Left ventricular underfilling in PAH: A potential indicator for adaptive‐to‐maladaptive transition

Pulmonary arterial hypertension (PAH) still remains a life‐threatening disorder with poor prognosis. The right ventricle (RV) adapts to the increased afterload by a series of prognostically significant morphological and functional changes, the adaptive nature should also be understood in the context of ventricular interdependence. We hypothesized that left ventricle (LV) underfilling could serve as an important imaging marker for identifying maladaptive changes and predicting clinical outcomes in PAH patients. We prospectively enrolled patients with PAH who underwent both cardiac magnetic resonance and right heart catheterization between October 2013 and December 2020. Patients were categorized into four groups based on their LV and RV mass/volume ratio (M/V). LV M/V was stratified using the normal value (0.7 g/mL for males and 0.6 g/mL for females) to identify patients with LV underfilling (M/V ≥ normal value), while RV M/V was stratified based on the median value. The primary endpoint was all‐cause mortality, and the composite endpoints included all‐cause mortality and heart failure‐related readmissions. A total of 190 PAH patients (53 male, mean age 37 years) were included in this study. Patients with LV underfilling exhibited higher NT‐proBNP levels, increased RV mass, larger RV but smaller LV, lower right ventricular ejection fraction, and shorter 6‐min walking distance. Patients with LV underfilling had a 2.7‐fold higher risk of mortality than those without and LV M/V (hazard ratio [per 0.1 g/mL increase]: 1.271, 95% confidence interval: 1.082–1.494, p = 0.004) was also independent predictors of all‐cause mortality. Moreover, patients with low LV M/V had a better prognosis regardless of the level of RV M/V. Thus, LV underfilling is an independent predictor of adverse clinical outcomes in patients with PAH, and it could be an important imaging marker for identifying maladaptive changes in these patients.