Tilmann Kramer1, Daniel Dumitrescu1, Felix Gerhardt1, Kristina Orlova1, Henrik Ten Freyhaus2, Martin Hellmich3, Stephan Baldus2, Stephan Rosenkranz4. 1. Klinik III für Innere Medizin, Herzzentrum der Universität zu Köln, Germany. 2. Klinik III für Innere Medizin, Herzzentrum der Universität zu Köln, Germany; Cologne Cardiovascular Research Center (CCRC), Heart Center at the University of Cologne, Germany. 3. Institut für Medizinische Statistik, Informatik und Epidemiologie (IMSIE), Universität zu Köln, Germany. 4. Klinik III für Innere Medizin, Herzzentrum der Universität zu Köln, Germany; Cologne Cardiovascular Research Center (CCRC), Heart Center at the University of Cologne, Germany. Electronic address: stephan.rosenkranz@uk-koeln.de.
Abstract
OBJECTIVE: Heart failure with preserved ejection fraction (HFpEF) is frequently associated with pulmonary hypertension (PH), which substantially impacts survival. Based on pulmonary vascular resistance (PVR) and the diastolic pressure gradient (DPG), current guidelines distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). However, the therapeutic consequences of this sub-classification remain entirely unclear. We specifically investigated the efficacy and safety of PDE5i in patients with HFpEF and CpcPH. METHODS: In 40 hemodynamically precisely characterized patients with HFpEF and Cpc-PH who were treated with a PDE5i for at least 12 months, the therapeutic effect on 6-minute walk distance (6MWD), WHO functional class (FC), NTproBNP levels, right ventricular function, and hospitalization rates was evaluated. RESULTS: Patients' mean age was 73 ± 9 years, and comorbidities were frequent (78% hypertension, 58% atrial fibrillation, 35% diabetes). Initially, 38 patients (95%) were in WHO-FC III and 2 patients (5%) in WHO-FC II. Prior to PDE5i initiation, mean PAPm was 46.2 ± 10.3 mmHg, PAWP 21.2 ± 4.7 mmHg, DPG 5.5 ± 7.2 mmHg, and PVR 6.2 ± 3.0 WU. After 12 months of PDE5i therapy, the 6MWD increased from initially 277 ± 17 to 340 ± 18 m (p < 0.001), and the proportion of patients in WHO-FC I/II increased from 5% to 37.5%. NTproBNP levels decreased by 33% (p = 0.004), and TAPSE improved from 16.8 ± 0.7 mm at baseline to 18.2 ± 0.6 mm (p = 0.01). The rate of HF-associated hospitalizations was substantially lower in the 12 months post PDE5i initiation compared to the prior 12 months. The DPG had no impact on the response to therapy. No deaths occurred, and typical side effects of PDE5i were observed. CONCLUSION: These data indicate that at least a subset of precisely characterized patients with HFpEF and CpcPH who tolerate PDE5i may benefit from targeted therapy. A randomized study in this particular sub-population is warranted.
OBJECTIVE:Heart failure with preserved ejection fraction (HFpEF) is frequently associated with pulmonary hypertension (PH), which substantially impacts survival. Based on pulmonary vascular resistance (PVR) and the diastolic pressure gradient (DPG), current guidelines distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). However, the therapeutic consequences of this sub-classification remain entirely unclear. We specifically investigated the efficacy and safety of PDE5i in patients with HFpEF and CpcPH. METHODS: In 40 hemodynamically precisely characterized patients with HFpEF and Cpc-PH who were treated with a PDE5i for at least 12 months, the therapeutic effect on 6-minute walk distance (6MWD), WHO functional class (FC), NTproBNP levels, right ventricular function, and hospitalization rates was evaluated. RESULTS:Patients' mean age was 73 ± 9 years, and comorbidities were frequent (78% hypertension, 58% atrial fibrillation, 35% diabetes). Initially, 38 patients (95%) were in WHO-FC III and 2 patients (5%) in WHO-FC II. Prior to PDE5i initiation, mean PAPm was 46.2 ± 10.3 mmHg, PAWP 21.2 ± 4.7 mmHg, DPG 5.5 ± 7.2 mmHg, and PVR 6.2 ± 3.0 WU. After 12 months of PDE5i therapy, the 6MWD increased from initially 277 ± 17 to 340 ± 18 m (p < 0.001), and the proportion of patients in WHO-FC I/II increased from 5% to 37.5%. NTproBNP levels decreased by 33% (p = 0.004), and TAPSE improved from 16.8 ± 0.7 mm at baseline to 18.2 ± 0.6 mm (p = 0.01). The rate of HF-associated hospitalizations was substantially lower in the 12 months post PDE5i initiation compared to the prior 12 months. The DPG had no impact on the response to therapy. No deaths occurred, and typical side effects of PDE5i were observed. CONCLUSION: These data indicate that at least a subset of precisely characterized patients with HFpEF and CpcPH who tolerate PDE5i may benefit from targeted therapy. A randomized study in this particular sub-population is warranted.
Authors: M Riccardi; M Pagnesi; E Sciatti; C M Lombardi; R M Inciardi; M Metra; E Vizzardi Journal: Heart Fail Rev Date: 2022-06-01 Impact factor: 4.214
Authors: Yi Tan; Zhiguo Zhang; Chao Zheng; Kupper A Wintergerst; Bradley B Keller; Lu Cai Journal: Nat Rev Cardiol Date: 2020-02-20 Impact factor: 32.419
Authors: Thibault Petit; Guido Claessen; Mathias Claeys; Andre La Gerche; Piet Claus; Stefan Ghysels; Marion Delcroix; Agnieszka Ciarka; Walter Droogne; Johan Van Cleemput; Rik Willems; Jens-Uwe Voigt; Jan Bogaert; Stefan Janssens Journal: ESC Heart Fail Date: 2021-09-03