Heart failure therapy challenges in obese patients

Abstract

Obesity is one of the most significant independent risk factor for developing heart failure (HF) through direct and indirect mechanisms. Excessive secretion of aldosterone and activation of the renin-angiotensin system (RAAS) in obese patients leads to sodium retention and an increase in extracellular volume, which contributes to the development of heart failure and increased cardiovascular risk. Abdominal visceral obesity is associated not only with an increased risk for the development of heart failure with preserved ejection fraction (HFpEF), but also with a high risk for the development of diabetes mellitus and hypertension in both sexes, but more dominantly in women, with an increase in incidence with menopause. Multiple studies and meta-analyses have confirmed that obese patients with heart failure regardless of ejection fraction (HFpEF and HFrEF) have better survival compared to those of normal or underweight, a phenomenon known as the obesity paradox. The HF-ACTION trial showed that even small improvements in cardiorespiratory fitness could lead to significant improvements in cardiovascular outcomes, reducing the impact of the obesity paradox on the clinical outcome of heart failure. The ESC recommendations for heart failure advise weight loss in order to prevent cardiovascular disease in obese and overweight patients, and gradual weight loss should be considered in patients with heart failure and BMI > 35 kg/m2 , while in patients with heart failure and BMI<35 kg/m2 , weight loss is not recommended. The goal of bariatric procedures is to prevent or delay the onset of heart failure, not only by reducing body weight but also by reducing risk factors. The randomized DAPA-HF trial showed that the use of dapagliflozin proved to reduce the composite outcome of worsening heart failure or cardiovascular death in heart failure patients with BMI>30 kg/m2 and in HF patients with BMI<30 kg/m2 . The EMPEROR-preserved and DELIVER trials showed that therapy with SGLT2 inhibitors in patients with HFpEF and BMI>30kg/m2 reduces the risk of hospitalization and cardiovascular death. It is recommended that patients in the terminal stage of heart failure in the pre-transplantation period and placed on the list for heart transplantation achieve target values of BMI<30 kg/m2 in order to achieve a better clinical outcome and reduce mortality after transplantation.