SummaryBackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91–1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

AimsCardiac resynchronisation therapy (CRT) is effective treatment for selected patients with heart failure (HF) but has ~30% non-response rate. We evaluated whether specific biomarkers can predict outcome.MethodsA prospective single-centre pilot study of consecutive unselected patients undergoing CRT for HF between November 2013 and December 2015 evaluating cardiac extracellular matrix biomarkers and micro-ribonucleic acid (miRNA) expression before and after CRT assessing ability to predict functional response and survival. Each underwent three assessments (pre-implant, 6  weeks and 6  months postimplant) including: New York Heart Association (NYHA) class, echocardiography, electrocardiography, 6  min walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Plasma markers of cardiac fibrosis assessed were: N-terminal pro-peptides of collagen I and III, collagen I C-terminal telopeptides (CTx) and matrix metalloproteinases (MMP-2 and MMP-9) as well as a panel of miRNAs (miRNA-21, miRNA-30d, miRNA-122, miRNA-133a, miRNA-210 and miRNA-486).ResultsA total of 52 patients were recruited; mean age (±SD) was 72.4±9.4 years; male=43 (82.7%), ischaemic aetiology=30 (57.7%), mean QRS duration=166.4±23.5  ms, left bundle branch block (LBBB) morphology = 39 (75.0%), mean NYHA=2.7±0.6, 6MWT=238.8±130.6  m, MLHFQ=46.4±21.3  and left ventricular ejection fraction (LVEF)=24.3%±8.0%. Mean follow-up=1.7±0.3  and 5.8±0.7 months. There were 27 (55.1%) functional responders (3 no definable 6-month response; 2 missed assessments and 1 long-term lead displacement). No marker predicted response, however, CTx and LBBB trended most towards predicting functional response.ConclusionNo specific biomarkers reached significance for predicting functional response to CRT. CTx showed a trend towards predicting response and warrants further study.Trial registration numberNCT02541773.

AimsBody composition (BC) is known to alter in heart failure. Cardiac resynchronisation therapy (CRT) improves left ventricular geometry but the impact on BC is unknown. Our aim was to evaluate BC in these patients before and after CRT implantation.MethodsProspective proof-of-concept pilot study of heart failure patients undergoing CRT between September 2014 and December 2015. Assessments performed pre-CRT and post-CRT (6 weeks and 6 months) were: BC parameters (using air-displacement plethysmography), New York Heart Failure classification for assessing symptom severity, echocardiography to assess left ventricular geometry, electrocardiography, Minnesota Heart Failure Questionnaire and N-terminal probrain natriuretic peptide (NT-pro-BNP). Repeated measures analysis of variance was performed to assess relative change over time and potential correlations.ResultsTwenty-five patients were recruited; mean-age (±SD) was 73.4±10.0 years, 23 males, 18 CRT defibrillators (remainder CRT pacemakers), 16 had ischaemic aetiology, 6 diabetics, 17 with left bundle-branch morphology on ECG and 10 had atrial fibrillation. Significant inverse correlations were observed in the first 6 weeks following CRT between fat mass and left ventricular end-diastolic volume (r=−0.69, p<0.01) and NT-pro-BNP and fat mass (r=0.41, p=0.05). No significant differences were noted over 6 months. There was an observed trend towards reduced fat mass in the first 6 weeks post-CRT implant driven by non-responders. There was no significant difference between responders and non-responders in BC over 6 months.ConclusionThis is the first study to observe interplay between BC and cardiac geometry/function following CRT; a trend in overall fat mass reduction was noted following CRT and merits further study.

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