Exercise training improves exercise capacity and physical dimensions of QoL in HFpEF. This benefit is associated with atrial reverse remodeling and improved left ventricular diastolic function. (Exercise Training in Diastolic Heart Failure-Pilot Study: A Prospective, Randomised, Controlled Study to Determine the Effects of Physical Training on Exercise Capacity and Quality of Life [Ex-DHF-P]; ISRCTN42524037).

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In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65–80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a ‘left ventricular phenotype’ to a ‘right ventricular phenotype’ across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context.

BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.

Aims To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). Methods and results TRANSITION was a randomised, multicentre, open‐label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre‐admission use of renin–angiotensin–aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12‐h pre‐discharge or between Days 1–14 post‐discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up‐ or down‐titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day –1 and Day +1 in the pre‐discharge group and the post‐discharge group, respectively. Comparable proportions of patients in the pre‐ and post‐discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79–1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83–0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92–1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90–2.46). Conclusions Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. Clinical Trial Registration: http://ClinicalTrials.gov ID: NCT02661217

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There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.

OBJECTIVES The objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF.BACKGROUND Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symp-