Rider, Oliver J.

Abstract Obesity and heart failure with preserved ejection fraction (HFpEF) represent two intermingling epidemics driving perhaps the greatest unmet health problem in cardiovascular medicine in the 21st century. Many patients with HFpEF are either overweight or obese, and recent data have shown that increased body fat and its attendant metabolic sequelae have widespread, protean effects systemically and on the cardiovascular system leading to symptomatic HFpEF. The paucity of effective therapies in HFpEF underscores the importance of understanding the distinct pathophysiological mechanisms of obese HFpEF to develop novel therapies. In this review, we summarize the current understanding of the cardiovascular and non-cardiovascular features of the obese phenotype of HFpEF, how increased adiposity might pathophysiologically contribute to the phenotype, and how these processes might be targeted therapeutically.

Abstract Aims We aimed to determine the effect of increasing body weight upon right ventricular (RV) volumes, energetics, systolic function, and stress responses using cardiovascular magnetic resonance (CMR). Methods and results We first determined the effects of World Health Organization class III obesity [body mass index (BMI) > 40 kg/m2, n = 54] vs. healthy weight (BMI < 25 kg/m2, n = 49) upon RV volumes, energetics and systolic function using CMR. In less severe obesity (BMI 35 ± 5 kg/m2, n = 18) and healthy weight controls (BMI 21 ± 1 kg/m2, n = 9), we next performed CMR before and during dobutamine to evaluate RV stress response. A subgroup undergoing bariatric surgery (n = 37) were rescanned at median 1 year to determine the effects of weight loss. When compared with healthy weight, class III obesity was associated with adverse RV remodelling (17% RV end-diastolic volume increase, P < 0.0001), impaired cardiac energetics (19% phosphocreatine to adenosine triphosphate ratio reduction, P < 0.001), and reduction in RV ejection fraction (by 3%, P = 0.01), which was related to impaired energetics (R = 0.3, P = 0.04). Participants with less severe obesity had impaired RV diastolic filling at rest and blunted RV systolic and diastolic responses to dobutamine compared with healthy weight. Surgical weight loss (34 ± 15 kg weight loss) was associated with improvement in RV end-diastolic volume (by 8%, P = 0.006) and systolic function (by 2%, P = 0.03). Conclusion Increasing body weight is associated with significant alterations in RV volumes, energetic, systolic function, and stress responses. Adverse RV modelling is mitigated with weight loss. Randomized trials are needed to determine whether intentional weight loss improves symptoms and outcomes in patients with obesity and heart failure.

Introduction: The mechanisms linking obesity to increased mortality in patients with coronavirus-disease 2019 (COVID-19) are unclear. Hypothesis: We hypothesised that obesity would be associated with adverse right ventricular (RV) remodelling and function which might be further exacerbated by COVID-19 associated increases in RV afterload/demand. Methods: We used echocardiography and computed tomography to establish links between RV dimensions and function and bodyweight in patients with severe COVID-19. In obese and non-obese participants without COVID-19, we used cardiovascular magnetic resonance to define the effects of obesity upon RV volumes, energetics, systolic function and stress reserve. Results: In patients with severe COVID-19, increasing bodyweight was associated with disproportionate RV dilatation (n=26, echocardiography, R=0.42, P=0.03, CT n=34, R=0.23, P=0.004) and impairment of RV systolic function (fractional area change (FAC) R=-0.45, P=0.04); obesity (BMI >30kg/m2) was associated with a 32% reduction in RV FAC (P=0.03). Similar associations were seen in a validation cohort (n=91, all P<0.05). In participants without COVID-19, class III obesity (n=54, BMI 47±4 kg/m 2 ) was associated with RV remodelling, impaired cardiac energetics (PCr/ATP ratio 23% lower, P<0.001) and reduction in RV systolic function at rest (by 3±1%, P=0.01), which was related to reduced energetics (R=0.3, P=0.04). Participants with class I-II obesity (BMI 35±5 kg/m 2 , n=27) had impaired RV diastolic filling rate at rest (P<0.001) and blunted RV dobutamine stress systolic response (by 68%, P=0.03) and diastolic response (by 78%, P=0.008). Surgical weight loss in patients obesity (n=37, 34±15kg weight loss) was associated with improvement in RV volume (12±26 ml lower, P=0.006) and function (ejection fraction 2±5% higher, P=0.03). Conclusions: Increasing body weight is associated with both significant alterations in RV volumes, systolic function and stress responses which are mitigated with weight loss and also with disproportionate RV dilatation and dysfunction in severe COVID-19. RV dysfunction is a modifiable mechanism which might link obesity to adverse outcomes in patients with COVID-19 and other disorders stressing the right heart.