Clinical and Hemodynamic Improvement in Pulmonary Hypertension After Switching to Sacubitril/Valsartan in Patients With Heart Failure With Preserved Ejection Fraction.

ABSTRACT: Patients with heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension have poor survival, and established medical therapies for both conditions are not available. In this retrospective study of 69 patients with HFpEF and either isolated postcapillary pulmonary hypertension (IpcPH, n = 53) or combined postcapillary and precapillary pulmonary hypertension (CpcPH, n = 16), we investigated the effects of sacubitril/valsartan on pulmonary hypertension measured using right heart catheterization at baseline (ie, presacubitril/valsartan) and 99 (94-123) days after switching to sacubitril/valsartan. After switching to sacubitril/valsartan, right heart catheterization showed significantly lower pulmonary artery pressures (systolic/diastolic/mean) in both patient groups compared with presacubitril/valsartan [IpcPH: 44 (38-52)/15 (12-19)/28 (22-33) mm Hg vs. 47 (40-55)/18 (15-23)/31 (26-35) mm Hg, P < 0.01; CpcPH: 54 (43-57)/18 (12-23)/34 (30-36) mm Hg vs. 61 (50-79)/24 (19-30)/40 (31-53) mm Hg, P < 0.05]. The median sacubitril/valsartan dose at follow-up was 24/26 (24/26-49/51) mg twice daily in both patients with IpcPH and CpcPH. Clinically, the New York Heart Association functional class improved by at least 1 class in 32 of 69 patients ( P < 0.01). In conclusion, sacubitril/valsartan therapy improves pulmonary hypertension in patients with HFpEF and either IpcPH or CpcPH. Further prospective randomized trials are needed for confirmation of our results.

An Unexpected Endobronchial Mass Appearing During Bronchoscopy.

A 60-year-old man was admitted to the hospital with productive cough and yellowish sputum, severe fatigue, and weight loss of 4 kg over the past month; furthermore, he reported a slowly progressive shortness of breath on exertion over the past 6 months. Before admission, he received ampicillin/sulbactam (750 mg) orally twice daily for 7 days without significant clinical improvement.

Safety and tolerability of inhaled heparin in idiopathic pulmonary fibrosis.

BACKGROUND: Abnormalities in alveolar coagulation occur in idiopathic pulmonary fibrosis (IPF). Anticoagulants attenuate bleomycin-induced lung fibrosis in animals. In this study, we first examined the pharmacokinetics of inhaled heparin in healthy subjects. Second, we investigated the safety and tolerability of heparin inhalation in IPF patients. METHODS: Coagulation assays were performed in blood and bronchoalveolar lavage fluid samples from 19 healthy volunteers after inhalation of increasing amounts of unfractionated heparin. The acute effects of heparin inhalation on lung function and exercise capacity and the safety and tolerability of chronic heparin inhalation for 28 days were assessed in 20 IPF patients in an open-label exploratory pilot study. RESULTS: In healthy subjects, inhalation of 150,000 IU heparin ("filled dose") significantly increased the partial thromboplastin time and anti-factor Xa activity in blood samples indicating the threshold dose. The local alveolar anticoagulant effect was detectable up to 72 h, and the alveolar half-life was estimated at 28 h. In IPF-patients, no acute deleterious effects on pulmonary function, gas exchange, or exercise capacity were noted after inhalation of the threshold dose. During chronic treatment, where one-fourth of the threshold dose was inhaled every 12 h for 28 days to obtain a steady-state anticoagulant activity in the alveolar space approximating the anticoagulant activity observed after threshold dose inhalation, no heparin-related side effects, such as hemoptysis or heparin-induced antibodies and thrombocytopenia, were detected in any patient, and median lung function values, exercise capacity, and quality of life scores appeared largely unaltered. Three adverse and one serious adverse events were noted; however, the relation of these events to the heparin inhalation was assessed as "unlikely" or "no relation" in each case. CONCLUSIONS: Inhaled heparin appears to be safe and well tolerated in IPF patients. Future clinical trials are required to demonstrate the long-term safety and efficacy of inhaled heparin in IPF.