Forty years after mediastinal radiotherapy for Hodgkin lymphoma: how late is late cardiotoxicity? A case report.

Radiation-associated cardiovascular disease is well-described yet under-recognized. Mediastinal radiation is known to affect any component of the heart. We present a case of valvular, coronary, and conduction abnormalities up to decades after initial radiotherapy.

Sudden cardiac death related to physical exercise in the young: a nationwide cohort study of Australia.

BACKGROUND: Sudden cardiac death (SCD) during physical exercise is devastating. AIMS: To evaluate causes and circumstances of exercise-related SCD in the young in Australia. METHODS: We reviewed the National Coronial Information System database for deaths in Australia relating to cardiovascular disease in cases aged 10-35 years between 2000 and 2016. Cases who had undertaken physical exercise at the time of the event were included. We collected demographics, circumstances of death, type of physical exercise, bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use prior to ambulance arrival. RESULTS: Over a 17-year period, 1925 SCD cases were identified, of which 110 (6%) cases (median age 27 years (interquartile range 21-32 years); 92% male) were related to sports/physical exercise. Thirteen (12%) cases occurred in active athletes. Most common causes were coronary artery disease (CAD; 37%) and sudden arrhythmic death syndrome (SADS; 20%). Among Aboriginal and Torres Strait Islanders (n = 10), all deaths were related to CAD. Australian Rules Football (24%), running/jogging (14%) and soccer (14%) were the most frequent physical exercise activities. Prior symptoms were present in 39% (chest pain 37%, pre-syncope/syncope 26%). Most (87%) were witnessed, with bystander CPR in 70%. AED use prior to ambulance arrival was 8%. CONCLUSIONS: The present study demonstrates the high occurrence of CAD and SADS in SCD in the young related to physical exercise. Aboriginal and Torres Strait Islanders were disproportionately affected by CAD. Although events were commonly witnessed, AED was seldom used prior to ambulance arrival and highlights an important opportunity to improve outcomes in the post-arrest chain of survival.

Pacing-induced cardiomyopathy: A systematic review and meta-analysis of definition, prevalence, risk factors, and management.

Pacing-induced cardiomyopathy is a potential complication of right ventricular pacing. Definition varies between studies and the optimal management approach is uncertain. We aimed to characterize definition, prevalence, risk factors, and treatment strategies of pacing-induced cardiomyopathy (PiCM). We performed a systematic review and meta-analysis of studies that evaluated PiCM after pacemaker implantation identified through a literature search of PubMed and EMBASE up to March 2022. We collected data on the study definition of PiCM and calculated pooled prevalence across studies. Meta-analysis with random effects modeling was used to assess the association between potential risk factors and PiCM, reported as odds ratio with 95% confidence interval. Twenty-six studies (6 prospective studies) with a total of 57,993 patients (mean/median age range was 51-78 years; female 45%) were included in the final analysis. Fifteen unique definitions of PiCM were reported. The pooled prevalence of PiCM was 12% (95% confidence interval 11%-14%). In meta-analysis, risk factors included male sex, history of myocardial infarction, chronic kidney disease, atrial fibrillation, baseline left ventricular ejection fraction, native QRS duration, right ventricular pacing percentage, and paced QRS duration. Treatment strategies identified included biventricular cardiac resynchronization therapy (6 studies) and His-bundle pacing (3 studies). Definition of PiCM varied significantly between studies. More than 1 in 10 patients with chronic right ventricular pacing developed PiCM. Key risk factors included baseline left ventricular ejection fraction, native QRS duration, RV pacing percentage, and paced QRS duration. The optimal management strategy has yet to be defined. Further research is needed to define and treat this understated complication.

Frailty in patients with aortic stenosis awaiting intervention.

Aortic stenosis (AS) is a common valvular disease in older age. Definitive interventions include surgical aortic valve replacement or transcatheter aortic valve implantation (TAVI). In high-risk patients, frailty is observed in up to 50% awaiting TAVI. Frailty is now an established predictor of outcomes in patients with AS who undergo intervention. There is currently no consensus definition for frailty. It is widely described as a syndrome of loss in physiological reserve predisposing to increased vulnerability for death or dependency. Frailty encompasses a holistic view including domains of physical function, cognition, depression, nutrition and medical comorbidities. Individual components of frailty have been shown to significantly predict mortality, functional recovery and quality of life after TAVI. The addition of frailty components to conventional risk prediction models traditionally used in cardiac surgery has been shown to augment overall prediction for post-operative mortality and morbidity. Identifying patients who are frail at baseline provides an opportunity to modify dynamic aspects of frailty prior to, and after definitive intervention for AS. A multidisciplinary approach including comprehensive geriatric pre-operative assessment will likely become standard of care to identify and optimise frail patients awaiting TAVI. In this review, we discuss the definition and measurement of frailty in patients with AS, evaluate recent data on risk prediction associated with frailty, and outline approaches to optimisation of dynamic components of frailty to improve outcomes after AS intervention.

Sudden Cardiac Death in the Young: Incidence, Trends, and Risk Factors in a Nationwide Study.

BACKGROUND: Sudden cardiac death (SCD) in the young is devastating. Contemporary incidence remains unclear with few recent nationwide studies and limited data addressing risk factors for causes. We aimed to determine incidence, trends, causes, and risk factors for SCD in the young. METHODS AND RESULTS: The National Coronial Information System registry was reviewed for SCD in people aged 1 to 35 years from 2000 to 2016 in Australia. Subjects were identified by the International Classification of Diseases, Tenth Revision code relating to circulatory system diseases (I00-I99) from coronial reports. Baseline demographics, circumstances, and cause of SCD were obtained from coronial and police reports, alongside autopsy and toxicology analyses where available. During the study period, 2006 cases were identified (median age, 28±7 years; men, 75%; mean body mass index, 29±8 kg/m2). Annual incidence ranged from 0.91 to 1.48 per 100 000 age-specific person-years, which was the lowest in 2013 to 2015 compared with previous 3-year intervals on Poisson regression model (P=0.001). SCD incidence was higher in nonmetropolitan versus metropolitan areas (0.99 versus 0.53 per 100 000 person-years; P<0.001). The most common cause of SCD was coronary artery disease (40%), followed by sudden arrhythmic death syndrome (14%). Incidence of coronary artery disease-related SCD decreased from 2001-2003 to 2013-2015 (P<0.001). Proportion of SCD related to sudden arrhythmic death syndrome increased during the study period (P=0.02) although overall incidence was stable (P=0.22). Residential remoteness was associated with coronary artery disease-related SCD (odds ratio, 1.44 [95% CI, 1.24-1.67]; P<0.001). For every 1-unit increase, body mass index was associated with increased likelihood of SCD from cardiomegaly (odds ratio, 1.08 [95% CI, 1.05-1.11]; P<0.001) and dilated cardiomyopathy (odds ratio, 1.04 [95% CI, 1.01-1.06]; P=0.005). CONCLUSIONS: Incidence of SCD in the young and specifically coronary artery disease-related SCD has declined in recent years. Proportion of SCD related to sudden arrhythmic death syndrome increased over the study period. Geographic remoteness and obesity are risk factors for specific causes of SCD in the young.

Imaging in Suspected Cardiac Sarcoidosis: A Diagnostic Challenge.

Cardiac Sarcoidosis (CS) represents a unique diagnostic dilemma. Guidelines have been recently revised to reflect the established role of sophisticated imaging techniques. Trans-thoracic Echocardiography (TTE) is widely adopted for initial screening of CS. Contemporary TTE techniques could enhance detection of subclinical Left Ventricular (LV) dysfunction, particularly LV global longitudinal strain assessment which predicts event-free survival (meta-analysis of 5 studies, hazard ratio 1.28, 95% confidence interval 1.18-1.37, p < 0.0001). However, despite the wide availability of TTE, it has limited sensitivity and specificity for CS diagnosis. Cardiac Magnetic resonance Imaging (CMR) is a crucial diagnostic modality for suspected CS. Presence of late gadolinium enhancement signifies myocardial scar and enables risk stratification. Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) coupled with myocardial perfusion imaging can identify active CS and guide immunosuppressant therapy. Gallium scintigraphy may be considered although FDG-PET is often preferred. While CMR and FDG-PET provide complementary information in CS evaluation, current guidelines do not recommend which imaging modalities are essential in suspected CS and if so, which modality should be performed first. The utility of hybrid imaging combining both advanced imaging modalities in a single scan is currently being explored, although not yet widely available. In view of recent, significant advances in cardiac imaging techniques, this review aims to discuss changes in guidelines for CS diagnosis, the role of various cardiac imaging modalities and the future direction in CS.

Accuracy of wrist-worn heart rate monitors for rate control assessment in atrial fibrillation.

BACKGROUND: Wrist-worn heart rate (HR) monitors are increasingly popular. A paucity of data exists on their accuracy in atrial fibrillation (AF) in ambulatory patients. We sought to assess the HR accuracy of two commercially available smart watches [SW] (Fitbit Charge HR [FB] and Apple Watch Series 3 [AW]) compared with Holter monitoring in an ambulant patient cohort. METHODS: Thirty-two participants ≥18 years referred for 24-hour Holter monitoring were prospectively recruited. Each participant was randomly allocated to wear either a FB or AW along with their Holter monitor. RESULTS: Across all devices, 53,288 heart rate values were analysed from 32 participants. Twenty wore the AW (17 had persistent AF and 3 had sinus rhythm [SR]) while 12 participants wore the FB (9 in persistent AF and 3 in SR). Participants in SR demonstrated strong agreement compared to Holter monitoring (bias <1 beat, limits of agreement [LoA] -11 to 11 beats). In AF, both devices underestimated HR measurements (bias -9 beats, LoA -41 to 23). The degree of underestimation was more pronounced when HR > 100 bpm (bias of -28 beats for HR range 100-120 bpm, -48 for 120-140 bpm, and -69 for >140 bpm) compared to a slower HR (bias of -6 for HR range 80-100 bpm, <1 for 60-80 bpm, and -1 for <60 bpm). CONCLUSION: In ambulatory patients, smartwatches underestimated HR in AF particularly at HR ranges >100 bpm. Further improvements in device technology are needed before integrating them into the clinical management of rate control in AF.

Permanent pacing and conduction recovery in patients undergoing cardiac surgery for active infective endocarditis in an Australian Tertiary Center.

BACKGROUND: Postoperative heart block is common among patients undergoing surgery for infective endocarditis (IE). Limited data exists allowing cardiologists to predict who will require permanent pacemaker (PPM) implantation postoperatively. We aimed to determine the rate of postoperative PPM insertion, predictors for postoperative PPM, and describe PPM utilization and rates of device-related infection during follow-up. MATERIALS AND METHODS: A retrospective analysis was performed of 191 consecutive patients from a single institution who underwent cardiac surgery for IE between 2001 and 2017. Preoperative and operative predictors for postoperative PPM were evaluated using univariate and multivariate logistic regression. RESULTS: The rate of postoperative PPM implantation was 11% (17/154). The PPM group had more preoperative prolonged PR interval alone (33% vs 12%; P = .03), coexistent prolonged PR and QRS durations (13% vs 2%; P = .01), infection beyond the valve leaflets (82% vs 41%; P = .001), aortic root debridement (65% vs 23%; P = <.001), patch repair (47% vs 20%; P = .01), postoperative prolonged PR interval (50% vs 24%; P = .01), and prolonged QRS duration (47% vs 15%; P = .001). On multivariate analysis, infection beyond the valve leaflets emerged as an independent predictor for postoperative PPM (odds ratio, 1.94, 95% confidence interval, 1.14-3.28; P = .014). A reduction in PPM utilization was observed in five patients while eight patients continued to show significant ventricular pacing with no underlying rhythm at 12 months. There were no device-related infections. CONCLUSION: Postoperative PPM was required in 11% of patients undergoing surgery for IE over a 16-year period. Infection beyond the valve leaflet was an independent predictor for postoperative PPM insertion.

Outcomes of incidental findings on multi-detector computed tomography for transcatheter aortic valve implantation assessment: A single-centre study and review of the literature.

INTRODUCTION: Patients with severe aortic stenosis (AS) require multi-detector computed tomography (MDCT) when considered for transcatheter aortic valve implantation (TAVI). Incidental findings on MDCT are common given the age group and region imaged. Our aim was to evaluate the frequency and outcome of incidental findings (IF) identified on MDCT and the impact on survival. METHODS: This single-centre analysis retrospectively reviewed severe AS patients who underwent MDCT during TAVI workup. MDCT reports were reviewed for any IF and defined into three categories: IF of no relevant clinical significance (IF-NoCS), IF of non-immediate clinical significance (IF-NICS) and IF of immediate clinical significance (IF-ICS). Demographics, follow-up of IF and survival were calculated from MDCT date. RESULTS: Two hundred and sixty-five patients underwent MDCT for TAVI suitability (mean age 83 ± 6 years, 52% male). The majority proceeded to TAVI (65%). Renal lesions (25%) and lung nodules (18%) were the most common IF. Fifty-nine patients (22%) had IF-NICS; 39% (23/59) were benign, 59% were not further investigated and one patient had suspected lung cancer. Six patients (2.3%) had IF-ICS and all were diagnosed with lung cancer. During a median follow-up of 272 days, there was no survival difference between patients with IF-ICS or IF-NICS versus patients without IF or IF-NoCS in the overall cohort (P = 0.44) or in TAVI patients (P = 0.88). CONCLUSION: Incidental findings on MDCT are common with one-quarter having IF-ICS or IF-NCIS. Most patients with IF-NICS did not undergo further investigation. Standardized reporting of MDCT may assist in clarifying the need for further investigation which will in turn influence decision and timing to proceed with TAVI.

Timing of brain metastases development in metastatic renal cell cancer patients treated with targeted therapies and survival outcomes: An Australian multicenter study.

AIM: Targeted therapy (TT) has improved survival for metastatic renal cell carcinoma (mRCC). However, survival is usually limited if brain metastases (BMs) develop. We aimed to evaluate survival outcomes in mRCC patients based on timing of BM diagnosis. METHODS: We conducted a multicenter, retrospective study of mRCC patients with BM who received TT at any point between 2005 and 2014. We determined overall survival (OS) from stage IV diagnosis, TT initiation and BM diagnosis, and prognostic factors. Patients were grouped into three categories: synchronous-BM, metachronous-BM diagnosed while conservatively managed (metachronous-BM before TT) and metachronous-BM diagnosed during TT. Survival was calculated by Kaplan-Meier method and predictors were calculated using Cox hazards regression. RESULTS: Incidence of BM was 17% in mRCC patients treated with TT (two centers). Fifty-four mRCC-BM patients were identified from five tertiary centers. Twenty-eight percentage (15/54) had synchronous-BM, 28% (15/54) had metachranous-BM before TT and 44% (24/54) had metachronous-BM during TT. Most had central nervous system (CNS) symptoms at BM diagnosis (78%; 42/54). Median OS from stage IV diagnosis, TT commencement and BM diagnosis was 28 months (95% confidence interval [CI] 16-43), 19 months (95% CI 9-26) and 9 months (95% CI 5-16), respectively. Synchronous-BM group trended toward poorer survival from TT commencement (P = 0.06). Metachronous-BM during TT group had lower survival from BM diagnosis than synchronous-BM and metachronous-BM before TT group (P < 0.001). Eight of 50 deaths (16%) were from neurological complications. The presence of CNS symptoms did not predict worse survival from stage IV diagnosis (P = 0.73). CONCLUSION: In patients with mRCC, the development of BM while on TT portends shorter prognosis compared with synchronous diagnosis of BM at stage IV disease or metachronous BM developed prior to commencing TT. The presence of CNS symptoms does not predict worse survival.

Prevalence and prevention of oesophageal injury during atrial fibrillation ablation: a systematic review and meta-analysis.

AIMS: Atrio-oesophageal fistula (AOF) is a potentially lethal complication of atrial fibrillation (AF) ablation. Many studies have evaluated the presence and prevention of endoscopically-detected oesophageal lesions (EDOL) as a proxy measure for risk of AOF. This systematic review and meta-analysis sought to determine the prevalence of EDOL and effectiveness of general preventive measures during AF ablation. METHODS AND RESULTS: We searched electronic databases for studies reporting prevalence or prevention of EDOL post-AF ablation. Pooled prevalence were reported with 95% confidence intervals (CI) while studies evaluating preventive measures including oesophageal temperature monitoring (OTM), esophageal manipulation and type of anaesthesia were analyzed descriptively or by random-effects modeling. Twenty-five studies were included in the analysis. Any and ulcerated EDOL pooled prevalence was 11% (95%CI, 6-15%) and 5% (95%CI, 3-7%), respectively. In six studies, there was no difference in EDOL with or without OTM (pooled OR 1.65, 95%CI, 0.22-12.55). There was no difference using a multi-sensor versus single-sensor OTM (one study) nor when using a deflectable probe (two studies). Oesophageal displacement was associated with significant instrumentation injury in one study. Two studies evaluating Oesophageal cooling showed conflicting results. General anaesthesia was associated with more EDOL than conscious sedation in two studies. CONCLUSION: The pooled prevalence of any and ulcerated EDOL post-ablation was 11% and 5%, but varied between studies. Techniques such as OTM and oesophageal displacement or cooling have not conclusively demonstrated a reduction in EDEL, while general anaesthesia may be associated with higher EDOL risk. Further randomized data are critically needed to validate and develop measures to prevent EDOL and AOF.

Mitral Valve Prolapse and Sudden Cardiac Death: A Systematic Review.

Background The relationship between mitral valve prolapse ( MVP ) and sudden cardiac death ( SCD ) remains controversial. In this systematic review, we evaluate the relationship between isolated MVP and SCD to better define a potential high-risk subtype. In addition, we determine whether premortem parameters could predict SCD in patients with MVP and the incidence of SCD in MVP . Methods and Results Electronic searches were conducted in PubMed and Embase for all English literature articles published between 1960 and 2018 regarding MVP and SCD or cardiac arrest. We also identified articles investigating predictors of ventricular arrhythmias or SCD and cohort studies reporting SCD outcomes in MVP . From 2180 citations, there were 79 articles describing 161 cases of MVP with SCD or cardiac arrest. The median age was 30 years and 69% of cases were female. Cardiac arrest occurred during situations of stress in 47% and was caused by ventricular fibrillation in 81%. Premature ventricular complexes on Holter monitoring (92%) were common. Most cases had bileaflet involvement (70%) with redundancy (99%) and nonsevere mitral regurgitation (83%). From 22 articles describing predictors for ventricular arrhythmias or SCD in MVP , leaflet redundancy was the only independent predictor of SCD . The incidence of SCD with MVP was estimated at 217 events per 100 000 person-years. Conclusions Isolated MVP and SCD predominantly affects young females with redundant bileaflet prolapse, with cardiac arrest usually occurring as a result of ventricular arrhythmias. To better understand the complex relationship between MVP and SCD , standardized reporting of clinical, electrophysiological, and cardiac imaging parameters with longitudinal follow-up is required.

Communicating prognosis of patients with advanced cancer between health care providers: a tertiary cancer center review of written correspondence.

BACKGROUND: Communication of prognosis and goals of care between oncologists, community health care providers (HCPs) and patients treated for advanced cancer facilitates optimal care planning. We aimed to review the frequency, content and timing of documented prognosis in written correspondence during the last year of life of advanced cancer patients. METHODS: All patients who died during palliative care or medical oncology admission in 2015 at a large, Australian tertiary center were identified. Patients with incurable solid organ cancer and reviewed ≥1 times in oncology outpatient (OP) clinic were included. We reviewed all oncology OP consultation notes and letters, oncology discharge summaries and advanced care plans over a 12-month period before death. Both internal (OP notes) and external correspondence (OP letters; discharge summaries) were reviewed for documentation of qualitative and quantitative prognosis. RESULTS: One hundred and forty-seven patients were included in the analysis [median age of 70 years, interquartile range (IQR), 58-77 years; males, 60%]. Most patients had a previous inpatient admission (73%). The median OP consultations per patient was 6 (IQR, 2-9) with a median rate of 63% (IQR, 41-87%) resulting in a correspondence letter. The majority of patients had a qualitative statement of prognosis documented in OP notes (63%) and external correspondence letters (61%). However only a minority had a documented quantitative prognosis in either OP notes (14%) or external correspondence letters (7%). The median time from documentation of qualitative and quantitative prognosis to death was 3.5 (IQR, 1.6-6.9) and 2.2 (IQR, 1.1-4.4) months, respectively. While almost all patients had a completed goals-of-care (GOC) form (99%), only 15% of patients had an advanced care plan. CONCLUSIONS: Documentation of qualitative and quantitative prognosis is infrequent despite multiple clinical encounters prior to patient death. This infers inadequate communication between oncologists and other HCPs which reduces insight into patient clinical trajectory and could result in differing care between providers.

Routine blood investigations have limited utility in surveillance of aggressive lymphoma in asymptomatic patients in complete remission.

BACKGROUND: Patients with aggressive lymphoma achieving complete remission (CR) after first-line combination chemotherapy undergo regular surveillance to detect relapse. Current international guidelines recommend routine follow-up blood tests in this context, but evidence supporting this practice is limited. METHODS: We conducted a multi-centre retrospective analysis of all patients diagnosed with aggressive lymphoma treated with curative-intent chemotherapy who achieved CR for at least 3 months between 2000 and 2015. An abnormal blood test was defined as any new and unexplained abnormality for full blood examination, lactate dehydrogenase or erythrocyte sedimentation rate. RESULTS: Three hundred and forty-six patients attended a total of 3084 outpatient visits; blood tests were performed at 90% of these appointments. Fifty-six (16%) patients relapsed. Routine laboratory testing detected relapse in only three patients (5% of relapses); in the remaining patients, relapse was suspected clinically (80%) or detected by imaging (15%). The sensitivity of all blood tests was 42% and the positive predictive value was 9%. No significant difference in survival was shown in patients who underwent a routine blood test within 3 months prior to relapse versus those who did not (p = 0.88). CONCLUSIONS: Routine blood tests demonstrate unacceptably poor performance characteristics, have no impact on survival and thus have limited value in the detection of relapse in routine surveillance.

Polymer-free versus permanent polymer-coated drug eluting stents for the treatment of coronary artery disease: A meta-analysis of randomized trials.

BACKGROUND: Polymer-free drug eluting stents (PF-DES) were developed, in part, to overcome risk of late ischemic events observed with permanent polymer-coated DES (PP-DES). However, trial results are inconsistent with longer-term safety and efficacy of PF-DES remaining unknown. We performed a meta-analysis of randomized trials assessing outcomes of patients receiving PF-DES versus PP-DES for treatment of coronary artery disease (CAD). METHODS: Electronic searches were performed for randomized trials comparing outcomes between PF-DES and PP-DES. Trials reporting major adverse cardiovascular events (MACE), myocardial infarction (MI), stent thrombosis (ST), all-cause death, target lesion/vessel revascularization (TLR/TVR), and late lumen loss (LLL) were included. Analyses were performed at longest follow-up and landmarked beyond 1-year. RESULTS: Twelve trials (6,943 patients) were included. There was no significant difference in MACE between PF-DES and PP-DES at longest follow-up (Odds Ratio [OR] 0.96, 95%CI 0.85-1.10, P = 0.59) or landmark analysis beyond 1-year (OR 0.96, 95%CI 0.76-1.20, P = 0.70). Although PF-DES were associated with a significant reduction in all-cause death (OR 0.85, 95%CI 0.72-1.00, P < 0.05), this effect was not present on landmark analysis beyond 1-year (OR 0.89, 95%CI 0.73-1.10, P = 0.30). There were no differences observed for MI (OR 1.00, 95%CI 0.77-1.28, P = 0.99) or ST (OR 0.95, 95%CI 0.54-1.68, P = 0.86), with similar efficacy outcomes including TVR (OR 1.07, 95%CI 0.91-1.26, P = 0.42), TLR (OR 1.03, 95%CI 0.88-1.21, P = 0.68) and angiographic LLL (pooled mean difference 0.01 mm, 95%CI -0.08 to 0.11, P = 0.76). CONCLUSIONS: PF-DES are as safe and efficacious as PP-DES for the treatment of patients with CAD, but do not significantly reduce late ischemic complications.

Continuous and minimally-interrupted direct oral anticoagulant are both safe compared with vitamin K antagonist for atrial fibrillation ablation: An updated meta-analysis.

BACKGROUND: The appropriate and safe peri-procedural anticoagulation schedule for patients on a direct oral anticoagulant (DOAC) undergoing AF ablation is not known. We aimed to evaluate the safety and efficacy of both continuous and minimally-interrupted novel oral anticoagulant (DOAC) strategies compared with uninterrupted vitamin K antagonist (VKA) for atrial fibrillation (AF) ablation. METHODS: We searched electronic databases for randomized or prospective controlled observational studies comparing DOAC (continuous or interrupted) versus uninterrupted VKA. The primary endpoint was major bleeding. Secondary endpoints were total bleeding (composite of major and minor bleeding) and symptomatic thromboembolism. Data were analyzed by random-effects modeling and sensitivity analyses performed according to study design and peri-procedural DOAC schedule. RESULTS: Thirteen studies (4 randomized, 9 observational) with 5463 patients were included in final analysis (45% on DOAC). DOAC was associated with less major bleeding compared with VKA in pooled randomized studies (odds ratio [OR] 0.27, 95% confidence interval [CI] 0.09-0.80, p = 0.03, I2 = 0%), however there was no difference on overall analyses (OR 0.70, 95% CI 0.39-1.24, p = 0.22, I2 = 27%). When stratified by DOAC dose schedule, there was no difference in major bleeding for continuous DOAC (OR 0.48, 95% CI 0.21-1.11, p = 0.09, I2 = 6%) or minimally-interrupted DOAC (OR 0.81, 95% CI 0.37-1.76, p = 0.60, I2 = 43%) compared with VKA. There was no difference between DOAC and VKA for risk of total bleeding (p = 0.20) or symptomatic thromboembolism (p = 0.78). CONCLUSION: Continuous and minimally-interrupted DOAC are both safe and non-inferior peri-procedural anticoagulation strategies compared with uninterrupted VKA for AF ablation. DOAC in general is associated with reduced major bleeding as demonstrated in pooled randomized studies.