Evolution of a Geriatric Syndrome: Pathophysiology and Treatment of Heart Failure With Preserved Ejection Fraction

Bharathi Upadhya, MD; Barbara Pisani, MD; Dalane W. Kitzman, MD


J Am Geriatr Soc. 2017;65(11):2431-2440. 

In This Article

Nonpharmacological Approaches

Exercise Training

In a single-blind trial evaluating the effects of 16 weeks of endurance exercise training (ET) in older adults with HFpEF, ET was associated with greater peak oxygen consumption (VO2), ventilatory anaerobic threshold, 6-minute walk distance, and physical quality-of-life scores.[77] These results were confirmed in a subsequent multicenter, randomized trial of 3 months of combined ET and strength training in individuals with HFpEF.[78] In a second, separate, randomized, attention-controlled, single-blind trial of 4 months of upper and lower extremity endurance ET, a significant increase in peak VO2 was demonstrated without alterations in carotid arterial stiffness or brachial artery flow–mediated dilation.[79] A subsequent multicenter trial confirmed that ET improves exercise capacity and symptoms.[78] In a recent pilot study, 4 weeks of high-intensity interval training significantly improved peak VO2 and LV diastolic dysfunction in individuals with HFpEF.[80] A recent metaanalysis found that ET in individuals with HFpEF was associated with improvements in cardiorespiratory fitness and quality of life without significant changes in LV systolic or diastolic function,[81] and another study showed that endurance ET increased peak VO2 more in individuals with HFpEF than in those with HFrEF.[82]

Because ET is one of the only proven interventions for improving symptoms and quality of life in individuals with HFpEF, it would be useful to know what the mechanisms for these improvements are. ET may improve exercise capacity by increasing exercise cardiac output (by increasing HR or stroke volume) or increasing arteriovenous oxygen difference (A-VO2 diff) by improving peripheral vascular function, leading to greater diffusive oxygen transport or greater oxygen use by skeletal muscle. Studies indicate that an ET-induced increase in A-VO2 diff is the primary contributor to ET-related improvement in peak VO2.[83] Skeletal muscle oxidative metabolism is impaired at baseline in older adults with HFpEF, but ET can improve it to more efficient muscle oxygen use.[42] There does not appear to be any ET-related beneficial effect on LV diastolic function in older adults with HFpEF, even after 1 year of exercise.[84] Although the above studies support mechanisms for the beneficial effects of ET that are independent of LV systolic or diastolic function, some studies have attributed ET-related improvements to exercise-induced favorable changes in LV function and cardiac output, atrial reverse remodeling, and improved LV diastolic function.[78,80]

Dietary Modifications

As previously stated, more than 80% of older adults with HFpEF are overweight or obese. Because greater body adiposity promotes inflammation and impairs cardiac, arterial, renal, and skeletal muscle function, weight loss could be beneficial in the large proportion of individuals with the obese HFpEF phenotype. Recently, it was shown that weight loss through caloric restriction was feasible, appeared to be safe, and significantly improved exercise capacity and quality of life in older obese adults with clinically stable HFpEF and that the effect was additive to ET (Figure 3, Supplemental Table S1).[85] Caloric restriction improved quality of life much more than ET. The improvements from caloric restriction were associated with reduced total body and skeletal muscle adipose and reduced inflammation. In a recent trial in symptomatic individuals with chronic HF (25% of whom had HFpEF), dietary sodium restriction was associated with greater risk of adverse outcomes, particularly HF hospitalization.[86]

Figure 3.

Effects of a 20 week caloric restriction diet on exercise capacity and quality of life in HFpEF. The graph displays percent changes ± standard errors at the 20-week follow-up relative to baseline by randomized group for: peak VO2 (ml/kg/min, panel A), and KCCQ (Kansas City Cardiomyopathy Questionnaire) overall score (= Quality of Life Score) (panel B). AT = aerobic exercise training; CR = caloric restriction diet. P-values represent effects for AT and CR.