Gender and Right Ventricular Function Predict Prognosis in Group 3 PH, Study Shows

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by Santiago Gisler |

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Male patients with group 3 pulmonary hypertension (PH) have worse right ventricular (RV) function compared with female patients, according to a  study. Impaired RV function also was found to be associated with reduced overall survival and higher hospitalization rates linked to heart failure.

The group study “Clinical Determinants and Prognostic Implications of Right Ventricular Dysfunction in Pulmonary Hypertension Caused by Chronic Lung Disease” was published in the Journal of the American Heart Association.

A PH characteristic is its wide range of causes that can affect patients’ symptoms, prognosis, and treatment options. As a result, the World Health Organization (WHO) has implemented a classification of PH into five different groups, based on the cause of disease.

Group 3 PH — PH due to lung disease and/or chronic hypoxia (oxygen deficiency) — is the second-leading cause of PH among all groups, and is the group with the worst long-term survival. Traditional therapies against pulmonary arterial hypertension (PAH) are inefficient in group 3 PH patients, and the only treatment option to date is lung transplant.

Previous studies have shown that group 3 PH patients have worse RV systolic (contracting) function, compared with PAH patients.

In the study, researchers investigated the association between RV function and factors that can explain risk and clinical outcome in group 3 PH patients.

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The team studied prospective registry data from 147 adult group 3 PH patients (mean age of 65 years, 48% male), registered in the Minnesota Pulmonary Hypertension Repository. Enrolled patients had PH associated with chronic obstructive pulmonary disease (COPD; 39% of the patients), interstitial lung disease (ILD; 43%), combined pulmonary fibrosis and emphysema (9%), or obesity lung disease (9%).

Ninety percent of the patients showed significant functional impairments, as defined by WHO functional classes. According to the classification, these patients experienced marked or severe limitations (class III or IV, respectively).

The team assessed RV function using RV fractional area change (RVFAC), which is an echocardiographic (heart live-imaging) measurement of the relative difference between systole and diastole surface area. Of note, RVFAC of less than 35% indicates a reduced RV function.

Researchers showed that RV systolic function was mild-to-moderately severe in group 3 PH patients, measured by RVFAC (29%). Results also showed that RVFAC had the strongest correlation with PH-associated pulmonary vascular resistance (PVR), whereas low RVFAC associated with high PVR.

Apart from the observed association between RVFAC and PVR, researchers also found that lower pulmonary arterial compliance and higher mPAP were associated with lower RVFAC.

Furthermore, correlation analyses showed that being male, having a high heart rate, and right artery and ventricle enlargements also were associated with lower RVFAC.

Of all the factors, being male was found to be the strongest predictor of RVFAC. Overall, men showed a significantly lower RVFAC (26%) compared with women (31%), suggesting a gender-dependent effect on RV systolic function. However, when comparing RV diastolic function between men and women,  the team found no significant differences.

The team noted that the impaired RV function found in males, compared with females, is supported by previous studies performed on healthy subjects, as well as group 1 and group 2 PH patients.

“There is strong preclinical and clinical data that demonstrate that sex hormones contribute to the sex differences in RV function,” the researchers wrote.

Finally, researchers compared the clinical outcome between patients with normal and dysfunctional RV, based on median RVFAC (28%).

Patients with impaired RV showed pronounced markers associated with heart failure, including serum hemoglobin, N-terminal pro b-type natriuretic peptide (NT-proBNP), and heart structure enlargements.

Importantly, the team found that patients with impaired RV functions (RVFAC lower than 28%) had worse overall survival and higher hospitalization rates.

Overall, the team concluded that “RV dysfunction increases the risk of heart failure hospitalization and death in group 3 PH,” and that “male sex is associated with RV dysfunction in Group 3 PH.”

The researchers also emphasized that “RV dysfunction (RVFAC less than 28%) identifies group 3 PH patients at risk for poor outcomes,” and suggested “that therapies that improve RV function may be beneficial” for this patient population.