Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure.

BACKGROUND: We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure (HF) might explain any potential effect on clinical outcomes. METHODS: We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of ≥ 0.3 mg/dL and ≥ 25%, or increase in estimated glomerular filtration rate of ≥ 25% between baseline and day 2. Worsening renal function (WRF) was defined as the reverse. We performed causal mediation analyses regarding 180-day all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for HF/renal failure. RESULTS: Improvement in renal function was more frequently observed with serelaxin when compared with placebo [OR 1.88 (95% CI 1.64-2.15, p < 0.0001)], but was not associated with subsequent clinical outcomes. WRF occurred less frequent with serelaxin [OR 0.70 (95% CI 0.60-0.83, p < 0.0001)] and was associated with increased risk of ACM, worsening HF and the composite of CVD and HF or renal failure hospitalization. Improvement in renal function did not mediate the treatment effect of serelaxin [CVD HR 1.01 (0.99-1.04), ACM HR 1.01 (0.99-1.03), HF/renal failure hospitalization HR 0.99 (0.97-1.00)]. CONCLUSIONS: Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF. Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function.

Once daily ledipasvir/sofosbuvir fixed-dose combination with ribavirin in patients with inherited bleeding disorders and hepatitis C genotype 1 infection.

AIM: People with inherited bleeding disorders have been disproportionally affected by HCV. We assessed the fixed-dose combination of the NS5A inhibitor ledipasvir (LDV) with the NS5B polymerase inhibitor sofosbuvir (SOF) with ribavirin (RBV) in patients with genotype 1 HCV and inherited bleeding disorders. METHODS: To be eligible, patients had to be over 18 years of age and have an inherited bleeding disorder. HCV treatment-naïve and -experienced patients could enrol. All patients received LDV 90 mg per SOF 400 mg once daily and weight-based RBV in a divided dose for 12 weeks. The primary efficacy endpoint was sustained virologic response (SVR), defined as HCV RNA below the limit of detection (15 IU mL-1 ) 12 weeks after the end of treatment (SVR12). RESULTS: Of the 14 patients enrolled, 8 (57%) had haemophilia A, 3 (21%) had haemophilia B and 2 (14%) had von Willebrand disease, and 1 (7%) had factor XIII deficiency. All 14 patients (100%, 95% CI: 77-100%) achieved SVR12. Treatment was well tolerated: all patients completed therapy, with mostly mild adverse events. No specific safety concerns associated with the patient's underlying bleeding disorders were noted. CONCLUSION: These results appear to suggest that people with HCV and inherited bleeding disorders can be safely and effectively treated with 12 weeks of LDV/SOF plus RBV.

Persistent pulmonary congestion before discharge predicts rehospitalization in heart failure: a lung ultrasound study.

BACKGROUND: B-lines evaluated by lung ultrasound (LUS) are the sonographic sign of pulmonary congestion, a major predictor of morbidity and mortality in patients with heart failure (HF). Our aim was to assess the prognostic value of B-lines at discharge to predict rehospitalization at 6 months in patients with acute HF (AHF). METHODS: A prospective cohort of 100 patients admitted to a Cardiology Department for dyspnea and/or clinical suspicion of AHF were enrolled (mean age 70 ± 11 years). B-lines were evaluated at admission and before discharge. Subjects were followed-up for 6-months after discharge. RESULTS: Mean B-lines at admission was 48 ± 48 with a statistically significant reduction before discharge (20 ± 23, p < .0001). During follow-up, 14 patients were rehospitalized for decompensated HF. The 6-month event-free survival was highest in patients with less B-lines (≤ 15) and lowest in patients with more B-lines (> 15) (log rank χ(2) 20.5, p < .0001). On multivariable analysis, B-lines > 15 before discharge (hazard ratio [HR] 11.74; 95 % confidence interval [CI] 1.30-106.16) was an independent predictor of events at 6 months. CONCLUSIONS: Persistent pulmonary congestion before discharge evaluated by ultrasound strongly predicts rehospitalization for HF at 6-months. Absence or a mild degree of B-lines identify a subgroup at extremely low risk to be readmitted for HF decompensation.