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Obesity-related heart failure with preserved ejection fraction: new treatment strategies

ABSTRACT Objectives: Obesity has risen in the US and worldwide, and has become a major risk factor for type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease, and mostly HF with preserved ejection fraction (HFpEF). Also, the prevalence of HF is quite high in the US accounting for 6.6 million adults at present and is projected to reach 8.5 million by the year 2030 and is equally divided between HFpEF and heart failure reduced ejection fraction (HFrEF). Patients with HFpEF are resistant to treatment with drugs usually used for the treatment of HFrEF, but the reasons for this resistance are not clearly known. Methods: In order to get a better perspective on the current status of the underlying pathophysiology and treatment of patients with HFpEF, a Medline search of the English language literature was conducted between 2015 and 2018 using the terms obesity, HFpEF, diabetes, treatment, SGLT2 inhibitors, and neprilysin inhibitors and 24 pertinent papers were selected. Results: The review of these papers revealed that patients with HFpEF have expanded plasma volume, restricted left ventricular distension with increased end-diastolic volume and depressed natriuretic peptide levels. In this respect, drugs that cause increased diuresis and natriuresis should a reasonable choice to treat these patients. The recently FDA approved sodium-glucose cotransporter-2 (SGLT2) inhibitors for the treatment of T2DM, are a good choice, for the treatment of HFpEF, since they cause osmotic diuresis from glucose excretion and increase salt and water excretion and decrease plasma volume. In addition, they produce loss of calories leading to weight and blood pressure reduction and have shown to prevent the new onset HFpEF and decrease hospitalizations and death from this disease. Conclusion: The results of this analysis has shown that HFpEF has different pathophysiology from HFrEF and is difficult to treat. Drugs that block renal tubular glucose reabsorption and cause osmotic diuresis and natriuresis could be a good choice to treat patients with HFpEF alone or in combination with diuretics and other drugs.