Perspective

In HFrEF, women face poorer quality of life, receive less treatment vs. men

Mary Norine Walsh
Mary Norine Walsh

Women with HF with reduced ejection fraction live longer than men diagnosed with HFrEF but live a poorer quality of life with greater self-reported psychological and physical disabilities, according to findings published in the Journal of the American College of Cardiology.

Pooja Dewan, MBChB, of the BHF Cardiovascular Research Centre at the University of Glasgow, and colleagues sought to identify the changes in treatment to get a new perspective in the management of and outcomes in women with HF.

Dewan and colleagues analyzed 12,058 men and 3,357 women enrolled in two large HFrEF trials, PARADIGM-HF and ATMOSPHERE, with similar inclusion and exclusion criteria and identical principal outcomes. The primary outcome was the composite of first HF hospitalization or CV death. Outcomes were adjusted for other prognostic variables, such as N-terminal pro-B-type natriuretic peptide.

Researchers identified, using baseline characteristics, no significant difference in BMI between women and men, but women in the study were more often obese (33.4% vs. 29.2%). Dewan and colleagues also identified in women higher rates of hypertension (70.6% vs. 65.5%) and clinically significant valvular disease (5.3% vs. 4.6%), but lower rates of major comorbid conditions such as atrial fibrillation (32.6% vs. 36.4%), previous MI (30% vs. 45.4%) and stroke (7.4% vs. 8%) compared with men.

Mariell Jessup
Mariell Jessup

In non-CV comorbidities, compared with men, women had similar rates of diabetes (women, 31%; men, 31.6%), lower rates of chronic obstructive pulmonary disease (8.5% vs. 13.1%) and smoking (6.2% vs. 15.8%), and greater likelihood of reporting moderate to extreme anxiety or depression (44% vs. 29%; P < .0001) based on the EQ-5D-3L state of health score in PARADIGM-HF.

Dewan and colleagues identified that women experienced more HF symptoms compared with men such as pedal edema (23.4% vs. 19.9%; P < .0001) and a worse quality of life based on median Kansas City Cardiomyopathy Questionnaire summary score (71.3 vs. 81.3; P = .001) despite similar left ventricular ejection fraction and NT-proBNP.

The researchers identified that women had a lower mortality rate (adjusted HR = 0.68; 95% CI, 0.62-0.74) and risk for HF hospitalization (HR = 0.8; 95% CI, 0.72-0.89).

According to the researchers, the use of diuretics and anticoagulants were underused in women with a history of AF. The use of devices was also less in women compared with men; for example, 8.6% of women had an implantable cardioverter defibrillator vs. 16.6% of men (P < .0001).

JoAnn Lindenfeld
JoAnn Lindenfeld

Women with HFrEF have fewer comorbidities, better survival and lower rates of hospitalization, but they have more symptoms and worse health-related quality of life than men, Dewan and colleagues wrote.

“This different sex-related experience of HFrEF is unexplained, and it is uncertain whether physicians recognize it,” Dewan and colleagues wrote. “Women continue to receive suboptimal treatment, compared with men.”

In a related editorial, Cardiology Today Editorial Board Member Mary Norine Walsh, MD, of St. Vincent Heart Center in Indianapolis, Mariell Jessup, MD, of the American Heart Association, and JoAnn Lindenfeld, MD, of Vanderbilt University School of Medicine, wrote: “Sex as an independent biologic variable has recently been identified as important in a policy of the National Institutes of Health. All future funded research will need to account for sex as a biological variable in the development of research question and study designs, data collection, analysis and publication of results. ... Only with these measures will we be able to offer all our patients, both women and men, diagnostic and therapeutic strategies that are patient-centric and optimally beneficial.” – by Earl Holland Jr.

Disclosures: Dewan, Jessup and Walsh report no relevant financial disclosures. Lindenfeld reports she served as a consultant for Abbott, Boehringer Ingelheim, CVRx, Edwards, Novartis, Relypsa and VWave. Please see the study for all other authors’ relevant financial disclosures.

Mary Norine Walsh
Mary Norine Walsh

Women with HF with reduced ejection fraction live longer than men diagnosed with HFrEF but live a poorer quality of life with greater self-reported psychological and physical disabilities, according to findings published in the Journal of the American College of Cardiology.

Pooja Dewan, MBChB, of the BHF Cardiovascular Research Centre at the University of Glasgow, and colleagues sought to identify the changes in treatment to get a new perspective in the management of and outcomes in women with HF.

Dewan and colleagues analyzed 12,058 men and 3,357 women enrolled in two large HFrEF trials, PARADIGM-HF and ATMOSPHERE, with similar inclusion and exclusion criteria and identical principal outcomes. The primary outcome was the composite of first HF hospitalization or CV death. Outcomes were adjusted for other prognostic variables, such as N-terminal pro-B-type natriuretic peptide.

Researchers identified, using baseline characteristics, no significant difference in BMI between women and men, but women in the study were more often obese (33.4% vs. 29.2%). Dewan and colleagues also identified in women higher rates of hypertension (70.6% vs. 65.5%) and clinically significant valvular disease (5.3% vs. 4.6%), but lower rates of major comorbid conditions such as atrial fibrillation (32.6% vs. 36.4%), previous MI (30% vs. 45.4%) and stroke (7.4% vs. 8%) compared with men.

Mariell Jessup
Mariell Jessup

In non-CV comorbidities, compared with men, women had similar rates of diabetes (women, 31%; men, 31.6%), lower rates of chronic obstructive pulmonary disease (8.5% vs. 13.1%) and smoking (6.2% vs. 15.8%), and greater likelihood of reporting moderate to extreme anxiety or depression (44% vs. 29%; P < .0001) based on the EQ-5D-3L state of health score in PARADIGM-HF.

Dewan and colleagues identified that women experienced more HF symptoms compared with men such as pedal edema (23.4% vs. 19.9%; P < .0001) and a worse quality of life based on median Kansas City Cardiomyopathy Questionnaire summary score (71.3 vs. 81.3; P = .001) despite similar left ventricular ejection fraction and NT-proBNP.

The researchers identified that women had a lower mortality rate (adjusted HR = 0.68; 95% CI, 0.62-0.74) and risk for HF hospitalization (HR = 0.8; 95% CI, 0.72-0.89).

According to the researchers, the use of diuretics and anticoagulants were underused in women with a history of AF. The use of devices was also less in women compared with men; for example, 8.6% of women had an implantable cardioverter defibrillator vs. 16.6% of men (P < .0001).

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JoAnn Lindenfeld
JoAnn Lindenfeld

Women with HFrEF have fewer comorbidities, better survival and lower rates of hospitalization, but they have more symptoms and worse health-related quality of life than men, Dewan and colleagues wrote.

“This different sex-related experience of HFrEF is unexplained, and it is uncertain whether physicians recognize it,” Dewan and colleagues wrote. “Women continue to receive suboptimal treatment, compared with men.”

In a related editorial, Cardiology Today Editorial Board Member Mary Norine Walsh, MD, of St. Vincent Heart Center in Indianapolis, Mariell Jessup, MD, of the American Heart Association, and JoAnn Lindenfeld, MD, of Vanderbilt University School of Medicine, wrote: “Sex as an independent biologic variable has recently been identified as important in a policy of the National Institutes of Health. All future funded research will need to account for sex as a biological variable in the development of research question and study designs, data collection, analysis and publication of results. ... Only with these measures will we be able to offer all our patients, both women and men, diagnostic and therapeutic strategies that are patient-centric and optimally beneficial.” – by Earl Holland Jr.

Disclosures: Dewan, Jessup and Walsh report no relevant financial disclosures. Lindenfeld reports she served as a consultant for Abbott, Boehringer Ingelheim, CVRx, Edwards, Novartis, Relypsa and VWave. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Jane E. Wilcox

    Jane E. Wilcox

    Women enrolled in HF trials were more likely to have non-ischemic etiology of HF, and as such, lower rates of atherosclerotic CVD. They had lower rates of AF and valvular disease, but on average, were older and more obese, with similar rates of diabetes and worse renal function.

    Despite having similar biomarker profiles, women had more objective evidence of congestion and were more symptomatic than men. Men and women were treated similar in terms of baseline medications, but women were far less likely to receive indicated anticoagulation for stroke prevention and ICD and cardiac resynchronization therapy.

    Women were referred to cardiac rehab less and were even recommended influenza vaccination less. Despite these inequities in optimal HF care delivery, women fared better than men in both primary and secondary trial outcomes. Women also had lower rates of hospitalization for HF, CV and all-cause death.

    Medical professionals who treat HF should consider optimizing delivery for HF care in a standardized way, as to avoid subconscious bias and undertreatment of women with HF.  Electronic reminders regarding guideline-directed medical and device therapies HF, cardiac rehab referral and even vaccinations may be helpful to close this gap.

    Additionally, even though rates of diuretics were similar between men and women, women had more subjective and objective evidence of congestion and worse renal function, suggesting higher doses of diuretics may be warranted for some symptomatic women.

    Only one-fifth of patients with HF enrolled in contemporary clinical trials were women.  Frankly, this is appalling. The NIH has required that sex be reported as a biologically important variable and has focused efforts to increase women and racial and ethnic minorities in all clinical trials.

    Drs. Walsh, Jessup and Lindenfeld brilliantly summarized requirements for future investigations in HF in their recent editorial of this paper: “Women must be enrolled in research trials in adequate numbers, subgroup endpoints must be prespecified, analyzed, and required for publication by journal editors and reviewers of manuscripts.”

    • Jane E. Wilcox, MD, MSc, FHFSA
    • Assistant Professor of Medicine–Cardiology
      Director, Myocardial Recovery Program
      Northwestern University Feinberg School of Medicine

    Disclosures: Wilcox reports no relevant financial disclosures.