BackgroundPulmonary hypertension (PH) is a common and morbid complication of left heart disease (LHD), comprising two subtypes: (1) isolated post-capillary pulmonary hypertension (Ipc-PH) and (2) combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Knowledge regarding the physiological characteristics that distinguish Cpc-PH, which has a worse prognosis, from Ipc-PH remains limited. Therefore, this study aimed to assess the utility of cardiopulmonary exercise testing (CPET) variables in detecting Cpc-PH.Methods and resultsAmong 105 consecutive patients with LHD (age: 55 ± 13 years; male/female = 79/26) who underwent right heart catheterization and CPET, 45 (43%) were classified as PH-LHD (mean pulmonary artery pressure >20 mmHg). Ipc-PH (n = 24) was defined as pulmonary vascular resistance (PVR) ≤ 3 WU and Cpc-PH (n = 21) as PVR > 3 WU. Patients with Cpc-PH had a significantly lower peak partial pressure of carbon dioxide (PETCO2) (Non-PH/Ipc-PH/Cpc-PH = 38.2 ± 6.6 vs. 38.3 ± 6.0 vs 33.0 ± 4.4 mmHg, p = 0.006), higher VE vs. VCO2slope (Non-PH/Ipc-PH/Cpc-PH = 33.0 [28.3, 36.6] vs. 32.5 [28.1, 37.8] vs. 40.6 [33.6, 46.1], p = 0.007), and lower ΔVO2/ΔWR (Non-PH/Ipc-PH/Cpc-PH = 8.5 ± 1.4 vs. 8.0 ± 1.7 vs. 6.8 ± 2.0 mL/min/watt, p = 0.001) than those with Ipc-PH and non-PH. Using multivariable logistic regression analysis, CPET variables were found to be independent predictors of Cpc-PH (lower peak PETCO2: odds ratio, 0.728 [95% confidence interval {CI}: 0.616–0.840], p = 0.003 and lower ΔVO2/ΔWR: odds ratio, 0.747 [95% CI: 0.575–0.872], p = 0.003).ConclusionFrom our exploratory analysis, CPET variables, especially in the lower peak PETCO2and lower ΔVO2/ΔWR, were associated with Cpc-PH in patients with left heart disease.