Efficacy and safety of sacubitril/valsartan in an outpatient setting: A single-center real-world retrospective study in HFrEF patients with focus on possible predictors of clinical outcome.

BACKGROUND: Currently, data on sacubitril/valsartan therapy from the real-world settings are scarce and the predictors of a good clinical responsiveness to this drug are unknown. OBJECTIVES: To assess efficacy and safety profile of sacubitril/valsartan and to identify predictors for a better clinical outcome. MATERIAL AND METHODS: Clinical, laboratory and echocardiographic data of 95 chronic heart failure (CHF) patients with reduced ejection fraction (HFrEF) were retrospectively analyzed. A good efficacy of sacubitril/valsartan was defined as the fulfilment of at least 2 of the following criteria: improvement of left ventricular ejection fraction (LVEF) or functional status, and reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels or hospitalization rates. RESULTS: Under sacubitril/valsartan, major improvements were observed in LVEF, the New York Heart Association (NYHA) class, NT-proBNP levels, and hospitalization rates. Patients with a good efficacy of sacubitril/valsartan were characterized by initially worse LVEF (median (interquartile range (IQR)): 29.0% (23.0-33.0%) compared to 32.0% (28.5-38.0%) with more frequent nonischemic etiology (65.4% compared to 41.9%) and hospitalizations for CHF/month (0.016 (0.004-0.057) compared to 0.000 (0.000-0.012)), lower cholesterol (42.3% compared to 65.1%), higher C-reactive protein (CRP) levels at baseline (0.5 mg/L (0.5-1.0 mg/L) compared to 0.5 mg/L (0.5-0.5 mg/L)), and a shorter timespan between CHF diagnosis and the start of sacubitril/valsartan treatment (66.0 (11.0-127.0) compared to 111 (73.0-211.0) months) (p < 0.05 each). In a multivariate Cox analysis, only the last 2 parameters were shown to be independent predictors of good clinical responsiveness to sacubitril/valsartan (hazard ratio (HR) = 1.263, 95% confidence interval (95% CI) = [1.048; 1.521]; HR = 0.992, 95% CI = [0.987; 0.997], p < 0.05, respectively). CONCLUSIONS: Sacubitril/valsartan improved LVEF, NYHA class, NT-proBNP levels, and hospitalization rates, mostly without relevant side effects. The independent predictors of a good clinical efficacy were higher CRP levels at baseline and a shorter delay between CHF diagnosis and the initialization of sacubitril/valsartan therapy.

Myocardial injury in severe COVID-19 is similar to pneumonias of other origin: results from a multicentre study.

AIMS: COVID-19, a respiratory viral disease causing severe pneumonia, also affects the heart and other organs. Whether its cardiac involvement is a specific feature consisting of myocarditis, or simply due to microvascular injury and systemic inflammation, is yet unclear and presently debated. Because myocardial injury is also common in other kinds of pneumonias, we investigated and compared such occurrence in severe pneumonias due to COVID-19 and other causes. METHODS AND RESULTS: We analysed data from 156 critically ill patients requiring mechanical ventilation in four European tertiary hospitals, including all n = 76 COVID-19 patients with severe disease course requiring at least ventilatory support, matched to n = 76 from a retrospective consecutive patient cohort of severe pneumonias of other origin (matched for age, gender, and type of ventilator therapy). When compared to the non-COVID-19, mortality (COVID-19 = 38.2% vs. non-COVID-19 = 51.3%, P = 0.142) and impairment of systolic function were not significantly different. Surprisingly, myocardial injury was even more frequent in non-COVID-19 (96.4% vs. 78.1% P = 0.004). Although inflammatory activity [C-reactive protein (CRP) and interleukin-6] was indifferent, d-dimer and thromboembolic incidence (COVID-19 = 23.7% vs. non-COVID-19 = 5.3%, P = 0.002) driven by pulmonary embolism rates (COVID-19 = 17.1% vs. non-COVID-19 = 2.6%, P = 0.005) were higher. CONCLUSIONS: Myocardial injury was frequent in severe COVID-19 requiring mechanical ventilation, but still less frequent than in similarly severe pneumonias of other origin, indicating that cardiac involvement may not be a specific feature of COVID-19. While mortality was also similar, COVID-19 is characterized with increased thrombogenicity and high pulmonary embolism rates.