Heart Failure with Reduced Ejection Fraction—Does Sex Matter?

Abstract

Purpose of Review There is an increasing recognition of the importance of sex in susceptibility, clinical presentation, and outcomes for heart failure. This review focusses on heart failure with reduced ejection fraction (HFrEF), unravelling differences in biology, clinical and demographic features and evidence for diagnostic and therapeutic strategies. This is intended to inform clinicians and researchers regarding state-of-the-art evidence relevant to women, as well as areas of unmet need. Recent Findings Females are well recognised to be under-represented in clinical trials, but there have been some improvements in recent years. Data from the last 5 years reaffirms that women presenting with HFrEF women are older and have more comorbidities like hypertension, diabetes and obesity compared with men and are less likely to have ischaemic heart disease. Non-ischaemic aetiologies are more likely to be the cause of HFrEF in women, and women are more often symptomatic. Whilst mortality is less than in their male counterparts, HFrEF is associated with a bigger impact on quality of life in females. The implications of this for improved prevention, treatment and outcomes are discussed. Summary This review reveals distinct sex differences in HFrEF pathophysiology, types of presentation, morbidity and mortality. In light of this, in order for future research and clinical medicine to be able to manage HFrEF adequately, there must be more representation of women in clinical trials as well as collaboration for the development of sex-specific management guidelines. Future research might also elucidate the biochemical foundation of the sex discrepancy in HFrEF.

Clinical Characteristics, Management, and In-Hospital Mortality in Patients with Heart Failure with Reduced Ejection Fraction According to Sex and the Presence of Type 2 Diabetes Mellitus

“…When we performed PSM among diabetic subjects by sex, we observed a higher frequency of women over 85 years of age during hospital admission. These findings may be due to the greater life expectancy of women than men and to the greater frequency of atrial fibrillation, chronic renal failure, and obesity, factors that increase the risk of developing heart failure over the years [21]. The presence of hyponatremia was greater in diabetic women than in diabetic men in the study.…”

“…Women hospitalized for diabetes in our setting had a lower rate of prior echocardiograms than men. Some studies relate that women undergo fewer complementary tests than men for the management of heart failure or atrial fibrillation [21]. However, on the other hand, they received a greater number of noninvasive mechanical ventilations, probably due to a worse cardiorespiratory situation than men upon admission.…”

“…Chin-Hsiao et al reported a higher in-hospital mortality in men [27]. This result may be explained by the higher number of women over 85 years of age who are hospitalized and the higher disease burden in terms of anemic syndrome, chronic renal dysfunction, dementia, and depression that probably reflect a higher degree of advanced and terminal heart failure than male patients without diabetes [21].…”

Sex Differences in the Evaluation of Congestion Markers in Patients with Acute Heart Failure

“…Healthy women demonstrated reduced vasoconstrictive properties of their vascular tree, as well as smaller cardiac volumes and wall thickness after exercise training as compared to men [ 36 ]. Women are more prone to left and right ventricular-arterial uncoupling, and therefore higher left ventricle filling pressure and lower stroke volume, increased arterial stiffness and endothelial dysfunction, which predispose to increased pulmonary pressures and sex differences in pulmonary vascular reactivity, as well as poorer exercise tolerance [ 1 , 2 ]. These alterations in cardiovascular hemodynamics may account for the occurrence of signs and symptoms of HF.…”

“…Sex difference is a well-established issue in a heart failure (HF) setting [ 1 , 2 ] as well as in the context of acute myocardial infarction [ 3 ]. Women with HF effectively show advanced age as compared to men, non-ischemic aetiology of HF, higher incidences of HF with preserved ejection fraction (HFpEF), and more symptomatic forms of HF [ 4 , 5 , 6 , 7 , 8 ].…”