Right Heart Size Should be Part of PAH Risk Models, Study Suggests
Women are more likely to have pulmonary arterial hypertension, but men tend to have worse outcomes and worse treatment responses.
Sex-specific differences in right-heart size warrant a re-examination of risk-stratification measures used in pulmonary arterial hypertension (PAH), a new report suggests.
The study, published in the Journal of the American Society of Echocardiography, found right atrial (RA)-based risk stratification could be improved if the measures used were sex-specific.
Corresponding author Nicola Benjamin, Dr. Sc. Hum., of Heidelberg University Hospital, and colleagues, noted that treatment decisions in PAH are generally guided by a patient’s risk level. Guidelines published by the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) call for the use of a three-strata risk-stratification model at baseline, and a four-strata model to guide follow-up.
The strata used in initial risk assessment include echocardiographic assessment of right atrial (RA) area, pericardial effusion, and tricuspid annular plane systolic excursion (TAPSE) divided by systolic arterial pressure (sPAP). Benjamin and colleagues said the efficacy of those prognostic indicators is well-documented. However, they said the model does not take into account known sex differences in PAH, of which there are several.
For instance, a 2013 registry-based analysis showed that among patients with PAH under the age of 65, women outnumbered men by a more than 2-to-1 ratio. That sex-based gap disappears as patients age and have increased comorbidities. Yet, the current risk-stratification guidelines were developed for people without comorbidities.
“Therefore, the question arises whether echocardiographic parameters for risk stratification with low, intermediate, and high one-year mortality risk differs between males and females,” Benjamin and colleagues wrote. “In the current guidelines, no distinction between risk stratification thresholds for men and women is made.”
Previous research has also shown females have smaller mean right atrial and right ventricular (RV) areas than men, but it is not yet known whether sex differences affect TAPSE/sPAP readings.
Benjamin and colleagues wanted to better understand the degree to which sex-based differences might affect survival and risk assessment among people with PAH. They therefore decided to retrospectively analyze a cohort of 748 patients with PAH who were treated at the Thoraxklinik Heidelberg between 2015 and 2022. Most of the participants (63%) were female, and the cohort had a mean age of 65±15 years.
The investigators found that right heart size was consistently larger in men compared with women. Men had a mean RA area of 21.76±7.64 cm2 vs. 17.65±6.82 cm2 for women. Mean right ventricular area was 24.02±7.15 cm2 among men vs. 18.41±5.75 cm2 among women. The findings held true for all World Health Organization functional classes except Class IV, and for all cardiac index risk groups except the “high-risk” group.
“Thus, sex differences in right heart size seem to be persistent, even when corrected for disease severity,” the authors noted.
The authors said the disappearance of the gap in high-risk groups may be due to a “ceiling effect” of maximum right atrium dilation. The sex-based right-heart gap was also independent of a patient’s physical body size area.
Benjamin and colleagues found that sex-specific right atrial area thresholds adjusted by body size area were superior to general thresholds.
Sex did not appear to matter, however, when it came to TAPSE/sPAP values. The investigators found the European TAPSE/sPAP-based risk stratification model was a “robust” prognostic indicator of one-year mortality for both men and women.
Benjamin and colleagues noted while women are more likely to have PAH, men tend to have worse outcomes and worse treatment responses.
“It has also been shown that women with PAH have better contractile RA function and RV-to-pulmonary artery coupling than men, despite a similar afterload, as measured by pulmonary arterial pressure and PVR,” they wrote. “It is possible that females, especially younger ones, can compensate a higher afterload better than males, which leads to a better RV function.”
Additionally, they said hormonal influences may be at play, noting emerging research which suggests estrogen might be a risk factor for development of PAH but then turn into a cardioprotective factor once PAH develops.
More work is needed to fully understand the potential role of those factors, but in the meantime the investigators said sex-specific thresholds are warranted, at least for echocardiographic measurements of right atrial and right ventricular areas.
Such thresholds would make it possible to refine treatment recommendations for men and women with the disease, they noted.
“The impact of sex differences on diagnosis and treatment of PAH remains to be investigated,” they concluded.
