Meyer, Markus

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) is now the predominant HF subtype, largely driven by the syndemic of physical inactivity and overweight/obesity in an aging population. Deranged skeletal muscle energetics and regional ectopic adipose depots are key cardiometabolic pathways in the pathogenesis of HFpEF, both of which may be favorably modified by 1-2 hours/week of resistance exercise (RE). However, its association with HFpEF risk has not been thoroughly examined. We investigated the association between midlife RE behaviors and incident HFpEF in the Atherosclerosis Risk in Communities (ARIC) study. Hypothesis: Participation in RE at midlife is inversely associated with the risk of incident HFpEF. Methods: Our exposure (RE)—including weightlifting and bodyweight resistance exercises—was assessed using the validated Baecke questionnaire and reported weekly RE duration was averaged across Visits 1 and 3 (1987-1995). We dichotomized averaged RE as 0 hr/wk (‘No RE’, reference) and >0 hr/wk (‘Any RE’). Our outcome (incident HFpEF) was identified through committee-adjudicated HF hospitalizations (January 1, 2005 to December 31, 2023) using medical chart abstraction. Participants with prevalent HF, death, or loss to follow-up before January 1, 2005 were excluded. We constructed Cox regression models to evaluate the association between midlife RE and incident HFpEF. Model 1 adjusted for age, sex, race, field center, education, smoking status, alcohol consumption, and non-RE physical activity. Given that adiposity may lie on the causal pathway, waist-height ratio (WHtR; both measured in cm) was added in Model 2. Results: 10,751 Black and White participants (803 incident HFpEF cases) were analyzed over a median follow-up time of 14.4 years (mean±SD Visit 1 age, 53.3±5.6 years; average Visit 1 and 3 WHtR, 0.58±0.08; 24.7% Black; 57.4% female). 1,217 participants (11.3%) reported engaging in RE at Visits 1 and/or 3, with a median duration of 0.84 hr/wk (IQR, 0.50-1.61). Compared to No RE, the fully adjusted hazard ratio (HR) for Model 1 for Any RE was: 0.78 (95% CI, 0.61-1.00, P = 0.05). The association was attenuated after adjustment for WHtR: HR = 0.84 (0.65-1.07, P = 0.16). Conclusion: Participation in RE at midlife is associated with a 22% lower risk of incident HFpEF. To inform public health and clinical guidelines, further studies are needed to clarify the role of RE in HFpEF prevention.

Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy. The effects of heart rate on this structural phenotype are not known. Analogous with the benefits of a low heart rate on a dilated heart, we hypothesized that increased heart rates could lead to potentially beneficial remodeling of a concentrically hypertrophied LV. This was explored in an established porcine model of concentric LV hypertrophy and fibrosis. Our results suggest that a moderate increase in heart rate can be used to reduce wall thickness, normalize LV chamber volumes, decrease myocardial fibrosis, and improve LV compliance. Our results also indicate that the effects of heart rate can be titrated, are reversible, and do not induce HF. These findings may provide the rationale for a novel therapeutic approach for HFpEF and its antecedent disease substrate. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/heart-rate-modeling/ .