Heart failure with preserved EF: more respect for exercise?

LONG BEACH, Calif. Supervised exercise has enormous potential to improve outcomes for people with heart failure with preserved ejection fraction (HFpEF). That was a message in a session on heart failure in elderly patients at the 2023 American Geriatrics Society (AGS) Annual Scientific Meeting.

HFpEF accounts for about half of all heart failure cases and affects about 10 percent of Americans over the age of 75. In a scientific statement released in March 2023 by the American Heart Association and the American College of Cardiology, experts said that supervised exercise training, unlike most drugs, produced a sustained improvement in exercise capacity for people with HFpEF.

Speakers also discussed the latest information on risks, diagnosis, drug management, and inequalities in access to care.

Supervised exercise

The case for physical rehabilitation, or supervised exercise training, to help patients with HFpEF is strong, said Amy M. Pastva, PT, MA, PhD, professor of orthopedics, medicine, population health, and cell biology at the Duke University School of Medicine, in Durham, North Carolina. Pastva cited the scientific statement, published studies, and an ongoing multicenter study funded by the National Institute on Aging.

“When we review studies of exercise-based interventions in chronic HFpEF, we’ve consistently demonstrated these large, meaningful, and clinically meaningful improvements in symptoms, exercise capacity, and usually quality of life,” she said.

These can be attributed to the pleiotropic effects of such training, he said, and can influence the full range of abnormalities that contribute to exercise intolerance. These peripheral effects may lead to changes in exercise capacity. “What we don’t know yet in these studies is whether it affects clinical events,” she said. “But exercise capacity or cardiorespiratory fitness is an independent and clinically significant patient outcome.”

Pastva highlighted some of the studies cited in the scientific statement showing positive results. However, he said, gaps remain and information is needed about how much exercise is ideal, among other questions. “We know about the short term, but not so much about the long term,” he said she.

Another interesting area of ​​research, Pastva said, is the effect of combining interventions, such as weight loss, with supervised exercise. She cited a recently published study that focused on the effect of adding resistance training to calorie restriction and exercise for patients with HFpEF and obesity. The researchers found a dramatic improvement in VO2₂peak and quality of life with restriction and training; the addition of resistance training increased leg strength and muscle quality with no additional effect on either measure.

“The addition of resistance training to calorie restriction was well tolerated,” she said. Physical rehabilitation that begins during a hospital stay and continues for 3 months afterward could also help frail and elderly patients who are hospitalized for acute decompensated heart failure with HFpEF, Pastva said, citing his research and that of other groups.

These ideas led to the REHAB-HFpEF study, which started earlier this year. The study is expected to be completed by 2025. The study aims to follow up to 880 older men and women with HFpEF who have been hospitalized for heart failure. Participants will be randomly assigned before discharge to either undergo physical rehabilitation three times a week for 12 weeks or receive conventional care. The primary outcome is hospitalization and death at 6 months.

Other speakers updated epidemiology, diagnosis, pharmacology and inequities.

Epidemiology and diagnosis of HFpEF

HFpEF was originally believed to be a milder form of heart failure, but that’s no longer thought to be the case, according to Michael W. Rich, MD, a professor of medicine at Washington University School of Medicine in St. Louis.

HFpEF is defined as heart failure with an ejection fraction of 50% or greater. Women are twice as likely as men to have the condition; the incidence in Blacks is higher than in Whites, as is the rate of increase. From 2008 to 2018, the increase in hospitalizations increased 2.6-fold.

Signs and symptoms of this form of heart failure include exertional dyspnea, exercise intolerance, rales and elevated jugular venous pressure, he said.

“The diagnosis of HFpEF can also be made using the so-called H2F-PEF score, which includes weight, hypertension, atrial fibrillation, pulmonary hypertension, older age, and elevated filling pressure,” Rich said. “It has been shown in those with unexplained dyspnea, an H₂An F-PEF score of 6 points or higher is highly diagnostic of HFpEF.”

For the B-type natriuretic peptide biomarker, Rich said the diagnostic cutoff for NT-pro-BNP is 450 pg/mL for subjects younger than 50, 900 pg/mL for those aged between 50 and 75 years old and 1800 450 pg/mL for those 75 years and older. If the result is <300 pg/mL, acute heart failure is unlikely at any age, she said.

Evaluation should include a history and physical data, laboratory tests (CBC, CMP, TFT, UA, possibly lipids), a 12-lead ECG, and transthoracic Doppler ultrasound. Additional tests may be required, decided on an individual basis. The differential diagnosis includes cardiac amyloid, hypertrophic cardiomyopathy, cardiac sarcoid, iron overload, tumors, esophageal enlargement, and other problems.

Rich advises physicians to see a cardiologist when a patient is hospitalized more than twice a year, when the patient’s blood pressure is low (<90100 mm Hg), or if the patient has diuretic resistance or cardiorenal syndrome.

Pharmacological management

Pharmacotherapy management for HFpEF carries an inherent tension between the benefits of therapy and the risks of polypharmacy, said Parag Goyal, MD, director of the HFpEF and cardiac amyloidosis program and associate professor of medicine at Weill Cornell Medicine, in New York City .

Goyal has provided several recommendations for balancing that tension.

• Decongestion should be done with loop diuretics. What is the best? Goyal cited a 2023 study comparing torsemide and furosemide. There was no difference in mortality at the 12-month follow-up, she said. “It probably doesn’t make any difference which diuretic you use,” but the drugs help patients feel better and stay out of the hospital.

• SGLT-2 inhibitors should be prescribed. “Multiple organs are involved in HFpEF, and that includes the heart, vasculature and kidneys, and SGLT-2 inhibitors actually target each of those,” she said.

• Mineralocorticoid receptor agonists should be prescribed. A post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) study found that in the Americas, but not in Russia, spironolactone reduced cardiovascular deaths and heart failure hospitalizations.

• Other drugs to consider include angiotensin receptor blockers/neprilysin, angiotensin receptor blockers, and angiotensin converting enzyme inhibitors. But care should be taken if the patient has low blood pressure, he said.

• Deprescribing beta-blockers, which may not be helpful, should be considered, Goyal said, citing recent research.

• The use of statins should be considered. “The jury is still out,” he said, but he also cited preliminary research from his group and others who have found benefit.

“The field is moving towards phenotype-based therapy,” he said, which makes more individualized treatments possible.

Inequalities

Heart failure affects everyone, said Khadijah Breathett, MD, an advanced heart failure and transplant cardiologist and associate professor of medicine at Indiana University, Indianapolis. There are ethnic and racial differences, he said.

Datasets differ, and changing definitions make it more difficult to assess the differences. Overall, he said, the highest prevalence of heart failure is among black patients; the condition affects 3.6% of black men and 3.3% of black women, compared to 2.4% of white men and 1.4% of white women. Inequalities are getting worse.

Hospitalization rates for HFpEF are higher among black patients, but mortality is higher among whites, and men fare worse than women.

Research by Breathett and others found in a multiracial cohort that obesity and hypertension were strong risk factors for HFpEF, with obesity being strongest for black women.

Advice for clinicians? Heed the 2022 ACC/AHA heart failure guidelines, she advised, which recommend addressing risk factors often seen in disparities.

“Support clinical trials so you can get better data,” he added.

Rich and Pastva have not disclosed any relevant financial relationships. Goyal has received research support from the National Institute on Aging and the American Heart Association. Breathett has received funding from the National Heart, Lung, and Blood Institute and HRSA Prime.

American Geriatrics Society (AGS) 2023 Annual Scientific Meeting: Presented May 5, 2023.

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