Physical Activity in Heart Failure With Preserved Ejection Fraction: Moving Toward a Newer Treatment Paradigm

Ambarish Pandey, MD; Jarett D. Berry, MD, MS


Circulation. 2017;136(11):993-995. 

Physical inactivity and low fitness are important, modifiable risk factors for the development of heart failure (HF).[1–4] Recent studies have demonstrated strong, dose-dependent inverse associations among physical activity, fitness, and risk of incident HF.[5] Physical activity has been shown to have a stronger and more graded association with risk of HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction.[6] However, the prognostic role of physical activity among patients with established HFpEF is less well established. This finding is particularly relevant given the near-universal presence of exercise intolerance among patients with HFpEF.

In this issue of Circulation, Hegde et al[7] have addressed this knowledge gap by evaluating the association between physical activity levels and risk of adverse clinical outcomes among 1751 patients with HFpEF in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). The authors observed several important findings. First, only 11% of the study participants engaged in guideline-recommended physical activity levels at baseline. Second, compared with individuals with ideal physical activity, those with poor and intermediate self-reported physical activity had a higher risk of HF hospitalization and mortality within the first 2 years of follow-up. Third, the authors observed a particularly interesting, dose-response relationship between physical activity levels and risk of adverse clinical outcomes, such that only physical activity levels at or above current guideline recommended doses were associated with a lower risk of HF hospitalization or mortality.

Thus, these data suggest that some exercise may not be an improvement over no exercise among HFpEF patients and that a higher dose of exercise may be required to achieve clinical benefits. This is consistent with the dose-response association between physical activity levels and risk of incident HFpEF that was reported recently, with significant reductions in HFpEF risk only at physical activity levels above guideline recommendations.[6] This is in stark contrast to prior reports of the dose-response relationship between exercise and other outcomes such as coronary artery disease where the majority of the benefit of physical activity was apparent at just modest doses of physical activity.[8] Thus, the recommendation to get off the couch appears to be inadequate for the prevention and management of HFpEF—rather, we should be recommending doses of physical activity that are at or well-above the current recommendation of 30 minutes, 5 days per week of moderate intensity (ie, walking) exercise.

What explains this unique, dose-response relationship between exercise and HFpEF? We suggest 2 potential explanations. First, higher levels of regular physical activity may have a direct effect on the underlying HFpEF substrate, reflecting higher levels of cardiorespiratory fitness in these individuals, which may have a more direct and favorable effect on cardiac structure and function. Along these lines, previous studies have demonstrated that higher levels of cardiorespiratory fitness are associated with more favorable left ventricular geometry, less diastolic stiffness, and reduced left ventricular filling pressures.[9,10] Another potential explanation for the inverse associations between physical activity and HFpEF may be reverse causation, such that lower levels of physical activity represent a marker for more severe disease and a higher burden of comorbidities. This is supported by the observation that the inverse association between physical activity and risk of adverse outcomes was significant only in short-term follow-up and attenuated beyond the first 2 years. Furthermore, recent work from the NEAT-HF trial (Nitrate's Effect on Activity Tolerance in Heart Failure) demonstrated that individuals with lower levels of objectively measured physical activity had a higher burden of comorbidities.[11]

The present study findings have implications for future research because they support the hypothesis that exercise training might improve outcomes among patients with HFpEF. Recent work from our group suggests that the benefits of exercise are much more apparent among patients with HFpEF than HFrEF. Specifically, we observed that 12 weeks of exercise training was associated with 19% improvement in peak VO2 among HFpEF patients and no improvement in peak VO2 in HFrEF patients.[12] Nevertheless, supervised exercise in cardiac rehab is only approved for HFrEF. Given the modest impact of exercise training observed in HF-ACTION,[13] taken together, these data suggest that we may be exercising the wrong HF patients. Thus, a clinical trial comparing exercise training versus usual care is warranted—an HF-ACTION trial for HFpEF.

These findings also have implications for clinical practice. In the absence of established therapies for the prevention and treatment of HFpEF, we should be emphasizing to patients the importance of achieving or exceeding the guideline-recommended doses of physical activity. Exercise is not a categorical yes/no variable, but rather can best be considered as a medicine as emphasized by the Exercise is Medicine campaign. For both HFpEF prevention and treatment, the preponderance of evidence suggests that doses more than the current recommendations may be necessary. Higher doses of exercise can be achieved by increasing the intensity of exercise or by increasing the duration of exercise. For patients with established HFpEF, achieving a higher dose of exercise may be best met by doubling the recommended duration of walking from 30 minutes to an hour a day.

We would like to congratulate Hegde et al for taking an important step in clarifying the prognostic role of physical activity levels among patients with HFpEF. Future studies are needed to test whether modifying physical activity levels might modify risk in HFpEF patients. In the interim, in the absence of documented treatments for these patients, this study reminds us that we may already have one of the safest and cost-effective therapies available for HFpEF patients. Shouldn't we be prescribing it?