Oral Class I and III antiarrhythmic drugs for maintaining sinus rhythm after catheter ablation of atrial fibrillation.

BACKGROUND: Recurrence of atrial tachyarrhythmias (ATa) following catheter ablation for atrial fibrillation (AF) is a common problem. Antiarrhythmic drugs have been used shortly after ablation in an attempt to maintain sinus rhythm, particularly Class I and III agents. However, it still needs to be established if the use of Class I or III antiarrhythmic medications, or both, reduce the risk of recurrence of ATa. OBJECTIVES: To assess the effects of oral Class I and III antiarrhythmic drugs versus control (standard medical therapy without Class I or III antiarrhythmics, or placebo) for maintaining sinus rhythm in people undergoing catheter ablation for AF. SEARCH METHODS: We systematically searched CENTRAL, MEDLINE, Embase, Web of Science Core Collection, and two clinical trial registers without restrictions on language or date to 5 August 2022. SELECTION CRITERIA: We sought published, unpublished, and ongoing parallel-design, randomised controlled trials (RCTs) involving adult participants undergoing ablation for AF, with subsequent comparison of Class I and/or III antiarrhythmic use versus control (standard medical therapy or non-Class I and/or III antiarrhythmic use). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and performed meta-analyses with risk ratios (RR) and Peto odds ratios (Peto OR). Our primary outcomes were recurrence of atrial tachyarrhythmias; adverse events: thromboembolic events; adverse events: myocardial infarction; adverse events: new diagnosis of heart failure; and adverse events: requirement for one or more hospitalisations for atrial tachyarrhythmia. Our secondary outcomes were: all-cause mortality; and requirement for one or more repeat ablations. Where possible, we performed comparison analysis by Class I and/or III antiarrhythmic and divided follow-up periods for our primary outcome. We performed comprehensive assessments of risk of bias and certainty of evidence applying the GRADE methodology. MAIN RESULTS: We included nine RCTs involving a total of 3269 participants. Participants were on average 59.3 years old; 71.0% were male; and 72.9% and 27.4% had paroxysmal and persistent AF, respectively. Class I and/or III antiarrhythmics may reduce recurrence of ATa at 0 to 3 months postablation (risk ratio (RR) 0.74, 95% confidence interval (CI) 0.59 to 0.94, 8 trials, 3046 participants, low-certainty evidence) and likely reduce recurrence at > 3 to 6 months, our a priori primary time point (RR 0.85, 95% CI 0.78 to 0.93, 5 trials, 2591 participants, moderate-certainty evidence). Beyond six months the evidence is very uncertain, and the benefit of antiarrhythmics may not persist (RR 1.14, 95% CI 0.84 to 1.55, 4 trials, 2244 participants, very low-certainty evidence). The evidence suggests that Class I and/or III antiarrhythmics may not increase the risk of thromboembolic events, myocardial infarction, all-cause mortality, or requirement for repeat ablation, at 0 to 3, > 3 to 6, and > 6 months (where data were available; low- to very low-certainty evidence). The use of Class I and/or III antiarrhythmics postablation likely reduces hospitalisations for ATa by approximately 57% at 0 to 3 months (RR 0.43, 95% CI 0.28 to 0.64, moderate-certainty evidence). No data were available beyond three months. No data were available on new diagnoses of heart failure. Fewer data were available for Class I and III antiarrhythmics individually. Based on only one and two trials (n = 125 to 309), Class I antiarrhythmics may have little effect on recurrence of ATa at 0 to 3, > 3 to 6, and > 6 months (RR 0.88, 95% CI 0.64 to 1.20, 2 trials, 309 participants; RR 0.54, 95% CI 0.25 to 1.19, 1 trial, 125 participants; RR 0.87, 95% CI 0.57 to 1.32, 1 trial, 125 participants; low-certainty evidence throughout); requirement for hospitalisation for ATa at 0 to 3 months (low-certainty evidence); or requirement for repeat ablation at 0 to 3 months (low-certainty evidence). No data were available for thromboembolic events, myocardial infarction, new diagnosis of heart failure, or all-cause mortality at any time points, or hospitalisation or repeat ablation beyond three months. Class III antiarrhythmics may have little effect on recurrence of ATa at up to 3 months and at > 3 to 6 months (RR 0.76, 95% CI 0.50 to 1.16, 4 trials, 599 participants, low-certainty evidence; RR 0.82, 95% CI 0.62 to 1.09, 2 trials, 318 participants, low-certainty evidence), and beyond 6 months one trial reported a possible increase in recurrence of ATa (RR 1.95, 95% CI 1.29 to 2.94, 1 trial, 112 participants, low-certainty evidence). Class III antiarrhythmics likely reduce hospitalisations for ATa at 0 to 3 months (RR 0.40, 95% CI 0.26 to 0.63, moderate-certainty evidence), and may have little effect on all-cause mortality (low- to very low-certainty evidence). The effect of Class III antiarrhythmics on thromboembolic events and requirement for repeat ablation was uncertain (very low-certainty evidence for both outcomes). No data were available for myocardial infarction or new diagnosis of heart failure at any time point, outcomes other than recurrence beyond 6 months, or for hospitalisation and repeat ablation > 3 to 6 months. We assessed the majority of included trials as at low or unclear risk of bias. One trial reported an error in the randomisation process, raising the potential risk of selection bias; most of the included trials were non-blinded; and two trials were at high risk of attrition bias. AUTHORS' CONCLUSIONS: We found evidence to suggest that the use of Class I and/or III antiarrhythmics up to 3 months after ablation is associated with a reduced recurrence of ATa 0 to 6 months after ablation, which may not persist beyond 6 months, and an immediate reduction in hospitalisation for ATa 0 to 3 months after ablation. The evidence suggests there is no difference in rates of all-cause mortality, thromboembolic events, or myocardial infarction between Class I and/or III antiarrhythmics versus control.

Intralesional delivery of glycoprotein IIb/IIIa inhibitors in acute myocardial infarction: Review and recommendations.

Plaque rupture leads to a cascade of events culminating in collagen disruption, tissue factor release, platelet activation and thrombus formation. Pro-inflammatory conditions, hyperglycemia and smoking predispose to high thrombus burden (HTB) which is an independent predictor of slow or no-reflow. In patients with acute myocardial infarction (AMI), glycoprotein IIb/IIIa inhibitors (GPI) reduce thrombus burden and improve myocardial perfusion. These agents are typically administered systemically via the intravenous route or locally via an intracoronary (IC) route. However, as higher local concentrations of GPI are associated with enhanced platelet inhibition, intralesional (IL) GPI administration may be particularly effective in cases of HTB. Modest-sized randomized trials comparing IL and IC GPI delivery have reported conflicting outcomes. Some trials have demonstrated improved coronary flow and myocardial perfusion with reduced major adverse cardiac events with IL compared with IC GPI administration, whereas others have shown no significant benefits. Furthermore, although no direct comparison has been made between IL delivery using an aspiration catheter, microcatheter or a dedicated balloon-based "weeping" infusion-catheter, improved outcomes have been most consistent following GPI administration at the site of the lesion and thrombus with the dedicated infusion catheter. This review provides an update on the role and outcomes of IL GPI administration in patients with AMI and HTB. Based on the evidence we offer an algorithm demonstrating when to consider IL administration in patients with AMI undergoing intervention. We conclude with a perspective on the management of patients with STEMI and COVID-19 in whom a prothrombotic state often results in HTB.

Trapped without a diagnosis: Tumour necrosis factor receptor-associated periodic syndrome (TRAPS).

Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant condition caused by mutations in the TNFRSF1A gene. It is characterised by recurrent episodes of myalgia, followed by prolonged fever, migratory rashes, headache, serositis, arthralgia, abdominal pain and periorbital oedema. We describe a 49-year-old man with a self-limiting episode of paraparesis who reported recurrent bouts of abdominal symptoms and headaches since childhood. He had a persistent inflammatory response with night sweats and weight loss. We diagnosed TRAPS 2 years after having identified a TNFRSF1A gene mutation. His symptoms and inflammatory response resolved dramatically with the interleukin-1 receptor antagonist anakinra.

A decade's summary of transcatheter tricuspid valve repair.

Tricuspid regurgitation (TR) is the most common pathology for the tricuspid valve. Moderate to severe TR is associated with morbidity and adverse outcomes. The concept that TR resolves on its own if the underlying disease is successfully treated has proven to be false. Only a few patients with significant TR are deemed suitable for surgery. Given the late presentation of patients with high perioperative risks and substantial perioperative mortality, the development of transcatheter therapies and the experience gained with transcatheter aortic valve implantation operations have turned attention towards treating this challenging group of patients. In this article, we review the treatment options and highlight the role of transcatheter valve therapies in patients with severe TR.

Prognostic Value of Late Gadolinium Enhancement Detected on Cardiac Magnetic Resonance in Cardiac Sarcoidosis.

BACKGROUND: Sarcoidosis is a complex multisystem inflammatory disorder, with approximately 5% of patients having overt cardiac involvement. Patients with cardiac sarcoidosis are at an increased risk of both ventricular arrhythmias and sudden cardiac death. Previous studies have shown that the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with an increased risk of mortality and ventricular arrhythmias and may be useful in predicting prognosis. OBJECTIVES: This systematic review and meta-analysis assessed the value of LGE on CMR imaging in predicting prognosis for patients with known or suspected cardiac sarcoidosis. METHODS: The authors searched the Embase and MEDLINE databases from inception to March 2022 for studies reporting individuals with known or suspected cardiac sarcoidosis referred for CMR with LGE. Outcomes were defined as all-cause mortality, ventricular arrhythmia, or a composite outcome of either death or ventricular arrhythmias. The primary analysis evaluated these outcomes according to the presence of LGE. A secondary analysis evaluated outcomes specifically according to the presence of biventricular LGE. RESULTS: Thirteen studies were included (1,318 participants) in the analysis, with an average participant age of 52.0 years and LGE prevalence of 13% to 70% over a follow-up of 3.1 years. Patients with LGE on CMR vs those without had higher odds of ventricular arrhythmias (odds ratio [OR]: 20.3; 95% CI: 8.1-51.0), all-cause mortality (OR: 3.45; 95% CI: 1.6-7.3), and the composite of both (OR: 9.2; 95% CI: 5.1-16.7). Right ventricular LGE is invariably accompanied by left ventricular LGE. Biventricular LGE is also associated with markedly increased odds of ventricular arrhythmias (OR: 43.6; 95% CI: 16.2-117.2). CONCLUSIONS: Patients with known or suspected cardiac sarcoidosis with LGE on CMR have significantly increased odds of both ventricular arrhythmias and all-cause mortality. The presence of biventricular LGE may confer additional prognostic information regarding arrhythmogenic risk.

MIRACLE2 Score Compared With Downtime and Current Selection Criterion for Invasive Cardiovascular Therapies After OHCA.

BACKGROUND: The MIRACLE2 score is the only risk score that does not incorporate and can be used for selection of therapies after out-of-hospital cardiac arrest (OHCA). OBJECTIVES: This study sought to compare the discrimination performance of the MIRACLE2 score, downtime, and current randomized controlled trial (RCT) recruitment criteria in predicting poor neurologic outcome after out-of-hospital cardiac arrest (OHCA). METHODS: We used the EUCAR (European Cardiac Arrest Registry), a retrospective cohort from 6 centers (May 2012-September 2022). The primary outcome was poor neurologic outcome on hospital discharge (cerebral performance category 3-5). RESULTS: A total of 1,259 patients (total downtime = 25 minutes; IQR: 15-36 minutes) were included in the study. Poor outcome occurred in 41.8% with downtime <30 minutes and in 79.3% for those with downtime >30 minutes. In a multivariable logistic regression analysis, MIRACLE2 had a stronger association with outcome (OR: 2.23; 95% CI: 1.98-2.51; P < 0.0001) than zero flow (OR: 1.07; 95% CI: 1.01-1.13; P = 0.013), low flow (OR: 1.04; 95% CI: 0.99-1.09; P = 0.054), and total downtime (OR: 0.99; 95% CI: 0.95-1.03; P = 0.52). MIRACLE2 had substantially superior discrimination for the primary endpoint (AUC: 0.877; 95% CI: 0.854-0.897) than zero flow (AUC: 0.610; 95% CI: 0.577-0.642), low flow (AUC: 0.725; 95% CI: 0.695-0.754), and total downtime (AUC: 0.732; 95% CI: 0.701-0.760). For those modeled for exclusion from study recruitment, the positive predictive value of MIRACLE2 ≥5 for poor outcome was significantly higher (0.92) than the CULPRIT-SHOCK (Culprit lesion only PCI Versus Multivessel PCI in Cardiogenic Shock) (0.80), EUROSHOCK (Testing the value of Novel Strategy and Its Cost Efficacy In Order to Improve the Poor Outcomes in Cardiogenic Shock) (0.74) and ECLS-SHOCK (Extra-corporeal life support in Cardiogenic shock) criteria (0.81) (P < 0.001). CONCLUSIONS: The MIRACLE2 score has superior prediction of outcome after OHCA than downtime and higher discrimination of poor outcome than the current RCT recruitment criteria. The potential for the MIRACLE2 score to improve the selection of OHCA patients should be evaluated formally in future RCTs.

Robotic-Assisted PCI: The Future of Coronary Intervention?

Robotic percutaneous coronary intervention (R-PCI) is a novel approach to performing percutaneous coronary intervention (PCI) whereby the operator can utilise remotely controlled technology to manipulate guidewires and catheter devices. This enables the procedure to be undertaken from within a radiation-shielded cockpit. Success in early trials has led to the release of commercially available robotic platforms which have now received regulatory approval and are available for use in clinical practice. Recent trials evaluating R-PCI have demonstrated high technical success rates with low complication rates. Despite this, a significant number of cases, particularly those with complex anatomy, still require at least partial conversion to a manual procedure. Advantages of R-PCI include accurate stent placement, reduced operator radiation exposure and a presumed reduction in orthopedic injuries. Limitations include current incompatibility with certain intravascular imaging catheters and the inability to manipulate multiple guidewires and stents simultaneously. Patients presenting with ST-elevation myocardial infarction requiring primary-PCI have also largely been excluded from existing R-PCI studies. Given these caveats, R-PCI remains a novel technology and has yet to become commonplace in cardiac catheterisation laboratories, however with increasing safety and feasibility data emerging, it is possible that R-PCI may form part of standard practice in the future.

Radiation-induced coronary artery disease: a difficult clinical conundrum.

Accelerated coronary artery disease seen following radiation exposure is termed 'radiation-induced coronary artery disease' (RICAD) and results from both the direct and indirect effects of radiation exposure. Long-term data are available from survivors of nuclear explosions and accidents, nuclear workers as well as from radiotherapy patients. The last group is, by far, the biggest cause of RICAD presentation.The incidence of RICAD continues to increase as cancer survival rates improve and it is now the second most common cause of morbidity and mortality in patients treated with radiotherapy for breast cancer, Hodgkin's lymphoma and other mediastinal malignancies. RICAD will frequently present atypically or even asymptomatically with a latency period of at least 10 years after radiotherapy treatment. An awareness of RICAD, as a long-term complication of radiotherapy, is therefore essential for the cardiologist, oncologist and general medical physician alike.Prior cardiac risk factors, a higher radiation dose and a younger age at exposure seem to increase a patient's risk ratio of developing RICAD. Significant radiation exposure, therefore, requires a low threshold for screening for early diagnosis and timely intervention.

MIRACLE2 Score and SCAI Grade to Identify Patients With Out-of-Hospital Cardiac Arrest for Immediate Coronary Angiography.

OBJECTIVES: The purpose of this study was to evaluate the impact of performing immediate coronary angiography (CAG) after out-of-hospital cardiac arrest (OHCA) with stratification of predicted neurologic injury and cardiogenic shock on arrival to a center. BACKGROUND: The role of immediate CAG for patients with OHCA is unclear, which may in part be explained by the majority of patients dying of hypoxic brain injury. METHODS: Between May 2012 and July 2020, patients from 5 European centers were included in the EUCAR (European Cardiac Arrest Registry). Patients were retrospectively classified into low vs high neurologic risk (MIRACLE2 score 0-3 vs ≥4) and degree of cardiogenic shock on arrival (Society for Cardiovascular Angiography and Interventions [SCAI] grade A vs B-E). A multivariable logistic regression analysis including immediate CAG was performed for the primary outcome of survival with good neurologic outcome (Cerebral Performance Category 1 or 2) at hospital discharge. RESULTS: Nine hundred twenty-six patients were included in the registry, with 405 (43.7%) in the low-risk group and 521 (56.3%) in the high-risk group. Immediate CAG was independently associated with improved survival with good neurologic outcome in the low MIRACLE2 risk group with ST-segment elevation myocardial infarction (OR: 11.80; 95% CI: 2.24-76.74; P = 0.048) and with SCAI grade B to E shock (OR: 3.23; 95% CI: 1.10-9.50; P = 0.031). No subgroups, including those with ST-segment elevation myocardial infarction and with SCAI grade B to E shock, achieved any benefit from early CAG in the high MIRACLE2 group. CONCLUSIONS: Combined classification of patients with OHCA with 12-lead electrocardiography, MIRACLE2 score 0 to 3, and SCAI grade B to E identifies a potential cohort of patients at low risk for neurologic injury who benefit most from immediate CAG.

A framework to establish a mentoring programme in surgery.

INTRODUCTION: Mentoring programmes help to facilitate the process of continuous professional development in surgery, providing an organizational structure around a mentor-mentee relationship which helps to develop the mentee. The lack of guidelines outlining how to set up such mentoring programmes, the fragmented inter-relationships of existing schemes and the lack of a unified strategy for their implementation are obstacles to the creation of such initiatives within many surgical departments. METHODS: We draw upon previous research, the experiences of certain authors and our own reflections to identify the key features of a surgical mentoring programme. RESULTS: We propose a ten step process which aims to encourage the development of formalised mentoring programmes in surgery. CONCLUSION: This outline may improve the delivery and effectiveness of mentoring programmes, which may ultimately enhance surgical training and hence quality of patient care.

The impact of COVID-19 on cardiology training.

The coronavirus disease 2019 (COVID-19) pandemic has produced a dramatic shift in how we practise medicine, with changes in working patterns, clinical commitments and training. Cardiology trainees in the UK have experienced a significant loss in training opportunities due to the loss of specialist outpatient clinics and reduction in procedural work, with those on subspecialty fellowships perhaps losing out the most. Training days, courses and conferences have also been cancelled or postponed. Many trainees have been redeployed during the crisis, and routes of career progression have been greatly affected, prompting concerns about extensions in training time, along with effects on mental health. With the pandemic ongoing and its effects on training likely long-lasting, we examine areas for improvement and opportunities for change in preparation for the 'new normal', including how other specialties have adapted. The increasingly routine use of video conferencing and online education has been a rare positive of the pandemic, and simulation will play a larger role. A more coordinated, national approach will need to be introduced to ensure curriculum components are covered and trainees around the country have equal access to ensure cardiology training in the UK remains world class.

COVID-19 Infection and High Intracoronary Thrombus Burden.

Coronavirus 2019 (COVID-19) is an acute respiratory disease that has rapidly spread around the world and been declared a global pandemic by the World Health Organization. Emerging evidence demonstrates a strong association with a pro-thrombotic state and we present the first patient admitted with COVID-19 and an inferior ST-segment elevation myocardial infarction (STEMI) with evidence of high intracoronary thrombus burden. We review the mechanism of the high thrombus burden, which may be driven by the significant cytokine storm, endothelial dysfunction, increase risk of coronary plaque rupture and hypercoagulability.

Hydroxychloroquine use in COVID-19: is the risk of cardiovascular toxicity justified?

The outbreak of COVID-19 in Wuhan, China and its declaration as a global pandemic by WHO has left the medical community under significant pressure to rapidly identify effective therapeutic and preventative strategies. Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were found to be efficacious against SARS-CoV-2 when investigated in preliminary in vitro experiments. Reports of success in early clinical studies were widely publicised by news outlets, politicians and on social media. These results led several countries to approve the use of these drugs for the treatment of patients with COVID-19. Despite having reasonable safety profiles in the treatment of malaria and certain autoimmune conditions, both drugs are known to have potential cardiotoxic side effects. There is a high incidence of myocardial injury and arrhythmia reported with COVID-19 infection, and as such this population may be more susceptible to this side-effect profile. Studies to date have now demonstrated that in patients with COVID-19, these drugs are associated with significant QTc prolongation, as well as reports of ventricular arrhythmias. Furthermore, subsequent studies have failed to demonstrate clinical benefit from either drug. Indeed, clinical trials have also been stopped early due to safety concerns over HCQ. There is an urgent need for credible solutions to the global pandemic, but we argue that in the absence of high-quality evidence, there needs to be greater caution over the routine use or authorisation of drugs for which efficacy and safety is unproven.

Collaborative patterns, authorship practices and scientific success in biomedical research: a network analysis.

OBJECTIVE: To investigate the relationship between biomedical researchers' collaborative and authorship practices and scientific success. DESIGN: Longitudinal quantitative analysis of individual researchers' careers over a nine-year period. SETTING: A leading biomedical research institution in the United Kingdom. PARTICIPANTS: Five hundred and twenty-five biomedical researchers who were in employment on 31 December 2009. MAIN OUTCOME MEASURES: We constructed the co-authorship network in which nodes are the researchers, and links are established between any two researchers if they co-authored one or more articles. For each researcher, we recorded the position held in the co-authorship network and in the bylines of all articles published in each three-year interval and calculated the number of citations these articles accrued until January 2013. We estimated maximum likelihood negative binomial panel regression models. RESULTS: Our analysis suggests that collaboration sustained success, yet excessive co-authorship did not. Last positions in non-alphabetised bylines were beneficial for higher academic ranks but not for junior ones. A professor could witness a 20.57% increase in the expected citation count if last-listed non-alphabetically in one additional publication; yet, a lecturer suffered from a 13.04% reduction. First positions in alphabetised bylines were positively associated with performance for junior academics only. A lecturer could experience a 8.78% increase in the expected citation count if first-listed alphabetically in one additional publication. While junior researchers amplified success when brokering among otherwise disconnected collaborators, senior researchers prospered from socially cohesive networks, rich in third-party relationships. CONCLUSIONS: These results help biomedical scientists shape successful careers and research institutions develop effective assessment and recruitment policies that will ultimately sustain the quality of biomedical research and patient care.