Venoarterial extracorporeal membrane oxygenation or standard care in patients with cardiogenic shock complicating acute myocardial infarction: the multicentre, randomised EURO SHOCK trial.

BACKGROUND: Cardiogenic shock (CGS) occurs in 10% of patients presenting with acute myocardial infarction (MI), with in-hospital mortality rates of 40-50% despite revascularisation. AIMS: The EURO SHOCK trial aimed to determine if early use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) could improve outcomes in patients with persistent CGS following primary percutaneous coronary intervention (PPCI). METHODS: This multicentre, pan-European trial randomised patients with persistent CGS 30 minutes after PPCI of the culprit lesion to receive either VA-ECMO or continue with standard therapy. The primary outcome measure was 30-day all-cause mortality in an intention-to-treat analysis. Secondary endpoints included 12-month all-cause mortality and 12-month composite of all-cause mortality or rehospitalisation due to heart failure. RESULTS: Due to the impact of the COVID-19 pandemic, the trial was stopped before completion of recruitment, after randomisation of 35 patients (standard therapy n=18, VA-ECMO n=17). Thirty-day all-cause mortality occurred in 43.8% of patients randomised to VA-ECMO and in 61.1% of patients randomised to standard therapy (hazard ratio [HR] 0.56, 95% confidence interval [CI]: 0.21-1.45; p=0.22). One-year all-cause mortality was 51.8% in the VA-ECMO group and 81.5% in the standard therapy arm (HR 0.52, 95% CI: 0.21-1.26; p=0.14). Vascular and bleeding complications occurred more often in the VA-ECMO arm (21.4% vs 0% and 35.7% vs 5.6%, respectively). CONCLUSIONS: Due to the limited number of patients recruited to the trial, no definite conclusions could be drawn from the available data. Our study demonstrates the feasibility of randomising patients with CGS complicating acute MI but also illustrates the challenges. We hope these data will inspire and inform the design of future large-scale trials.

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.

Long-Term Follow-Up of Complete Versus Lesion-Only Revascularization in STEMI and Multivessel Disease: The CvLPRIT Trial.

BACKGROUND: Randomized trials have shown that complete revascularization in patients with ST-segment elevation myocardial infarction (MI) with multivessel disease results in lower major adverse cardiovascular events (MACE) (all-cause death, MI, ischemia-driven revascularization, heart failure). OBJECTIVES: The goal of this study was to determine whether the benefits of complete revascularization are sustained long-term and their impact on hard endpoints. METHODS: CvLPRIT (Complete versus Lesion-only Primary PCI Trial) was a randomized trial of complete inpatient revascularization versus infarct-related artery revascularization only at the index admission. Randomized patients have been followed longer-term. The components of the original primary endpoint were collected from physical and electronic patient records, and from local databases for all readmissions. RESULTS: The median follow-up (achieved in >90% patients) from randomization to first event or last follow-up was 5.6 years (0.0 to 7.3 years). The primary MACE endpoint rate at this time point was 24.0% in the complete revascularization group but 37.7% of the infarct-related artery-only group (hazard ratio: 0.57; 95% confidence interval: 0.37 to 0.87; p = 0.0079). The composite endpoint of all-cause death/MI was 10.0% in the complete revascularization group versus 18.5% in the infarct-related artery-only group (hazard ratio: 0.47; 95% confidence interval: 0.25 to 0.89; p = 0.0175). In a landmark analysis (from 12 months to final follow-up), there was no significant difference between MACE, death/MI, and individual components of the primary endpoint. CONCLUSIONS: Long-term follow-up of the CvLPRIT trial shows that the significantly lower rate of MACE in the complete revascularization group, previously seen at 12 months, is sustained to a median of 5.6 years. A significant difference in composite all-cause death/MI favoring the complete revascularization was also observed. (Complete versus Lesion-only Primary PCI Trial; ISRCTN70913605).

A risk scoring system to predict coronary stent thrombosis.

OBJECTIVE: Stent thrombosis (ST) is a potentially life-threatening complication of percutaneous coronary intervention (PCI). We aimed to develop a scoring system to predict the risk of ST following PCI. RESEARCH DESIGN AND METHODS: Odds ratios (ORs) for risk factors associated with ST were identified from a meta-analysis based on a systematic literature review, and through consensus expert opinion (Delphi-RAND method). The combined ORs were used to calculate risk scores for acute (within 24 hours), early (within 30 days) and late (31 days to 1 year) ST. Risk scores were validated against patient-level data from the TRITON-TIMI 38 study. Twenty risk factors were identified. RESULTS: The most highly predictive factor for early and late ST was "incomplete duration of dual antiplatelet therapy". Derived total risk scores ranged from 0 to 22 for acute and early ST, and from 0 to 20 for late ST. Increasing scores were associated with an increasing risk of ST when applied to trial data. Model discrimination was 0.60 (p = .0028), 0.67 (p < .0001) and 0.66 (p < .0001) for acute, early and late ST respectively, indicating good discriminatory power for predicting ST. Key limitations included a lack of published data on acute ST, resulting in a risk score for this time point being based predominantly on expert opinion, and that it was not possible to map all risk factors to variables collected in the TRITON-TIMI 38 study. CONCLUSION: Our weighted scoring system may help to stratify ST risk and individualize antiplatelet therapy in patients undergoing PCI.

A propensity matched comparison of return to work and quality of life after stenting or coronary artery bypass surgery.

OBJECTIVES: We sought to determine (1) return to work (RTW) rates, (2) long-term employment (>12 months postprocedure), (3) time taken to RTW, and (4) quality of life (QoL), in patients treated with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). METHODS: Questionnaires regarding RTW were sent to 689 PCI and 169 CABG patients who underwent PCI or CABG at University Hospitals of Leicester Trust, UK, from May 2012 to May 2013. QoL was also measured using the European QoL 5-dimensions questionnaire (EQ-5D). Responses from patients employed preprocedure were analysed using multivariate logistic regression. Propensity score-matching was further used to compare similar patient populations receiving PCI or CABG. RESULTS: The response rate was 38% (235 PCI and 88 CABG patients). 241 respondents (75%) were employed preprocedure. Of these 162 (93%) PCI and 51 (77%) CABG patients returned to work, whereas 147 (85%) PCI and 41 (62%) CABG patients were still employed at >12 months postprocedure. After propensity analysis, there was no significant difference between PCI and CABG patients in RTW, long-term employment, nor QoL. The median time taken to RTW was 6 weeks after PCI and 13 weeks after CABG (p=0.001). The effect remained significant after multivariate analysis (p=0.001) and propensity analysis (p=0.001). CONCLUSIONS: In this first propensity score-matched study comparing RTW and QoL after PCI or CABG strict propensity matching indicates that RTW or QoL, is similar for PCI or CABG, albeit the number of matched pairs was small. There are differences, however, in delay in RTW.

Management of Multivessel Disease and Cardiogenic Shock.

Cardiogenic shock represents a state of low cardiac output and systemic hypoperfusion resulting in insufficient end-organ perfusion and consequent multiorgan failure. The main cause of this complication in the context of acute ST-elevation myocardial infarction is left ventricular dysfunction secondary to poor myocardial perfusion. In over 50% of cardiogenic shock cases, there is evidence of significant coronary stenosis within noninfarct-related arteries. Persistent ischemia in the noninfarct territory may contribute to ongoing hypotension. Currently, ESC and ACC/AHA/SCAI guidelines advocate complete revascularization in the context of multivessel coronary artery disease in the context of cardiogenic shock, although the evidence is weak.

Management of Multivessel Coronary Disease in ST-segment Elevation Myocardial Infarction.

Primary PCI of infarct-related arteries is the preferred reperfusion strategy in patients presenting with ST-segment elevation myocardial infarction (STEMI). Up to 40 % of such patients demonstrate evidence of multivessel, non-infarct-related artery coronary disease. Previous non-randomised observational studies and their associated meta-analyses have suggested that in such cases only the culprit infarct-related artery (IRA) lesion should be treated. However, recent randomised controlled trials have demonstrated improved clinical outcomes with lower major adverse cardiovascular events (MACE) rates when complete revascularisation is undertaken either at index primary percutaneous coronary intervention (PPCI) or during index admission. These trials suggest that current guidelines pertaining to treatment of non-infarct-related artery (N-IRA) lesions in STEMI patients with multivessel disease may need to be reconsidered depending on future trials. However, issues remain around timing of N-IRA intervention, the use of fractional flow reserve (FFR) or intravascular imaging to guide intervention in N-IRA lesions and the need to demonstrate reductions in hard clinical endpoints (death and MI) after complete revascularisation; these issues will need to be addressed through future trials. Clinicians must judge on the currently available data, whether it is still safer to leave important stenosis in N-IRA untreated.

Driving and arrhythmia: a review of scientific basis for international guidelines.

In patients with arrhythmias, the most feared complication while driving is of driver incapacity resulting in a road traffic accident. Patients with implantable cardioverter-defibrillators (ICDs) may suffer incapacity as a result of device therapy itself. The aim of this review article was to examine the types of arrhythmia that occur while driving, the impact of arrhythmia on driving as well as evidence to support that driving itself can precipitate arrhythmias. We will also review the postulated mechanisms by which driving can precipitate arrhythmias. Finally, we will compare guidelines from the USA, Europe, and UK in fitness to drive in patients with arrhythmias and ICDs.

Malabsorption causing failure of pharmacological therapy in the treatment of atrial fibrillation.

We report a case of atrial fibrillation (AF) refractory to medical management. The patient had previously undergone extensive gastric and small bowel surgery. Subsequently we demonstrated malabsorption of administered anti-arrhythmics as the cause of her refractory AF. Malabsorption, even to lesser degrees and from other causes should be considered in cases of unexplained therapeutic refractoriness.