Vasodilator challenge test with isosorbide dinitrate during right heart catheterization: any role in post-capillary pulmonary hypertension phenotyping?

Abstract Background and aims Despite recent advances in the diagnosis and treatment of pulmonary arterial hypertension (PAH), pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF-PH) still represents a diagnostic and therapeutic dilemma. Among HFpEF-PH patients, discriminating between isolated post-capillary (IpcPH) from combined post-/pre-capillary (CpcPH) PH, and especially a better understanding of the latter, is still challenging. Such a distinction can have an important therapeutic impact, as new evidence suggests that therapy with PDE5i might be beneficial in specific CpcPH patients [Humbert M, Kovacs G, Hoeper M et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J, 2022]. Our study sought to comprehensively assess and explore the role of Isosorbide Dinitrate (ISDN) testing in HFpEF-PH phenotyping. Methods From November 2019, all patients referred to our service to investigate PH and elevated pulmonary artery wedge pressures (PAWP) at rest or after fluid challenge at the time of the right heart catheterization, had a vasodilator test with a slow IV bolus of ISDN (with a specific protocol). Clinical, echocardiographic and hemodynamic data were collected. Results 38 patients (25 CpcPH, 13 IpcPH) were included in the analysis. Baseline characteristics are shown in table 1. Based on ISDN response, patients were stratified into three groups (Table 2). Group 1 showed a lack of significant pressures reduction after ISDN (“vasodilator negative Cpc-PH”). Group 2 displayed a significant reduction of PAWP < 15 mmHg, but persistent PH and high Pulmonary Vascular Resistance (PVR) (“vasodilator positive Cpc-PH”). Group 3 were patients whose pulmonary pressures normalized after ISDN (Ipc-PH). Conclusions albeit on a small group of patients, our preliminary results warrant further studies on the potential role of ISDN in better phenotyping HFpEF-PH and identify subgroups of patients who might benefit from PH specific therapies (“vasodilator positive Cpc-PH”) after treatment of the underling left heart disease.