The year in cardiology: acute coronary syndromes

There is an unmet need in the management of acute coronary syndromes (ACS). In 2019, there were a number of important papers published in the European Heart Journal and other journals that deepened our knowledge of the spectrum of ACS and their management

Outcome selection and role of patient reported outcomes in contemporary cardiovascular trials: systematic review

Objectives To systematically assess the type of outcomes selected and the prevalence of patient reported outcomes in contemporary cardiovascular trials and to quantify any misuse or underuse of patient reported outcomes using a specially developed tool that would allow estimation of the relevance of such outcomes to clinical decision making

Timing of invasive strategy in non-ST-elevation acute coronary syndrome: a meta-analysis of randomized controlled trials

AIMS: The optimal timing of an invasive strategy (IS) in non-ST-elevation acute coronary syndrome (NSTE-ACS) is controversial. Recent randomized controlled trials (RCTs) and long-term follow-up data have yet to be included in a contemporary meta-analysis. METHODS AND RESULTS: A systematic review of RCTs that compared an early IS vs. delayed IS for NSTE-ACS was conducted by searching MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. A meta-analysis was performed by pooling relative risks (RRs) using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), recurrent ischaemia, admission for heart failure (HF), repeat re-vascularization, major bleeding, stroke, and length of hospital stay. This study was registered with PROSPERO (CRD42021246131). Seventeen RCTs with outcome data from 10 209 patients were included. No significant differences in risk for all-cause mortality [RR: 0.90, 95% confidence interval (CI): 0.78-1.04], MI (RR: 0.86, 95% CI: 0.63-1.16), admission for HF (RR: 0.66, 95% CI: 0.43-1.03), repeat re-vascularization (RR: 1.04, 95% CI: 0.88-1.23), major bleeding (RR: 0.86, 95% CI: 0.68-1.09), or stroke (RR: 0.95, 95% CI: 0.59-1.54) were observed. Recurrent ischaemia (RR: 0.57, 95% CI: 0.40-0.81) and length of stay (median difference: -22 h, 95% CI: -36.7 to -7.5 h) were reduced with an early IS. CONCLUSION: In all-comers with NSTE-ACS, an early IS does not reduce all-cause mortality, MI, admission for HF, repeat re-vascularization, or increase major bleeding or stroke when compared with a delayed IS. Risk of recurrent ischaemia and length of stay are significantly reduced with an early IS

GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

Background: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. Methods/design: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free ( including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy

Prolonged High-Dose Bivalirudin Infusion Reduces Major Bleeding Without Increasing Stent Thrombosis in Patients Undergoing Primary Percutaneous Coronary Intervention:Novel Insights From an Updated Meta-Analysis

BACKGROUND: The optimal antithrombotic therapy in patients with ST‐segment‐elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) remains a matter of debate. This updated meta‐analysis investigated the impact of (1) bivalirudin (with and without prolonged infusion) and (2) prolonged PCI‐dose (1.75 mg/hg per hour) bivalirudin infusion compared with conventional antithrombotic therapy on clinical outcomes in patients undergoing primary PCI. METHODS AND RESULTS: Eligible randomized trials were searched through MEDLINE, EMBASE, Cochrane database, and proceedings of major congresses. Prespecified outcomes were major bleeding (thrombolysis in myocardial infarction major and Bleeding Academic Research Consortium 3–5), acute stent thrombosis, as well as all‐cause and cardiac mortality at 30 days. Six randomized trials (n=17 294) were included. Bivalirudin compared with heparin (+/− glycoprotein‐IIb/IIIa inhibitor) was associated with reduction in major bleeding (odds ratio [OR]: 0.65, 95% CI: 0.48–0.88, P=0.006, derived from all 6 trials), increase in acute stent thrombosis (OR: 2.75, 95% CI: 1.46–5.18, P=0.002, 5 trials), and lower rate of all‐cause mortality (OR: 0.81, 95% CI: 0.67–0.98, P=0.03, 6 trials) as well as cardiac mortality (OR: 0.69, 95% CI: 0.55–0.87, P=0.001, 5 trials). The incidence of acute stent thrombosis did not differ between the prolonged PCI‐dose bivalirudin and comparator group (OR: 0.81, 95% CI: 0.27–2.46, P=0.71, 3 trials), whereas the risk of bleeding was reduced despite treatment with high‐dose bivalirudin infusion (OR: 0.28, 95% CI: 0.13–0.60, P=0.001, 3 trials). CONCLUSIONS: Bivalirudin (with and without prolonged infusion) compared with conventional antithrombotic therapy in ST‐segment‐elevation myocardial infarction patients undergoing primary PCI reduces major bleeding and death, but increases the rate of acute stent thrombosis. However, prolonging the bivalirudin infusion at PCI‐dose (1.75 mg/kg per hour) for 3 hours eliminates the excess risk of acute stent thrombosis, while maintaining the bleeding benefits

Cardiovascular magnetic resonance by non contrast T1-mapping allows assessment of severity of injury in acute myocardial infarction

BACKGROUND: Current cardiovascular magnetic resonance (CMR) methods, such as late gadolinium enhancement (LGE) and oedema imaging (T2W) used to depict myocardial ischemia, have limitations. Novel quantitative T1-mapping techniques have the potential to further characterize the components of ischemic injury. In patients with myocardial infarction (MI) we sought to investigate whether state-of the art pre-contrast T1-mapping (1) detects acute myocardial injury, (2) allows for quantification of the severity of damage when compared to standard techniques such as LGE and T2W, and (3) has the ability to predict long term functional recovery. METHODS: 3T CMR including T2W, T1-mapping and LGE was performed in 41 patients [of these, 78% were ST elevation MI (STEMI)] with acute MI at 12-48 hour after chest pain onset and at 6 months (6M). Patients with STEMI underwent primary PCI prior to CMR. Assessment of acute regional wall motion abnormalities, acute segmental damaged fraction by T2W and LGE and mean segmental T1 values was performed on matching short axis slices. LGE and improvement in regional wall motion at 6M were also obtained. RESULTS: We found that the variability of T1 measurements was significantly lower compared to T2W and that, while the diagnostic performance of acute T1-mapping for detecting myocardial injury was at least as good as that of T2W-CMR in STEMI patients, it was superior to T2W imaging in NSTEMI. There was a significant relationship between the segmental damaged fraction assessed by either by LGE or T2W, and mean segmental T1 values (P < 0.01). The index of salvaged myocardium derived by acute T1-mapping and 6M LGE was not different to the one derived from T2W (P = 0.88). Furthermore, the likelihood of improvement of segmental function at 6M decreased progressively as acute T1 values increased (P < 0.0004). CONCLUSIONS: In acute MI, pre-contrast T1-mapping allows assessment of the extent of myocardial damage. T1-mapping might become an important complementary technique to LGE and T2W for identification of reversible myocardial injury and prediction of functional recovery in acute MI

Very early invasive angiography versus standard of care in higher-risk non-ST elevation myocardial infarction: study protocol for the prospective multicentre randomised controlled RAPID N-STEMI trial

Background: There are a paucity of randomised data on the optimal timing of invasive coronary angiography (ICA) in higher-risk patients with non-ST elevation myocardial infarction (N-STEMI). International guideline recommendations for early ICA are primarily based on retrospective subgroup analyses of neutral trials. Aims: The RAPID N-STEMI trial aims to determine whether very early percutaneous revascularisation improves clinical outcomes as compared with a standard of care strategy in higher-risk N-STEMI patients. Methods and analysis: RAPID N-STEMI is a prospective, multicentre, open-label, randomised-controlled, pragmatic strategy trial. Higher-risk N-STEMI patients, as defined by Global Registry of Acute Coronary Events 2.0 score ≥118, or >90 with at least one additional high-risk feature, were randomised to either: very early ICA±revascularisation or standard of care timing of ICA±revascularisation. The primary outcome is the proportion of participants with at least one of the following events (all-cause mortality, non-fatal myocardial infarction and hospital admission for heart failure) at 12 months. Key secondary outcomes include major bleeding and stroke. A hypothesis generating cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage and residual ischaemia post percutaneous coronary intervention. On 7 April 2021, the sponsor discontinued enrolment due to the impact of the COVID-19 pandemic and lower than expected event rates. 425 patients were enrolled, and 61 patients underwent CMR. Ethics and dissemination: The trial has been reviewed and approved by the East of England Cambridge East Research Ethics Committee (18/EE/0222). The study results will be submitted for publication within 6 months of completion. Trial registration number: NCT03707314; Pre-results

Metabolomic Profiling in Acute ST-Segment-Elevation Myocardial Infarction Identifies Succinate as an Early Marker of Human Ischemia-Reperfusion Injury.

BACKGROUND: Ischemia-reperfusion injury following ST-segment-elevation myocardial infarction (STEMI) is a leading determinant of clinical outcome. In experimental models of myocardial ischemia, succinate accumulation leading to mitochondrial dysfunction is a major cause of ischemia-reperfusion injury; however, the potential importance and specificity of myocardial succinate accumulation in human STEMI is unknown. We sought to identify the metabolites released from the heart in patients undergoing primary percutaneous coronary intervention for emergency treatment of STEMI. METHODS AND RESULTS: Blood samples were obtained from the coronary artery, coronary sinus, and peripheral vein in patients undergoing primary percutaneous coronary intervention for acute STEMI and in control patients undergoing nonemergency coronary angiography or percutaneous coronary intervention for stable angina or non-STEMI. Plasma metabolites were analyzed by targeted liquid chromatography and mass spectrometry. Metabolite levels for coronary artery, coronary sinus, and peripheral vein were compared to derive cardiac and systemic release ratios. In STEMI patients, cardiac magnetic resonance imaging was performed 2 days and 6 months after primary percutaneous coronary intervention to quantify acute myocardial edema and final infarct size, respectively. In total, 115 patients undergoing acute STEMI and 26 control patients were included. Succinate was the only metabolite significantly increased in coronary sinus blood compared with venous blood in STEMI patients, indicating cardiac release of succinate. STEMI patients had higher succinate concentrations in arterial, coronary sinus, and peripheral venous blood than patients with non-STEMI or stable angina. Furthermore, cardiac succinate release in STEMI correlated with the extent of acute myocardial injury, quantified by cardiac magnetic resonance imaging. CONCLUSION: Succinate release by the myocardium correlates with the extent of ischemia