Right ventriculo-arterial coupling - independent predictor of all-cause long-term mortality in heart failure with preserved ejection fraction

Abstract Introduction The interdependence between the right ventricular (RV) systolic force and the RV afterload defines the RV-pulmonary artery coupling (RVPAC). The echocardiographically derived ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) has been proposed as a noninvasive surrogate method to assess RV-PA coupling (RVPAC) and has been reported as an independent prognostic marker in heart failure (HF) with reduced ejection fraction (HFrEF). Although elevated PASP is a common complication in HF with preserved ejection fraction (HFpEF), however limited data exist on the predictive value of RV-PA uncoupling in this population. Purpose To evaluate the prognostic role of the TAPSE/PASP ratio as a surrogate marker of RV-PA uncoupling in patients with HFpEF. Methods We conducted a retrospective cohort study including adult patients with HFpEF consecutively admitted to our cardiology department between January 2019 and December 2020. We excluded cases with acute coronary syndrome, pulmonary embolism, inflammatory bowel disease, autoimmune disorders, repeated admissions of the same patient, in-hospital death, and absence of necessary echocardiographic data from the index admission. All-cause mortality was assessed in October 2024, with a mean follow-up duration of 4 years. Receiver operating characteristic (ROC) analysis was used to determine optimal cut-off values, sensitivity (Se), and specificity (Sp), based on the Youden index. Results Our study sample included 121 HFpEF patients (mean age 72.21±9.68 years, 61.78% female). Long-term all-cause mortality was 29.26%. The mean TAPSE/PASP ratio was 0.65±0.32 mm/mmHg. ROC analysis showed significant associations with all-cause mortality for: TAPSE/PASP (AUC 0.76, 95% CI 0.68–0.83, cut-off ≤0.46, Se 69.44%, Sp 80.23%, p0.001), PASP (AUC 0.77, 95% CI 0.69–0.84, cut-off 39 mmHg, Se 66.67%, Sp 80.23%, p0.001), TAPSE (AUC 0.64, 95% CI 0.55–0.72, cut-off ≤16 mm, Se 36.11%, Sp 91.86%, p=0.016), NT-proBNP (AUC 0.77, 95% CI 0.68–0.87, p0.001) In multivariate analysis, TAPSE/PASP 0.46 mm/mmHg (HR 5.59, 95% CI 2.02–15.45, p0.001) was an independent predictor of mortality, along with Log10NT-proBNP (HR 9.64, 95% CI 2.46–37.66, p=0.001) and malignancies (HR 13.27, 95% CI 2.29–76.61, p=0.004), outperforming PASP 39 mmHg and TAPSE ≤16 mm. The mortality prediction model including these parameters demonstrated an overall predictive power of 78%, with AUC 0.85 (95% CI 0.78–0.92, p0.001). Kaplan-Meier analysis showed significant differences of mortality and duration of survival between the two groups defined by TAPSE/PASP 0.46 mm/mmHg (Image). Conclusion Right ventricular-pulmonary artery uncoupling, quantified in our cohort by a TAPSE/PASP ratio below 0.46 mm/mmHg, was an independent predictor of all-cause mortality in patients with HFpEF. This parameter outperformed individual assessments of PASP and TAPSE in mortality risk stratification.