Histidine-Rich Glycoprotein Modulates the Toxic Effects of High-Dose Polyphosphate in Mice.

BACKGROUND: Polyphosphate (polyP), a procoagulant released from platelets, activates coagulation via the contact system and modulates cardiomyocyte viability. High-dose intravenous polyP is lethal in mice, presumably because of thrombosis. Previously, we showed that HRG (histidine-rich glycoprotein) binds polyP and attenuates its procoagulant effects. In this study, we investigated the mechanisms responsible for the lethality of intravenous polyP in mice and the impact of HRG on this process. METHODS: The survival of wild-type or HRG-deficient mice given intravenous synthetic or platelet-derived polyP in doses up to 50 mg/kg or saline was compared. To determine the contribution of thrombosis, the effect of FXII (factor XII) knockdown or enoxaparin on polyP-induced fibrin deposition in the lungs was examined. To assess cardiotoxicity, the ECG was continuously monitored, the levels of troponin I and the myocardial band of creatine kinase were quantified, and the viability of a cultured murine cardiomyocyte cell line exposed to polyP in the absence or presence of HRG was determined. RESULTS: In HRG-deficient mice, polyP was lethal at 30 mg/kg, whereas it was lethal in wild-type mice at 50 mg/kg. Although FXII knockdown or enoxaparin administration attenuated polyP-induced fibrin deposition in the lungs, neither affected mortality. PolyP induced dose-dependent ECG abnormalities, including heart block and ST-segment changes, and increased the levels of troponin and myocardial band of creatine kinase, effects that were more pronounced in HRG-deficient mice than in wild-type mice and were attenuated when HRG-deficient mice were given supplemental HRG. Consistent with its cardiotoxicity, polyP reduced the viability of cultured cardiomyocytes in a dose-dependent manner, an effect attenuated with supplemental HRG. CONCLUSIONS: High-dose intravenous polyP is cardiotoxic in mice, and HRG modulates this effect.

Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.

Reference ranges for ambulatory heart rate measurements in a middle-aged population.

BACKGROUND: Elevated heart rate (HR) predicts cardiovascular disease and mortality, but there are no established normal limits for ambulatory HR. We used data from the Swedish CArdioPulmonary Imaging Study to determine reference ranges for ambulatory HR in a middle-aged population. We also studied clinical correlates of ambulatory HR. METHODS: A 24-hour ECG was registered in 5809 atrial fibrillation-free individuals, aged 50-65 years. A healthy subset (n=3942) was used to establish reference values (excluding persons with beta-blockers, cardiovascular disease, hypertension, heart failure, anaemia, diabetes, sleep apnoea or chronic obstructive pulmonary disease).Minimum HR was defined as the lowest 1-minute HR. Reference ranges are reported as means±SDs and 2.5th-97.5th percentiles. Clinical correlates of ambulatory HR were analysed with multivariable linear regression. RESULTS: The average mean and minimum HRs were 73±9 and 48±7 beats per minute (bpm) in men and 76±8 and 51±7 bpm in women; the reference range for mean ambulatory HR was 57-90 bpm in men and 61-92 bpm in women. Average daytime and night-time HRs are also reported. Clinical correlates, including age, sex, height, body mass index, physical activity, smoking, alcohol intake, diabetes, hypertension, haemoglobin level, use of beta-blockers, estimated glomerular filtration rate, per cent of predicted forced expiratory volume in 1 s and coronary artery calcium score, explained <15% of the interindividual differences in HR. CONCLUSION: Ambulatory HR varies widely in healthy middle-aged individuals, a finding with relevance for the management of patients with a perception of tachycardia. Differences in ambulatory HR between individuals are largely independent of common clinical correlates.

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Landiolol for the prevention of postoperative atrial fibrillation after cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. Although the evidence suggests that beta blockers prevent POAF, they often cause hypotension. Landiolol, an ultra-short-acting ß1 blocker, may prevent POAF, without adverse hemodynamic consequences. SOURCE: We searched MEDLINE, CENTRAL, Embase, and trial registries between January 1970 and March 2022. We included randomized controlled trials (RCTs) that evaluated the effect of landiolol for the prevention of POAF after cardiac surgery. Two reviewers independently assessed eligibility, extracted data, and assessed risk of bias using the Risk of Bias 2.0 tool. We pooled data using random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess certainty of evidence. PRINCIPAL FINDINGS: Nine RCTs including 868 participants met the eligibility criteria. Patients randomized to landiolol (56/460) had less POAF compared with controls (133/408) with a relative risk (RR) of 0.40 (95% confidence interval [CI], 0.30 to 0.54; I2 = 0%;) and an absolute risk of 12.2% vs 32.6% (absolute risk difference, 20.4%; 95% CI, 15.0 to 25.0). Landiolol resulted in a shorter hospital length-of-stay (LOS) (268 patients; mean difference, -2.32 days; 95% CI, -4.02 to -0.57; I2 = 0%). We found no significant difference in bradycardia (RR, 1.11; 95% CI, 0.48 to 2.56; I2 = 0%). No hypotension was reported with landiolol. We judged the certainty of evidence as moderate for POAF (because of indirectness as outcomes were not clearly defined) and low for LOS (because of imprecision and concern of reporting bias). CONCLUSION: In patients undergoing cardiac surgery, landiolol likely reduces POAF and may reduce LOS. A definitive large RCT is needed to confirm these findings. STUDY REGISTRATION: PROSPERO (CRD42021262703); registered 25 July 2021.

RéSUMé: OBJECTIF: La fibrillation auriculaire postopératoire (FAPO) est une complication fréquente après une chirurgie cardiaque. Bien que les données probantes suggèrent que les bêta-bloqueurs préviennent la FAPO, ces agents provoquent souvent une hypotension. Le landiolol, un ß1-bloqueur à action ultra-courte, pourrait prévenir la FAPO sans conséquences hémodynamiques indésirables. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, CENTRAL et Embase, et dans les registres d'études publiées entre janvier 1970 et mars 2022. Nous avons inclus les études randomisées contrôlées (ERC) évaluant l'effet du landiolol pour la prévention de la FAPO après une chirurgie cardiaque. Deux personnes ont indépendamment révisé l'éligibilité, extrait les données et évalué le risque de biais à l'aide de l'outil Risque de biais 2.0. Nous avons regroupé les données à l'aide de modèles à effets aléatoires. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Neuf ERC incluant 868 personnes remplissaient les critères d'éligibilité. Les patient·es randomisé·es dans le groupe landiolol (56/460) présentaient moins de FAPO que les témoins (133/408), avec un risque relatif (RR) de 0,40 (intervalle de confiance [IC] à 95 %, 0,30 à 0,54; I2 = 0 %) et un risque absolu de 12,2 % vs 32,6 % (différence de risque absolue, 20,4 %; IC 95 % 95 %, 15,0 à 25,0). Le landiolol a entraîné une durée de séjour hospitalier plus courte (268 patient·es; différence moyenne, −2,32 jours; IC 95 %, −4,02 à −0,57; I2 = 0 %). Nous n'avons trouvé aucune différence significative en matière de bradycardie (RR, 1,11; IC 95 %, 0,48 à 2,56; I2 = 0 %). Aucune hypotension n'a été rapportée avec le landiolol. Nous avons jugé que la certitude des données probantes était modérée pour la FAPO (en raison du caractère indirect car les critères d'évaluation n'étaient pas clairement définis) et faible pour la durée de séjour hospitalier (en raison de l'imprécision et de questionnements concernant le biais de déclaration). CONCLUSION: Chez les patient·es bénéficiant d'une chirurgie cardiaque, le landiolol réduit probablement la FAPO et peut réduire la durée de séjour hospitalier. Une ERC définitive à grande échelle est nécessaire pour confirmer ces résultats. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262703); enregistrée le 25 juillet 2021.

Risk Scores for Prediction of Postoperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-Analysis.

Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and is associated with poor clinical outcomes. The objective of this systematic review and meta-analysis was to assess the performance of risk scores to predict POAF in cardiac surgery patients. We searched MEDLINE, Embase, and Cochrane CENTRAL for studies that developed/evaluated a POAF risk prediction model. Pairs of reviewers independently screened studies and extracted data. We pooled area under the receiver operating curves (AUCs), sensitivity and specificity, and adjusted odds ratios from multivariable regression analyses using the generic inverse variance method and random effects models. Forty-three studies (n = 63,847) were included in the quantitative synthesis. Most scores were originally developed for other purposes but evaluated for predicting POAF. Pooled AUC revealed moderate POAF discrimination for the EuroSCORE II (AUC 0.59, 95% confidence interval [CI] 0.54 to 0.65), Society of Thoracic Surgeons (AUC 0.60, 95% CI 0.56 to 0.63), EuroSCORE (AUC 0.63, 95% CI 0.58 to 0.68), CHADS2 (AUC 0.66, 95% CI 0.57 to 0.75), POAF Score (AUC 0.66, 95% CI 0.63 to 0.68), HATCH (AUC 0.67, 95% CI 0.57 to 0.75), CHA2DS2-VASc (AUC 0.68, 95% CI 0.60 to 0.75) and SYNTAX scores (AUC 0.74, 95% CI 0.71 to 0.78). Pooled analyses at specific cutoffs of the CHA2DS2-VASc, CHADS2, HATCH, and POAF scores demonstrated moderate-to-high sensitivity (range 46% to 87%) and low-to-moderate specificity (range 31% to 70%) for POAF prediction. In conclusion, existing clinical risk scores offer at best moderate prediction for POAF after cardiac surgery. Better models are needed to guide POAF risk stratification in cardiac surgery patients.

Atrial Fibrillation Recurrence in Patients With Transient New-Onset Atrial Fibrillation Detected During Hospitalization for Noncardiac Surgery or Medical Illness : A Matched Cohort Study.

BACKGROUND: Atrial fibrillation (AF) is often detected for the first time in patients who are hospitalized for another reason. Long-term risks for AF recurrence in these patients are unclear. OBJECTIVE: To estimate risk for AF recurrence in patients with new-onset AF during a hospitalization for noncardiac surgery or medical illness compared with a matched population without AF. DESIGN: Matched cohort study. (ClinicalTrials.gov: NCT03221777). SETTING: Three academic hospitals in Hamilton, Ontario, Canada. PARTICIPANTS: The study enrolled patients hospitalized for noncardiac surgery or medical illness who had transient new-onset AF. For each participant, an age- and sex-matched control participant with no history of AF from the same hospital ward was recruited. All participants left the hospital in sinus rhythm. MEASUREMENTS: 14-day electrocardiographic (ECG) monitor at 1 and 6 months and telephone assessment at 1, 6, and 12 months. The primary outcome was AF lasting at least 30 seconds on the monitor or captured by ECG 12-lead during routine care at 12 months. RESULTS: Among 139 participants with transient new-onset AF (70 patients with medical illness and 69 surgical patients) and 139 matched control participants, the mean age was 71 years (SD, 10), the mean CHA2DS2-VASc score was 3.0 (SD, 1.5), and 59% were male. The median duration of AF during the index hospitalization was 15.8 hours (IQR, 6.4 to 49.6 hours). After 1 year, recurrent AF was detected in 33.1% (95% CI, 25.3% to 40.9%) of participants in the transient new-onset AF group and 5.0% (CI, 1.4% to 8.7%) of matched control participants; after adjustment for the number of ECG monitors worn and for baseline clinical differences, the adjusted relative risk was 6.6 (CI, 3.2 to 13.7). After exclusion of participants who had electrical or pharmacologic cardioversion during the index hospitalization (n = 40) and their matched control participants and limiting to AF events detected by the patch ECG monitor, recurrent AF was detected in 32.3% (CI, 23.1% to 41.5%) of participants with transient new-onset AF and 3.0% (CI, 0% to 6.4%) of matched control participants. LIMITATIONS: Generalizability is limited, and the study was underpowered to evaluate subgroups and clinical predictors. CONCLUSION: Among patients who have transient new-onset AF during a hospitalization for noncardiac surgery or medical illness, approximately 1 in 3 will have recurrent AF within 1 year. PRIMARY FUNDING SOURCE: Peer-reviewed grants.

Oral Anticoagulation Use and Left Atrial Appendage Occlusion in LAAOS III.

BACKGROUND: LAAOS III (Left Atrial Appendage Occlusion Study III) showed that left atrial appendage (LAA) occlusion reduces the risk of ischemic stroke or systemic embolism in patients with atrial fibrillation undergoing cardiac surgery. This article examines the effect of LAA occlusion on stroke reduction according to variation in the use of oral anticoagulant (OAC) therapy. METHODS: Information regarding OAC use was collected at every follow-up visit. Adjusted proportional hazards modeling, including using landmarks of hospital discharge, 1 and 2 years after randomization, evaluated the effect of LAA occlusion on the risk of ischemic stroke or systemic embolism, according to OAC use. Adjusted proportional hazard modeling, with OAC use as a time-dependent covariate, was also performed to assess the effect of LAA occlusion, according to OAC use throughout the study. RESULTS: At hospital discharge, 3027 patients (63.5%) were receiving a vitamin K antagonist, and 879 (18.5%) were receiving a non-vitamin K antagonist oral anticoagulant (direct OAC), with no difference in OAC use between treatment arms. There were 2887 (60.5%) patients who received OACs at all follow-up visits, 1401 (29.4%) who received OAC at some visits, and 472 (9.9%) who never received OACs. The effect of LAA occlusion on the risk of ischemic stroke or systemic embolism was consistent after discharge across all 3 groups: hazard ratios of 0.70 (95% CI, 0.51-0.96), 0.63 (95% CI, 0.43-0.94), and 0.76 (95% CI, 0.32-1.79), respectively. An adjusted proportional hazards model with OAC use as a time-dependent covariate showed that the reduction in stroke or systemic embolism with LAA occlusion was similar whether patients were receiving OACs or not. CONCLUSIONS: The benefit of LAA occlusion was consistent whether patients were receiving OACs or not. LAA occlusion provides thromboembolism reduction in patients independent of OAC use.

Cardiac Interventions in Patients With Active, Advanced Solid and Hematologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Invasive cardiac interventions are recommended to treat ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndromes, multivessel coronary disease, severe symptomatic aortic stenosis, and cardiomyopathy. These recommendations are based on randomized controlled trials that historically included few individuals with active, advanced malignancies. Advanced malignancies represent a significant competing risk for mortality, and there is limited evidence to inform the risks and benefits of invasive cardiac interventions in affected patients. We review the benefit conferred by invasive cardiac interventions; the periprocedural considerations; the contemporary survival expectations of patients across several types of active, advanced malignancy; and the literature on cardiovascular interventions in these populations. Our objective is to develop a rational framework to guide clinical recommendations on the use of invasive cardiac interventions in patients with active, advanced cancer.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Rhythm vs. Rate Control in Patients with Postoperative Atrial Fibrillation after Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is associated with morbidity and mortality. We undertook this review to compare the effects of rhythm vs. rate control in this population. METHODS: We searched MEDLINE, Embase and CENTRAL to March 2023. We included randomized trials and observational studies comparing rhythm to rate control in cardiac surgery patients with POAF. We used a random-effects model to meta-analyze data and rated the quality of evidence using GRADE. RESULTS: From 8,110 citations, we identified 8 randomized trials (990 patients). Drug regimens used for rhythm control included amiodarone in four trials, other class III anti-arrhythmics in one trial, class I anti-arrhythmics in four trials and either a class I or III anti-arrhythmic in one trial. Rhythm control compared to rate control did not result in a significant difference in length of stay (mean difference -0.8 days; 95% CI -3.0 to +1.4, I2 = 97%), AF recurrence within 1 week (130 events; risk ratio [RR] 1.1; 95%CI 0.6-1.9, I2 = 54%), AF recurrence up to 1 month (37 events; RR 0.9; 95%CI 0.5-1.8, I2 = 0%), AF recurrence up to 3 months (10 events; RR 1.0; 95%CI 0.3-3.4, I2 = 0%) or mortality (25 events; RR 1.6; 95%CI 0.7-3.5, I2 = 0%). Effect measures from seven observational studies (1428 patients) did not differ appreciably from those in randomized trials. CONCLUSIONS: Although atrial fibrillation is common after cardiac surgery, limited low-quality data guide its management. Limited available evidence suggests no clear advantage to either rhythm or rate control. A large-scale randomized trial is needed to inform this important clinical question.

Ventricular Tachycardia and ICD Therapy Burden With Catheter Ablation Versus Escalated Antiarrhythmic Drug Therapy.

BACKGROUND: Catheter ablation improves ventricular tachycardia (VT) event-free (time to event) survival in patients with antiarrhythmic drug (AAD)-refractory VT and previous myocardial infarction (MI). The effects of ablation on recurrent VT and implantable cardioverter-defibrillator (ICD) therapy (burden) have yet to be investigated. OBJECTIVES: This study sought to compare the VT and ICD therapy burden following treatment with either ablation or escalated AAD therapy among patients with VT and previous MI in the VANISH (Ventricular tachycardia AblatioN versus escalated antiarrhythmic drug therapy in ISchemic Heart disease) trial. METHODS: The VANISH trial randomized patients with previous MI and VT despite initial AAD therapy to either escalated AAD treatment or catheter ablation. VT burden was defined as the total number of VT events treated with ≥1 appropriate ICD therapy. Appropriate ICD therapy burden was defined as the total number of appropriate shocks or antitachycardia pacing therapies (ATPs) delivered. The Anderson-Gill recurrent event model was used to compare burden between the treatment arms. RESULTS: Of the 259 enrolled patients (median age, 69.8 years; 7.0% women), 132 patients were randomized to ablation and 129 patients were randomized to escalated AAD therapy. Over 23.4 months of follow-up, ablation-treated patients had a 40% lower shock-treated VT event burden and a 39% lower appropriate shock burden compared with patients who received escalated AAD therapy (P <0.05 for all). A reduction in VT burden, ATP-treated VT event burden, and appropriate ATP burden among ablation patients was only demonstrated in the stratum of patients with amiodarone-refractory VT (P <0.05 for all). CONCLUSIONS: Among patients with AAD-refractory VT and a previous MI, catheter ablation reduced shock-treated VT event burden and appropriate shock burden compared with escalated AAD therapy. There was also lower VT burden, ATP-treated VT event burden, and appropriate ATP burden among ablation-treated patients; however, the effect was limited to patients with amiodarone-refractory VT.

Anticoagulation use in perioperative atrial fibrillation after noncardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Perioperative atrial fibrillation is associated with an increased risk of stroke, myocardial infarction, and death after noncardiac surgery. Anticoagulation therapy is effective for stroke prevention in nonsurgical atrial fibrillation, but its efficacy and safety in perioperative atrial fibrillation are unknown. METHODS: We searched MEDLINE, EMBASE, and CENTRAL from database inception until January 2022. We included studies comparing anticoagulation versus no anticoagulation use in patients with perioperative atrial fibrillation after noncardiac surgery. Our study outcomes included stroke ± systemic embolism, bleeding, mortality, myocardial infarction, and venous thromboembolism. We pooled studies using fixed-effects models. We reported summary risk ratios (RRs) for studies reporting multivariable-adjusted results. RESULTS: Seven observational studies but no randomised trials were included. Of the 27,822 patients, 29.1% were prescribed therapeutic anticoagulation. Anticoagulation use was associated with a lower risk of stroke ± systemic embolism (RR 0.73; 95% CI, 0.62-0.85; I2 = 81%; 3 studies) but a higher risk of bleeding (RR 1.14; 95% CI, 1.04-1.25; 1 study). There was a lower risk of mortality associated with anticoagulation use (RR 0.45; 95% CI, 0.40-0.51; I2 = 80%; 2 studies). There was no difference in the risk of myocardial infarction (RR 2.19; 95% CI, 0.97-4.96; 1 study). The certainty of the evidence was very low across all outcomes. CONCLUSION: Anticoagulation is associated with a reduced risk of stroke and death but an increased risk of bleeding. The quality of the evidence is very poor. Randomised trials are needed to better determine the effects of anticoagulation use in this population.

Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial.

BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023. CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

Incremental value of the signal-averaged ECG for diagnosing arrhythmogenic cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is currently diagnosed using a combination of clinical features, imaging, electrocardiography, and genetic investigations. An abnormal signal-averaged electrocardiogram (SAECG) is defined as a minor diagnostic criterion by the 2010 Task Force Criteria, but doubts remain about the value of this investigation. OBJECTIVE: We evaluated the utility of the SAECG in diagnosing ARVC using the Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry, a population representative registry of probands with ARVC and relatives, less influenced by referral bias. METHODS: Probands with ARVC and family members from the Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry underwent phenotype review. SAECG parameters were compared individually and in combination between those with varying degrees of ARVC severity and healthy controls (family members of probands with ARVC and unexplained sudden death, free of evidence of cardiac disease). RESULTS: A total of 196 patients with ARVC and 205 controls were included (mean age 44 ± 15 years; 186 of 401 men [46%]). SAECG abnormalities were seen in 83 of 205 controls (40%), 33 of 68 patients with ARVC and mild disease (51%), and 31 of 42 with severe disease (74%). The SAECG associated strongly with imaging abnormalities (major: odds ratio 3.0, 95% confidence interval 1.3-6.9; minor: odds ratio 3.5, 95% confidence interval 0.7-16.5) but not with other aspects of phenotype. Patients carrying pathogenic variants but with minimal phenotype had similar SAECGs to healthy controls (filtered QRS duration 111.2 ± 11.2 ms vs 111 ± 7.6 ms, P = .93; duration of low amplitude signals < 40 µV 32.3 ± 8.9 ms vs 34.2 ± 7.2 ms, P = .32; root mean square of the terminal 40 ms of the filtered QRS complex 43.1 ± 25.2 ms vs 38.2 ± 20.2 ms, P = .38). CONCLUSION: The SAECG appears to be a surrogate marker for structural abnormalities seen on imaging in those with ARVC. Great caution is required in interpreting SAECG findings in those without other corroborating evidence of an ARVC phenotype.

Advances in Cardiac Electrophysiology.

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.

Consumer-Led Screening for Atrial Fibrillation: Frontier Review of the AF-SCREEN International Collaboration.

The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.

Use of Anticoagulation Therapy in Patients With Perioperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-analysis.

Background: Perioperative atrial fibrillation (POAF) after cardiac surgery is associated with an increased risk of stroke. However, the efficacy and safety of using anticoagulation therapy in this population are unknown. Methods: We performed a systematic review and meta-analysis of studies comparing use of anticoagulation therapy vs no anticoagulation therapy in patients with POAF after cardiac surgery. Outcomes included arterial thromboembolism (ie, stroke ± systemic embolism) and bleeding. Data were pooled using fixed-effects models. We reported summary risk ratios (RRs) for studies with multivariable adjustment and estimated absolute risk differences with 95% confidence intervals (CIs). Results: Nine observational studies met eligibility criteria. No randomized trials were identified. Of the 254,200 POAF patients included, 27.3% received anticoagulation. Six studies reported outcomes after long-term follow-up (median 5.0 years; range 4.2-10.0). The risk of arterial thromboembolism was lower in patients receiving anticoagulation therapy (RR 0.83; 95% CI, 0.69-0.99; I2 = 57%; P = 0.04; 6 studies). The estimated short-term and long-term absolute risk reductions in arterial thromboembolism with use of anticoagulation therapy were 0.8% (95% CI, 0.4-1.4) and 2 events per 1000 person-years (95% CI, 0-4), respectively. The risk of bleeding was higher in patients receiving anticoagulation therapy (RR 3.22; 95% CI, 2.82-3.68; I2 = 98%; P < 0.001; 2 studies). The estimated short-term and long-term absolute risk increases in bleeding with use of anticoagulation therapy were 0.5% (95% CI, 0.4-0.6) and 42 events per 1000 person-years (95% CI, 35-51), respectively. Conclusions: Use of anticoagulation therapy is associated with a small reduction in the risk of arterial thromboembolism, but also an increased risk of bleeding. Randomized controlled trials are needed to address this issue.

Introduction: La fibrillation auriculaire périopératoire (FAPO) après l'intervention chirurgicale au cœur est associée à une augmentation du risque d'accident vasculaire cérébral (AVC). Toutefois, on ne connaît pas l'efficacité et l'innocuité de la l'anticoagulothérapie de cette population. Méthodes: Nous avons réalisé une revue systématique et une méta-analyse d'études qui comparaient l'utilisation de l'anticoagulothérapie vs l'absence d'anticoagulothérapie chez les patients atteints de FAPO après l'intervention chirurgicale au cœur. Les résultats étaient notamment la thromboembolie artérielle (c.-à-d. l'AVC ± l'embolie systémique) et les hémorragies. Nous avons regroupé les données à l'aide de modèles à effets fixes. Nous avons rapporté les risques relatifs (RR) sommaires d'études avec l'ajustement multivarié et l'estimation des différences du risque absolu avec des intervalles de confiance (IC) à 95 %. Résultats: Neuf études observationnelles répondaient aux critères d'admissibilité. Aucun essai à répartition aléatoire n'a été trouvé. Parmi les 254 200 patients atteints de FAPO sélectionnés, 27,3 % avaient reçu une anticoagulation. Six études révélaient des résultats après le suivi à long terme (médiane 5,0 ans ; fourchette 4,2-10,0). Le risque de thromboembolie artérielle était plus faible chez les patients qui avaient reçu une anticoagulothérapie (RR 0,83 ; IC à 95 %, 0,69-0,99 ; I2 = 57 % ; P = 0,04 ; six études). Les estimations de réduction du risque absolu à court terme et à long terme lors de thromboembolie artérielle avec l'utilisation de l'anticoagulothérapie étaient respectivement de 0,8 % (IC à 95 %, 0,4-1,4) et de deux événements par 1000 personnes-années (IC à 95 %, 0-4). Le risque d'hémorragie était plus élevé chez les patients qui avaient reçu une anticoagulothérapie (RR 3,22 ; IC à 95 %, 2,82-3,68 ; I2 = 98 % ; P < 0,001 ; deux études). Les estimations d'augmentation du risque absolu à court terme et à long terme des hémorragies avec l'utilisation de l'anticoagulothérapie étaient respectivement de 0,5 % (IC à 95 %, 0,4-0,6) et de 42 événements par 1000 personnes-années (IC à 95 %, 35-51). Conclusions: L'utilisation de l'anticoagulothérapie est associée à une réduction minime du risque de thromboembolie artérielle, mais aussi à une augmentation du risque d'hémorragie. Des essais cliniques à répartition aléatoire sont nécessaires pour aborder cette question.

Short-term and Long-term Risk of Stroke in Patients With Perioperative Atrial Fibrillation After Cardiac Surgery: Systematic Review and Meta-analysis.

BACKGROUND: Perioperative atrial fibrillation (POAF) after cardiac surgery has been associated with an increased risk of stroke in some studies. However, the exact magnitude of this association during short-term and long-term follow-up remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for the time period from database inception to October 2020. We included observational studies with ≥ 100 patients that reported data on short-term or long-term stroke risk in patients with and without POAF after cardiac surgery. Data were pooled using random-effects models. We reported summary risk ratios (RRs) for studies reporting multivariable adjusted results and calculated absolute risk differences (ARDs) with 95% confidence intervals (CIs). RESULTS: A total of 55 studies with 540,209 patients were included. POAF was associated with both an increased relative risk (RR 1.69; 95% CI, 1.41-2.03; I2 = 82%; 9 studies) and absolute risk of short-term stroke (4.5% vs 2.5%; ARD 2.0%; 95% CI, 1.28-2.89). POAF was associated with an increased relative risk (RR 1.20; 95% CI, 1.12-1.29; I2 = 16%; 10 studies) and absolute risk of long-term stroke (1.06 vs 0.88 per 100 patient-years; ARD 0.18 per 100 patient-years; 95% CI, 0.07-0.26). Sensitivity analyses of high-quality studies and studies reporting either ischemic or embolic strokes yielded similar findings. CONCLUSIONS: POAF after cardiac surgery was associated with an increased risk of both short-term and long-term stroke. However, the long-term stroke ARD was small, and whether these patients will benefit from long-term oral anticoagulation therapy is unclear.

CONTEXTE: La fibrillation auriculaire périopératoire (FAPO) après une chirurgie cardiaque a été associée à un risque accru d'accident vasculaire cérébral (AVC) dans certaines études. Cependant, l'ampleur exacte de cette association durant le suivi à court et à long terme reste incertaine. MÉTHODOLOGIE: Nous avons effectué des recherches dans les bases de données PubMed, Embase et CENTRAL (Cochrane Central Register of Controlled Trials) pour la période allant de la création de ces bases à octobre 2020. Nous avons inclus des études d'observation comptant ≥ 100 patients et rapportant des données sur le risque d'AVC à court ou à long terme chez les patients ayant présenté ou non une FAPO après une chirurgie cardiaque. Les données ont été regroupées à l'aide de modèles à effets aléatoires. Nous avons consigné les rapports de risque (RR) sommaires pour les études rapportant des résultats corrigés multivariables et calculé les différences de risque absolu (DRA) avec des intervalles de confiance (IC) à 95 %. RÉSULTATS: Au total, 55 études portant sur 540 209 patients ont été incluses. La FAPO était associée à une augmentation tant du risque relatif (RR : 1,69; IC à 95 % : 1,41 à 2,03; I2 = 82 %; 9 études) que du risque absolu d'AVC à court terme (4,5 % vs 2,5 %; DRA : 2,0 %; IC à 95 % : 1,28 à 2,89). La FAPO était également associée à une augmentation du risque relatif (RR : 1,20; IC à 95 % : 1,12 à 1,29; I2 = 16 %; 10 études) et du risque absolu d'AVC à long terme (1,06 vs 0,88 par 100 années-patients; DRA : 0,18 par 100 années-patients; IC à 95 % : 0,07 à 0,26). Les analyses de sensibilité des études de haute qualité et des études rapportant des AVC ischémiques ou emboliques ont donné des résultats similaires. CONCLUSIONS: La FAPO après une chirurgie cardiaque a été associée à un risque accru d'AVC à court et à long terme. Cependant, comme la différence de risque absolu d'AVC à long terme était faible, la possibilité qu'une anticoagulothérapie orale à long terme soit bénéfique pour ces patients est incertaine.