Women remain underrepresented in studies on advanced heart failure (HF) despite a higher mortality rate once diagnosed when compared with men. “There are well-recognized sex differences in the use of heart replacement therapies, with only 30% of all heart transplantations and 20% of all left ventricular assist devices (LVADs) implanted in women,” explains Garrick C. Stewart MD, MPH. Women are just as likely to develop HF as men; however, they have a lower rate of heart replacement and higher rate of morbidity, which is concerning for researchers such as Dr. Stewart. “Women are equally likely to benefit from heart replacement therapies like transplant or LVAD,” he says.

For a study published in JACC: Heart Failure, Dr. Stewart and colleagues examined sex-based differences in a well-defined cohort of patients with ambulatory advanced HF, including “the use of guideline-directed medical therapy, use of surgical HF therapies, and patient-reported outcome measures, including quality of life (QOL).”  The study consisted of the largest prospective cohort of female patients with ambulatory advanced HF to date. All participants were part of the Registry Evaluation for Vital Information for VADs in Ambulatory Life (REVIVAL). “REVIVAL enrolled 400 outpatients on oral medical therapy, 25% of whom were women, with New York Heart Association functional class II to IV, left ventricular ejection fraction of 35% of lower, a HF diagnosis of longer than12 months, and one additional high-risk feature (such as HF hospitalization, laboratory marker of advanced prognosis, or objectively reduced functional capacity),” explains Dr. Stewart.

The researchers found no difference between men and women in the use of guideline-directed medical electrical therapies for HF. Patients’ burden of HF— defined by physician-assigned INTERMACS profile— also did not differ by sex. However, the study team did find “a disproportionate burden of reduced functional capacity, reduced quality of life related to physical limitation, and depression in women with ambulatory, advanced HF, findings that merit further study,” says Dr. Stewart. “These results suggest an opportunity to further optimize treatments to reduce these observed disparities.”

Men and women in the study had a similar 1-year combined risk of death, durable mechanical circulatory support (MCS), or transplantation (Table). “Despite similar medication use and similar profiles of HF severity, women demonstrated a consistent reduction in objective functional capacity and QOL related to physical limitation,” explains Dr. Stewart. “Patient-reported outcome measures can identify disparities in HF burden and inform shared decision making about the timing of mechanical support.”

The researchers were encouraged by finding that the overall rate of advanced HF  therapies and mortality did not differ by sex. The study included patient-centered measures of functioning and QOL in the entry criteria and outcome measures. “These data suggest that women with advanced HF report worse objective functional capacity and QOL related to physical limitation than men, despite similar physician-assigned HF severity and similar application of medical therapy,” says Dr. Stewart. “We feel that iterative assessment of quality of life and functional capacity will inform shared decision making in women with advanced ambulatory HF.” Dr. Stewart and his team also believe that an unadjusted 6-minute walk measurement for advanced HF clinical trial inclusion is flawed. They site body size and limb length as factors that impact how far a person will be able to walk in 6 minutes and which differ between groups of women and men. “The use of a single unadjusted cutoff for 6-minute walk distance in a trial could systemically bias enrollment or outcomes by sex despite otherwise similar levels of HF severity,” he says. Because of these anthropometric differences, Dr. Stewart suggests adjusting the 6-minute walk when designing clinical trials for HF.

Dr. Stewart feels it is important to include patient-reported QOL and functioning in outcome measures for advanced HF trials. “Understanding the patient-reported measures that should trigger LVAD referral is essential,” he says. “These measures can inform the conversation about the timing and trade-offs of LVAD therapy in ambulatory patients where the timeline for a decision is extended.”