In patients with PAH, improvement in 6MWD does not reflect benefit in clinical outcomes.

Aims  Glucose-lowering, glucagon-like peptide-1 (GLP-1) receptor agonists reduce incidence of major cardiovascular (CV) events in patients with Type 2 diabetes mellitus (DM). However, randomized clinical trials reported inconsistent effects on myocardial infarction (MI) and stroke, and limited data in DM patients without established CV disease (CVD). Very recently, new relevant evidence was available from additional CV outcome trials (CVOTs) that also included large subgroups of patients with DM without established CVD. Thus, the aim of this meta-analysis was to investigate the effects of GLP-1 receptor agonists on major CV events and safety in DM patients with and without established CVD. Methods and results  In this trial-level meta-analysis, we analysed data from randomized placebo-controlled CVOTs assessing efficacy and safety of GLP-1 receptor agonists in adult patients with Type 2 DM. We searched PubMed, Embase, Cochrane, ISI Web of Science, SCOPUS, and clinicaltrial.gov databases for eligible trials. Of 360 articles identified and screened for eligibility, seven CVOTs were included, with an overall of 56 004 patients included. The difference in efficacy with respect to the major adverse cardiovascular events (MACE) primary endpoint (including CV mortality, non-fatal MI, and non-fatal stroke) between patients with established CVD and patients with CV risk factors only was not significant [pooled interaction effect, expressed as ratio of hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.85–1.34]. In the analysis of the whole population of DM patients, GLP-1 receptor agonists showed a significant 12% reduction in the hazard of the three-point MACE composite endpoint (HR 0.88, 95% CI 0.80–0.96) and a significant reduction in the risk of CV mortality (HR 0.88, 95% CI 0.79–0.98), all-cause mortality (HR 0.89, 95% CI 0.81–0.97), fatal and non-fatal stroke (HR 0.84, 95% CI 0.76–0.94), and heart failure (HF) hospitalization (HR 0.92, 95% CI 0.86–0.97). No significant effect was observed for fatal and non-fatal MI (HR 0.91, 95% CI 0.82–1.02), although in a sensitivity analysis, based on a less conservative statistical approach, the pooled HR become statistically significant (HR 0.91, 95% CI 0.83–1.00; P = 0.039). No excess of hypoglycaemia, pancreatitis, and pancreatic cancer was observed between GLP-1 receptor agonists and placebo. Conclusion  Glucagon-like peptide-1 receptor agonists significantly reduce MACE, CV and total mortality stroke, and hospitalization for HF, with a trend for reduction of MI, in patients with Type 2 DM with and without established CVD.

Our study demonstrates that CCBs reduce the risk of all-cause mortality compared with active therapy and prevent heart failure compared with placebo. Furthermore, with the inclusion of recent trials, we confirm that they reduce the risk of stroke, also in comparison to angiotensin-converting enzyme inhibitors and do not increase the risk of cardiovascular death, myocardial infarction and major cardiovascular events.

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In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.

Myriad advances in all fields of cardiac imaging have stimulated and reflected new understanding of cardiac performance, myocardial damage and the mechanisms of heart failure. In this paper, the Heart Failure Association assesses the potential usefulness of innovative imaging modalities in enabling more precise diagnostic and prognostic evaluation, as well as in guiding treatment strategies. Many new methods have gradually penetrated clinical practice and are on their way to becoming a part of routine evaluation. This paper focuses on myocardial deformation and three‐dimensional ultrasound imaging; stress tests for the evaluation of contractile and filling function; the progress of magnetic resonance techniques; molecular imaging and other sound innovations.The Heart Failure Association aims to highlight the ways in which paradigms have shifted in several areas of cardiac assessment. These include reassessing of the simplified concept of ejection fraction and implementation of the new parameters of cardiac performance applicable to all heart failure phenotypes; switching from two‐dimensional to more accurate and reproducible three‐dimensional ultrasound volumetric evaluation; greater tissue characterization via recently developed magnetic resonance modalities; moving from assessing cardiac function and congestion at rest to assessing it during stress; from invasive to novel non‐invasive hybrid techniques depicting coronary anatomy and myocardial perfusion; as well as from morphometry to the imaging of pathophysiologic processes such as inflammation and apoptosis. This position paper examines the specific benefits of imaging innovations for practitioners dealing with heart failure aetiology, risk stratification and monitoring, and, in addition, for scientists involved in the development of future research.

The purpose of this study was to clarify whether changes in cardiopulmonary haemodynamics induced by pharmacological therapy correlate with exercise capacity and clinical events in patients with pulmonary arterial hypertension.16 randomised trials including 2353 patients, followed up for 16.4¡10.6 weeks, measuring cardiopulmonary haemodynamics by right heart catheterisation and reporting clinical events were included. Meta-analysis and meta-regression analysis were performed to assess the effects of treatments on clinical events and the relationship between haemodynamic changes (pulmonary artery pressure, pulmonary vascular resistance, cardiac index and right atrial pressure) and clinical events.Treatments significantly reduced all-cause death (OR 0.5, 95% CI 0.3-0.7; p,0.01), hospitalisation for pulmonary arterial hypertension (OR 0.4, 95% CI 0.2-0.7; p,0.01), initiation of rescue therapy (OR 0.3, 95% CI 0.2-0.6; p,0.01) and the composite outcome (OR 0.3, 95% CI 0.3-0.5; p,0.01). No relationship was found between changes of haemodynamic parameters and clinical events, whereas changes of cardiac index and pulmonary vascular resistance significantly correlated with changes in the 6-min walking distance (r50. 64, p50.03; r5 -0.55, p50.04, respectively).In patients with pulmonary arterial hypertension, improvements of cardiopulmonary haemodynamics observed in randomised clinical trials correlate with exercise capacity changes but do not predict clinical events in a short-term follow-up. @ERSpublications In PAH, cardiopulmonary haemodynamic improvements correlate with exercise capacity changes but not with clinical events

BACKGROUND AND PURPOSE Sympathetic nervous system (SNS) hyperactivity is characteristic of chronic heart failure (HF) and significantly worsens prognosis. The success of β‐adrenoceptor antagonist (β‐blockers) therapy in HF is primarily attributed to protection of the heart from the noxious effects of augmented catecholamine levels. β‐Blockers have been shown to reduce SNS hyperactivity in HF, but the underlying molecular mechanisms are not understood. The GPCR kinase‐2 (GRK2)–α2adrenoceptor–catecholamine production axis is up‐regulated in the adrenal medulla during HF causing α2‐adrenoceptor dysfunction and elevated catecholamine levels. Here, we sought to investigate if β‐blocker treatment in HF could lower SNS activation by directly altering adrenal GRK2 levels. EXPERIMENTAL APPROACH Four weeks after myocardial infarction‐induced HF, adult rats were randomized to 10‐week treatment with vehicle (HF/C) or bisoprolol (HF/B). Cardiac function and dimensions were measured. In heart and adrenal gland, GRK2 levels were assessed by RT‐PCR and Western blotting and adrenoceptors studied with radioligand binding. Catecholamines and α2adrenoceptors in adrenal medulla chromaffin cell cultures were also measured. KEY RESULTS Bisoprolol treatment ameliorated HF‐related adverse cardiac remodelling and reduced plasma catecholamine levels, compared with HF/C rats. Bisoprolol also attenuated adrenal GRK2 overexpression as observed in HF/C rats and increased α2adrenoceptor density. In cultures of adrenal medulla chromaffin cells from all study groups, bisoprolol reversed HF‐related α2adrenoceptor dysfunction. This effect was reversed by GRK2 overexpression. CONCLUSION AND IMPLICATIONS Blockade of β‐adrenoceptors normalized the adrenal α2adrenoceptor‐catecholamine production axis by reducing GRK2 levels. This effect may contribute significantly to the decrease of HF‐related sympathetic overdrive by β−blockers.