Heart Failure Subtypes and Cardiomyopathies in Women

Abstract

Heart failure affects over 2.6 million women and 3.4 million men in the United States with known sex differences in epidemiology, management, response to treatment, and outcomes across a wide spectrum of cardiomyopathies that include peripartum cardiomyopathy, hypertrophic cardiomyopathy, stress cardiomyopathy, cardiac amyloidosis, and sarcoidosis. Some of these sex-specific considerations are driven by the cellular effects of sex hormones on the renin-angiotensin-aldosterone system, endothelial response to injury, vascular aging, and left ventricular remodeling. Other sex differences are perpetuated by implicit bias leading to undertreatment and underrepresentation in clinical trials. The goal of this narrative review is to comprehensively examine the existing literature over the last decade regarding sex differences in various heart failure syndromes from pathophysiological insights to clinical practice.

Keywords: cardiomyopathies; estrogens; heart failure; peripartum; women.

Figure 1.

Sex Differences in the Pathophysiology and Treatment of Heart Failure with Reduced Ejection Fraction Notable sex differences exist with respect to the epidemiology of heart failure with reduced ejection fraction. Additionally, trials have shown differential effect of neurohormonal blockade and device therapy in men and women. ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; CRT = cardiac resynchronization therapy; HFrEF = heart failure with reduced ejection fraction; ICD = implantable cardioverter defibrillator; LVAD = left ventricular assist device

Figure 2.

Postulated Estrogen-Mediated Mechanisms in Heart Failure Estrogen modulates a variety of pathophysiologic processes including endothelial response to injury, the renin-angiotensin-aldosterone system, and left ventricular remodeling. Additionally, estrogen has roles in maintaining diastolic function and in the coronary microvasculature. These may explain sex differences in heart failure pathophysiology at a mechanistic level.

Figure 3.

Sex Differences in the Pathophysiology and Treatment of Heart Failure with Preserved Ejection Fraction Sex differences also exist in the epidemiology of heart failure with preserved ejection fraction. Differences in vascular aging, concomitant comorbidities, and therapeutic response have all been demonstrated in the literature. ARNI =angiotensin receptor neprilysin inhibitor; HFpEF = heart failure with preserved ejection fraction; RV = right ventricle; PCWP = pulmonary capillary wedge pressure

Figure 4.

Approach to Peripartum Cardiomyopathy Peripartum cardiomyopathy is the leading cause of HF in pregnancy. Risk factors, presentation, treatment, prognosis, and the role of transplantation are depicted here. GDMT = guideline-directed medical therapy; LV = left ventricular; LVEF = left ventricular ejection fraction; MCS = mechanical circulatory support; PPCM = peripartum cardiomyopathy

Figure 5.

Sex Differences in Other Cardiomyopathies Although overall less data are available in women, infiltrative and restrictive cardiomyopathies as well as stress cardiomyopathy have unique sex differences. In cardiac amyloidosis, it is unclear to what extent the male predominance of the disease is due to ascertainment bias and the potential role for sex-specific diagnostic criteria. Similarly, women with HCM are typically more symptomatic at first evaluation which may be due to the use of similar wall thickness cutoffs for both sexes.