Dementia Risk of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation: Systematic Review and Meta-Analysis.

Background: Direct-acting oral anticoagulants (DOACs) have demonstrated superior efficacy in preventing stroke and death compared with warfarin in patients with atrial fibrillation (AF), but their influence on dementia risk remains unclear. Objectives: The purpose of this study was to evaluate the relative risks of dementia in DOAC vs warfarin in patients with AF. Methods: An electronic literature search was conducted to retrieve studies reporting comparisons of dementia incidence between patients treated with DOACs and warfarin for AF. HRs and 95% CI were pooled in a random-effects meta-analysis. Meta-regression was performed to identify prognostic baseline variables. Network meta-analysis was performed to determine dementia risk between individual DOACs and warfarin. Results: Ten studies (n = 342,624) were retrieved. DOAC was associated with a significantly lower risk of developing dementia compared with warfarin (HR: 0.88; 95% CI: 0.80-0.98; P = 0.017; I2 = 75%); significance was also seen in Asian patients (HR: 0.81; 95% CI: 0.68-0.86) but not non-Asian patients. Subgroup analyses of propensity score-matched studies and patients aged 65-75 years showed similar significance, but not for patients aged ≥75 years. Meta-regression found that a lower mean age corresponded to significantly greater favoring of DOAC over warfarin. Network meta-analysis found significant reductions in dementia risk over warfarin for rivaroxaban (HR: 0.854; 95% CI: 0.763-0.955), apixaban (HR: 0.881; 95% CI: 0.778-0.997), and dabigatran (HR: 0.871; 95% CI: 0.770-0.987); the highest-ranked treatment based on P scores was edoxaban. Conclusions: The use of DOAC in AF significantly reduces dementia risk compared with warfarin, particularly in Asian patients. The possible reversal of this effect with increasing age merits further randomized trials with long-term follow-up. (Dementia Risk of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation: A Systematic Review and Meta-Analysis; CRD42022365634).

Systematic Review and Meta-Analysis of Direct Oral Anticoagulants Versus Warfarin in Atrial Fibrillation With Low Stroke Risk.

Pivotal trials comparing direct oral anticoagulants (DOACs) against warfarin in patients with atrial fibrillation (AF) predominantly involved patients with high stroke risk. This study aimed to evaluate the efficacy and safety of DOAC versus warfarin in patients with low stroke risk. An online literature search was conducted to retrieve studies comparing clinical outcomes between patients treated with DOAC versus warfarin for AF, reporting outcomes for patients at low or minimal risk of stroke (CHA2DS2-VASc scores ranging from 0 to 2 or CHADS2 scores ranging from 0 to 1). The primary outcome was the occurrence of stroke or systemic embolism. Secondary outcomes included major bleeding, intracranial hemorrhage, and all-cause mortality. Hazard ratios for all outcomes were pooled in random-effects meta-analyses. A network meta-analysis of individual DOACs versus warfarin was also conducted. In total, 11 studies (132,980 patients) were included. DOAC was associated with a significantly lower risk of stroke or systemic embolism (hazard ratio 0.85, 95% confidence interval 0.75 to 0.96, p = 0.008, I2 = 0%), major bleeding, intracranial hemorrhage, and mortality compared with warfarin. This benefit persisted even when study arms which had CHA2DS2-VASc scores of 2 were excluded. When restricted to 3 studies investigating only patients with a single nongender-related stroke risk factor, significant benefit was seen only for the outcome of major bleeding. In the network meta-analysis, only dabigatran was superior to warfarin for all 4 outcomes. In conclusion, DOACs should be the standard of care in low-risk patients with AF who require anticoagulation. In particular, dabigatran appears to have the best balance of stroke prevention and reduction in major bleeding.

Cell-free DNA as a potential biomarker for acute myocardial infarction: A systematic review and meta-analysis.

Background: Tissue necrosis releases cell-free deoxyribonucleic acid (cfDNA), leading to rapid increases in plasma concentration with clearance independent of kidney function. Aim: To explore the diagnostic role of cfDNA in acute myocardial infarction (AMI). Methods: This systematic review and meta-analysis included studies of cfDNA in patients with AMI and a comparator group without AMI. The quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool was used, with AMI determined from the criteria of the original study. Standardised mean differences (SMD) were obtained using a random-effects inverse variance model. Heterogeneity was reported as I2. Pooled sensitivity and specificity were computed using a bivariate model. The area under the curve (AUC) was estimated from a hierarchical summary receiver operating characteristics curve. Results: Seventeen studies were identified involving 1804 patients (n = 819 in the AMI group, n = 985 in the comparator group). Circulating cfDNA concentrations were greater in the AMI group (SMD 3.47 (95%CI: 2.54-4.41, p < 0.001)). The studies were of variable methodological quality with substantial heterogeneity (I2 = 98%, p < 0.001), possibly due to the differences in cfDNA quantification methodologies (Chi2 25.16, p < 0.001, I2 = 92%). Diagnostic accuracy was determined using six studies (n = 804), which yielded a sensitivity of 87% (95%CI: 72%-95%) and specificity of 96% (95%CI: 92%-98%). The AUC was 0.96 (95%CI: 0.93-0.98). Two studies reported a relationship between peak cfDNA and peak troponin. No studies reported data for patients with pre-existing kidney impairment. Conclusion: Plasma cfDNA appears to be a reliable biomarker of myocardial injury. Inferences from existing results are limited owing to methodology heterogeneity.

Ablation therapies for paroxysmal atrial fibrillation: A systematic review and patient-level network meta-analysis.

INTRODUCTION: Despite promising trials, catheter ablation is still regarded as an adjunct to antiarrhythmic drugs (AADs) in the treatment of paroxysmal atrial fibrillation (PAF). This study aimed to compare the effectiveness of various ablation therapies and AADs. METHOD: Randomised controlled trials or propensity score-matched studies comparing atrial tachyarrhythmia recurrence among any combination of ablation modalities or AAD were retrieved. Kaplan-Meier curves and risk tables for this outcome were graphically reconstructed to extract patient-level data. Frequentist network meta-analysis (NMA) using derived hazard ratios (HRs), as well as 2 restricted mean survival time (RMST) NMAs, were conducted. Treatment strategies were ranked using P-scores. RESULTS: Across 24 studies comparing 6 ablation therapies (5,132 patients), Frequentist NMA-derived HRs of atrial fibrillation recurrence compared to AAD were 0.35 (95% confidence interval [CI]=0.25-0.48) for cryoballoon ablation (CBA), 0.34 (95% CI=0.25-0.47) for radiofrequency ablation (RFA), 0.14 (95% CI=0.07-0.30) for combined CBA and RFA, 0.20 (95% CI=0.10-0.41) for hot-balloon ablation, 0.43 (95% CI=0.15-1.26) for laser-balloon ablation (LBA), and 0.33 (95% CI=0.18-0.62) for pulmonary vein ablation catheter. RMST-based NMAs similarly showed significant benefit of all ablation therapies over AAD. The combination of CBA + RFA showed promising long-term superiority over CBA and RFA, while LBA showed favourable short-term efficacy. CONCLUSION: The advantage of ablation therapies over AAD in preventing atrial tachyarrhythmia recurrence suggests that ablation should be considered as the first-line treatment for PAF in patients fit for the procedure. The promising nature of several specific therapies warrants further trials to elicit their long-term efficacy and perform a cost-benefit analysis.

A single-centre experience of His bundle pacing without electrophysiological mapping system: implant success rate, safety, pacing characteristics and one-year follow up.

Introduction: Despite the challenges related to His bundle pacing (HBP), recent data suggest an improved success rate with experience. As a non-university, non-electrophysiology specialised centre in Singapore, we report our experiences in HBP using pacing system analyser alone. Methods: Data of 28 consecutive patients who underwent HBP from August 2018 to February 2019 was retrospectively obtained. The clinical and technical outcomes of these patients were compared between two timeframes of three months each. Patients were followed up for 12 months. Results: Immediate technical success was achieved in 21 (75.0%) patients (mean age 73.3 ± 10.7 years, 47.6% female). The mean left ventricular ejection fraction was 53.9% ± 12.1%. The indications for HBP were atrioventricular block (n = 13, 61.9%), sinus node dysfunction (n = 7, 33.3%) and upgrade from implantable cardioverter-defibrillator to His-cardiac resynchronisation therapy (n = 1, 4.8%). No significant difference was observed in baseline characteristics between Timeframe 1 and Timeframe 2. Improvements pertaining to mean fluoroscopy time were achieved between the two timeframes. There was one HBP-related complication of lead displacement during Timeframe 1. All patients with successful HBP achieved non-selective His bundle (NSHB) capture, whereas only eight patients had selective His bundle (SHB) capture. NSHB and SHB capture thresholds remained stable at the 12-month follow-up. Conclusion: Permanent HBP is feasible and safe, even without the use of an electrophysiology recording system. This was successfully achieved in 75% of patients, with no adverse clinical outcomes during the follow-up period.

Validation of MyDiagnostick tool to identify atrial fibrillation in a multi-ethnic Asian population.

Introduction: MyDiagnostick is an atrial fibrillation (AF) screening tool that has been validated in the Caucasian population in the primary care setting. Methods: In our study, we compared MyDiagnostick with manual pulse check for AF screening in the community setting. Results: In our cohort of 671 candidates from a multi-ethnic Asian population, AF prevalence was found to be 1.78%. Of 12 candidates, 6 (50.0%) had a previous history of AF and another 6 (50.0%) were newly diagnosed with AF. Candidates found to have AF during the screening were older (72.0 ± 11.7 years vs. 56.0 ± 13.0 years, P < 0.0001) and had a higher CHADSVASC risk score (2.9 ± 1.5 vs. 1.5 ± 1.1, P = 0.0001). MyDiagnostick had a sensitivity of 100.0% and a specificity of 96.2%. In comparison, manual pulse check had a sensitivity of 83.3% and a specificity of 98.9%. Conclusion: MyDiagnostick is a simple AF screening device that can be reliably used by non-specialist professionals in the community setting. Its sensitivity and specificity are comparable and validated across various studies performed in different population cohorts.

Catheter Ablation of Ventricular Arrhythmia in Patients With an Implantable Cardioverter-Defibrillator: A Systematic Review and Meta-analysis.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) shocks are associated with higher rates of mortality and reduced quality of life. In this study we aimed to investigate the effectiveness of catheter ablation (CA) of ventricular tachycardia in patients with an ICD. METHODS: An electronic literature search was conducted to identify randomized controlled trials that compared CA vs control. The primary outcomes were recurrence of ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation) and mortality. Kaplan-Meier curves for these outcomes were digitized to obtain individual patient data, which were pooled in a 1-stage meta-analysis to determine hazard ratios (HRs) and 95% confidence intervals (CIs). Secondary outcomes included cardiac hospitalization, electrical storm, syncope, appropriate ICD therapies, appropriate ICD shocks, and inappropriate shocks. For these, study-level HRs or risk ratios were obtained and pooled in random effects meta-analyses. Subgroup analysis was performed for trials that investigated prophylactic CA (before or during ICD implantation). RESULTS: Data on 9 studies and 1103 patients were retrieved. CA significantly reduced ventricular tachycardia/ventricular fibrillation recurrence compared with control (shared frailty HR, 0.63; 95% CI, 0.49-0.81; P < 0.001) but not mortality (shared frailty HR, 0.84; 95% CI, 0.57-1.23; P = 0.361). CA was associated with significantly lower rates of cardiac hospitalization, electrical storm, appropriate ICD therapies and shocks, but not syncope or inappropriate shocks. Subgroup analysis showed similar results for prophylactic CA except that no significant difference was observed for cardiac hospitalizations. CONCLUSIONS: CA is associated with reduced ventricular arrhythmia recurrence, appropriate ICD therapies/shocks, electrical storm, and cardiac hospitalization, and might be effective in preventing future morbidity. Future trials are needed to support the continued benefit of these promising results, and to investigate the optimal timing of ablation.

Undiagnosed cardiovascular risk factors including elevated lipoprotein(a) in patients with ischaemic heart disease.

Objectives: This study aims to investigate the prevalence of undiagnosed cardiovascular risk factors in patients with ischaemic heart disease (IHD). Methods: We assessed the prevalence of previously undiagnosed cardiovascular risk factors, including elevated lipoprotein(a) [Lp(a)], among consenting patients with IHD who were admitted to hospital. Clinical information, including dietary history, from patients with newly diagnosed IHD and known IHD were compared. Results: Of the 555 patients, 82.3% were males and 48.5% of Chinese ethnicity. Overall, 13.3% were newly diagnosed with hypertension, 14.8% with hypercholesterolemia, and 5% with type 2 diabetes (T2DM). Patients with newly diagnosed IHD, compared to those with known IHD, had a higher prevalence of new diagnoses of hypercholesterolemia (29.1% vs. 2.0%, p < 0.001), hypertension (24.5% vs. 3.4%, p < 0.001) and T2DM (7.3% vs. 3.1%, p = 0.023). Active smoking was prevalent in 28.3% of patients, and higher in newly diagnosed IHD (34.1% vs. 23.2%, p = 0.005). Elevated Lp(a) of ≥120 nmol/L was detected in 15.6% of all patients, none of whom were previously diagnosed. Dietary habits of >50% of patients in both groups did not meet national recommendations for fruits, vegetables, wholegrain and oily fish intake. However, patients with known IHD had a more regular omega-3 supplement intake (23.4% vs. 10.3%, p = 0.024). Conclusion: Increased detection efforts is necessary to diagnose chronic metabolic diseases (hypertension, hypercholesterolemia, T2DM) especially among patients at high risk for IHD. Cardiovascular risk factors, in particular elevated Lp(a), smoking, and suboptimal dietary intake in patients with IHD deserve further attention.

Omnipolar activation EGM to identify the earliest breakout site of atrial tachycardia.

AT was mapped with Advisor HD Grid for earliest breakout site via local activation timing (LAT) map and Omnipolar map. While both maps point to earliest breakout site from low anterior right atrium, omnipolar map localised it to a more precise location compared to the earliest breakout site from LAT map. Ablation in this same spot rendered AT non inducible.

A meta-analysis of extended ECG monitoring in detection of atrial fibrillation in patients with cryptogenic stroke.

OBJECTIVE: The aim of this systematic review is to evaluate the various modalities available for extended ECG monitoring in the detection of atrial fibrillation (AF) following a cryptogenic stroke. METHODS: MEDLINE (Ovid), EMBASE (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL) were searched from January 2011 to November 2021. All randomised controlled trials and prospective cohort studies including the use of extended ECG monitoring >24 hours with a minimum duration of AF of 30 s in patients with either cryptogenic strokes or transient ischaemic attacks were included. A random-effects model was used to pool effect estimates of AF detection rates from different ECG modalities. RESULTS: 3924 studies were identified, of which 47 were included reporting on a pooled population of 6448 patients with cryptogenic stroke. The pooled AF rate for implantable loop recorders (ILRs) increased from 4.9% (3.0%-7.9%) at 1 month to 38.4% (20.4%-60.2%) at 36 months. Mobile cardiac outpatient telemetry (MCOT) had a significantly higher pooled AF detection rate of 12.8% (8.9%-17.9%) versus 4.9% (3.0%-7.9%) for ILR at 1 month (p<0.0001). Predictors for AF detection include duration of monitoring (p<0.0001) and age (p<0.0001) for ILRs, but only age for MCOTs (p<0.020). CONCLUSION: MCOT has a higher rate of detection at 1 month and is less invasive. Beyond 1 month, compliance becomes a significant limitation for MCOT. MCOT may be a reasonable alternative AF screening tool for patients with cryptogenic stroke if ILR is not available. PROSPERO REGISTRATION NUMBER: CRD42022297782.

Clinicopathological correlates of out-of-hospital cardiac arrests.

Background: Sudden cardiac arrest with or without sudden cardiac death (SCD) represents a heterogeneous spectrum of underlying etiology but is often a catastrophic event. Despite improvements in pre-hospital response and post-resuscitation care, outcomes remain grim. Thus, we aim to evaluate the predictors of survival in out-of-hospital cardiac arrests (OHCAs) and describe autopsy findings of those with the uncertain cause of death (COD). Methods: This is a subgroup analysis of the Singapore cohort from the Pan Asian Resuscitation Outcome Study which studied 933 OHCAs admitted to two Singapore tertiary hospitals from April 2010 to May 2012. Results: Of the patients analysed, 30.2% (n = 282) had an initial return of spontaneous circulation (ROSC) at the emergency department, 18.0% (n = 168) had sustained ROSC with subsequent admission and 3.4% (n = 32) had survival to discharge. On multivariate analysis, an initial shockable rhythm, a witnessed event, prehospital defibrillation, and shorter time to hospital predicted ROSC as well as survival to discharge. A total of 163 (17.5%) autopsies were performed of which a cardiac etiology of SCD was noted in 92.1% (n = 151). Ischemic heart disease accounted for 54.3% (n = 89) of the autopsy cohort, with acute myocardial infarction (26.9%, n = 44) and myocarditis (3.7%, n = 6) rounding out the top three causes of demise. Conclusion: OHCA remains a clinical presentation that portends a poor prognosis. Of those with uncertain COD, cardiac etiology appears to predominate from autopsy study. Identification of prognostic factors will play an important role in improving individual-level and systemic-level variables to further optimize outcomes.

A case report of bidirectional ventricular tachycardia secondary to aconitum toxicity.

We present a case of malignant ventricular arrhythmia secondary to unintentional aconite poisoning. Healthcare workers need to be vigilant regarding cases of aconitum toxicities, especially in atypical presentations. There is also a need to educate the public regarding the consumption and preparation of potent TCM herbs that may result in lethal toxicity.

Subcutaneous Versus Transvenous Implantable Defibrillator Therapy: A Systematic Review and Meta-Analysis of Randomized Trials and Propensity Score-Matched Studies.

Background Subcutaneous implantable cardioverter-defibrillators (S-ICDs) have been of great interest as an alternative to transvenous implantable cardioverter-defibrillators (TV-ICDs). No meta-analyses synthesizing data from high-quality studies have yet been published. Methods and Results An electronic literature search was conducted to retrieve randomized controlled trials or propensity score-matched studies comparing S-ICD against TV-ICD in patients with an implantable cardioverter-defibrillator indication. The primary outcomes were device-related complications and lead-related complications. Secondary outcomes were inappropriate shocks, appropriate shock, all-cause mortality, and infection. All outcomes were pooled under random-effects meta-analyses and reported as risk ratios (RRs) and 95% CIs. Kaplan-Meier curves of device-related complications were digitized to retrieve individual patient data and pooled under a 1-stage meta-analysis using Cox models to determine hazard ratios (HRs) of patients undergoing S-ICD versus TV-ICD. A total of 5 studies (2387 patients) were retrieved. S-ICD had a similar rate of device-related complications compared with TV-ICD (RR, 0.59 [95% CI, 0.33-1.04]; P=0.070), but a significantly lower lead-related complication rate (RR, 0.14 [95% CI, 0.07-0.29]; P<0.0001). The individual patient data-based 1-stage stratified Cox model for device-related complications across 4 studies yielded no significant difference (shared-frailty HR, 0.82 [95% CI, 0.61-1.09]; P=0.167), but visual inspection of pooled Kaplan-Meier curves suggested a divergence favoring S-ICD. Secondary outcomes did not differ significantly between both modalities. Conclusions S-ICD is clinically superior to TV-ICD in terms of lead-related complications while demonstrating comparable efficacy and safety. For device-related complications, S-ICD may be beneficial over TV-ICD in the long term. These indicate that S-ICD is likely a suitable substitute for TV-ICD in patients requiring implantable cardioverter-defibrillator implantation without a pacing indication.

The utilization of atrial sensing dipole in single lead implantable cardioverter defibrillator for detection of new-onset atrial high-rate episodes or subclinical atrial fibrillation: A systematic review and meta-analysis.

This meta-analysis aims to evaluate the performance of atrial sensing dipole in single lead implantable cardioverter defibrillator (VDD-ICD) recipients in particular diagnosing new-onset atrial high-rate episodes (AHREs) defined as rate threshold of 200 beats per minute, or subclinical atrial fibrillation (SCAF) defined as device-detected AF without symptoms. We comprehensively searched PubMed, Embase, and ClinicalTrials.gov. Studies comparing contemporary single- and dual-chamber ICD (VVI-/DDD-ICD) versus VDD-ICD were included. Restricted maximum likelihood method for random effect model and Mantel-Haenszel method for fixed effect model were used to estimate the effect size of new-onset AHREs, or SCAF detection in each group. Three prospective studies were identified and total of 991 participants were included. There were 330 (33.3%) in VDD-ICD and 661 (66.7%) in VVI-/DDD-ICD. Most (78%) participants were men. Median follow-up was from 365 days to 847 days. VDD-ICD has a higher likelihood of detecting AHREs or SCAF as compared to VVI-/DDD-ICD [(OR random effect : 2.6; 95% CI: 1.2, 5.8; p = .018); I-squared = 67.8%, p = .019]. This difference was more apparently seen in the comparison between VDD-ICD and VVI-ICD [(OR random effect: 3.8; 95% CI: 2.1, 6.6, p < .001), I-squared = 0.0%, p = .518]. The result is same as fixed effect. Rate of AHREs detection observed in VDD-ICD was not statistically different when compared to the only group with DDD-ICD from SENSE trial. In conclusion, this meta-analysis reveals that the use of floating atrial sensing dipole in VDD-ICD increases the detection of new-onset AHREs or SCAF when compared to VVI-ICD, with similar atrial sensing performance to DDD-ICD.

Case report: Wide-complex tachycardia one week post-CRT-D implantation in a patient with pre-existing left bundle branch block.

A 37-year-old female with dilated cardiomyopathy, whose baseline ECG showed sinus rhythm with left bundle branch block pattern, received a cardiac resynchronization therapy defibrillator (CRTD). One week post-implantation, she presented to the emergency department with palpitations, diaphoresis and chest discomfort. ECG showed a wide-complex tachycardia (WCT) episode, which spontaneously converted to sinus rhythm, and was later diagnosed as typical slow-fast atrioventricular nodal re-entrant tachycardia. This report outlines the differential diagnoses for WCT and the reasoning behind the eventual diagnosis, taking into consideration the device interrogation findings and results of the electrophysiology study.

Adopting permanent His bundle pacing: learning curves and medium-term outcomes.

AIMS: This study aims to determine procedural characteristics, acute success rates, and medium-term outcomes of consecutive patients undergoing His bundle pacing (HBP); and learning curves of experienced electrophysiologists adopting HBP. METHODS AND RESULTS: Consecutive HBP patients at three hospitals were recruited. Clinical characteristics, acute procedural details, and medium-term outcomes were extracted from electronic medical records. Two hundred and thirty-three patients [mean age 74.6 ± 10.1 years, 48% female, 68% narrow QRS, 71% normal left ventricular ejection fraction (LVEF), 55.8% atrioventricular block] underwent HBP. Acute procedural success was 81.1% (mean procedural and fluoroscopic times of 105.5 ± 36.5 and 13.8 ± 9.3 min). Broad QRS was associated with lower HBP success (odds ratio 0.39, P = 0.02). Fluoroscopic and procedural times decreased and plateaued after 30-40 cases per operator. Implant HBP threshold was 1.3 ± 0.7 V at 1.0 ± 0.2 ms and R wave was 5.0 ± 3.9 mV. During follow-up, loss of HBP occurred in a further 12.4% and 11.3% of patients experienced a ≥1 V increase in HBP threshold. Five (2.6%) patients required HBP revision for pacing difficulties. About 8.6% of patients had a >50% decrease in R wave but lead revision for sensing issues was not necessary. On an intention to treat basis, 56.7% of patients in whom HBP was attempted had persisting HBP capture and thresholds of <2 V. CONCLUSION: Physicians adopting HBP should be cognizant of the learning curve and preferentially select non-dependent patients with normal QRS and LVEF, to minimize risk of lead revision. Further rises in HBP threshold may increase battery drain and need for reoperations, important considerations when choosing HBP for cardiac resynchronization therapy.