Lala: ‘Recognize and personalize’ approaches to heart failure therapies for women
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Key takeaways:
- Women have distinct risk factors for HF compared with men and respond differently to therapies.
- Words matter: Emphasize heart “function” when discussing HF with patients.
DANA POINT, Calif. — Clinicians must use a tailored approach when treating women with HF, who have risk factors, biomarkers and manifestations of disease that are often distinctly different from men, according to a speaker.
Data demonstrate there are sex-related differences in risk factors for HF that have implications for treatment, yet there is not an adequate body of sex-specific evidence, Anu Lala, MD, associate professor of medicine (cardiology) at Icahn School of Medicine at Mount Sinai, said during a presentation at the Cardiometabolic Health Congress (CMHC) Women’s Cardiometabolic Health and Wellness Masterclass. Lala said clinicians should consider HF across a continuum, not simply defined by age, ejection fraction or QRS, and remember that HF therapies are not one-size-fits-all.
“We need to recognize and personalize our approach to these therapies for men and women,” said Lala, who is also deputy editor of the Journal of Cardiac Failure.
Sex differences in HF
There are differences in the predisposition of HF that have to do with traditional and sex-specific risk factors, Lala said, as well as sex-specific differences in the manifestation of HF.
“We know we see more HF with preserved EF among women, and there are differences in acuity and severity of presentation,” Lala said.
Hypertension, diabetes, smoking and obesity tend to be less prevalent risk factors among women vs. men; however, when present, they are much more potent risk factors for development of HF, Lala said. Obesity in particular is associated with much higher risk for HFpEF among women vs. men. Women also tend to have a higher EF and smaller left ventricular size relative to men.
All of those factors could explain why women respond to some HF therapies differently than men, Lala said.
“We have these hard [EF] cutoffs for when people are eligible for certain therapies,” Lala said. “Maybe we need to rethink that.”
Functional limitations are also different, with women usually more symptomatic with HF vs. men, likely due to increased arterial stiffness, she said.
In addition to traditional risk factors, pregnancy-associated complications such as eclampsia increase risk for HF, Lala said. Breast cancer-related treatments, specific responses to stressors — as in stress cardiomyopathy, most commonly encountered among women — and a greater prevalence of autoimmune diseases such as lupus also may contribute to development of HF. Lala encouraged all clinicians to take a thorough reproductive history for every women.
There are also sex differences in biomarkers. Lala said women with HFpEF have lower natriuretic peptide levels than men, usually potentiated by obesity as part of a larger cardiometabolic syndrome.
“At menopause, the loss of estrogen downregulates cyclic GMP protein signaling and what does that relate to?” Lala said. “Lower rates of nitric oxide release, therefore less myocardial relaxation, less arterial compliance, increased fibrosis and decreased microvascular flow. These are all the things that we see in HFpEF. There is a lot of hormonal interplay here, particularly for postmenopausal women.”
For all of these reasons, it is paramount that clinicians do not assume “one size fits all” with respect to pharmacologic therapies for HF, Lala said.
“We know one size fits all is not the case,” Lala said. “Women have different absorption, different distribution of medicines, different metabolism, different forms of eliminations, different changes in hepatic blood flow, especially during pregnancy. We have to take that into account. If I am giving a women carvedilol 25 mg twice a day, is that equivalent to what I would prescribe for a man? We must tailor our [HF] therapies.”
Defining HF for women: ‘Words matter’
Definitions of HF have evolved over the past 2 years and are now reflected in the updated HF guidelines that redefine HF stages and emphasize prevention, Lala said. Guidelines now define HF along a continuum of ejection fraction, with the addition of the term “mildly reduced EF” for patients with an EF of 41% to 49%.
“Guideline-directed medical therapy applies across the spectrum of ejection fraction and the spectrum of symptoms,” Lala said. “This is a really important shift in how we conceptualize treatment and personalized care for patients living with HF.”
When it comes to HF, “heart function and prevention go hand-in-hand,” Lala said, adding that exercise should remain a core component of any HF treatment plan.
“Obesity, hypertension, emotional and spiritual well-being, smoking, diabetes, diet, exercise — all of these factors are highly relevant when we care for patients, regardless of the spectrum of disease,” Lala said.
Clinicians should also rethink how they describe HF to their patients, Lala said.
“What does the word ‘failure’ make you feel like?” Lala said. “It feels awful, right? Heart ‘failure’ is not an engaging term. Particularly for our women patients, our words matter, in terms of engagement and empowerment. I like to use the term ‘heart function.’ I do not like to downplay the morbidity and mortality associated with the diagnosis, but I do like to emphasize the spectrum [of disease] and focus on improving function not only of the heart, but how patients function in real life, day to day.”
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Lala A. Unique cardiometabolic risk factors in women across the life span. Presented at: CMHC Women’s Cardiometabolic Health and Wellness Masterclass; Aug. 17-20, 2023; Dana Point, California.
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