Integrating ΔPCO₂ and Ca-vO₂ Into a Heart-Lung Coupling Index: A Novel Approach to Evaluate Cardiopulmonary Uncoupling in Pulmonary Arterial Hypertension

AIM: To evaluate arterio-venous gas parameters-P(ca-v)CO2 or ΔPCO2, Ca-vO2, and P(v-a) CO2/Ca-vO2 ratio, and to develop a novel Heart-Lung Coupling (HLC) index defined as (ΔPCO2/Ca-vO2)/Cardiac Index to quantify the interaction between ventilatory efficiency and circulatory performance in pulmonary arterial hypertension (PAH). METHODS: In this single-center retrospective study, patients with PAH who underwent right heart catheterization between September 2019 and May 2024 were evaluated. After exclusions, 115 patients were included (35 idiopathic PAH [IPAH] and 80 congenital heart disease-associated PAH [CHD-PAH]). Hemodynamics, arteriovenous gas parameters, and functional indices, including 6-min walk distance (6MWD) and NT-proBNP, were analyzed. The HLC was calculated and compared between groups. Association with functional parameters was assessed using Spearman correlation and multivariate linear regression after LASSO selection. Receiver operating characteristic analysis evaluated the ability of HLC to identify impaired exercise capacity (6MWD < 350 m). RESULTS: ΔPCO2, Ca-vO2 and P(v-a) CO2/Ca-vO2 ratio were significantly higher in IPAH than CHD-PAH (8.3 vs. 3.5 mmHg, p < 0.001; 4.8 vs. 3.4 mL/dL, p = 0.005; 1.84 vs. 1.11, p < 0.001, respectively). The HLC index was also higher in IPAH (median 0.82 vs. 0.40, p = 0.001). HLC showed modest correlation with 6MWD (r = 0.27, p = 0.04) and NT-proBNP (r = 0.24, p = 0.021). In multivariate regression, HLC remained independently associated with 6MWD (β = 32.86, 95% CI: 5.15-60.57, p = 0.021). Discrimination of impaired exercise capacity was limited (AUC of 0.55). CONCLUSION: The HLC index integrates gas exchange and cardiac output to characterize heart-lung interaction in PAH. This novel physiological metric may provide complementary insights into cardiopulmonary coupling and functional limitation.