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.

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Background: In patients with heart failure, inflammation has been associated with worse functional capacity, but it is uncertain whether it could affect their response to exercise training. We evaluated whether inflammatory biomarkers are related to differential effect of exercise on the peak oxygen uptake ( _ VO 2 ) among patients with heart failure. Design: Open, parallel group, randomized controlled trial. Methods: Patients with heart failure and ejection fraction 0.4 were randomized into exercise training or control for 12 weeks. Patients were classified according to: 1) inflammatory biomarkers blood levels, defined as 'low' if both interleukin-6 and tumor necrosis factor-alpha blood levels were below median, and 'high' otherwise; and 2) galectin-3 blood levels, which also reflect pro-fibrotic processes. Results: Forty-four participants (50 AE 7 years old, 55% men, 25% ischemic) were allocated to exercise training (n ¼ 28) or control (n ¼ 16). Exercise significantly improved peak _ VO 2 among participants with 'low' inflammatory biomarkers (3.5 AE 0.9 vs. À0.7 AE 1.1 ml/kg per min, p ¼ 0.006), as compared with control, but not among those with 'high' inflammatory biomarkers (0.4 AE 0.6 vs. À0.2 AE 0.7 ml/kg per min, p ¼ 0.54, p for interaction ¼ 0.009). Similarly, exercise improved peak _ VO 2 among participants with below median (2.4 AE 0.8 vs. À0.3 AE 0.9 ml/kg per min, p ¼ 0.032), but not among those with above median galectin-3 blood levels (0.3 AE 0.7 vs. À0.7 AE 1.0 ml/kg per min, p ¼ 0.41, p for interaction ¼ 0.053). Conclusion: In patients with heart failure, levels of biomarkers that reflect pro-inflammatory and pro-fibrotic processes were associated with differential effect of exercise on functional capacity. Further studies should evaluate whether exercise training can improve clinical outcomes in patients with heart failure and low levels of these biomarkers.

HEx and LEx promoted similar reductions in ABP of heart transplant recipients, which suggests that they may be a tool to counteract hypertension in this high-risk population.