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.

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Background--Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvascular endothelial function and will be reflected in the peripheral microvascular circulation.Methods and Results--In 38 patients aged 59AE8 years undergoing coronary angiography, endothelium-dependent and endothelium-independent coronary epicardial and microvascular responses were measured using intracoronary acetylcholine and nitroprusside, respectively, and after MS induced by mental arithmetic testing. Peripheral microvascular tone during MS was measured using peripheral arterial tonometry (Itamar Inc, Caesarea, Israel) as the ratio of digital pulse wave amplitude compared to rest (peripheral arterial tonometry ratio). MS increased the rate-pressure product by 22% (AE23%) and constricted epicardial coronary arteries by À5.9% (À10.5%, À2.6%) (median [interquartile range]), P=0.001, without changing CBF. Acetylcholine increased CBF by 38.5% (8.1%, 91.3%), P=0.001, without epicardial coronary diameter change (0.1% [À10.9%, 8.2%], P=not significant). The MS-induced CBF response correlated with endothelium-dependent CBF changes with acetylcholine (r=0.38, P=0.03) but not with the response to nitroprusside. The peripheral arterial tonometry ratio also correlated with the demandadjusted change in CBF during MS (r=À0.60, P=0.004), indicating similarity between the microcirculatory responses to MS in the coronary and peripheral microcirculation.Conclusions--The coronary microvascular response to MS is determined by endothelium-dependent, but not endotheliumindependent, coronary microvascular function. Moreover, the coronary microvascular responses to MS are reflected in the peripheral microvascular circulation. ( J Am Heart Assoc. 2018;7:e008532. Gensini score 7.0 [2.5, 15.5] Percentage stenosis of the study vessel 10% [10%, 20%]ACE indicates angiotensin-converting enzyme; bpm, beats per minute; CAD, coronary artery disease; IQR, interquartile range; PTSD, posttraumatic stress disorder; RPP, ratepressure product.