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In addition, the RV-ESA and PASP together with parameters of RV-PA coupling (TAPSE/PASP ratio and RVOT-VTI/PASP ratio) improved significantly in the PK-titration group as compared to the placebo group ( I Table i 1 and I Figure i 1). Our analyses demonstrated that 20 weeks of OM treatment in patients with HFrEF improved RV-SET, RV-VTI in both OM groups, and improved RV-ESA, RV afterload and RV-PA coupling only in the PK-titration group, whereas OM did not significantly improve TAPSE or RV-FAC. Right ventricular (RV) dysfunction due to post-capillary pulmonary hypertension is a common sequela of elevated left ventricular (LV) filling pressures in patients with heart failure (HF) which has been demonstrated to be associated with poor clinical outcomes.1-3 Measures of RV-pulmonary artery (RV-PA) coupling that evaluate indices of RV function and pulmonary hypertension severity have been shown to be associated with clinical outcomes.4,5 A phase 2 trial, COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure, NCT01786512) demonstrated that treatment with omecamtiv mecarbil (OM), a selective cardiac myosin activator, known as a myotrope, was related to an improved LV systolic function, beneficial reverse remodelling, sympathetic withdrawal and a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients with HF with reduced ejection fraction (HFrEF).6 In this research letter, we report the treatment effect of OM on RV structure and function together with RV-PA coupling in patients with HFrEF. [Extracted from the article]

Aims: Worsening heart failure (HF) is associated with shorter left ventricular systolic ejection time (SET), but there are limited data describing the relationship between SET and clinical outcomes. Thus, the objective was to describe the association between SET and clinical outcomes in an ambulatory HF population irrespective of ejection fraction (EF).Methods and Results: We identified ambulatory patients with HF with reduced EF (HFrEF) and HF with preserved EF (HFpEF) who had an outpatient transthoracic echocardiogram performed between August 2008 and July 2010 at a tertiary referral centre. Multivariable logistic regression was used to evaluate the association between SET and 1-year outcomes. A total of 545 HF patients (171 HFrEF, 374 HFpEF) met eligibility criteria. Compared with HFpEF, HFrEF patients were younger [median age 60 years (25th-75th percentiles 50-69) vs. 64 years (25th-75th percentiles 53-74], with fewer females (30% vs. 56%) and a similar percentage of African Americans (36% vs. 35%). Median (25th-75th percentiles) EF with HFrEF was 30% (25-35%) and with HFpEF was 54% (48-58%). Median SET was shorter (280 ms vs. 315 ms, P < 0.001), median pre-ejection period was longer (114 ms vs. 89 ms, P < 0.001), and median relaxation time was shorter (78.7 ms vs. 93.3 ms, P < 0.001) among patients with HFrEF vs. HFpEF. Death or HF hospitalization occurred in 26.9% (n = 46) HFrEF and 11.8% (n = 44) HFpEF patients. After adjustment, longer SET was associated with lower odds of the composite of death or HF hospitalization at 1 year among HFrEF but not HFpEF patients.Conclusion: Longer SET is independently associated with improved outcomes among HFrEF patients but not HFpEF patients, supporting a potential role for normalizing SET as a therapeutic strategy with systolic dysfunction. [ABSTRACT FROM AUTHOR]

Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way. [ABSTRACT FROM AUTHOR]

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research. [ABSTRACT FROM AUTHOR]