FROM JAMA

Diet and exercise, either in combination or alone, improved exercise capacity in older obese patients with clinically stable heart failure with preserved ejection fraction in a controlled trial reported Jan. 5 in JAMA.

In a controlled trial of 100 obese persons aged 60 years or over, 81 of whom were women, all with stable but chronic HFpEF, participants were randomly assigned to a diet intervention, exercise, both, or to a control group that did not modify behavior. The diet and exercise combination arm had double the increased oxygen intake capacity (VO2) when compared with the other test arms. The groups assigned to either diet or exercise saw virtually the same increase in their peak VO2 compared with controls, although, across the study, there were no statistically significant changes in quality-of-life scores as measured by the Minnesota Living with Heart Failure Questionnaire.

The trial was the first to explore a nonpharmaceutical approach to improving this cohort’s capacity to exercise, as well as its overall heart function and reduced symptoms of HFpEF.

The results are “intriguing, and worthy of further investigation in a community population with longer follow-up,” Dr. Nanette K. Wenger , professor of medicine in cardiology at Emory University, Atlanta, wrote in an accompanying editorial ( JAMA. 2016;315[1]:31-3. doi: 10.1001/jama.2015.17347 ).

Despite HFpEF being the most common form of heart failure in the United States, primarily affecting older women, there are no treatment guidelines specifically for its management. Exercise intolerance, typically with exertional dyspnea leading to a reduced quality of life, is HFpEF’s primary symptom. Because of the so-called heart failure “obesity paradox” that indicates persons who are slightly overweight or obese have less mortality from heart failure than do their average or underweight counterparts, diet is a controversial aspect of treating HFpEF ( Circ Heart Fail. 2011 May;4[3]:324-31 ).

Although the condition is nearly always associated with being overweight or obese, the 2013 American Heart Association/American College of Cardiology Guideline for the Management of Heart Failure does not include dietary recommendations for weight loss as a HFpEF management strategy, but it does recommend treating the condition by way of lowering hypertension pharmaceutically.

“Diet to achieve weight loss could be an important new strategy to help patients with HFpEF, particularly those afflicted with severe exercise intolerance,” said the study’s lead author, Dr. Dalane W. Kitzman , professor of internal medicine in cardiology and geriatrics at Wake Forest University, Winston-Salem, N.C.

The study’s focus on diet alone and in combination with exercise for the sake of impacting peak oxygen intake was to help clarify the role of diet in heart failure. In the non-HFpEF older, obese population, restricting calories has been shown to improve left ventricular function and exercise capacity, lower inflammation markers, and improve skeletal muscular function.

Over the course of the study’s 20 weeks, the group that was assigned a hypocaloric dietary intervention had an increase in its peak oxygen consumption, the study’s primary endpoint, of 1.3 mL/kg per min. The exercise-only group increased by 1.2 mL/kg per min. Meanwhile, the group assigned to a reduced-calorie diet and exercise increased by 2.5 mL/kg per min ( JAMA. 2016;315[1]:36-46. doi: 10.1001/jama.2015.17346 ). The accepted clinically meaningful increase in peak oxygen consumption is 1.0 mL/kg per min.

Diet and exercise together also produced the most significant weight loss, with the combination group dropping an average of 22 pounds while the diet-alone group lost an average of 15 pounds. The exercise-only group lost an average of 6.5 pounds. Exercise for the groups assigned to it consisted of 1-hour supervised sessions, three times weekly.

As for why there was no notable improvement in quality of life, the other endpoint of the study, Dr. Wenger theorized in her editorial that “patients with HFpEF test their newly acquired activity tolerance to the precipitation of exertional dyspnea, [in other words], they remain symptomatic.”

Dr. Kitzman and his colleagues, however, wrote that upward trends in two other quality-of-life measures – the Kansas City Cardiomyopathy Questionnaire score and the Rand SF-36 – showed a possible effect on quality of life.

The overall findings indicate that intentional weight loss via calorie restriction is “feasible, appeared safe, and significantly improved the coprimary outcome of exercise capacity,” according to the authors.

Also in this study, the change in peak VO2 levels positively correlated with the change in the percentage of lean body mass (P = .003) and the change in the ratio between thigh muscle and intermuscular fat. This seemed to equal an increase in leg muscle and leg muscle quality.

Because higher levels of adipose tissue are associated with inflammation, hypertension, insulin resistance, and dyslipidemia, the study authors theorized that, as the body mass ratios of study participants improved, their bodies became more efficient at extracting oxygen from the blood, and thus could better sustain physical activity.

Although there were few adverse events observed in the study, including acute shortness of breath in a member of the exercise-only group, Dr. Kitzman said in a JAMA podcast that, of some concern was that a third of the body mass lost by participants was muscle tissue. “That’s important because persons with heart failure have less-than-normal amounts of muscle tissue as part of their heart failure syndrome and as part of growing old. It could have adverse long-term consequences,” he said.

Dr. Kitzman said in an interview that he and his colleagues have decided next to focus on resistance training’s impact on VO2, after this study showed that overall muscle mass decreased mildly with diet, even with aerobic exercise. The new study will seek to establish a correlation between improved retention of skeletal muscle, strength, and overall function and resistance training combined with diet and aerobic exercise in HFpEF.

“We chose resistance training because it is known to increase skeletal muscle mass. On the other hand, resistance training can temporarily increase blood pressure and left ventricular afterload, which are already increased in HFpEF,” he said.

The net effect is that, at least for now, “resistance training in HFpEF should be formally tested before applying to patients,” Dr. Kitzman noted. The same is true, he added, for recommending dietary restrictions in HFpEF patients.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

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