Effect of long-term remote ischemic conditioning on inflammation and cardiac remodeling.

Background. Remote ischemic conditioning (RIC) protects against acute ischemia-reperfusion injury and may have beneficial effects in patients with stable cardiovascular disease. We investigated the effect of long-term RIC treatment in patients with chronic ischemic heart failure (CIHF). Methods. Prespecified post-hoc analysis of a prospective, exploratory and outcome-assessor blinded study. Twenty-one patients with compensated CIHF and 21 matched controls without heart failure or ischemic heart disease were treated with RIC once daily for 28 ± 4 days. RIC was conducted as 4 cycles of 5 minutes upper arm ischemia followed by 5 minutes of reperfusion. We evaluated circulating markers of inflammation and cardiac remodeling at baseline and following long-term RIC. Results. RIC reduced C-reactive protein from 1.5 (0.6-2.5) to 1.3 (0.6-2.1) mg/l following long-term RIC treatment (p = .02) and calprotectin from 477 (95% CI 380 to 600) to 434 (95% CI 354 to 533) ng/ml (p = .03) in patients with CIHF, but not in matched controls. Overall, RIC did not affect circulating markers related to adaptive or innate immunology or cardiac remodeling in patients with CIHF. Among patients with CIHF and N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels above the geometric mean of 372 ng/l, long-term RIC treatment reduced soluble ST2 (n = 9) from 22.0 ± 3.7 to 20.3 ± 3.9 ng/ml following long-term RIC treatment (p = .01). Conclusion. Our findings suggest that long-term RIC treatment has mild anti-inflammatory effects in patients with compensated CIHF and anti-remodeling effects in those with increased NT-proBNP levels. This should be further investigated in a randomized sham-controlled trial.

Influence of preinfarction angina and coronary collateral blood flow on the efficacy of remote ischaemic conditioning in patients with ST segment elevation myocardial infarction: post hoc subgroup analysis of a randomised controlled trial.

OBJECTIVES: Remote ischaemic conditioning (RIC) confers cardioprotection in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We investigated whether preinfarction angina and coronary collateral blood flow (CCBF) to the infarct-related artery modify the efficacy of RIC. DESIGN: Post hoc subgroup analysis of a randomised controlled trial. PARTICIPANTS: A total of 139 patients with STEMI randomised to treatment with pPCI or RIC+pPCI. INTERVENTIONS: RIC was performed prior to pPCI as four cycles of 5 min upper arm ischaemia and reperfusion with a blood pressure cuff. PRIMARY OUTCOME MEASURE: Myocardial salvage index (MSI) assessed by single-photon emission computerised tomography. We evaluated the efficacy of RIC in subgroups of patients with or without preinfarction angina or CCBF. RESULTS: Of 139 patients included in the study, 109 had available data for preinfarction angina status and 54 had preinfarction angina. Among 83 patients with Thrombolysis In Myocardial Infarction flow 0/1 on arrival, 43 had CCBF. Overall, RIC+pPCI increased median MSI compared with pPCI alone (0.75 vs 0.56, p=0.045). Mean MSI did not differ between patients with and without preinfarction angina in either the pPCI alone (0.58 and 0.57; 95% CI -0.17 to 0.19, p=0.94) or the RIC+pPCI group (0.66 and 0.69; 95% CI -0.18 to 0.10, p=0.58). Mean MSI did not differ between patients with and without CCBF in the pPCI alone group (0.51 and 0.55; 95% CI -0.20 to 0.13, p=0.64), but was increased in patients with CCBF versus without CCBF in the RIC+pPCI group (0.75 vs 0.58; 95% CI 0.03 to 0.31, p=0.02; effect modification from CCBF on the effect of RIC on MSI, p=0.06). CONCLUSIONS: Preinfarction angina did not modify the efficacy of RIC in patients with STEMI undergoing pPCI. CCBF to the infarct-related artery seems to be of importance for the cardioprotective efficacy of RIC. TRIAL REGISTRATION NUMBER: NCT00435266, Post-results.

Effect of remote ischaemic conditioning on clinical outcomes in patients presenting with an ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

The rationale and study design for the multicentre, randomized, controlled CONDI2/ERIC-PPCI study are discussed.