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Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (<8 g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy. We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin <10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary end point is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary end points include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary end points. The MINT trial will inform RBC transfusion practice in patients with acute MI.

At a median of 2.2 years, patients with stable coronary artery disease and advanced kidney disease who were treated with an invasive strategy of coronary angiography with revascularization if indicated did not have a lower risk of death or MI than those who were treated with a conservative strategy of medical therapy alone.

Patients with ischemic heart disease and advanced kidney disease were randomly assigned to an invasive or a conservative strategy. As reported separately, the invasive strategy did not reduce clinical events. In this analysis of health-status outcomes, there were no benefits with the invasive strategy.

This clinical trial compared mitral-valve repair with replacement for severe ischemic mitral regurgitation. There were no significant between-group differences in left ventricular remodeling and clinical outcomes, but replacement was associated with more durable correction. Functional ischemic mitral regurgitation affects 1.6 million to 2.8 million patients in the United States and is associated with a doubling in mortality among patients with mild or greater degrees of mitral regurgitation after myocardial infarction. 1 – 3 Ischemic mitral regurgitation is a consequence of adverse left ventricular remodeling after myocardial injury with enlargement of the left ventricular chamber and mitral annulus, apical and lateral migration of the papillary muscles, leaflet tethering, and reduced closing forces. These processes lead to malcoaptation of the leaflets and variable degrees of mitral regurgitation that can fluctuate dynamically as a function of volume status, afterload, . . .

This trial compared coronary-artery bypass grafting alone with CABG plus mitral-valve repair in patients with coronary artery disease and moderate ischemic mitral regurgitation. Mitral-valve repair provided no apparent benefit and was associated with more neurologic complications. Each year, approximately 1 million Americans have a myocardial infarction, and nearly 8 million Americans have a history of myocardial infarction. 1 Ischemic mitral regurgitation, which results from functional-valve incompetence due to myocardial injury and adverse left ventricular remodeling, develops in approximately 50% of patients after an infarction, and moderate regurgitation occurs in more than 10% of patients. 2 – 4 Ischemic mitral regurgitation is associated with excess mortality regardless of management. 5 , 6 The valve leaflets and chordal structures in affected patients are “innocent bystanders”; mitral regurgitation results from papillary muscle displacement, leaflet tethering, reduced closing forces, and annular dilatation. 7 – 10 Many patients . . .

Background/Objective: There is little randomised evidence using a whole food plant-based (WFPB) diet as intervention for elevated body mass index (BMI) or dyslipidaemia. We investigated the effectiveness of a community-based dietary programme. Primary end points: BMI and cholesterol at 6 months (subsequently extended). Subjects: Ages 35–70, from one general practice in Gisborne, New Zealand. Diagnosed with obesity or overweight and at least one of type 2 diabetes, ischaemic heart disease, hypertension or hypercholesterolaemia. Of 65 subjects randomised (control n =32, intervention n =33), 49 (75.4%) completed the study to 6 months. Twenty-three (70%) intervention participants were followed up at 12 months. Methods: All participants received normal care. Intervention participants attended facilitated meetings twice-weekly for 12 weeks, and followed a non-energy-restricted WFPB diet with vitamin B 12 supplementation. Results: At 6 months, mean BMI reduction was greater with the WFPB diet compared with normal care (4.4 vs 0.4, difference: 3.9 kg m −2 (95% confidence interval (CI)±1), P <0.0001). Mean cholesterol reduction was greater with the WFPB diet, but the difference was not significant compared with normal care (0.71 vs 0.26, difference: 0.45 mmol l −1 (95% CI±0.54), P =0.1), unless dropouts were excluded (difference: 0.56 mmol l −1 (95% CI±0.54), P =0.05). Twelve-month mean reductions for the WFPB diet group were 4.2 (±0.8) kg m − 2 BMI points and 0.55 (±0.54, P =0.05) mmol l −1 total cholesterol. No serious harms were reported. Conclusions: This programme led to significant improvements in BMI, cholesterol and other risk factors. To the best of our knowledge, this research has achieved greater weight loss at 6 and 12 months than any other trial that does not limit energy intake or mandate regular exercise.

Ixmyelocel-T is an expanded, multicellular therapy produced from a patient's own bone marrow by selectively expanding two key types of bone marrow mononuclear cells: CD90+ mesenchymal stem cells and CD45+ CD14+ auto-fluorescent+ activated macrophages. Early phase clinical trials suggest that intramyocardial delivery of ixmyelocel-T might improve clinical, functional, symptomatic, and quality-of-life outcomes in patients with heart failure due to ischaemic dilated cardiomyopathy. We aimed to assess the safety and efficacy of catheter-based transendocardial injection of ixmyelocel-T cell therapy in patients with heart failure and reduced ejection fractions. In this randomised, double-blind, placebo-controlled phase 2B trial (ixCELL-DCM), patients from 31 sites in North America with New York Heart Association class III or IV symptomatic heart failure due to ischaemic dilated cardiomyopathy, who had left ventricular ejection fraction 35% or less, an automatic implantable cardioverter defibrillator, and who were ineligible for revascularisation procedures were randomly assigned (1:1) to receive ixmyelocel-T or placebo at the time of bone marrow aspiration and followed for 12 months. Randomisation was done through an interactive (voice/web) response system. The pharmacist, treating physician, and coordinator at each site were unblinded, but the the follow-up team was completely blinded. The primary endpoint was a composite of all-cause death, cardiovascular admission to hospital, and unplanned clinic visits to treat acute decompensated heart failure based on the blinded adjudication of an independent clinical endpoint committee. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01670981. Between April 2, 2013, and Jan 28, 2015, 126 participants were randomly assigned to receive either ixmyelocel-T (n=66) or placebo (n=60). 114 (90%) patients comprised the modified intention-to-treat population and 109 (87%) patients were included in the per-protocol primary efficacy analysis (58 in the ixmyelocel-T group and 51 in the placebo group). The primary efficacy endpoint was observed in 47 patients: 50 events in 25 (49%) of 51 patients in the placebo group and 38 events in 22 (38%) of 58 patients in the ixmyelocel-T group, which represents a 37% reduction in cardiac events compared with placebo (risk ratio 0·63 [95% CI 0·42–0·97]; p=0·0344). 41 (75%) of 51 participants in the placebo group had serious adverse events versus 31 (53%) of 58 in the ixmyelocel-T group (p=0·0197). To the best of our knowledge, ixCELL-DCM is the largest cell therapy study done in patients with heart failure so far. The transendocardial delivery of ixmyelocel-T in patients with heart failure and reduced ejection fraction due to ischaemic dilated cardiomyopathy resulted in a significant reduction in adjudicated clinical cardiac events compared with placebo leading to improved patient outcomes. Vericel Corporation.

Guidelines recommendations regarding anticoagulant therapy after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF) rely on retrospective, nonrandomized observational data. Currently, patients are treated with triple-therapy (dual antiplatelet therapy [DAPT] + oral anticoagulation therapy), but neither the duration of DAPT nor the level of anticoagulation has been studied in a randomized fashion. Recent studies also suggest dual pathway therapy with clopidogrel plus oral anticoagulation therapy may be superior, and other studies suggest that novel oral anticoagulants such as rivaroxaban may further improve patient outcomes. PIONEER AF-PCI (ClinicalTrials.gov NCT01830543) is an exploratory, open-label, randomized, multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and 1 vitamin K antagonist (VKA) treatment strategy in subjects who have paroxysmal, persistent, or permanent nonvalvular AF and have undergone PCI with stent placement. Approximately 2,100 subjects will be randomized in a 1:1:1 ratio to receive either rivaroxaban 15 mg once daily plus clopidogrel 75 mg daily for 12 months (a WOEST trial–like strategy), or rivaroxaban 2.5 mg twice daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, an ATLAS trial–like strategy), or dose-adjusted VKA once daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, traditional triple therapy). All patients will be followed up for 12 months for the primary composite end point of Thrombolysis in Myocardial Infarction major bleeding, bleeding requiring medical attention, and minor bleeding (collectively, clinically significant bleeding). The PIONEER AF-PCI study is the first randomized comparison of VKA vs novel oral anticoagulant therapy in patients with NVAF receiving antiplatelet therapy after PCI to assess the relative risks of bleeding complications.

Patients with chronic kidney disease (CKD) and stable ischemic heart disease are at markedly increased risk of cardiovascular events. Prior trials comparing a strategy of optimal medical therapy (OMT) with or without revascularization have largely excluded patients with advanced CKD. Whether a routine invasive approach when compared with a conservative strategy is beneficial in such patients is unknown. ISCHEMIA-CKD is a National Heart, Lung, and Blood Institute–funded randomized trial designed to determine the comparative effectiveness of an initial invasive strategy (cardiac catheterization and optimal revascularization [percutaneous coronary intervention or coronary artery bypass graft surgery, if suitable] plus OMT) versus a conservative strategy (OMT alone, with cardiac catheterization and revascularization [percutaneous coronary intervention or coronary artery bypass graft surgery, if suitable] reserved for failure of OMT) on long-term clinical outcomes in 777 patients with advanced CKD (defined as those with estimated glomerular filtration rate <30 mL/min/1.73m2 or on dialysis) and moderate or severe ischemia on stress testing. Participants were randomized in a 1:1 fashion to the invasive or a conservative strategy. The primary end point is a composite of death or nonfatal myocardial infarction. Major secondary endpoints are a composite of death, nonfatal myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest; angina control; and disease-specific quality of life. Safety outcomes such as initiation of maintenance dialysis and a composite of initiation of maintenance dialysis or death will be reported. The trial is projected to have 80% power to detect a 22% to 24% reduction in the primary composite end point with the invasive strategy when compared with the conservative strategy. ISCHEMIA-CKD will determine whether an initial invasive management strategy improves clinical outcomes when added to OMT in patients with advanced CKD and stable ischemic heart disease.

Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year). Part 2 is a 52-week, efficacy and safety study where 360 eligible patients will be randomized to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst-to-best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient-reported HF symptoms will be used to assess efficacy. The PANORAMA-HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function. Design of the two-stage, seamless, adaptive PANORAMA-HF study assessing the PK/PD, safety, and efficacy of sacubitril/valsartan versus enalapril in pediatric heart failure patients with systemic left ventricle and reduced left ventricular systolic function. bid, twice-weekly; m, month; mg, milligram; kg, kilogram; PD, pharmacodynamics; PK, pharmacokinetics. [Display omitted]