The following are key points to remember from this article on physical activity, fitness, and obesity in heart failure with preserved ejection fraction (HFpEF):

1. Two relatively distinct phenotypes for heart failure (HF) have been described: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). There is an overlap or grey zone considering the range of left ventricular ejection fraction (LVEF) and the decrease in systolic function in some patients with HFpEF, and the pathobiology and pathophysiology appear to differ. There is no specific therapy available for HFpEF and the role of exercise is not clear. In this review, the authors discuss the role of physical inactivity, low fitness levels, and obesity in development and progression of HFpEF and how they might be targeted to combat the growing incidence.
2. Low fitness and physical inactivity are more strongly associated with the risk of HFpEF than HFrEF, as shown in healthy adults and in middle-aged adults followed from young adulthood, which is independent of interval development of other risk factors including hypertension. High doses of lifelong exercise are significantly associated with lower LV stiffness, and a strong inverse graded association with physical activity and risk of HFpEF. Further, regular exercise and a 1-MET improvement in fitness is associated with a 17% lower risk of HF. There is some evidence from clinical trials assessing aldosterone receptor blockade in HFpEF, that improving physical activity with high-intensity physical activity may improve exercise capacity, quality of life, and long-term clinical outcomes. But importantly, studies suggest that early initiation of exercise training in middle age, when the cardiac plasticity is still preserved, may be a strategy to reverse LV stiffness associated with sedentary aging and reduce the risk of HFpEF in older persons.
3. More than 80% of patients with HFpEF are overweight or obese. It is difficult to separate the relationship between exercise, fitness, and obesity as a risk factor for HF. Obese persons often have good fitness. In a longitudinal study, compared with normal body mass index participants, overweight and obese class I participants had 38% and 56% higher risk of HFpEF independent of other risk factors, and the association was greater than in HFrEF. There is a favorable association between weight loss and risk of HFrEF for both dietary as well as bariatric surgery. The relationship between weight loss and risk of HFpEF has not been studied, but aggressive weight loss is associated with significant improvements in diastolic function and LV concentric remodeling.
4. Among the explanations for the high risk of HFpEF in obesity include indirectly via hypertension, diabetes, and coronary disease, and a direct role for adipose tissue, particularly visceral including abdominal and epicardial, which are associated with a higher LV mass and LV diastolic dysfunction. Obesity is associated with increased leptin and decreased B-type natriuretic peptide levels, which result in renin-angiotensin-aldosterone activation leading to increased plasma volume, sodium levels, and inflammation and pathology of cardiac fibrosis, renal fibrosis, and arterial stiffness. Each of these is associated with increasing LV stiffness and filling pressure along with traditional cardiovascular risk factors of hypertension and diabetes, and potentially the contribution of coronary disease and ischemia.
5. Cardiac rehabilitation is an approved indication for New York Heart Association class II-IV HFrEF with improvement in quality of life, exercise capacity, and reduced hospitalization. Whereas cardiac rehabilitation and intentional weight loss through caloric restriction, physical activity, and/or bariatric surgery are promising strategies to improve exercise capacity in these patients, it remains to be studied whether such interventions may modify the risk of long-term adverse clinical outcomes.

Keywords: Adipose Tissue, Aldosterone, Bariatric Surgery, Body Mass Index, Caloric Restriction, Cardiac Rehabilitation, Coronary Artery Disease, Diabetes Mellitus, Diastole, Exercise, Heart Failure, Hypertension, Inflammation, Obesity, Overweight, Physical Fitness, Primary Prevention, Quality of Life, Risk Factors, Sodium, Stroke Volume, Vascular Stiffness, Weight Loss

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