Right heart size differs between men and women with PAH: Study
Men with disease have larger hearts, worse survival rates
Men with pulmonary arterial hypertension (PAH) have a larger right heart size and worse survival rates than women, independent of body size and functional status, a study reports.
Moreover, sex-specific mortality risk thresholds, with higher risk indicated by a larger area of the right pulmonary artery, as measured by an echocardiogram, were superior to general thresholds after adjusting for body surface area.
“Risk stratification in PAH patients should consider sex-specific differences and account for [body surface area],” the researchers wrote in the study, “Sex-specific differences in echocardiographic parameters of risk stratification in pulmonary arterial hypertension,” which was published in the Journal of the American Society of Echocardiography.
In PAH, narrowing of the the blood vessels that pass through the lungs, or pulmonary arteries, restricts blood flow and leads to high blood pressure, or hypertension. This makes the right heart work harder to pump blood, which can lead to heart failure later in life.
According to the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines for pulmonary hypertension, treatment decisions for PAH patients should be based on an estimated one-year mortality risk, stratified by echocardiogram findings of the right heart at diagnosis.
Differences between men, women
Echocardiograms do show differences between the sexes in healthy people, but it hasn’t been known if PAH patients show these differences and if they impact outcomes, leading a team led by researchers in Germany to review the medical records of 748 adult PAH patients who’d undergone echocardiography.
“Due to sex-specific differences it may be possible that the general thresholds given in the guidelines are not appropriate,” the researchers wrote.
The mean age of the patients was 65, more than half were women (63.4%), and the mean follow-up time was 3.2 years.
The patients were severely affected, with more than half (56.3%) in the World Health Organization (WHO) functional class 3, wherein the disease limits physical activity, but people are comfortable at rest. About 1 in 10 (9.7%) was in WHO functional class 4, where symptoms are present at rest and severe with activity, and 1 in 3 (33.1%) was in WHO class 2, which is similar to class 3, but with fewer limitations.
The right heart was assessed using various echocardiogram parameters. These included the right atrial area and the right ventricular area, tricuspid annular plane systolic excursion (TAPSE), a measure of right ventricular function, and systolic pulmonary arterial pressure (sPAP), or the blood pressure in the pulmonary arteries during a heartbeat.
The analysis revealed that men with PAH had a significantly larger mean right heart size than women, both in the right atrial area (21.76 vs. 17.65 square centimeters, cm2) and right ventricular area (24.02 vs. 18.93 cm2). These differences were consistent throughout all WHO functional classes, except for the right atrial area in WHO functional class 4, which was similar between the sexes.
TAPSE/sPAP values decreased with increasing disease severity but didn’t significantly differ between men and women with PAH, “which makes this parameter a robust prognostic predictor,” the researchers noted.
Assessing risk
The patients were then divided into three risk groups (low, intermediate, and high) according to ESC/ERS risk stratification of the right atrial area, with larger areas indicating higher mortality risk. Across all the risk groups, men were taller, heavier, and had a higher body surface area (BSA) than women.
One-year survival was worse among men than women in the low-risk (95.5% vs. 97.5%) and intermediate-risk groups (89.5% vs. 94.2%), but better in the high-risk group (93.9% vs. 90.8%). Despite worse survival in the lower-risk groups, men presented with significantly less severe signs of disease, including a lower pulmonary vascular resistance (PVR), or resistance to blood flow, than women. In fact, the highest PVR values were almost exclusively in women.
During follow-up, 54 out of 235 men (23%) and 54 out of 406 women (13.3%) died. ESC/ERS risk stratification showed a significant distinction in survival between men and women, with men presenting with large right atrial areas and worse survival in the same risk group than women. After adjusting for age, however, the right atrial area no longer predicted survival.
When the right atrial area was adjusted for BSA, risk stratification adequately predicted one-year mortality according to ESC/ERS and after adjusting for age for men and women.
Consistent with these findings, right atrial area values accounting for BSA showed more pronounced differences for an age-adjusted survival analysis than ESC/ERS risk stratification thresholds. Moreover, sex-specific right atrial area/BSA-based thresholds were an independent outcome predictor, but not the ESC/ERS right atrial area thresholds alone.
Finally, age-adjusted TAPSE/sPAP survival curves also showed adequate estimation of one-year mortality according to ESC/ERS risk stratification for both sexes with significant differentiation between risk groups.
“This study indicates that risk stratification in PAH by [right atrial] area could be refined by developing sex specific thresholds and adjusting risk thresholds e.g. by BSA,” the researchers wrote. “Further research is required in large populations to validate these findings and consider whether adjustments should be made to other parameters to reflect the impact of BSA and sex.”
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