Sex-Based Differences in Heart Failure

The Women’s Cardiometabolic Health and Wellness Masterclass, which took place August 17-20, 2023, in Dana Point, California, explored diverse topics, with a focus on cardiometabolic sex-based differences between male and female patients. Anu Lala, MD, an advanced heart failure and transplant physician and associate professor of medicine at the Mount Sinai Health System, discussed sex-specific differences in heart failure.

Dr. Lala illustrated how the traditional risk factors for developing heart failure are more potent in females, who may have sex-specific risk factors, including a higher prevalence of autoimmune disease, as well as reproductive-associated risk factors, higher prevalence of breast cancer, or exposure to cancer-related therapies.^1,2 They are also disproportionately affected by acute coronary syndrome without obstructive coronary artery disease, with entities such as Takotsubo syndrome and spontaneous coronary artery dissection.²

When heart failure develops, it tends to manifest differently in female patients compared with male patients. Females are less likely to develop heart failure with reduced ejection fraction and more likely to develop heart failure with preserved ejection fraction (HFpEF).³ These 2 classifications are defined based on left ventricular ejection fraction (LVEF); however, this definition does not consider that an LVEF of 50% is not the same for males and females. Females tend to have higher LVEF and smaller left ventricular size compared with males.⁴ This difference can affect proper diagnosis and also the therapeutic options available to female patients.

The PARAGON trial, which analyzed the use of sacubitril/valsartan in HFpEF, illustrated a 27% reduction in the composite of total hospitalizations for heart failure and death from cardiovascular causes in women. This subgroup analysis showed how medications may affect females and males differently. It raises the question: Should therapeutics be tested for efficacy separately in male and female patients?

Dr. Lala concluded that it is time to incorporate sex-specific guidelines for cardiovascular disease.

Dr. Breanna Hansen is a cardiology fellow at Vanderbilt University Medical Center and was The CardioNerds Conference Scholar for the 2023 Women’s Cardiometabolic Health and Wellness Masterclass.