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.

Background Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). In addition to glucose, other glucose-related indices, such as HbA1c, glucose-HbA1c ratio (GHR), and stress-hyperglycaemia ratio (SHR) are potential predictors of clinical outcomes following AMI. However, the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting 1-year all cause mortality in diabetic and non-diabetic ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients. Methods We undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values using the Youden’s formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-off values in the diabetic and non-diabetic subgroups, stratified by the type of AMI. Results There were 5841 STEMI and 4105 NSTEMI in the study. In STEMI patients, glucose, GHR, and SHR were independent predictors of 1-year all-cause mortality [glucose: OR 2.19 (95% CI 1.74–2.76); GHR: OR 2.28 (95% CI 1.80–2.89); SHR: OR 2.20 (95% CI 1.73–2.79)]. However, in NSTEMI patients, glucose and HbA1c were independently associated with 1-year all-cause mortality [glucose: OR 1.38 (95% CI 1.01–1.90); HbA1c: OR 2.11 (95% CI 1.15–3.88)]. In diabetic STEMI patients, SHR performed the best in terms of area-under-the-curve (AUC) analysis (glucose: AUC 63.3%, 95% CI 59.5–67.2; GHR 68.8% 95% CI 64.8–72.8; SHR: AUC 69.3%, 95% CI 65.4–73.2). However, in non-diabetic STEMI patients, glucose, GHR, and SHR performed equally well (glucose: AUC 72.0%, 95% CI 67.7–76.3; GHR 71.9% 95% CI 67.7–76.2; SHR: AUC 71.7%, 95% CI 67.4–76.0). In NSTEMI patients, glucose performed better than HbA1c for both diabetic and non-diabetic patients in AUC analysis (For diabetic, glucose: AUC 52.8%, 95% CI 48.1–57.6; HbA1c: AUC 42.5%, 95% CI 37.6–47. For non-diabetic, glucose: AUC 62.0%, 95% CI 54.1–70.0; HbA1c: AUC 51.1%, 95% CI 43.3–58.9). The optimal cut-off values for glucose, GHR, and SHR in STEMI patients were 15.0 mmol/L, 2.11, and 1.68 for diabetic and 10.6 mmol/L, 1.72, and 1.51 for non-diabetic patients respectively. For NSTEMI patients, the optimal glucose values were 10.7 mmol/L for diabetic and 8.1 mmol/L for non-diabetic patients. Conclusions SHR was the most consistent independent predictor of 1-year all-cause mortality in both diabetic and non-diabetic STEMI, whereas glucose was the best predictor in NSTEMI patients.

Cardiovascular disease and cancer are leading contributors to the global disease burden. As a result of cancer therapy-related cardiotoxicities, cardiovascular disease results in significant morbidity and mortality in cancer survivors and patients with active cancer. There is an unmet need for management of cardio-oncology conditions, which is predicted to reach epidemic proportions, and better understanding of their pathophysiology and treatment is urgently required. The proposed mechanisms underlying cardiotoxicity induced by 5-fluorouracil (5-FU) are vascular endothelial damage followed by thrombus formation, ischaemia secondary to coronary artery vasospasm, direct toxicity on myocardium and thrombogenicity. In patients with angina and electrocardiographic evidence of myocardial ischaemia due to chemotherapy-related coronary artery vasospasm, termination of chemotherapy and administration of calcium channel blockers or nitrates can improve ischaemic symptoms. However, coronary artery vasospasm can reoccur with 5-FU re-administration with limited effectiveness of vasodilator prophylaxis observed. While pre-existing coronary artery disease may increase the ischaemic potential of 5-FU, cardiovascular risk factors do not appear to completely predict the development of cardiac complications. Pharmacogenomic studies and genetic profiling may help predict the occurrence and streamline the treatment of 5-FU-induced coronary artery vasospasm. Echocardiographic measures such as the Tei index may help detect subclinical 5-FU cardiotoxicity. Further research is required to explore the cardioprotective effect of agents such as coenzyme complex, GLP-1 analogues and degradation inhibitors on 5-FU-induced coronary artery vasospasm.

Lowering low-density lipoprotein (LDL-C) and triglyceride (TG) levels form the cornerstone approach of cardiovascular risk reduction, and a higher high-density lipoprotein (HDL-C) is thought to be protective. However, in acute myocardial infarction (AMI) patients, higher admission LDL-C and TG levels have been shown to be associated with better clinical outcomes-termed the 'lipid paradox'. We studied the relationship between lipid profile obtained within 72 hours of presentation, and all-cause mortality (during hospitalization, at 30-days and 12-months), and rehospitalization for heart failure and nonfatal AMI at 12-months in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients treated by percutaneous coronary intervention (PCI). We included 11543 STEMI and 8470 NSTEMI patients who underwent PCI in the Singapore Myocardial Infarction Registry between 2008-2015. NSTEMI patients were older (60.3 years vs 57.7 years, p < 0.001) and more likely to be female (22.4% vs 15.0%, p < 0.001). In NSTEMI, a lower LDL-C was paradoxically associated with worse outcomes for death during hospitalization, within 30-days and within 12-months (all p < 0.001), but adjustment eliminated this paradox. In contrast, the paradox for LDL-C persisted for all primary outcomes after adjustment in STEMI. For NSTEMI patients, a lower HDL-C was associated with a higher risk of death during hospitalization but in STEMI patients a lower HDL-C was paradoxically associated with a lower risk of death during hospitalization. For this endpoint, the interaction term for HDL-C and type of MI was significant even after adjustment. An elevated TG level was not protective after adjustment. These observations may be due to differing characteristics and underlying pathophysiological mechanisms in NSTEMI and STEMI.