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Aims: We hypothesized that the current gold standard for risk stratification of patients with acute heart failure (AHF), the Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF (MEESSI‐AHF) risk score, can be further improved by adding systemic inflammation as quantified by C‐reactive protein (CRP). Methods and results: In a prospective multicentre diagnostic study (BASEL V), AHF was centrally adjudicated by two independent cardiologists. The MEESSI‐AHF risk score was calculated using an established reduced and recalibrated model containing 12 independent risk factors. Model extension was performed by refitting and adding CRP in the logistic regression model with 30‐day mortality as binary outcome. Discrimination, calibration and clinical usefulness were used to assess the performance of the extended Multiple Estimation of risk based on the Emergency department Spanish Score In patients (MEESSI) model. Validation was performed in an independent, retrospective and single‐centre AHF cohort. Among 1208 AHF patients with complete data allowing calculation of the recalibrated MEESSI and the extended MEESSI models, the prognostic accuracy for 30‐day mortality of the extended MEESSI model (c‐statistic 0.83, 95% confidence interval [CI] 0.79–0.87) was significantly higher compared to the recalibrated model (c‐statistic 0.79, 95% CI 0.75–0.83, p = 0.013). The extended model allowed to stratify a higher percentage of patients into the lowest risk group compared to the recalibrated model (33.1% vs. 20.3%). Demonstrating a calibration plot's slope of 1.00 (95% CI 0.81–1.19) and an intercept of 0.0 (95% CI −0.22 to 0.22), the extended MEESSI model achieved excellent and improved calibration. Results were confirmed in the independent validation cohort (n = 575). Conclusions: Quantifying inflammation using CRP concentration provided incremental value in AHF risk stratification using the established MEESSI model. [ABSTRACT FROM AUTHOR]

Aims: Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity‐induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b–3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF. Methods: In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6‐min walk distance (6MWD) of 30–400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ‐TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ‐TSS. The sample size provides 85% power to detect placebo‐adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ‐TSS at overall two‐sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo. Conclusion: ENDEAVOR is the first phase 2b–3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF. [ABSTRACT FROM AUTHOR]

Aims We aimed to assess the long-term effect of a strategy of comprehensive vasodilation versus usual care on health-related quality of life (HRQL) among patients with acute heart failure (AHF). Methods and results Health-related quality of life was prospectively assessed by the generic 3-levelled EQ-5D and the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ) among adult AHF patients enrolled in an international, multicentre, randomised, open-label blinded-end-point trial of a strategy that emphasized early intensive and sustained vasodilation using maximally tolerated doses of established oral and transdermal vasodilators according to systolic blood pressure. Changes in EQ-5D and KCCQ from admission to 180 day follow-up were individually compared between the intensive vasodilatation and the usual care group. Among 666 patients eligible for 180 day follow-up, 284 (43%, median age 79 years, 35% women) and 198 (30%, median age 77 years, 35% women) had completed the EQ-5D and KCCQ at baseline and follow-up, respectively. There was a significant improvement in HRQL as quantified by both, EQ-5D and KCCQ, from hospitalization to 180 day follow-up, with no significant differences in the change of HRQL between both treatment strategies. For instance, 39 (26%) versus 33 (25%) patients had an improvement by at least one level in at least two categories in the EQ-5D. Median increase in KCCQ overall summary score (KCCQ-OSS) was 17.6 (IQR 2.0–42.6) in the intervention group versus 18.5 (IQR 3.9–39.3) in the usual care group (P < 0.001 vs. baseline, P = 0.945 between groups). Conclusions Among patients with AHF, long-term HRQL quantified by EQ-5D and KCCQ improved substantially, with overall no significant differences between a strategy of comprehensive vasodilation versus usual care. [ABSTRACT FROM AUTHOR]

Aims: Cardiac myosin‐binding protein C (cMyC) seems to be even more sensitive in the quantification of cardiomyocyte injury vs. high‐sensitivity cardiac troponin, and may therefore have diagnostic and prognostic utility. Methods and results: In a prospective multicentre diagnostic study, cMyC, high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) plasma concentrations were measured in blinded fashion in patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists centrally adjudicated the final diagnosis. Diagnostic accuracy for acute heart failure (AHF) was quantified by the area under the receiver operating characteristic curve (AUC). All‐cause mortality within 360 days was the prognostic endpoint. Among 1083 patients eligible for diagnostic analysis, 51% had AHF. cMyC concentrations at presentation were higher among AHF patients vs. patients with other final diagnoses [72 (interquartile range, IQR 39–156) vs. 22 ng/L (IQR 12–42), P < 0.001)]. cMyC's AUC was high [0.81, 95% confidence interval (CI) 0.78–0.83], higher than hs‐cTnT's (0.79, 95% CI 0.76–0.82, P = 0.081) and lower than NT‐proBNP's (0.91, 95% CI 0.89–0.93, P < 0.001). Among 794 AHF patients eligible for prognostic analysis, 28% died within 360 days; cMyC plasma concentrations above the median indicated increased risk of death (hazard ratio 2.19, 95% CI 1.66–2.89; P < 0.001). cMyC's prognostic accuracy was comparable with NT‐proBNP's and hs‐cTnT's. cMyC did not independently predict all‐cause mortality when used in validated multivariable regression models. In novel multivariable regression models including medication, age, left ventricular ejection fraction, and discharge creatinine, cMyC remained an independent predictor of death and had no interactions with medical therapies at discharge. Conclusion: Cardiac myosin‐binding protein C may aid physicians in the rapid triage of patients with suspected AHF. [ABSTRACT FROM AUTHOR]

This article describes the design and methodology of the POWER study (Physicians' Observational Work on Patient Education According to their Vascular Risk). POWER is an open-label multinational postmarketing study of the angiotensin II-receptor blocker eprosartan. The Systemic Coronary Risk Evaluation (SCORE) model has been used to estimate total cardiovascular risk and changes in total cardiovascular risk status during treatment for patients recruited in all countries other than Canada. Framingham Heart Study equations have been used to estimate risk in the Canadian contingent of POWER. Observations from POWER will provide insights into how clinicians try to achieve blood pressure goals within the framework of total cardiovascular risk management and how they integrate their treatment of blood pressure with other interventions. Experience during the POWER study may also help to affirm the utility, practicability and perhaps limitations of the SCORE system for estimating total cardiovascular risk and identify ways to improve the acceptance and implementation of risk estimation methods in cardiovascular primary prevention. [ABSTRACT FROM AUTHOR]