Obesity: the perfect storm for heart failure

Abstract

Obesity condition causes morphological and functional alterations involving the cardiovascular system. These can represent the substrates for different cardiovascular diseases, such as atrial fibrillation, coronary artery disease, sudden cardiac death, and heart failure (HF) with both preserved ejection fraction (EF) and reduced EF. Different pathogenetic mechanisms may help to explain the association between obesity and HF including left ventricular remodelling and epicardial fat accumulation, endothelial dysfunction, and coronary microvascular dysfunction. Multi-imaging modalities are required for appropriate recognition of subclinical systolic dysfunction typically associated with obesity, with echocardiography being the most cost-effective technique. Therapeutic approach in patients with obesity and HF is challenging, particularly regarding patients with preserved EF in which few strategies with high level of evidence are available. Weight loss is of extreme importance in patients with obesity and HF, being a primary therapeutic intervention. Sodium-glucose co-transporter-2 inhibitors have been recently introduced as a novel tool in the management of HF patients. The present review aims at analysing the most recent studies supporting pathogenesis, diagnosis, and management in patients with obesity and HF.

Keywords: Atrial fibrillation; Direct‐acting oral anticoagulants; Heart failure; Implantable cardioverter–defibrillators; Left ventricular remodelling; Natriuretic peptides; Obesity; Sacubitril/valsartan; Sodium–glucose co‐transporter‐2 inhibitors; Sudden cardiac death.

Figure 1

Schematic representation of the principal mechanisms involved in the pathogenesis of HF in obesity. FFA, free fatty acid; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LV, left ventricular; MEEi, mechano‐energetic efficiency; NPs, natriuretic peptides; RAAS, renin–angiotensin–aldosterone system; RBP‐4, retinol‐binding protein‐4; RV, right ventricular; SNS, sympathetic nervous system; VSMC, vascular smooth muscle cell.

Figure 2

Role of natriuretic peptides (NPs) in the regulation of homeostasis of the adipose tissue. In normal conditions, NPs [i.e. atrial NP (ANP) and BNP], released by the cardiomyocytes, act on the adipose tissue stimulating the release of adiponectin, which, in turn, promotes the lipolysis. This mechanism contributes to maintain the homeostasis of adipose tissue (green arrows). A combination of increased degradation and decreased cardiac release may contribute to relative deficiency of NPs in obesity, leading to volume overload, increased ventricular wall stress, and cardiac remodelling (red arrows). Altogether, these abnormalities favour the development of HF.

Figure 3

Two‐dimensional global longitudinal strain by speckle tracking echocardiography in a healthy subject with body mass index (BMI) of 23.4 kg/m² (left panel) and in an obese subject with BMI of 35.3 kg/m² (right panel). GS, global longitudinal strain.

Figure 4

Cardiovascular (CV) imaging in obese patients for the evaluation of cardiac geometry and function, epicardial fat thickness, coronary microvascular disease (CMVD) and coronary artery disease (CAD), and tissue characterization and fibrosis localization with a proposal of the imaging techniques in the order of priority on a cost/benefit basis. CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; SPECT, single‐photon emission computed tomography.

Figure 5

Future directions for the treatment of obesity with heart failure. AF, atrial fibrillation; DOACs, direct‐acting oral anticoagulants; HFpEF, heart failure with preserved ejection fraction.