 2020 scientific sessions and simultaneously published in the New England Journal of Medicine.

In a statement, Robert I. Blum, president and CEO of Cytokinetics, said, “We are disappointed there was not a greater consensus amongst committee members relating to the benefit-risk of omecamtiv mecarbil, and we maintain our conviction in the strength of evidence supporting its potential benefit for patients suffering from HFrEF.”

He added that the company plans to engage constructively with the FDA as it completes its review of the application for omecamtiv mecarbil. 

The drug has a Prescription Drug User Fee Act target date of Feb. 28, 2023.

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

There are some benefits and potentially serious risks associated with complementary and alternative medicines (CAM) patients with heart failure (HF) may use to manage symptoms, the American Heart Association noted in a new scientific statement on the topic.

For example, yoga and tai chi can be helpful for people with HF, and omega-3 polyunsaturated fatty acids may also have benefits. However, there are safety concerns with other commonly used over-the-counter CAM therapies, including vitamin D, blue cohosh, and Lily of the Valley, the writing group said.

It’s estimated that roughly one in three patients with HF use CAM. But often patients don’t report their CAM use to their clinicians and clinicians may not routinely ask about CAM use or have the resources to evaluate CAM therapies, writing group chair Sheryl L. Chow, PharmD, told this news organization.

“This represents a major public health problem given that consumers are frequently purchasing these potentially dangerous and minimally regulated products without the knowledge or advice from a health care professional,” said Dr. Chow, of Western University of Health Sciences, Pomona, Calif., and University of California, Irvine.

The 27-page statement was published online in Circulation.
 

CAM use common in HF

The statement defines CAM as medical practices, supplements, and approaches that do not conform to the standards of conventional, evidence-based practice guidelines. CAM products are available without prescriptions or medical guidance at pharmacies, health food stores, and online retailers.

“These agents are largely unregulated by the [Food and Drug Administration] and manufacturers do not need to demonstrate efficacy or safety. It is important that both health care professionals and consumers improve communication with respect to OTC therapies and are educated about potential efficacy and risk of harm so that shared and informed decision-making can occur,” Dr. Chow said.

The writing group reviewed research published before November 2021 on CAM among people with HF.

Omega-3 polyunsaturated fatty acids (PUFAs), such as fish oil, have the strongest evidence among CAM agents for clinical benefit in HF and may be used safely by patients in moderation and in consultation with their health care team, the writing group said.

Research has shown that omega-3 PUFAs are associated with a lower risk of developing HF as well as improvements in left ventricular systolic function in those with existing HF, they pointed out.

However, two clinical trials found a higher incidence of atrial fibrillation with high-dose omega-3 PUFA administration. “This risk appears to be dose-related and increased when exceeding 2 g/d of fish oil,” the writing group said.

Research suggests that yoga and tai chi, when added to standard HF treatment, may help improve exercise tolerance and quality of life and decrease blood pressure.
 

Inconclusive or potentially harmful CAM therapies

Other CAM therapies for HF have been shown as ineffective based on current data, have mixed findings, or appear to be harmful. The writers highlighted the following examples:

• Overall evidence regarding the value of vitamin D supplementation in patients with HF remains “inconclusive” and may be harmful when taken with HF medications such as digoxin, calcium channel blockers, and diuretics.
• Routine thiamine supplementation in patients with HF and without clinically significant thiamine deficiency may not be efficacious and should be avoided.
• Research on alcohol varies, with some data showing that drinking low-to-moderate amounts (one to two drinks per day) may help prevent HF, while habitual drinking or consuming higher amounts is known to contribute to HF.
• The literature is mixed on vitamin E. It may have some benefit in reducing the risk of HF with preserved ejection fraction but has also been associated with an increased risk of HF hospitalization.
• Coenzyme Q10 (Co-Q10), commonly taken as a dietary supplement, may help improve HF class, symptoms, and quality of life, but it also may interact with antihypertensive and anticoagulant medication. Co-Q10 remains of “uncertain” value in HF at this time. Large-scale randomized controlled trials are needed before any definitive conclusion can be reached.
• Hawthorn, a flowering shrub, has been shown in some studies to increase exercise tolerance and improve HF symptoms such as fatigue. Yet it also has the potential to worsen HF, and there is conflicting research about whether it interacts with digoxin.
• The herbal supplement blue cohosh, from the root of a flowering plant found in hardwood forests, could cause tachycardia, high blood pressure, chest pain, and increased blood glucose. It may also decrease the effect of medications taken to treat high blood pressure and type 2 diabetes, they noted.
• Lily of the Valley, the root, stems, and flower of which are used in supplements, has long been used in mild HF because it contains active chemicals similar to digoxin. But when taken with digoxin, it could lead to hypokalemia.

In an AHA news release, Dr. Chow said, “Overall, more quality research and well-powered randomized controlled trials are needed to better understand the risks and benefits” of CAM therapies for HF.

“This scientific statement provides critical information to health care professionals who treat people with heart failure and may be used as a resource for consumers about the potential benefit and harm associated with complementary and alternative medicine products,” Dr. Chow added.

The writing group encourages health care professionals to routinely ask their HF patients about their use of CAM therapies. They also say pharmacists should be included in the multidisciplinary health care team to provide consultations about the use of CAM therapies for HF patients.

The scientific statement does not include cannabis or traditional Chinese medicine, which have also been used in HF.

In 2020, the AHA published a separate scientific statement on the use of medical marijuana and recreational cannabis on cardiovascular health, as reported previously by this news organization.

The scientific statement on CAM for HF was prepared by the volunteer writing group on behalf of the AHA Clinical Pharmacology Committee and Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; the Council on Epidemiology and Prevention; and the Council on Cardiovascular and Stroke Nursing.

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

There are some benefits and potentially serious risks associated with complementary and alternative medicines (CAM) patients with heart failure (HF) may use to manage symptoms, the American Heart Association noted in a new scientific statement on the topic.

For example, yoga and tai chi can be helpful for people with HF, and omega-3 polyunsaturated fatty acids may also have benefits. However, there are safety concerns with other commonly used over-the-counter CAM therapies, including vitamin D, blue cohosh, and Lily of the Valley, the writing group said.

It’s estimated that roughly one in three patients with HF use CAM. But often patients don’t report their CAM use to their clinicians and clinicians may not routinely ask about CAM use or have the resources to evaluate CAM therapies, writing group chair Sheryl L. Chow, PharmD, told this news organization.

“This represents a major public health problem given that consumers are frequently purchasing these potentially dangerous and minimally regulated products without the knowledge or advice from a health care professional,” said Dr. Chow, of Western University of Health Sciences, Pomona, Calif., and University of California, Irvine.

The 27-page statement was published online in Circulation.
 

CAM use common in HF

The statement defines CAM as medical practices, supplements, and approaches that do not conform to the standards of conventional, evidence-based practice guidelines. CAM products are available without prescriptions or medical guidance at pharmacies, health food stores, and online retailers.

“These agents are largely unregulated by the [Food and Drug Administration] and manufacturers do not need to demonstrate efficacy or safety. It is important that both health care professionals and consumers improve communication with respect to OTC therapies and are educated about potential efficacy and risk of harm so that shared and informed decision-making can occur,” Dr. Chow said.

The writing group reviewed research published before November 2021 on CAM among people with HF.

Omega-3 polyunsaturated fatty acids (PUFAs), such as fish oil, have the strongest evidence among CAM agents for clinical benefit in HF and may be used safely by patients in moderation and in consultation with their health care team, the writing group said.

Research has shown that omega-3 PUFAs are associated with a lower risk of developing HF as well as improvements in left ventricular systolic function in those with existing HF, they pointed out.

However, two clinical trials found a higher incidence of atrial fibrillation with high-dose omega-3 PUFA administration. “This risk appears to be dose-related and increased when exceeding 2 g/d of fish oil,” the writing group said.

Research suggests that yoga and tai chi, when added to standard HF treatment, may help improve exercise tolerance and quality of life and decrease blood pressure.
 

Inconclusive or potentially harmful CAM therapies

Other CAM therapies for HF have been shown as ineffective based on current data, have mixed findings, or appear to be harmful. The writers highlighted the following examples:

• Overall evidence regarding the value of vitamin D supplementation in patients with HF remains “inconclusive” and may be harmful when taken with HF medications such as digoxin, calcium channel blockers, and diuretics.
• Routine thiamine supplementation in patients with HF and without clinically significant thiamine deficiency may not be efficacious and should be avoided.
• Research on alcohol varies, with some data showing that drinking low-to-moderate amounts (one to two drinks per day) may help prevent HF, while habitual drinking or consuming higher amounts is known to contribute to HF.
• The literature is mixed on vitamin E. It may have some benefit in reducing the risk of HF with preserved ejection fraction but has also been associated with an increased risk of HF hospitalization.
• Coenzyme Q10 (Co-Q10), commonly taken as a dietary supplement, may help improve HF class, symptoms, and quality of life, but it also may interact with antihypertensive and anticoagulant medication. Co-Q10 remains of “uncertain” value in HF at this time. Large-scale randomized controlled trials are needed before any definitive conclusion can be reached.
• Hawthorn, a flowering shrub, has been shown in some studies to increase exercise tolerance and improve HF symptoms such as fatigue. Yet it also has the potential to worsen HF, and there is conflicting research about whether it interacts with digoxin.
• The herbal supplement blue cohosh, from the root of a flowering plant found in hardwood forests, could cause tachycardia, high blood pressure, chest pain, and increased blood glucose. It may also decrease the effect of medications taken to treat high blood pressure and type 2 diabetes, they noted.
• Lily of the Valley, the root, stems, and flower of which are used in supplements, has long been used in mild HF because it contains active chemicals similar to digoxin. But when taken with digoxin, it could lead to hypokalemia.

In an AHA news release, Dr. Chow said, “Overall, more quality research and well-powered randomized controlled trials are needed to better understand the risks and benefits” of CAM therapies for HF.

“This scientific statement provides critical information to health care professionals who treat people with heart failure and may be used as a resource for consumers about the potential benefit and harm associated with complementary and alternative medicine products,” Dr. Chow added.

The writing group encourages health care professionals to routinely ask their HF patients about their use of CAM therapies. They also say pharmacists should be included in the multidisciplinary health care team to provide consultations about the use of CAM therapies for HF patients.

The scientific statement does not include cannabis or traditional Chinese medicine, which have also been used in HF.

In 2020, the AHA published a separate scientific statement on the use of medical marijuana and recreational cannabis on cardiovascular health, as reported previously by this news organization.

The scientific statement on CAM for HF was prepared by the volunteer writing group on behalf of the AHA Clinical Pharmacology Committee and Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; the Council on Epidemiology and Prevention; and the Council on Cardiovascular and Stroke Nursing.

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

There are some benefits and potentially serious risks associated with complementary and alternative medicines (CAM) patients with heart failure (HF) may use to manage symptoms, the American Heart Association noted in a new scientific statement on the topic.

For example, yoga and tai chi can be helpful for people with HF, and omega-3 polyunsaturated fatty acids may also have benefits. However, there are safety concerns with other commonly used over-the-counter CAM therapies, including vitamin D, blue cohosh, and Lily of the Valley, the writing group said.

It’s estimated that roughly one in three patients with HF use CAM. But often patients don’t report their CAM use to their clinicians and clinicians may not routinely ask about CAM use or have the resources to evaluate CAM therapies, writing group chair Sheryl L. Chow, PharmD, told this news organization.

“This represents a major public health problem given that consumers are frequently purchasing these potentially dangerous and minimally regulated products without the knowledge or advice from a health care professional,” said Dr. Chow, of Western University of Health Sciences, Pomona, Calif., and University of California, Irvine.

The 27-page statement was published online in Circulation.
 

CAM use common in HF

The statement defines CAM as medical practices, supplements, and approaches that do not conform to the standards of conventional, evidence-based practice guidelines. CAM products are available without prescriptions or medical guidance at pharmacies, health food stores, and online retailers.

“These agents are largely unregulated by the [Food and Drug Administration] and manufacturers do not need to demonstrate efficacy or safety. It is important that both health care professionals and consumers improve communication with respect to OTC therapies and are educated about potential efficacy and risk of harm so that shared and informed decision-making can occur,” Dr. Chow said.

The writing group reviewed research published before November 2021 on CAM among people with HF.

Omega-3 polyunsaturated fatty acids (PUFAs), such as fish oil, have the strongest evidence among CAM agents for clinical benefit in HF and may be used safely by patients in moderation and in consultation with their health care team, the writing group said.

Research has shown that omega-3 PUFAs are associated with a lower risk of developing HF as well as improvements in left ventricular systolic function in those with existing HF, they pointed out.

However, two clinical trials found a higher incidence of atrial fibrillation with high-dose omega-3 PUFA administration. “This risk appears to be dose-related and increased when exceeding 2 g/d of fish oil,” the writing group said.

Research suggests that yoga and tai chi, when added to standard HF treatment, may help improve exercise tolerance and quality of life and decrease blood pressure.
 

Inconclusive or potentially harmful CAM therapies

Other CAM therapies for HF have been shown as ineffective based on current data, have mixed findings, or appear to be harmful. The writers highlighted the following examples:

• Overall evidence regarding the value of vitamin D supplementation in patients with HF remains “inconclusive” and may be harmful when taken with HF medications such as digoxin, calcium channel blockers, and diuretics.
• Routine thiamine supplementation in patients with HF and without clinically significant thiamine deficiency may not be efficacious and should be avoided.
• Research on alcohol varies, with some data showing that drinking low-to-moderate amounts (one to two drinks per day) may help prevent HF, while habitual drinking or consuming higher amounts is known to contribute to HF.
• The literature is mixed on vitamin E. It may have some benefit in reducing the risk of HF with preserved ejection fraction but has also been associated with an increased risk of HF hospitalization.
• Coenzyme Q10 (Co-Q10), commonly taken as a dietary supplement, may help improve HF class, symptoms, and quality of life, but it also may interact with antihypertensive and anticoagulant medication. Co-Q10 remains of “uncertain” value in HF at this time. Large-scale randomized controlled trials are needed before any definitive conclusion can be reached.
• Hawthorn, a flowering shrub, has been shown in some studies to increase exercise tolerance and improve HF symptoms such as fatigue. Yet it also has the potential to worsen HF, and there is conflicting research about whether it interacts with digoxin.
• The herbal supplement blue cohosh, from the root of a flowering plant found in hardwood forests, could cause tachycardia, high blood pressure, chest pain, and increased blood glucose. It may also decrease the effect of medications taken to treat high blood pressure and type 2 diabetes, they noted.
• Lily of the Valley, the root, stems, and flower of which are used in supplements, has long been used in mild HF because it contains active chemicals similar to digoxin. But when taken with digoxin, it could lead to hypokalemia.

In an AHA news release, Dr. Chow said, “Overall, more quality research and well-powered randomized controlled trials are needed to better understand the risks and benefits” of CAM therapies for HF.

“This scientific statement provides critical information to health care professionals who treat people with heart failure and may be used as a resource for consumers about the potential benefit and harm associated with complementary and alternative medicine products,” Dr. Chow added.

The writing group encourages health care professionals to routinely ask their HF patients about their use of CAM therapies. They also say pharmacists should be included in the multidisciplinary health care team to provide consultations about the use of CAM therapies for HF patients.

The scientific statement does not include cannabis or traditional Chinese medicine, which have also been used in HF.

In 2020, the AHA published a separate scientific statement on the use of medical marijuana and recreational cannabis on cardiovascular health, as reported previously by this news organization.

The scientific statement on CAM for HF was prepared by the volunteer writing group on behalf of the AHA Clinical Pharmacology Committee and Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; the Council on Epidemiology and Prevention; and the Council on Cardiovascular and Stroke Nursing.

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

The exploration started in 2004 with a 62-year-old man who presented to an emergency department with acute shortness of breath, tachycardia with chest discomfort, and light-headedness, Amado Alejandro Baez, MD, said in a presentation at the 2022 scientific assembly of the American College of Emergency Physicians.

The patient arrived on day 20 after a radical cystoprostatectomy. He had driven 4 hours from another city for a urology follow-up visit. On arrival, he developed respiratory distress symptoms and presented to the emergency department, said Dr. Baez, professor of emergency medicine and epidemiology at the Medical College of Georgia/Augusta University and triple-board certified in EMS, emergency medicine, and critical care.

The patient developed a massive pulmonary embolism with acute cor pulmonale (right-sided heart failure). An electrocardiogram showed an S1Q3T3, demonstrating the distinctive nature of right ventricular failure, said Dr. Baez.

Research has demonstrated the differences in physiology between the right and left ventricles, he said.

Dr. Baez highlighted some of the features of right ventricle (RV) failure and how to manage it. Notably, the RV is thinner and less resilient. “RV failure patients may fall off the Starling curve,” in contrast to patients with isolated left ventricle (LV) failure.

RV pressure overload is associated with a range of conditions, such as pericardial disease, pulmonary embolism, acute respiratory distress syndrome, and pulmonary arterial hypertension. When combined with RV overload, patients may develop intracardiac shunting or coronary heart disease, Dr. Baez said. Decreased contractility associated with RV failure can result from sepsis, right ventricular myocardial infarction, myocarditis, and arrhythmia.

Dr. Baez cited the 2018 scientific statement from the American Heart Association on the evaluation and management of right-sided heart failure. The authors of the statement noted that the complicated geometry of the right heart makes functional assessment a challenge. They wrote that various hemodynamic and biochemical markers can help guide clinical assessment and therapeutic decision-making.

Increased RV afterload drives multiple factors that can ultimately lead to cardiogenic shock and death, said Dr. Baez. These factors include decreased RV oxygen delivery, decreased RV coronary perfusion, decreased systemic blood pressure, and low carbon monoxide levels. RV afterload also leads to decreased RV contractility, an increase in RV oxygen demand, and tension in the RV wall, and it may contribute to tricuspid valve insufficiency, neurohormonal activation, and RV ischemia.

Treatment strategies involve improving symptoms and stopping disease progression, said Baez. In its scientific statement, the AHA recommends steps for assessing RV and LV function so as to identify RV failure as soon as possible, he said. After excluding pericardial disease, the AHA advises diagnosis and treatment of etiology-specific causes, such as right ventricular MI, pulmonary embolism, and sepsis. For arrhythmias, it recommends maintaining sinus rhythm when possible and considering a pacemaker to maintain atrioventricular synchrony and to avoid excessive bradycardia.

In its statement, the AHA also recommends optimizing preload with right arterial pressure/central venous pressure of 8-12 mm Hg, said Dr. Baez. Preload optimization combined with afterload reduction and improved contractility are hallmarks of care for patients with RV failure.

Avoiding systemic hypotension can prevent sequelae, such as myocardial ischemia and further hypotension, he said.

Optimization of fluid status is another key to managing RV failure, said Dr. Baez. Right heart coronary perfusion pressure can be protected by maintaining mean arterial pressure, and consideration should be given to reducing the RV afterload. Other strategies include inotropic medications and rhythm stabilization.

In general, for RV failure patients, “correct hypoxia, hypercarbia, and acidosis and avoid intubation when possible,” he said. Extracorporeal membrane oxygenation (ECMO) may be an option, depending on how many mechanical ventilator settings need to be adjusted.

In a study by Dr. Baez and colleagues published in Critical Care Medicine, the authors presented a Bayesian probability model for plasma lactate and severity of illness in cases of acute pulmonary embolism. “This Bayesian model demonstrated that the combination of shock index and lactate yield superior diagnostic gains than those compare to the sPESI and lactate,” Dr. Baez said.

The care model needs to be specific to the etiology, he added. Volume management in congested pulmonary hypertension involves a “squeeze and diurese” strategy.

According to the Internet Book of Critical Care, for patients with mean arterial pressure (MAP) of 60 mm Hg, central venous pressure (CVP) of 25 mm Hg, renal perfusion pressure of 25 mm Hg, and no urine output, a vasopressor should be added to treatment, Dr. Baez said. In cases in which the MAP 75 mm Hg, the CVP is 25 mm Hg, the renal perfusion pressure is 50 mm Hg, and the patient has good urine output, vasopressors should be continued and fluid should be removed through use of a diuretic. For patients with a MAP of 75 mm Hg, a CVP of 12 mm Hg, and renal perfusion pressure of 63 mm Hg who have good urine output, the diuretic and the vasopressor should be discontinued.

Dr. Baez also reviewed several clinical studies of the utility of acute mechanical circulatory support systems for RV failure.

In two small studies involving a heart pump and a right ventricular assistive device, the 30-day survival rate was approximately 72%-73%. A study of 179 patients involving ECMO showed an in-hospital mortality rate of 38.6%, he said.

Overall, “prompt diagnosis, hemodynamic support, and initiation of specific treatment” are the foundations of managing RV failure, he concluded.

Dr. Baez disclosed no relevant financial relationships.

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

The exploration started in 2004 with a 62-year-old man who presented to an emergency department with acute shortness of breath, tachycardia with chest discomfort, and light-headedness, Amado Alejandro Baez, MD, said in a presentation at the 2022 scientific assembly of the American College of Emergency Physicians.

The patient arrived on day 20 after a radical cystoprostatectomy. He had driven 4 hours from another city for a urology follow-up visit. On arrival, he developed respiratory distress symptoms and presented to the emergency department, said Dr. Baez, professor of emergency medicine and epidemiology at the Medical College of Georgia/Augusta University and triple-board certified in EMS, emergency medicine, and critical care.

The patient developed a massive pulmonary embolism with acute cor pulmonale (right-sided heart failure). An electrocardiogram showed an S1Q3T3, demonstrating the distinctive nature of right ventricular failure, said Dr. Baez.

Research has demonstrated the differences in physiology between the right and left ventricles, he said.

Dr. Baez highlighted some of the features of right ventricle (RV) failure and how to manage it. Notably, the RV is thinner and less resilient. “RV failure patients may fall off the Starling curve,” in contrast to patients with isolated left ventricle (LV) failure.

RV pressure overload is associated with a range of conditions, such as pericardial disease, pulmonary embolism, acute respiratory distress syndrome, and pulmonary arterial hypertension. When combined with RV overload, patients may develop intracardiac shunting or coronary heart disease, Dr. Baez said. Decreased contractility associated with RV failure can result from sepsis, right ventricular myocardial infarction, myocarditis, and arrhythmia.

Dr. Baez cited the 2018 scientific statement from the American Heart Association on the evaluation and management of right-sided heart failure. The authors of the statement noted that the complicated geometry of the right heart makes functional assessment a challenge. They wrote that various hemodynamic and biochemical markers can help guide clinical assessment and therapeutic decision-making.

Increased RV afterload drives multiple factors that can ultimately lead to cardiogenic shock and death, said Dr. Baez. These factors include decreased RV oxygen delivery, decreased RV coronary perfusion, decreased systemic blood pressure, and low carbon monoxide levels. RV afterload also leads to decreased RV contractility, an increase in RV oxygen demand, and tension in the RV wall, and it may contribute to tricuspid valve insufficiency, neurohormonal activation, and RV ischemia.

Treatment strategies involve improving symptoms and stopping disease progression, said Baez. In its scientific statement, the AHA recommends steps for assessing RV and LV function so as to identify RV failure as soon as possible, he said. After excluding pericardial disease, the AHA advises diagnosis and treatment of etiology-specific causes, such as right ventricular MI, pulmonary embolism, and sepsis. For arrhythmias, it recommends maintaining sinus rhythm when possible and considering a pacemaker to maintain atrioventricular synchrony and to avoid excessive bradycardia.

In its statement, the AHA also recommends optimizing preload with right arterial pressure/central venous pressure of 8-12 mm Hg, said Dr. Baez. Preload optimization combined with afterload reduction and improved contractility are hallmarks of care for patients with RV failure.

Avoiding systemic hypotension can prevent sequelae, such as myocardial ischemia and further hypotension, he said.

Optimization of fluid status is another key to managing RV failure, said Dr. Baez. Right heart coronary perfusion pressure can be protected by maintaining mean arterial pressure, and consideration should be given to reducing the RV afterload. Other strategies include inotropic medications and rhythm stabilization.

In general, for RV failure patients, “correct hypoxia, hypercarbia, and acidosis and avoid intubation when possible,” he said. Extracorporeal membrane oxygenation (ECMO) may be an option, depending on how many mechanical ventilator settings need to be adjusted.

In a study by Dr. Baez and colleagues published in Critical Care Medicine, the authors presented a Bayesian probability model for plasma lactate and severity of illness in cases of acute pulmonary embolism. “This Bayesian model demonstrated that the combination of shock index and lactate yield superior diagnostic gains than those compare to the sPESI and lactate,” Dr. Baez said.

The care model needs to be specific to the etiology, he added. Volume management in congested pulmonary hypertension involves a “squeeze and diurese” strategy.

According to the Internet Book of Critical Care, for patients with mean arterial pressure (MAP) of 60 mm Hg, central venous pressure (CVP) of 25 mm Hg, renal perfusion pressure of 25 mm Hg, and no urine output, a vasopressor should be added to treatment, Dr. Baez said. In cases in which the MAP 75 mm Hg, the CVP is 25 mm Hg, the renal perfusion pressure is 50 mm Hg, and the patient has good urine output, vasopressors should be continued and fluid should be removed through use of a diuretic. For patients with a MAP of 75 mm Hg, a CVP of 12 mm Hg, and renal perfusion pressure of 63 mm Hg who have good urine output, the diuretic and the vasopressor should be discontinued.

Dr. Baez also reviewed several clinical studies of the utility of acute mechanical circulatory support systems for RV failure.

In two small studies involving a heart pump and a right ventricular assistive device, the 30-day survival rate was approximately 72%-73%. A study of 179 patients involving ECMO showed an in-hospital mortality rate of 38.6%, he said.

Overall, “prompt diagnosis, hemodynamic support, and initiation of specific treatment” are the foundations of managing RV failure, he concluded.

Dr. Baez disclosed no relevant financial relationships.

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

The exploration started in 2004 with a 62-year-old man who presented to an emergency department with acute shortness of breath, tachycardia with chest discomfort, and light-headedness, Amado Alejandro Baez, MD, said in a presentation at the 2022 scientific assembly of the American College of Emergency Physicians.

The patient arrived on day 20 after a radical cystoprostatectomy. He had driven 4 hours from another city for a urology follow-up visit. On arrival, he developed respiratory distress symptoms and presented to the emergency department, said Dr. Baez, professor of emergency medicine and epidemiology at the Medical College of Georgia/Augusta University and triple-board certified in EMS, emergency medicine, and critical care.

The patient developed a massive pulmonary embolism with acute cor pulmonale (right-sided heart failure). An electrocardiogram showed an S1Q3T3, demonstrating the distinctive nature of right ventricular failure, said Dr. Baez.

Research has demonstrated the differences in physiology between the right and left ventricles, he said.

Dr. Baez highlighted some of the features of right ventricle (RV) failure and how to manage it. Notably, the RV is thinner and less resilient. “RV failure patients may fall off the Starling curve,” in contrast to patients with isolated left ventricle (LV) failure.

RV pressure overload is associated with a range of conditions, such as pericardial disease, pulmonary embolism, acute respiratory distress syndrome, and pulmonary arterial hypertension. When combined with RV overload, patients may develop intracardiac shunting or coronary heart disease, Dr. Baez said. Decreased contractility associated with RV failure can result from sepsis, right ventricular myocardial infarction, myocarditis, and arrhythmia.

Dr. Baez cited the 2018 scientific statement from the American Heart Association on the evaluation and management of right-sided heart failure. The authors of the statement noted that the complicated geometry of the right heart makes functional assessment a challenge. They wrote that various hemodynamic and biochemical markers can help guide clinical assessment and therapeutic decision-making.

Increased RV afterload drives multiple factors that can ultimately lead to cardiogenic shock and death, said Dr. Baez. These factors include decreased RV oxygen delivery, decreased RV coronary perfusion, decreased systemic blood pressure, and low carbon monoxide levels. RV afterload also leads to decreased RV contractility, an increase in RV oxygen demand, and tension in the RV wall, and it may contribute to tricuspid valve insufficiency, neurohormonal activation, and RV ischemia.

Treatment strategies involve improving symptoms and stopping disease progression, said Baez. In its scientific statement, the AHA recommends steps for assessing RV and LV function so as to identify RV failure as soon as possible, he said. After excluding pericardial disease, the AHA advises diagnosis and treatment of etiology-specific causes, such as right ventricular MI, pulmonary embolism, and sepsis. For arrhythmias, it recommends maintaining sinus rhythm when possible and considering a pacemaker to maintain atrioventricular synchrony and to avoid excessive bradycardia.

In its statement, the AHA also recommends optimizing preload with right arterial pressure/central venous pressure of 8-12 mm Hg, said Dr. Baez. Preload optimization combined with afterload reduction and improved contractility are hallmarks of care for patients with RV failure.

Avoiding systemic hypotension can prevent sequelae, such as myocardial ischemia and further hypotension, he said.

Optimization of fluid status is another key to managing RV failure, said Dr. Baez. Right heart coronary perfusion pressure can be protected by maintaining mean arterial pressure, and consideration should be given to reducing the RV afterload. Other strategies include inotropic medications and rhythm stabilization.

In general, for RV failure patients, “correct hypoxia, hypercarbia, and acidosis and avoid intubation when possible,” he said. Extracorporeal membrane oxygenation (ECMO) may be an option, depending on how many mechanical ventilator settings need to be adjusted.

In a study by Dr. Baez and colleagues published in Critical Care Medicine, the authors presented a Bayesian probability model for plasma lactate and severity of illness in cases of acute pulmonary embolism. “This Bayesian model demonstrated that the combination of shock index and lactate yield superior diagnostic gains than those compare to the sPESI and lactate,” Dr. Baez said.

The care model needs to be specific to the etiology, he added. Volume management in congested pulmonary hypertension involves a “squeeze and diurese” strategy.

According to the Internet Book of Critical Care, for patients with mean arterial pressure (MAP) of 60 mm Hg, central venous pressure (CVP) of 25 mm Hg, renal perfusion pressure of 25 mm Hg, and no urine output, a vasopressor should be added to treatment, Dr. Baez said. In cases in which the MAP 75 mm Hg, the CVP is 25 mm Hg, the renal perfusion pressure is 50 mm Hg, and the patient has good urine output, vasopressors should be continued and fluid should be removed through use of a diuretic. For patients with a MAP of 75 mm Hg, a CVP of 12 mm Hg, and renal perfusion pressure of 63 mm Hg who have good urine output, the diuretic and the vasopressor should be discontinued.

Dr. Baez also reviewed several clinical studies of the utility of acute mechanical circulatory support systems for RV failure.

In two small studies involving a heart pump and a right ventricular assistive device, the 30-day survival rate was approximately 72%-73%. A study of 179 patients involving ECMO showed an in-hospital mortality rate of 38.6%, he said.

Overall, “prompt diagnosis, hemodynamic support, and initiation of specific treatment” are the foundations of managing RV failure, he concluded.

Dr. Baez disclosed no relevant financial relationships.

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

CHICAGO – Extended follow-up of patients with heart failure enrolled in the RAFT trial strengthens the case for starting treatment early with a cardiac resynchronization therapy plus defibrillation (CRT-D) device in appropriate patients.

RAFT, which compared CRT-D with treatment with an implantable cardioverter defibrillator (ICD) alone, showed that the early survival benefit produced by CRT-D during an average 40-month follow-up in the original trial persisted during an additional mean follow-up of about 5 years. This result strengthens the case for starting treatment early with a CRT-D device in appropriate patients with heart failure.

Mitchel L. Zoler/MDedge News

During extended follow-up of more than half of the enrolled patients, out to an average of 7.6 years overall and to an average of 12.9 years among survivors, patients who received a CRT-D device had a significant 21% relative reduction in their rate of all-cause mortality compared with randomized patients who received an ICD and no cardiac resynchronization, John L. Sapp, MD, reported at the American Heart Association scientific sessions.

The primary results of RAFT were first reported in 2010.

This magnitude of a survival benefit among the patients originally randomized to CRT is “dramatic,” given that many of the comparator patients who initially received no CRT likely crossed over to receive a CRT-D device once the initial, randomized 4 years of the study finished, commented Lynne W. Stevenson, MD, director of cardiomyopathy and the Lisa M. Jacobson Professor of Cardiology at Vanderbilt University Medical Center in Nashville, Tenn., who was not involved with the study.

‘CRT can remap heart failure trajectory’

The new findings “strengthen our conviction that CRT can remap the trajectory” of selected patients with heart failure, and that “candidates for CRT should be vigorously identified,” Dr. Stevenson said in an interview.

She also noted that the benefit with extended follow-up was “strikingly parallel” to that seen at 12 years after the addition of an ACE inhibitor for mild heart failure during the 4 years of the landmark SOLVD trial. The new RAFT extended follow-up, as well as the 12-year follow-up of the SOLVD trial, “support the concept that longer follow-up reveals vital information not provided by the relatively short randomized trial period,” she said.

“The new data say ‘don’t delay starting CRT in appropriate patients with heart failure,’ and ‘don’t think of CRT as just a treatment that makes patients feel better.’

 

“The totality of these data shows that CRT also treats the underlying heart muscle weakness, which helps patients live longer. Previous data showed that patients with left bundle branch block eligible for CRT are unlikely to respond well to the usual, recommended heart medications so it is important to start treatment with CRT-D early,” declared Dr. Stevenson, who cochaired the session where Dr. Sapp gave his report.

RAFT randomized 1,798 patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of at least 120 msec to receive either a CRT-D or ICD device. The study’s primary endpoint was death from any cause or hospitalization for heart failure. After an average 40 months of randomized follow-up, the primary endpoint occurred in 40% of the patients with an ICD and in 33% of those with a CRT-D device, a significant 25% relative reduction linked with CRT-D use. Both endpoint components contributed to the combined result significantly and to about the same extent, and the incremental benefit from CRT-D was significant for patients with NYHA class II heart failure as well as for those with class III.

However, prespecified subgroup analyses showed that the incremental benefit from CRT-D was significantly limited to patients with an intrinsic QRS duration of at least 150 msec, while in those with a duration of 120-149 msec CRT-D had a neutral effect compared with ICD. The same pattern also appeared when the analysis split patients into those with a left bundle branch block, who significantly benefited from CRT-D, but the initial benefit was not apparent in patients with right bundle branch block.

A study subgroup with extended follow-up

The new, extended follow-up analysis presented by Dr. Sapp included 1,050 of the original 1,798 patients (58%) enrolled at any of eight participating Canadian centers that each enrolled at least 100 patients and followed them through the end of 2021 (the full study cohort came from 34 centers, including 10 centers outside Canada). This subgroup included 520 patients randomized to receive CRT-D and 530 who received an ICD. Although this was a post hoc subgroup analysis, the CRT-D and ICD arms matched closely in all measured baseline characteristics.

The prespecified primary outcome of this follow-up analysis was the rate of all-cause mortality. Because of their longer disease trajectory, this pared-down study cohort included many more patients with NYHA class II function, 803, and in this subgroup CRT-D exerted a significant 23% incremental reduction in mortality compared with ICD treatment. CRT-D also produced a 17% relative reduction in long-term mortality among patients with NYHA class III function at baseline, but this point estimate of relative benefit was not significant in this subgroup of just 247 patients, said Dr. Sapp, a cardiologist and professor at Dalhousie University & Nova Scotia Health in Halifax.

Based on the original RAFT results from 2010, as well as on evidence from several other trials, the current heart failure management guideline from the AHA, the American College of Cardiology, and the Heart Failure Society of America give the highest level of recommendation, level 1, for CRT in patients with a left ventricular ejection fraction of 35% or less, sinus rhythm with left bundle branch block, a QRS duration of at least 150 msec, and NYHA class II, III, or ambulatory IV symptoms while on guideline-directed medical therapy.

The guideline also gives class 2a (“can be useful”) or 2b (“may be considered”) recommendation for certain other heart failure patients, including those with a QRS duration of 120-149 msec, a left ventricular ejection fraction as high as 50%, no left bundle branch block, or NYHA class I symptoms.

Don’t wait to start CRT

Although this 2022 guideline, as well as earlier versions that had roughly similar recommendations for CRT for about a decade, have led to “common” use of CRT in appropriate patients in U.S. practice, “it has not been used as much as it should be, in part because there’s been a feeling that CRT mostly treats symptoms and so perhaps you can wait” to start it, said Dr. Stevenson.

The findings from the new, extended follow-up RAFT analysis give increased urgency to starting CRT “as soon as possible” in appropriate patients with heart failure, even before they stabilize on guideline-directed medical therapy, said Dr. Stevenson. She also downplayed any ambiguity in the RAFT findings about optimal medical therapy, which during the RAFT study included traditional triple therapy at a time before treatment with sacubitril/valsartan (Entresto) and sodium-glucose cotransporter 2 (SGLT2) inhibitors became recommended.

“There is no reason to think that these treatments will negate the benefit of CRT for patients with heart failure with reduced ejection fraction and a wide left bundle branch block,” Dr. Stevenson said.

She also believes that the extended follow-up results, which showed clear efficacy for CRT-D in patients with NYHA class II function, support the case for upgrading the current 2b recommendation for using CRT treatment in patients with NYHA class I function and ischemic heart failure to a 2a recommendation regardless of whether or not patients have coronary artery disease. “The difference between class I and class II depends more on a patient’s lifestyle rather than on the severity of their heart failure,” Dr. Stevenson noted. “The RAFT study results encourage us to reexamine the clinical class and timing for CRT” in the current heart failure guideline.

RAFT received partial sponsorship from Medtronic. Dr. Sapp has been a consultant to Abbott, Biosense Webster, Medtronic, and Varian and has received research funding from Abbott and Biosense Webster. Dr. Stevenson had no disclosures.

CHICAGO – Extended follow-up of patients with heart failure enrolled in the RAFT trial strengthens the case for starting treatment early with a cardiac resynchronization therapy plus defibrillation (CRT-D) device in appropriate patients.

RAFT, which compared CRT-D with treatment with an implantable cardioverter defibrillator (ICD) alone, showed that the early survival benefit produced by CRT-D during an average 40-month follow-up in the original trial persisted during an additional mean follow-up of about 5 years. This result strengthens the case for starting treatment early with a CRT-D device in appropriate patients with heart failure.

Mitchel L. Zoler/MDedge News

During extended follow-up of more than half of the enrolled patients, out to an average of 7.6 years overall and to an average of 12.9 years among survivors, patients who received a CRT-D device had a significant 21% relative reduction in their rate of all-cause mortality compared with randomized patients who received an ICD and no cardiac resynchronization, John L. Sapp, MD, reported at the American Heart Association scientific sessions.

The primary results of RAFT were first reported in 2010.

This magnitude of a survival benefit among the patients originally randomized to CRT is “dramatic,” given that many of the comparator patients who initially received no CRT likely crossed over to receive a CRT-D device once the initial, randomized 4 years of the study finished, commented Lynne W. Stevenson, MD, director of cardiomyopathy and the Lisa M. Jacobson Professor of Cardiology at Vanderbilt University Medical Center in Nashville, Tenn., who was not involved with the study.

‘CRT can remap heart failure trajectory’

The new findings “strengthen our conviction that CRT can remap the trajectory” of selected patients with heart failure, and that “candidates for CRT should be vigorously identified,” Dr. Stevenson said in an interview.

She also noted that the benefit with extended follow-up was “strikingly parallel” to that seen at 12 years after the addition of an ACE inhibitor for mild heart failure during the 4 years of the landmark SOLVD trial. The new RAFT extended follow-up, as well as the 12-year follow-up of the SOLVD trial, “support the concept that longer follow-up reveals vital information not provided by the relatively short randomized trial period,” she said.

“The new data say ‘don’t delay starting CRT in appropriate patients with heart failure,’ and ‘don’t think of CRT as just a treatment that makes patients feel better.’

 

“The totality of these data shows that CRT also treats the underlying heart muscle weakness, which helps patients live longer. Previous data showed that patients with left bundle branch block eligible for CRT are unlikely to respond well to the usual, recommended heart medications so it is important to start treatment with CRT-D early,” declared Dr. Stevenson, who cochaired the session where Dr. Sapp gave his report.

RAFT randomized 1,798 patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of at least 120 msec to receive either a CRT-D or ICD device. The study’s primary endpoint was death from any cause or hospitalization for heart failure. After an average 40 months of randomized follow-up, the primary endpoint occurred in 40% of the patients with an ICD and in 33% of those with a CRT-D device, a significant 25% relative reduction linked with CRT-D use. Both endpoint components contributed to the combined result significantly and to about the same extent, and the incremental benefit from CRT-D was significant for patients with NYHA class II heart failure as well as for those with class III.

However, prespecified subgroup analyses showed that the incremental benefit from CRT-D was significantly limited to patients with an intrinsic QRS duration of at least 150 msec, while in those with a duration of 120-149 msec CRT-D had a neutral effect compared with ICD. The same pattern also appeared when the analysis split patients into those with a left bundle branch block, who significantly benefited from CRT-D, but the initial benefit was not apparent in patients with right bundle branch block.

A study subgroup with extended follow-up

The new, extended follow-up analysis presented by Dr. Sapp included 1,050 of the original 1,798 patients (58%) enrolled at any of eight participating Canadian centers that each enrolled at least 100 patients and followed them through the end of 2021 (the full study cohort came from 34 centers, including 10 centers outside Canada). This subgroup included 520 patients randomized to receive CRT-D and 530 who received an ICD. Although this was a post hoc subgroup analysis, the CRT-D and ICD arms matched closely in all measured baseline characteristics.

The prespecified primary outcome of this follow-up analysis was the rate of all-cause mortality. Because of their longer disease trajectory, this pared-down study cohort included many more patients with NYHA class II function, 803, and in this subgroup CRT-D exerted a significant 23% incremental reduction in mortality compared with ICD treatment. CRT-D also produced a 17% relative reduction in long-term mortality among patients with NYHA class III function at baseline, but this point estimate of relative benefit was not significant in this subgroup of just 247 patients, said Dr. Sapp, a cardiologist and professor at Dalhousie University & Nova Scotia Health in Halifax.

Based on the original RAFT results from 2010, as well as on evidence from several other trials, the current heart failure management guideline from the AHA, the American College of Cardiology, and the Heart Failure Society of America give the highest level of recommendation, level 1, for CRT in patients with a left ventricular ejection fraction of 35% or less, sinus rhythm with left bundle branch block, a QRS duration of at least 150 msec, and NYHA class II, III, or ambulatory IV symptoms while on guideline-directed medical therapy.

The guideline also gives class 2a (“can be useful”) or 2b (“may be considered”) recommendation for certain other heart failure patients, including those with a QRS duration of 120-149 msec, a left ventricular ejection fraction as high as 50%, no left bundle branch block, or NYHA class I symptoms.

Don’t wait to start CRT

Although this 2022 guideline, as well as earlier versions that had roughly similar recommendations for CRT for about a decade, have led to “common” use of CRT in appropriate patients in U.S. practice, “it has not been used as much as it should be, in part because there’s been a feeling that CRT mostly treats symptoms and so perhaps you can wait” to start it, said Dr. Stevenson.

The findings from the new, extended follow-up RAFT analysis give increased urgency to starting CRT “as soon as possible” in appropriate patients with heart failure, even before they stabilize on guideline-directed medical therapy, said Dr. Stevenson. She also downplayed any ambiguity in the RAFT findings about optimal medical therapy, which during the RAFT study included traditional triple therapy at a time before treatment with sacubitril/valsartan (Entresto) and sodium-glucose cotransporter 2 (SGLT2) inhibitors became recommended.

“There is no reason to think that these treatments will negate the benefit of CRT for patients with heart failure with reduced ejection fraction and a wide left bundle branch block,” Dr. Stevenson said.

She also believes that the extended follow-up results, which showed clear efficacy for CRT-D in patients with NYHA class II function, support the case for upgrading the current 2b recommendation for using CRT treatment in patients with NYHA class I function and ischemic heart failure to a 2a recommendation regardless of whether or not patients have coronary artery disease. “The difference between class I and class II depends more on a patient’s lifestyle rather than on the severity of their heart failure,” Dr. Stevenson noted. “The RAFT study results encourage us to reexamine the clinical class and timing for CRT” in the current heart failure guideline.

RAFT received partial sponsorship from Medtronic. Dr. Sapp has been a consultant to Abbott, Biosense Webster, Medtronic, and Varian and has received research funding from Abbott and Biosense Webster. Dr. Stevenson had no disclosures.

CHICAGO – Extended follow-up of patients with heart failure enrolled in the RAFT trial strengthens the case for starting treatment early with a cardiac resynchronization therapy plus defibrillation (CRT-D) device in appropriate patients.

RAFT, which compared CRT-D with treatment with an implantable cardioverter defibrillator (ICD) alone, showed that the early survival benefit produced by CRT-D during an average 40-month follow-up in the original trial persisted during an additional mean follow-up of about 5 years. This result strengthens the case for starting treatment early with a CRT-D device in appropriate patients with heart failure.

Mitchel L. Zoler/MDedge News

During extended follow-up of more than half of the enrolled patients, out to an average of 7.6 years overall and to an average of 12.9 years among survivors, patients who received a CRT-D device had a significant 21% relative reduction in their rate of all-cause mortality compared with randomized patients who received an ICD and no cardiac resynchronization, John L. Sapp, MD, reported at the American Heart Association scientific sessions.

The primary results of RAFT were first reported in 2010.

This magnitude of a survival benefit among the patients originally randomized to CRT is “dramatic,” given that many of the comparator patients who initially received no CRT likely crossed over to receive a CRT-D device once the initial, randomized 4 years of the study finished, commented Lynne W. Stevenson, MD, director of cardiomyopathy and the Lisa M. Jacobson Professor of Cardiology at Vanderbilt University Medical Center in Nashville, Tenn., who was not involved with the study.

‘CRT can remap heart failure trajectory’

The new findings “strengthen our conviction that CRT can remap the trajectory” of selected patients with heart failure, and that “candidates for CRT should be vigorously identified,” Dr. Stevenson said in an interview.

She also noted that the benefit with extended follow-up was “strikingly parallel” to that seen at 12 years after the addition of an ACE inhibitor for mild heart failure during the 4 years of the landmark SOLVD trial. The new RAFT extended follow-up, as well as the 12-year follow-up of the SOLVD trial, “support the concept that longer follow-up reveals vital information not provided by the relatively short randomized trial period,” she said.

“The new data say ‘don’t delay starting CRT in appropriate patients with heart failure,’ and ‘don’t think of CRT as just a treatment that makes patients feel better.’

 

“The totality of these data shows that CRT also treats the underlying heart muscle weakness, which helps patients live longer. Previous data showed that patients with left bundle branch block eligible for CRT are unlikely to respond well to the usual, recommended heart medications so it is important to start treatment with CRT-D early,” declared Dr. Stevenson, who cochaired the session where Dr. Sapp gave his report.

RAFT randomized 1,798 patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of at least 120 msec to receive either a CRT-D or ICD device. The study’s primary endpoint was death from any cause or hospitalization for heart failure. After an average 40 months of randomized follow-up, the primary endpoint occurred in 40% of the patients with an ICD and in 33% of those with a CRT-D device, a significant 25% relative reduction linked with CRT-D use. Both endpoint components contributed to the combined result significantly and to about the same extent, and the incremental benefit from CRT-D was significant for patients with NYHA class II heart failure as well as for those with class III.

However, prespecified subgroup analyses showed that the incremental benefit from CRT-D was significantly limited to patients with an intrinsic QRS duration of at least 150 msec, while in those with a duration of 120-149 msec CRT-D had a neutral effect compared with ICD. The same pattern also appeared when the analysis split patients into those with a left bundle branch block, who significantly benefited from CRT-D, but the initial benefit was not apparent in patients with right bundle branch block.

A study subgroup with extended follow-up

The new, extended follow-up analysis presented by Dr. Sapp included 1,050 of the original 1,798 patients (58%) enrolled at any of eight participating Canadian centers that each enrolled at least 100 patients and followed them through the end of 2021 (the full study cohort came from 34 centers, including 10 centers outside Canada). This subgroup included 520 patients randomized to receive CRT-D and 530 who received an ICD. Although this was a post hoc subgroup analysis, the CRT-D and ICD arms matched closely in all measured baseline characteristics.

The prespecified primary outcome of this follow-up analysis was the rate of all-cause mortality. Because of their longer disease trajectory, this pared-down study cohort included many more patients with NYHA class II function, 803, and in this subgroup CRT-D exerted a significant 23% incremental reduction in mortality compared with ICD treatment. CRT-D also produced a 17% relative reduction in long-term mortality among patients with NYHA class III function at baseline, but this point estimate of relative benefit was not significant in this subgroup of just 247 patients, said Dr. Sapp, a cardiologist and professor at Dalhousie University & Nova Scotia Health in Halifax.

Based on the original RAFT results from 2010, as well as on evidence from several other trials, the current heart failure management guideline from the AHA, the American College of Cardiology, and the Heart Failure Society of America give the highest level of recommendation, level 1, for CRT in patients with a left ventricular ejection fraction of 35% or less, sinus rhythm with left bundle branch block, a QRS duration of at least 150 msec, and NYHA class II, III, or ambulatory IV symptoms while on guideline-directed medical therapy.

The guideline also gives class 2a (“can be useful”) or 2b (“may be considered”) recommendation for certain other heart failure patients, including those with a QRS duration of 120-149 msec, a left ventricular ejection fraction as high as 50%, no left bundle branch block, or NYHA class I symptoms.

Don’t wait to start CRT

Although this 2022 guideline, as well as earlier versions that had roughly similar recommendations for CRT for about a decade, have led to “common” use of CRT in appropriate patients in U.S. practice, “it has not been used as much as it should be, in part because there’s been a feeling that CRT mostly treats symptoms and so perhaps you can wait” to start it, said Dr. Stevenson.

The findings from the new, extended follow-up RAFT analysis give increased urgency to starting CRT “as soon as possible” in appropriate patients with heart failure, even before they stabilize on guideline-directed medical therapy, said Dr. Stevenson. She also downplayed any ambiguity in the RAFT findings about optimal medical therapy, which during the RAFT study included traditional triple therapy at a time before treatment with sacubitril/valsartan (Entresto) and sodium-glucose cotransporter 2 (SGLT2) inhibitors became recommended.

“There is no reason to think that these treatments will negate the benefit of CRT for patients with heart failure with reduced ejection fraction and a wide left bundle branch block,” Dr. Stevenson said.

She also believes that the extended follow-up results, which showed clear efficacy for CRT-D in patients with NYHA class II function, support the case for upgrading the current 2b recommendation for using CRT treatment in patients with NYHA class I function and ischemic heart failure to a 2a recommendation regardless of whether or not patients have coronary artery disease. “The difference between class I and class II depends more on a patient’s lifestyle rather than on the severity of their heart failure,” Dr. Stevenson noted. “The RAFT study results encourage us to reexamine the clinical class and timing for CRT” in the current heart failure guideline.

RAFT received partial sponsorship from Medtronic. Dr. Sapp has been a consultant to Abbott, Biosense Webster, Medtronic, and Varian and has received research funding from Abbott and Biosense Webster. Dr. Stevenson had no disclosures.

Heart failure associated with illicit use of the psychostimulant methamphetamine (methHF) is increasing in the United States and around the world across racial, ethnic, and socioeconomic groups, a literature review indicates.

MethHF is associated with increased severity for HF, longer inpatient stay, and more readmissions, compared with non-MethHF, the data show.

Clinicians “need to consider methamphetamine as a potential etiology for heart failure and include a substance use history when evaluating patients. Treating methamphetamine use disorder improves heart failure outcomes,” first author Veena Manja, MD, PhD, with Stanford (Calif.) University, said in an interview.

The study was published online in the journal Heart.
 

Poor outcomes, ‘staggering’ costs

This “thoughtful” review is “important and necessary,” Jonathan Davis, MD, director of the heart failure program, Zuckerberg San Francisco General Hospital, wrote in an editorial in the journal.

Dr. Davis noted that patients with Meth HF are at increased risk for poor outcomes and death and the health care costs related to MethHF are “staggering.”

As an example, inpatient data for California show annual charges related to MethHF rose by 840% from 2008 to 2018, from $41.5 million to $390.2 million, compared with 82% for all HF, which rose from $3.5 billion to $6.8 billion.

Illicit use of methamphetamine – also known as “crystal meth,” “ice,” and “speed” – has been linked to hypertension, MI, stroke, aortic dissection, and sudden death. But until now, there was no comprehensive systematic review of published studies on MethHF.

“Our goal was to compile current knowledge on the topic, increase awareness of this condition and identify areas for future research,” Dr. Manja said.

The researchers reviewed 21 observational studies, mostly from the United States (14 from California), between 1997 and 2020. The mean age of adults with MethHF ranged in age from 35 to 60 and more than half were male (57%).

Illicit methamphetamine was inhaled, injected, swallowed, smoked, and snorted. The reported frequency ranged from daily to every other week, and the total monthly dose ranged from 0.35 g to 24.5 g.

The average duration of meth use before HF diagnosis was 5 years. However, 18% of users developed HF within 1 year of starting to use illicit methamphetamine. In some cases, HF was diagnosed after a single use.

The researchers also note that MethHF with preserved left ventricular ejection fraction, seen in up to 44% of cases, is a distinct entity that may progress to reduced LVEF with continued use.

MethHF is also associated with a greater likelihood of other substance abuse, PTSD, depression, and other heart and kidney disease.

Factors associated with improved MethHF outcomes include female sex, meth abstinence, and adherence to guideline-directed HF therapy.

Improvement in MethHF outcomes is possible even if abstinence is not consistent, a finding that lends support to harm reduction principles of “meeting patients where they are instead of insisting on complete abstinence,” the researchers said.
 

Large gaps in knowledge

They were unable to combine the results into a meta-analysis because of heterogeneity in study design, population, comparator, and outcome assessment. Also, the overall risk of bias is moderate because of the presence of confounders, selection bias and poor matching, and the overall certainty in the evidence is very low,.

No study evaluated the incidence or prevalence of HF among methamphetamine users and inconsistent history taking and testing in patients with HF impeded accurate MethHF prevalence assessment.

Several studies, however, document an increasing incidence of MethHF, particularly over the past decade.

One study from California reported a 585% increase in MethHF hospital admissions between 2008 and 2018. An analysis of the National Inpatient Survey found a 12-fold increase in annual MethHF hospitalizations between 2002 and 2014.

“The results of this systematic review highlight large gaps in our knowledge” of MethHF, Dr. Manja said in an interview.

“We need to understand the epidemiology, prevalence, factors that confer susceptibility to cardiovascular outcomes, and need research into treatment targeted toward this disease,” Dr. Manja added. “We should consider options to integrate substance use treatment in HF/cardiology/primary care clinics and design a multidisciplinary patient-centered approach.”

Dr. Davis agreed. This work “highlights that the standard of care academically and clinically must be a broad team across the care spectrum to simultaneously address methamphetamine use, heart failure, and social determinants of health.”

This research had no specific funding. Dr. Manja and Dr. Davis reported no relevant disclosures.

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

Heart failure associated with illicit use of the psychostimulant methamphetamine (methHF) is increasing in the United States and around the world across racial, ethnic, and socioeconomic groups, a literature review indicates.

MethHF is associated with increased severity for HF, longer inpatient stay, and more readmissions, compared with non-MethHF, the data show.

Clinicians “need to consider methamphetamine as a potential etiology for heart failure and include a substance use history when evaluating patients. Treating methamphetamine use disorder improves heart failure outcomes,” first author Veena Manja, MD, PhD, with Stanford (Calif.) University, said in an interview.

The study was published online in the journal Heart.
 

Poor outcomes, ‘staggering’ costs

This “thoughtful” review is “important and necessary,” Jonathan Davis, MD, director of the heart failure program, Zuckerberg San Francisco General Hospital, wrote in an editorial in the journal.

Dr. Davis noted that patients with Meth HF are at increased risk for poor outcomes and death and the health care costs related to MethHF are “staggering.”

As an example, inpatient data for California show annual charges related to MethHF rose by 840% from 2008 to 2018, from $41.5 million to $390.2 million, compared with 82% for all HF, which rose from $3.5 billion to $6.8 billion.

Illicit use of methamphetamine – also known as “crystal meth,” “ice,” and “speed” – has been linked to hypertension, MI, stroke, aortic dissection, and sudden death. But until now, there was no comprehensive systematic review of published studies on MethHF.

“Our goal was to compile current knowledge on the topic, increase awareness of this condition and identify areas for future research,” Dr. Manja said.

The researchers reviewed 21 observational studies, mostly from the United States (14 from California), between 1997 and 2020. The mean age of adults with MethHF ranged in age from 35 to 60 and more than half were male (57%).

Illicit methamphetamine was inhaled, injected, swallowed, smoked, and snorted. The reported frequency ranged from daily to every other week, and the total monthly dose ranged from 0.35 g to 24.5 g.

The average duration of meth use before HF diagnosis was 5 years. However, 18% of users developed HF within 1 year of starting to use illicit methamphetamine. In some cases, HF was diagnosed after a single use.

The researchers also note that MethHF with preserved left ventricular ejection fraction, seen in up to 44% of cases, is a distinct entity that may progress to reduced LVEF with continued use.

MethHF is also associated with a greater likelihood of other substance abuse, PTSD, depression, and other heart and kidney disease.

Factors associated with improved MethHF outcomes include female sex, meth abstinence, and adherence to guideline-directed HF therapy.

Improvement in MethHF outcomes is possible even if abstinence is not consistent, a finding that lends support to harm reduction principles of “meeting patients where they are instead of insisting on complete abstinence,” the researchers said.
 

Large gaps in knowledge

They were unable to combine the results into a meta-analysis because of heterogeneity in study design, population, comparator, and outcome assessment. Also, the overall risk of bias is moderate because of the presence of confounders, selection bias and poor matching, and the overall certainty in the evidence is very low,.

No study evaluated the incidence or prevalence of HF among methamphetamine users and inconsistent history taking and testing in patients with HF impeded accurate MethHF prevalence assessment.

Several studies, however, document an increasing incidence of MethHF, particularly over the past decade.

One study from California reported a 585% increase in MethHF hospital admissions between 2008 and 2018. An analysis of the National Inpatient Survey found a 12-fold increase in annual MethHF hospitalizations between 2002 and 2014.

“The results of this systematic review highlight large gaps in our knowledge” of MethHF, Dr. Manja said in an interview.

“We need to understand the epidemiology, prevalence, factors that confer susceptibility to cardiovascular outcomes, and need research into treatment targeted toward this disease,” Dr. Manja added. “We should consider options to integrate substance use treatment in HF/cardiology/primary care clinics and design a multidisciplinary patient-centered approach.”

Dr. Davis agreed. This work “highlights that the standard of care academically and clinically must be a broad team across the care spectrum to simultaneously address methamphetamine use, heart failure, and social determinants of health.”

This research had no specific funding. Dr. Manja and Dr. Davis reported no relevant disclosures.

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

Heart failure associated with illicit use of the psychostimulant methamphetamine (methHF) is increasing in the United States and around the world across racial, ethnic, and socioeconomic groups, a literature review indicates.

MethHF is associated with increased severity for HF, longer inpatient stay, and more readmissions, compared with non-MethHF, the data show.

Clinicians “need to consider methamphetamine as a potential etiology for heart failure and include a substance use history when evaluating patients. Treating methamphetamine use disorder improves heart failure outcomes,” first author Veena Manja, MD, PhD, with Stanford (Calif.) University, said in an interview.

The study was published online in the journal Heart.
 

Poor outcomes, ‘staggering’ costs

This “thoughtful” review is “important and necessary,” Jonathan Davis, MD, director of the heart failure program, Zuckerberg San Francisco General Hospital, wrote in an editorial in the journal.

Dr. Davis noted that patients with Meth HF are at increased risk for poor outcomes and death and the health care costs related to MethHF are “staggering.”

As an example, inpatient data for California show annual charges related to MethHF rose by 840% from 2008 to 2018, from $41.5 million to $390.2 million, compared with 82% for all HF, which rose from $3.5 billion to $6.8 billion.

Illicit use of methamphetamine – also known as “crystal meth,” “ice,” and “speed” – has been linked to hypertension, MI, stroke, aortic dissection, and sudden death. But until now, there was no comprehensive systematic review of published studies on MethHF.

“Our goal was to compile current knowledge on the topic, increase awareness of this condition and identify areas for future research,” Dr. Manja said.

The researchers reviewed 21 observational studies, mostly from the United States (14 from California), between 1997 and 2020. The mean age of adults with MethHF ranged in age from 35 to 60 and more than half were male (57%).

Illicit methamphetamine was inhaled, injected, swallowed, smoked, and snorted. The reported frequency ranged from daily to every other week, and the total monthly dose ranged from 0.35 g to 24.5 g.

The average duration of meth use before HF diagnosis was 5 years. However, 18% of users developed HF within 1 year of starting to use illicit methamphetamine. In some cases, HF was diagnosed after a single use.

The researchers also note that MethHF with preserved left ventricular ejection fraction, seen in up to 44% of cases, is a distinct entity that may progress to reduced LVEF with continued use.

MethHF is also associated with a greater likelihood of other substance abuse, PTSD, depression, and other heart and kidney disease.

Factors associated with improved MethHF outcomes include female sex, meth abstinence, and adherence to guideline-directed HF therapy.

Improvement in MethHF outcomes is possible even if abstinence is not consistent, a finding that lends support to harm reduction principles of “meeting patients where they are instead of insisting on complete abstinence,” the researchers said.
 

Large gaps in knowledge

They were unable to combine the results into a meta-analysis because of heterogeneity in study design, population, comparator, and outcome assessment. Also, the overall risk of bias is moderate because of the presence of confounders, selection bias and poor matching, and the overall certainty in the evidence is very low,.

No study evaluated the incidence or prevalence of HF among methamphetamine users and inconsistent history taking and testing in patients with HF impeded accurate MethHF prevalence assessment.

Several studies, however, document an increasing incidence of MethHF, particularly over the past decade.

One study from California reported a 585% increase in MethHF hospital admissions between 2008 and 2018. An analysis of the National Inpatient Survey found a 12-fold increase in annual MethHF hospitalizations between 2002 and 2014.

“The results of this systematic review highlight large gaps in our knowledge” of MethHF, Dr. Manja said in an interview.

“We need to understand the epidemiology, prevalence, factors that confer susceptibility to cardiovascular outcomes, and need research into treatment targeted toward this disease,” Dr. Manja added. “We should consider options to integrate substance use treatment in HF/cardiology/primary care clinics and design a multidisciplinary patient-centered approach.”

Dr. Davis agreed. This work “highlights that the standard of care academically and clinically must be a broad team across the care spectrum to simultaneously address methamphetamine use, heart failure, and social determinants of health.”

This research had no specific funding. Dr. Manja and Dr. Davis reported no relevant disclosures.

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

The U.S. Food and Drug Administration has updated the Abiomed Impella RP System’s approved indications in a way that “better reflects the characteristics of the patients who may benefit the most from treatment with the device,” the agency has announced.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The revised language reflects the final results of a postapproval study in which survival rates for patients who met the premarket-study entry criteria were comparable to rates seen in the premarket studies, the FDA observed.

The postapproval study “further confirms that the device is safe and effective when used for the currently approved indication.” The indication’s added words, however, tighten the description of eligible patients in a way that more precisely reflects the premarket-study population.

The update states that the Impella RP System is “indicated for providing temporary right ventricular support for up to 14 days in patients with a body surface area ≥ 1.5 m², who develop acute right heart failure or decompensation for less than 48 hours following left ventricular assist device implantation, myocardial infarction, heart transplant, or open heart surgery, without the presence of profound shock, end organ failure, or acute neurologic injury.”

The FDA “believes that when the device is used for the currently approved indication in appropriately selected patients, the benefits of the Impella RP System continue to outweigh the risks.”

The reworded indication is the latest among several updates to the agency’s February 2019 letter to clinicians noting a signal of increased mortality associated with the Impella RP device in an interim analysis of the same postapproval study. Ultimately, no such signal has emerged among the subset of postapproval patients who would have been eligible for the premarket study.

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

The U.S. Food and Drug Administration has updated the Abiomed Impella RP System’s approved indications in a way that “better reflects the characteristics of the patients who may benefit the most from treatment with the device,” the agency has announced.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The revised language reflects the final results of a postapproval study in which survival rates for patients who met the premarket-study entry criteria were comparable to rates seen in the premarket studies, the FDA observed.

The postapproval study “further confirms that the device is safe and effective when used for the currently approved indication.” The indication’s added words, however, tighten the description of eligible patients in a way that more precisely reflects the premarket-study population.

The update states that the Impella RP System is “indicated for providing temporary right ventricular support for up to 14 days in patients with a body surface area ≥ 1.5 m², who develop acute right heart failure or decompensation for less than 48 hours following left ventricular assist device implantation, myocardial infarction, heart transplant, or open heart surgery, without the presence of profound shock, end organ failure, or acute neurologic injury.”

The FDA “believes that when the device is used for the currently approved indication in appropriately selected patients, the benefits of the Impella RP System continue to outweigh the risks.”

The reworded indication is the latest among several updates to the agency’s February 2019 letter to clinicians noting a signal of increased mortality associated with the Impella RP device in an interim analysis of the same postapproval study. Ultimately, no such signal has emerged among the subset of postapproval patients who would have been eligible for the premarket study.

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

The U.S. Food and Drug Administration has updated the Abiomed Impella RP System’s approved indications in a way that “better reflects the characteristics of the patients who may benefit the most from treatment with the device,” the agency has announced.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The revised language reflects the final results of a postapproval study in which survival rates for patients who met the premarket-study entry criteria were comparable to rates seen in the premarket studies, the FDA observed.

The postapproval study “further confirms that the device is safe and effective when used for the currently approved indication.” The indication’s added words, however, tighten the description of eligible patients in a way that more precisely reflects the premarket-study population.

The update states that the Impella RP System is “indicated for providing temporary right ventricular support for up to 14 days in patients with a body surface area ≥ 1.5 m², who develop acute right heart failure or decompensation for less than 48 hours following left ventricular assist device implantation, myocardial infarction, heart transplant, or open heart surgery, without the presence of profound shock, end organ failure, or acute neurologic injury.”

The FDA “believes that when the device is used for the currently approved indication in appropriately selected patients, the benefits of the Impella RP System continue to outweigh the risks.”

The reworded indication is the latest among several updates to the agency’s February 2019 letter to clinicians noting a signal of increased mortality associated with the Impella RP device in an interim analysis of the same postapproval study. Ultimately, no such signal has emerged among the subset of postapproval patients who would have been eligible for the premarket study.

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