CHAPTER SUMMARY AND CENTRAL ILLUSTRATION
Semaglutide in Patients with Heart failure with Preserved Ejection Fraction and Obesity: a New Addition to the Armamentarium of Heart Failure Therapies
The STEP-HFpEF Trial was a phase 3 clinical trial designed to assess the impact of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP1ra), on both heart failure quality-of-life metrics and reduction in weight in those with heart failure with preserved ejection fraction (HFpEF) and obesity. Read More
This chapter provides an in-depth description of heart failure with preserved ejection fraction (HFpEF), from pathophysiology to treatment. Patients with HFpEF have a multifaceted constellation of comorbidities and clinical presentations. Numerous pathogenic mechanisms, including diastolic dysfunction, impaired systolic reserve, abnormal ventricular-arterial coupling, inflammation, endothelial dysfunction, chronotropic incompetence, altered myocardial energetics, impaired peripheral skeletal muscle metabolism and perfusion, pulmonary hypertension, atrial fibrillation, coronary artery disease, obesity, and renal insufficiency, contribute to the disease burden of HFpEF (see Fuster and Hurst's Central Illustration). The prognosis of patients with HFpEF remains poor. Many treatments (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, sacubitril/valsartan, and sodium glucose cotransporter-2 inhibitors) have been tested in HFpEF. Candesartan, spironolactone, and sacubitril/valsartan all demonstrated a modest effect to reduce heart failure hospitalizations in patients with HFpEF, at least up to left ventricular ejection fractions in the 50% to 55% range. Empagliflozin showed a more pronounced effect to reduce the composite of heart failure hospitalizations or cardiovascular death across the spectrum of ejection fraction of HFpEF patients.
eFig 49-01 Chapter 49: Diagnosis and Management of Heart Failure with Preserved Ejection Fraction
For a general introduction on heart failure definition, classification, and diagnosis, please see Chapter 48, Diagnosis and Management of Chronic Heart Failure.
Given the multifaceted constellation of comorbidities and clinical presentation that is almost invariably present in patients with heart failure with preserved ejection fraction (HFpEF), its underlying pathophysiology remains subject to debate. Among the leading contenders over the last two decades are diastolic dysfunction, impaired systolic reserve, and perhaps even resting dysfunction, abnormal ventricular-arterial coupling, inflammation and endothelial dysfunction, depressed heart rate response (chronotropic incompetence), altered myocardial energetics and peripheral skeletal muscle metabolism and perfusion, pulmonary hypertension, and renal insufficiency. More recent myocardial tissue studies have revealed distinct transcriptomic profile in HFpEF compared to heart failure with reduced ejection fraction (HFrEF) and nonfailing hearts. A major challenge to the field is that truly representative experimental models of HFpEF do not fully capture the clinical syndrome, and yet human data, particularly direct myocardial analysis, remains very limited. The leading mechanisms of interest in HFpEF are subsequently summarized, and in Fig. 49–1.
Pathophysiology of HFpEF.