Heart failure with preserved ejection fraction

Diastolic dysfunction (DD) is defined as increased viscoelastic chamber stiffness, impaired ventricular relaxation, or a combination of both. Decline in left ventricular (LV) compliance occurs with aging and may be accelerated by conditions such as hypertension, diabetes, and obesity. DD can occur in the absence or presence of systolic dysfunction and may not necessarily lead to clinical symptoms. However in some instances, DD can impede LV filling, increase LV pressures, and reduce LV preload at rest and with exercise, leading to symptoms of dyspnea, orthopnea, and bilateral lower extremity swelling.

Impaired relaxation can lead to increased LV filling pressures, which can promote heart failure (HF) symptoms such as dyspnea and orthopnea. While DD has historically been the pathophysiological basis for these symptoms, recent investigation has discovered that numerous causal pathways may contribute to HFpEF. Hence, this condition is termed HFpEF, rather than diastolic HF. In contrast to HF with reduced EF (HFrEF), which is mechanistically linked to pathological LV remodeling, neurohormonal activation, and impairment in systolic function, regardless of the underlying etiology, no singular pathway is implicated in the development of HFpEF. Rather, multiple mechanisms related to systemic inflammation, disruption in cardiometabolic metabolism, microvascular dysfunction, and reduced LV compliance may all contribute to the development of HFpEF. Furthermore, studies have identified multiple phenogroups of HFpEF with distinct clinical characteristics and prognoses, highlighting the heterogeneity of this entity. The 2013 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) HF guidelines define HFpEF as the presence of HF symptoms with LVEF greater than or equal to 50%.

Five million individuals in the United States are estimated to have HF. Of these, approximately 50% have HFpEF. The prevalence of HFpEF relative to HFrEF is increasing by 1% every year. Accordingly, HFpEF is projected to be the dominant subtype of HF in the coming decades. Estimates of HFpEF prevalence range between 1% and 5% in the United States. HFpEF is projected to cost ~$70 billion to the United States healthcare system by 2030. The highest rates of HFpEF are observed in elderly women, though younger patients (<65 years old) account for 40% of all HFpEF cases. The age-adjusted incidence rates for HFpEF are 12.3 per 1000 persons in Black women, 9.7 per 1000 persons in Black men, 7.8 per 1000 persons in White women, and 6.3 per 1000 persons in White men. Lifetime risk of HF is higher in men than in women. However, lifetime risk of HFpEF is comparable between men and women (26% vs. 22%). Furthermore, lifetime risk of HFpEF is higher in non-Black than in Black individuals (11.2% vs. 7.7%).

Individuals at highest risk of incident HFpEF tend to be older women. Reduction in LV compliance with aging may contribute to excess risk of HFpEF among the elderly. Other risk factors for HFpEF include hypertension, obesity, physical inactivity, coronary artery disease, and atrial fibrillation. Valvular heart disease involving stenosis or insufficiency of the aortic or mitral valve can also lead to diastolic function and subsequent HFpEF. Noncardiac conditions such as chronic kidney disease, obesity, excess central adiposity, type 2 diabetes, sarcopenia, skeletal myopathy, and frailty increase the risk of developing HFpEF.