Biventricular Concordance Prioritizes Right Ventricular Remodeling Signals in Pulmonary Hypertension

Right ventricular (RV) adaptation and failure are major determinants of outcome in pulmonary hypertension (PH), yet transcriptomic signatures vary across models and cohorts. We investigated whether reproducible RV remodeling signals arise from chamber-restricted changes or a broader biventricular response. We analyzed eight public datasets from rat PH models and human disease. In a paired rat monocrotaline discovery cohort, genes meeting adjusted p < 0.05 and |log2 fold change| ≥ 1 were classified as Shared, left ventricular (LV)-only, or RV-only; replication was assessed in seven external datasets. LV and RV effects were correlated (r = 0.71), yielding 108 Shared, 494 LV-only, and 54 RV-only genes. Among genes with estimates in both ventricles, 97.4% of LV-only and 95.9% of RV-only genes changed in the same direction in the other chamber, suggesting that restricted labels often reflected threshold crossing rather than opposing regulation. Shared genes were enriched in extracellular matrix, remodeling, chemotactic, and immune processes and showed broader replication. Shared-anchored analysis identified an illustrative 35-gene consensus with a stable core and threshold-sensitive periphery; CRLF1 and TIMP1 had support in all eight datasets. In chronic thromboembolic pulmonary hypertension (CTEPH), discovery-direction concordance was 15/35, 18/35, and 20/35 genes in moderate-, intermediate-, and severe-risk pre-endarterectomy RV comparisons, indicating partial and heterogeneous agreement. Biventricular concordance is a robustness filter for prioritizing reproducible RV signals, not evidence of identical LV and RV mechanisms.