The conundrum of patients with obesity, exercise intolerance, elevated ventricular filling pressures and a measured ejection fraction in the normal range

Abstract

Patients with obesity, a reduced exercise capacity, increased cardiac filling pressures and a measured left ventricular ejection fraction in the normal range do not have a homogeneous disorder, but instead, exhibit one of three phenotypes. First, many obese people exhibit sodium retention, plasma volume expansion and cardiac enlargement, and some are likely to have heart failure that is related to hypervolaemia, even though cardiac index and circulating levels of natriuretic peptides are not meaningfully increased. Second, in some middle‐aged men and women (particularly those with minimal co‐morbidities), levels of natriuretic peptides increase markedly and can lower systemic vascular resistance, thus leading to high‐output heart failure (HOHF) and glomerular hyperfiltration. Third, older obese people, particularly women with multiple co‐morbidities, exhibit the syndrome of heart failure with a preserved ejection fraction (HFpEF). Despite degrees of plasma volume expansion similar to HOHF, these patients exhibit only modestly increased ventricular dimensions and circulating levels of natriuretic peptides (despite a high prevalence of atrial fibrillation), and glomerular function is characteristically impaired. A conceptual framework is proposed to distinguish among the three phenotypes seen in obese patients with exercise intolerance, increased ventricular filling pressures and a measured left ventricular ejection fraction in the normal range, since they may respond differently to therapeutic interventions. Efforts are needed to enhance the recognition of heart failure in obese people and to ensure that clinical trials that are designed to study patients with HFpEF actually enrol those who have the disease.

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

“…At the same time, the expansion of epicardial adipose tissue in obesity and type 2 diabetes can cause inflammatory changes in the adjoining LV, thereby impairing its distensibility and limiting its ability to accommodate increases in volume . Although systolic function is not meaningfully impaired, LV filling pressure rises, leading to exertional dyspnoea and effort intolerance . Changes in epicardial fat and its secretory products are also associated with worsening of glomerular function and proteinuria, suggesting that the inflammatory process in the epicardium may extend to other organs affected by obesity and diabetes .…”

“…Identification of HFpEF can be challenging ( Table ). Exertional dyspnoea is the cardinal feature of HF, but physicians may attribute this symptom to increased body mass or an accompanying arrhythmia, rather than to increased LV filling pressure. Furthermore, circulating natriuretic peptides may not accurately reflect LV filling pressures in patients who have HFpEF.…”

“…Symptoms of dyspnoea may be attributed to mechanisms other than increased left ventricular (LV) filling pressures (e.g. increased body mass or an accompanying arrhythmia) . Simultaneously, both obesity and diabetes act to suppress circulating levels of natriuretic peptides, which diminishes their usefulness as a means of identifying HF .…”

“…ageing and coexistent hypertension). As a result, in clinical practice, the diagnosis of HFpEF is missed in many patients who are obese or have diabetes and have exercise intolerance …”

February 2019 at a glance: pathophysiology, exercise capacity, diuretics and valve disease

“…Obesity may cause a distinct phenotype of heart failure (HF) with preserved ejection (HFpEF), characterized by plasma volume expansion, cardiac chamber overfilling and reduced ventricular compliance . Milton Packer has proposed a clinical classification of obese patients with HFpEF based on plasma volume status, left ventricular (LV) dimensions and natriuretic peptide levels . This classification may provide a framework for better targeted treatment of obese HFpEF patients.…”