The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.

sex in heart failure populations, the results are conflicting. 13, 14 This may explain why data were unable to discriminate between BNP and NT-proBNP in heterogeneous heart failure populations, yielding inconsistent results.The aim of this study was therefore to investigate differences between BNP and NT-proBNP with regard to cardiovascular events and extend the search for this difference to sex, in a large clinical population with cardiovascular risk factors. Methods SubjectsWe used baseline data from the Japan Morning SurgeHome Blood Pressure (J-HOP) Study. The protocol of the J-HOP study has been published (Supplementary File 1). 15 Briefly, the J-HOP study is a prospective observational study (University Hospital Medical Information Network Clinical Trials Registry, UMIN000000894) evaluating the use of home blood pressure (BP) measurements to predict S erum levels of natriuretic peptide hormones, in particular brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), are useful biomarkers for ruling out heart failure, 1-3 as well as strong prognostic markers for cardiovascular events in not only heart failure and hypertensive populations but also the general population. 4-6 BNP, in contrast to NT-proBNP, is biologically active when released into the circulation. 7, 8 In some studies comparing the utility of BNP and NT-proBNP for heart failure screening and prognostic value for cardiovascular events, no practical difference was observed. 3,9 The value of those studies, however, was limited by their evaluation of selected patients. One study involved a small sample of patients with suspected heart failure, 3 and another study was performed in a stable and symptomatic heart failure population. 9 In addition, both BNP and NT-proBNP are higher in women than in men. Background: Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are prognostic biomarkers. Although these 2 peptides differ with regard to biological characteristics, there are few reports on the differences between BNP and NT-proBNP with regard to cardiovascular events or according to sex.

Mutations in the bone morphogenetic protein receptor type II (BMPR2) gene may result in the development of pulmonary arterial hypertension (PAH). However, the contribution of disease-causing mutations to the disease characteristics and responsiveness to recent treatment remains to be elucidated. We report three Japanese cases of advanced PAH with novel BMPR2 mutations, including two splicing mutations (IVS8-6_7delTTinsA and IVS9-2A>G) and one deletion (c.1279delG) mutation.

production and clearance. The production of BNP and NT-proBNP is regulated in the same manner, but their mechanisms for clearance are different. In particular, NT-proBNP is unable to bind to the biologically active and clearance receptors of BNP; furthermore, NT-proBNP is not a substrate of neprilysin, which is an enzyme that degrades BNP. Therefore, NT-proBNP is assumed to be more affected by non-receptor-mediated clearance through the kidney and non-neprilysin-mediated degradation compared with BNP. Furthermore, the clearance receptor and neprilysin are abundantly expressed in adipose tissues. 11,12 Considering these factors, renal function and body mass B -type natriuretic peptide (BNP) and N-terminal (NT)-proBNP are the products of the same gene (BNP) that encodes proBNP, a 108-amino acid peptide mainly expressed in the ventricles. Prior to secretion, this prohormone is processed into the biologically active BNP and biologically inactive NT peptides. 1,2 Because heart failure (HF) severity augments BNP expression, BNP and NT-proBNP are commonly used for diagnosing HF, predicting outcomes in clinical settings, 3-8 and for assessing the effects of therapeutic interventions in patients with HF. 9,10 These 2 peptides are the most clinically useful biomarkers of HF and generally correlate with each other, but differences are observed in regard to changes in their plasma levels.Plasma levels of circulating peptides are regulated by their