P2587Therapeutic effects of phosphodiesterase 5 inhibitors in patients with heart failure with preserved ejection fraction (HFpEF) and combined post- and pre-capillary pulmonary hypertension (Cpc-PH)

Abstract

Background: The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing and frequently associated with pulmonary hypertension (PH), which is associated with a poorer prognosis. The current ESC/ERS guidelines subdivide post‐capillary PH into isolated post‐capillary PH (Ipc‐PH) and combined postand pre‐capillary PH (Cpc‐PH). The latter is hemodynamically defined by a mean pulmonary artery pressure (PAPm) ≥25 mmHg, a pulmonary artery Wedge pressure (PAWP) >15 mmHg and a diastolic pressure gradient (DPG) ≥7 mmHg and/or a pulmonary vascular resistance (PVR) >3 WU. However, the therapeutic consequences of this subclassification are entirely unclear. Preliminary studies on phosphodiesterase 5 inhibitors (PDE5i) in PH‐HFpEF yielded contradictory results. We specifically investigated the efficacy and safety of PDE5i in patients with HFpEF and Cpc‐PH. Methods: In 40 hemodynamically precisely characterized patients with HFpEF and Cpc‐PH who were treated with a PDE5i (sildenafil 60 mg/d, n=24 or tadalafil 40 mg/d, n=16) for at least 12 months, the therapeutic effect on 6 minute walk distance (6MWD), WHO functional class (WHO‐FC), echocardiographic parameters, right ventricular (RV) function and laboratory parameters (NTproBNP) was evaluated 3, 6, 9, and 12 months after the initiation of treatment. Results: The average patient age was 73±9 years, 53% were female, and comorbidities were frequent (75% atrial fibrillation, 78% arterial hypertension, 35% diabetes). Initially, 38 patients (95%) were inWHO‐FC III and 2 patients (5%) in WHO‐FC II. Prior to treatment initiation, PAPm was 45.6±1.6 mmHg, PAWP 20.9±0.8 mmHg, DPG 6.1±1.0 mmHg, PVR 6.1±0.5 WU, and RAP was 12.5±1.0 mmHg. After 12 months of PDE5i therapy, the 6MWD substantially increased from initially 277±17.0 to 340±17.7 m, resulting in a net increase of 63 m (p<0.001). The proportion of patients in WHO‐FC I/II increased from 5% at baseline to 37.5% after 12 months of therapy. In addition, there was moderate improvement in RV function at 12 months (TAPSE 18.8±0.8 vs. 16.9±0.7 mm at baseline, p=0.01), and NTproBNP levels decreased from 3.191±559 ng/L at baseline to 2.130±472 ng/L at 12 months (‐33%, p=0.004). Importantly, body weight of the patients remained constant throughout the observation period (71.7±3 kg initially vs. 71.5±2 kg at 12 months), so that the changes in measured parameters may not be attributable to optimized volume status and reduced left ventricular filling pressure. No deaths occurred in the investigated group, and the typical side effects of PDE5i (headache, flushing, nasal congestion) were observed. Conclusion: These data indicate that precisely characterized patients with HFpEF and Cpc‐PH who tolerate PDE5i may benefit from targeted therapy. A randomized study in this particular sub‐population is warranted.