Upfront Exercise Hemodynamic Phenotyping of Patients with Pulmonary Hypertension and Left Heart Disease Risk Factors: A Prospective Experience

Background Resting hemodynamic assessment of suspected pulmonary hypertension (PH) in older adults with cardiovascular risk factors may not effectively discriminate pre-capillary from post-capillary disease. Exercise right-heart catheterization (RHC) can improve the ability to make this distinction, yet its clinical value remains unclear. We aimed to describe the challenges encountered in hemodynamic exercise phenotyping in this population and evaluate the relationships of exercise classifications to worsening clinical events, including mortality. Methods We prospectively recruited patients aged > 50 years with ≥ 1 cardiovascular risk factor referred for hemodynamic assessment of suspected PH, to undergo cycle-ergometry during initial RHC. Resting hemodynamics were classified per the 2022 European Society of Cardiology/European Respiratory Society guidelines, and exercise pressure-flow relationships were analyzed but not disclosed to treating physicians. Win-ratio and Kaplan-Meier analyses evaluated associations between exercise hemodynamic phenotypes and worsening clinical events. Results Among 43 patients (aged 72 ± 9 years, 47% female), 37 completed exercise. Resting classifications included the following: No-PH (19%), pulmonary arterial hypertension (PAH) (53%), and PH associated with left-heart disease (PH-LHD; 28%). Exercise hemodynamics revealed predominantly PH-LHD (62%), and 22% of patients demonstrated limited increases in cardiac output. The win-ratio was unfavourable for resting PH-LHD vs PAH (0.59; P = 0.035), but no differences in mortality incidence were present ( P = 0.858). Conversely, the win-ratio was unfavourable for exercise PAH vs PH-LHD (0.59; P = 0.037), and exercise PAH demonstrated a higher mortality incidence ( P = 0.031). Conclusions In older patients with cardiovascular risk factors undergoing RHC to diagnose suspected incident PH, the upfront addition of exercise was challenging, yielding inconclusive results in approximately one-third of patients. Results also showed that time to death was more unfavourable for those with exercise PAH.