Continuous Pulmonary Artery Systolic Pressure and Right Ventricular Risk in Mitral Regurgitation

Background: Current ACC/AHA guidelines recommend watchful waiting in asymptomatic severe primary mitral regurgitation (MR) until pulmonary artery systolic pressure (PASP) reaches 50 mmHg. The right ventricle (RV) is a thin-walled, low-pressure chamber, and the biological consequences of sustaining elevated PASP while awaiting this threshold remain poorly characterized in a continuous dose-response framework. Methods: We systematically searched PubMed, MEDLINE, EMBASE, and the Cochrane Library from inception to March 2026 to identify relevant studies and a restricted cubic spline (RCS) meta-analysis was performed synthesizing dose-response data from nine published cohort studies (total N > 15,000 patients). Hazard ratios (HR) for postoperative right ventricular failure and long-term mortality were extracted at continuous PASP quantiles ranging from 20 to 68 mmHg. RCS knots were placed at 30, 40, and 50 mmHg. The "RV Cliff" was defined as the PASP value corresponding to maximum second-derivative acceleration of the log-HR curve. Results: The RCS curve revealed a clearly non-linear, exponentially accelerating dose-response relationship between PASP and risk. A mortality inflection was identified at PASP ~34 mmHg (HR 1.27, 95% CI 1.00-1.36). The "RV Cliff"—the point of maximum risk acceleration—was identified at PASP ≈ 52-53 mmHg (HR 2.10). At the current guideline threshold of 50 mmHg, HR was already 1.83. Risk escalated sharply beyond 55 mmHg (HR 4.05-8.64, 95% CI 5.27-14.10 for postoperative RVF). At PASP ≈ 60 mmHg, HR reached 12.82. RV-PA uncoupling (TAPSE/sPAP impaired) conferred HR ~2.0-2.74 even at mildly elevated PASP of 30-50 mmHg, demonstrating that the RV is already structurally compromised well before the 50 mmHg threshold. Conclusions: The guideline threshold of 50 mmHg does not represent a safe waiting boundary—it coincides precisely with the RV Cliff, the point of irreversible hemodynamic collapse. Risk begins accumulating at PASP ~34 mmHg and accelerates exponentially. These findings support earlier surgical intervention thresholds (PASP 40-45 mmHg) to preserve right ventricular integrity and long-term survival in primary MR.