Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear.

Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk.

Very early invasive angiography versus standard of care in higher-risk non-ST elevation myocardial infarction: study protocol for the prospective multicentre randomised controlled RAPID N-STEMI trial.

Background: There are a paucity of randomised data on the optimal timing of invasive coronary angiography (ICA) in higher-risk patients with non-ST elevation myocardial infarction (N-STEMI). International guideline recommendations for early ICA are primarily based on retrospective subgroup analyses of neutral trials.

Aims: The RAPID N-STEMI trial aims to determine whether very early percutaneous revascularisation improves clinical outcomes as compared with a standard of care strategy in higher-risk N-STEMI patients.

Redefining β-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis.

Background: Mortality remains unacceptably high in patients with heart failure and reduced left ventricular ejection fraction (LVEF) despite advances in therapeutics. We hypothesised that a novel artificial intelligence approach could better assess multiple and higher-dimension interactions of comorbidities, and define clusters of β-blocker efficacy in patients with sinus rhythm and atrial fibrillation.

Methods: Neural network-based variational autoencoders and hierarchical clustering were applied to pooled individual patient data from nine double-blind, randomised, placebo-controlled trials of β blockers.

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

Background: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy.

Objectives: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR).

Methods: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed.

B-type natriuretic peptide trumps other prognostic markers in patients assessed for coronary disease.

Background: Risk prediction for patients with suspected coronary artery disease is complex due to the common occurrence of prior cardiovascular disease and extensive risk modification in primary care. Numerous markers have the potential to predict prognosis and guide management, but we currently lack robust 'real-world' evidence for their use.

Methods: Prospective, multicentre observational study of consecutive patients referred for elective coronary angiography.

Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials.

Aims: Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials.

Methods And Results: Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.

Determinants of Length of Stay Following Total Anterior Circulatory Stroke.

Identification of factors that determine length of stay (LOS) in total anterior circulatory stroke (TACS) has potential for targeted intervention to reduce the associated health care burden. This study aimed to determine which factors predict LOS following either ischaemic or haemorrhagic TACS. The study sample population was drawn from the Norfolk and Norwich Stroke and Transient Ischemic Attack (TIA) Register (1996⁻2012), a prospective registry.

Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease.

Background: Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss- a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial.

Methods And Results: Baseline blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: "26-32 (All)" [lowest level], "20-25", "15-19", "1-14", and "No Teeth" [highest level].

Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial.

Background: Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little.

Inflammatory Differences in Plaque Erosion and Rupture in Patients With ST-Segment Elevation Myocardial Infarction.

Background: Plaque erosion causes 30% of ST-segment elevation myocardial infarctions, but the underlying cause is unknown. Inflammatory infiltrates are less abundant in erosion compared with rupture in autopsy studies. We hypothesized that erosion and rupture are associated with significant differences in intracoronary cytokines in vivo.

Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure.

Background: The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF).

Objectives: This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo.

Methods: The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials.

A 6-Point TACS Score Predicts In-Hospital Mortality Following Total Anterior Circulation Stroke.

Background And Purpose: Little is known about the factors associated with in-hospital mortality following total anterior circulation stroke (TACS). We examined the characteristics and comorbidity data for TACS patients in relation to in-hospital mortality with the aim of developing a simple clinical rule for predicting the acute mortality outcome in TACS.

Methods: A routine data registry of one regional hospital in the UK was analyzed.

Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis.

Objectives: To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials.

Design: Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45.

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration.

Rationale: A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial.

Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis.

Background: Atrial fibrillation and heart failure often coexist, causing substantial cardiovascular morbidity and mortality. β blockers are indicated in patients with symptomatic heart failure with reduced ejection fraction; however, the efficacy of these drugs in patients with concomitant atrial fibrillation is uncertain. We therefore meta-analysed individual-patient data to assess the efficacy of β blockers in patients with heart failure and sinus rhythm compared with atrial fibrillation.

The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study.

Aims: Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation.

Effects of nebivolol on biomarkers in elderly patients with heart failure.

Background: Heart failure activates neurohormones, and elevated levels of brain natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial showed that nebivolol, a highly selective beta-1 antagonist with vasodilating properties, reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure. We explored the effects of nebivolol on a range of neurohormones, cytokines and markers of nitric oxide activity in heart failure.

Darapladib for preventing ischemic events in stable coronary heart disease.

Background: Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2.

Methods: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo.

A prospective, randomized, placebo-controlled, double-blind, multicenter study of the effects of irbesartan on aortic dilatation in Marfan syndrome (AIMS trial): study protocol.

Background: Cardiovascular complications are the leading cause of mortality and morbidity in Marfan syndrome (MFS), a dominantly inherited disorder caused by mutations in the gene that encodes fibrillin-1. There are approximately 18,000 patients in the UK with MFS. Current treatment includes careful follow-up, beta blockers, and prophylactic surgical intervention; however, there is no known treatment which effectively prevents the rate of aortic dilatation in MFS.

Comparison of drug-eluting and bare-metal stents in patients with diabetes undergoing primary percutaneous coronary intervention: what is the evidence?

A best evidence topic was written according to a structured protocol. The question addressed was, should the practising interventional cardiologist use drug-eluting stents (DESs) or bare-metal stents (BMSs) when undertaking primary percutaneous coronary intervention (PCI) in diabetic patients. The relevant outcomes that were used to determine the answer to this question included: in-stent restenosis, target vessel revascularization (TVR), mortality, myocardial infarction and in-stent thrombosis.