Machine Learning Modeling to Predict Atrial Fibrillation Detection in Embolic Stroke of Undetermined Source Patients.

BACKGROUND: In patients with embolic stroke of undetermined source (ESUS), occult atrial fibrillation (AF) has been implicated as a key source of cardioembolism. However, only a minority acquire implantable cardiac loop recorders (ILRs) to detect occult paroxysmal AF, partly due to financial cost and procedural inconvenience. Without the initiation of appropriate anticoagulation, these patients are at risk of increased ischemic stroke recurrence. Hence, cost-effective and accurate methods of predicting AF in ESUS patients are highly sought after. OBJECTIVE: We aimed to incorporate clinical and echocardiography data into machine learning (ML) algorithms for AF prediction on ILRs in ESUS. METHODS: This was a single-center cohort study that included 157 consecutive patients diagnosed with ESUS from October 2014 to October 2017 who had ILR evaluation. We developed four ML models, with hyperparameters tuned, to predict AF detection on an ILR. RESULTS: The median age of the cohort was 67 (IQR 59-74) years old and the median monitoring duration was 1051 (IQR 478-1287) days. Of the 157 patients, 32 (20.4%) had occult AF detected on the ILR. Support vector machine predicted for AF with a 95% confidence interval area under the receiver operating characteristic curve (AUC) of 0.736-0.737, multilayer perceptron with an AUC of 0.697-0.708, XGBoost with an AUC of 0.697-0.697, and random forest with an AUC of 0.663-0.674. ML feature importance found that age, HDL-C, and admitting heart rate were important non-echocardiography variables, while peak mitral A-wave velocity and left atrial volume were important echocardiography parameters aiding this prediction. CONCLUSION: Machine learning modeling incorporating clinical and echocardiographic variables predicted AF in ESUS patients with moderate accuracy.

Prognostic benefits of His-Purkinje capture in physiological pacemakers for bradycardia.

INTRODUCTION: Clinical outcomes of long-term ventricular septal pacing (VSP) without His-Purkinje capture remain unknown. This study evaluated the differences in clinical outcomes between conduction system pacing (CSP), VSP, and right ventricular pacing (RVP). METHODS: Consecutive patients with bradycardia indicated for pacing from 2016 to 2022 were prospectively followed for the clinical endpoints of heart failure (HF)-hospitalizations and all-cause mortality at 2 years. VSP was defined as septal pacing due to unsuccessful CSP implant or successful CSP followed by loss of His-Purkinje capture within 90 days. RESULTS: Among 1016 patients (age 73.9 ± 11.2 years, 47% female, 48% atrioventricular block), 612 received RVP, 335 received CSP and 69 received VSP. Paced QRS duration was similar between VSP and RVP, but both significantly longer than CSP (p < .05). HF-hospitalizations occurred in 130 (13%) patients (CSP 7% vs. RVP 16% vs. VSP 13%, p = .001), and all-cause mortality in 143 (14%) patients (CSP 7% vs. RVP 19% vs. VSP 9%, p < .001). The association of pacing modality with clinical events was limited to those with ventricular pacing (Vp) > 20% (pinteraction < .05). Adjusting for clinical risk factors among patients with Vp > 20%, VSP (adjusted hazard ratio [AHR]: 4.74, 95% confidence interval [CI]: 1.57-14.36) and RVP (AHR: 3.08, 95% CI: 1.44-6.60) were associated with increased hazard of HF-hospitalizations, and RVP (2.52, 95% CI: 1.19-5.35) with increased mortality, compared to CSP. Clinical endpoints did not differ between VSP and RVP with Vp > 20%, or amongst groups with Vp < 20%. CONCLUSION: Conduction system capture is associated with improved clinical outcomes. CSP should be preferred over VSP or RVP during pacing for bradycardia.

Migraine and atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis. METHODS: A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 5 September 2022 with the following inclusion criteria: (a) cohort or cross-sectional studies; (b) studies that included only patients aged ≥18 years; and (c) studies that examined the association between atrial fibrillation and migraines. Exclusion criteria were case-control studies and the studies that included patients with previous diagnosis of atrial fibrillation or nonmigrainous headache. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS: Six studies were included, demonstrating a pooled prevalence of atrial fibrillation of 1.61% (95% confidence interval [CI] 0.51, 3.29) in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The overall prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46). CONCLUSION: In this systematic review and meta-analysis, the overall prevalence of atrial fibrillation in patients with migraine was low. Further studies are needed to clarify this relationship.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Comparison of Pacing Performance and Clinical Outcomes Between Left Bundle Branch and His Bundle Pacing.

BACKGROUND: Left bundle branch (LBBP) and His-bundle pacing (HBP) provide physiological ventricular activation. OBJECTIVES: This study investigated differences in feasibility, device performance, and clinical outcomes between LBBP and HBP. METHODS: Consecutive patients with LBBP and HBP from 2018 to 2021 in 2 centers were prospectively studied. The primary endpoint was optimal device performance during follow-up, defined as the presence of pacing thresholds <2.5 V, R-wave amplitude ≥5 V, and absence of conduction system pacing (CSP)-related complications. The secondary endpoint was the composite of heart failure hospitalizations or all-cause mortality. RESULTS: Among 338 patients, 282 underwent successful CSP (119 HBP, 163 LBBP). Success rates, CSP-related complications, and need for reoperations did not differ between LBBP and HBP (P > 0.05). Pacing thresholds were lower, whereas R-wave amplitudes and lead impedance were higher in LBBP (P < 0.05). The primary endpoint was more frequent in LBBP than HBP (79% vs 34%; P < 0.001), with LBBP independently associated with 9-fold increased odds of optimal device performance (adjusted OR: 9.31; 95% CI: 5.14-16.86). LBBP was less likely to have increased pacing thresholds by >1 V (1% vs 19% HBP, P < 0.001). The secondary outcome was less frequent in LBBP than HBP (9% vs 24%, P = 0.001), with LBBP trending towards higher event-free survival (HR: 0.62; 95% CI: 0.31-1.23). The secondary outcome was independent of pacing burden or pacing indication. CONCLUSIONS: Despite similar feasibility and safety profiles, LBBP confers additional benefits in pacing performance and reliability, shows trends towards improved survival compared to HBP, and should be the preferred first-line CSP modality of choice.

Detection of Atrial Fibrillation After Ischemic Stroke with an Insertable Cardiac Monitor: A Systematic Review and Individual Patient Data Meta-Analysis of Randomised Clinical Trials.

OBJECTIVE: In ischemic stroke patients, we compared the use of insertable cardiac monitor (ICM) versus non-ICM methods of cardiac monitoring on the incidence of atrial fibrillation (AF) detection and other clinical outcomes. BACKGROUND: Current guidelines recommend the routine use of 12-lead electrocardiography or Holter monitoring for AF detection after ischemic stroke. Recent randomised controlled trials have investigated the impact of ICM versus non-ICM methods of cardiac monitoring for AF detection in this population. However, precise recommendations for monitoring post-stroke AF are lacking; including the optimal timing, duration, and method of electrocardiography monitoring. METHODS: A systematic search was conducted on Embase and PubMed from database inception until 27 October 2022 to include randomised controlled trials that compared ICM with non-ICM methods of cardiac monitoring for post-stroke AF detection. This yielded 3 randomised controlled trials with a combined cohort of 1231 patients with a recent ischemic stroke. Individual patient data (IPD) was then reconstructed from Kaplan-Meier curves and analysed using the shared-frailty Cox model. An aggregate data meta-analysis was conducted for 1231 patients across all 3 studies for outcomes that could not be reconstructed using IPD. RESULTS: One-stage meta-analysis demonstrated an increase in the hazard ratio (HR 6.01, 95% CI 3.40-10.60; p<0.001) of AF detection in patients undergoing monitoring via ICM compared to standard care. Aggregate data meta analysis revealed a significant increase in initiation of anticoagulation (OR 3.09, 95% CI 2.05 - 4.66; p<0.00001) in the ICM group. However, no significant differences in the incidence of recurrent ischemic stroke, transient ischemic attack or death were found. CONCLUSIONS: In this meta-analysis, we found that the use of ICM increased the detection rate of post-stroke AF and the rate of anticoagulation initiation. However, this did not translate into a reduced incidence of recurrent ischemic stroke.

Stroke Recurrence in Embolic Stroke of Undetermined Source Without Atrial Fibrillation on Invasive Cardiac Monitoring.

BACKGROUND: More than half of patients with embolic stroke of undetermined source (ESUS) suffer from recurrent ischaemic stroke, despite the absence of atrial fibrillation (AF) on invasive cardiac monitoring (ICM). This study investigated the predictors and prognosis of recurrent stroke in ESUS without AF on ICM. METHOD: This prospective study included patients with ESUS at two tertiary hospitals from 2015 to 2021 who underwent comprehensive neurological imaging, transthoracic echocardiography, and inpatient continuous electrographic monitoring for ≥48 hours prior to ICM for definitive exclusion of AF. Recurrent ischaemic stroke, all-cause mortality, and functional outcome by the modified Rankin scale (mRS) at 3 months were evaluated in patients without AF. RESULTS: Of 185 consecutive patients with ESUS, AF was not detected in 163 (88%) patients (age 62±12 years, 76% men, 25% prior stroke, median time to ICM insertion 26 [7, 123] days), and stroke recurred in 24 (15%) patients. Stroke recurrences were predominantly ESUS (88%), within the first 2 years (75%), and involved a different vascular territory from qualifying ESUS (58%). Pre-existing cancer was the only independent predictor of recurrent stroke (adjusted hazard ratio [AHR] 5.43, 95% CI 1.43-20.64), recurrent ESUS (AHR 5.67, 95% CI 1.15-21.21), and higher mRS score at 3 months (ß 1.27, 95% CI 0.23-2.42). All-cause mortality occurred in 17 (10%) patients. Adjusting for age, cancer, and mRS category (≥3 vs <3), recurrent ESUS was independently associated with more than four times greater hazard of death (AHR 4.66, 95% CI 1.76-12.34). CONCLUSIONS: Patients with recurrent ESUS are a high-risk subgroup. Studies elucidating optimal diagnostic and treatment strategies in non-AF-related ESUS are urgently required.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Conduction system versus biventricular pacing in heart failure with non-left bundle branch block.

INTRODUCTION: The benefits of cardiac resynchronization therapy (CRT) with biventricular pacing (BiV) is significantly lower when applied to heart failure (HF) patients with non-left bundle branch block (LBBB) conduction delay. We investigated clinical outcomes of conduction system pacing (CSP) for CRT in non-LBBB HF. METHODS: Consecutive HF patients with non-LBBB conduction delay undergoing CSP were propensity matched for age, sex, HF-etiology, and atrial fibrillation (AF) in a 1:1 ratio to BiV from a prospective registry of CRT recipients. Echocardiographic response was defined as an increase in left ventricular ejection fraction (LVEF) by ≥10%. The primary outcome was the composite of HF-hospitalizations or all-cause mortality. RESULTS: A total of 96 patients were recruited (mean age 70 ± 11years, 22% female, 68% ischemic HF and 49% AF). Significant reductions in QRS duration and LV dimensions were seen only after CSP, while LVEF improved significantly in both groups (p < 0.05). Echocardiographic response occurred more frequently in CSP than BiV (51% vs. 21%, p < 0.01), with CSP independently associated with four-fold increased odds (adjusted odds ratio 4.08, 95% confidence interval [CI] 1.34-12.41). The primary outcome occurred more frequently in BiV than CSP (69% vs. 27%, p < 0.001), with CSP independently associated with 58% risk reduction (adjusted hazard ratio [AHR] 0.42, 95% CI 0.21-0.84, p = 0.01), driven by reduced all-cause mortality (AHR 0.22, 95% CI 0.07-0.68, p < 0.01), and a trend toward reduced HF-hospitalization (AHR 0.51, 95% CI 0.21-1.21, p = 0.12). CONCLUSIONS: CSP provided greater electrical synchrony, reverse remodeling, improved cardiac function and survival compared to BiV in non-LBBB, and may be the preferred CRT strategy for non-LBBB HF.

Clinical Outcomes in Conduction System Pacing Compared to Right Ventricular Pacing in Bradycardia.

BACKGROUND: Conduction system pacing (CSP) provides more physiological ventricular activation than right ventricular pacing (RVP). OBJECTIVES: This study evaluated the differences in clinical outcomes in patients receiving CSP and RVP. METHODS: Consecutive patients with pacemakers implanted for bradycardia from 2016 to 2021 in 2 centers were prospectively followed for the primary composite outcome of heart failure (HF) hospitalizations, upgrade to biventricular pacing, or all-cause mortality, stratified by ventricular pacing burden (Vp) . RESULTS: Among 860 patients (mean age 74 ± 11 years, 48% female, 48% atrioventricular block), 628 received RVP and 231 received CSP (95 His-bundle pacing, 136 left bundle branch pacing). The primary outcome occurred in 217 (25%) patients, more commonly in patients with RVP than CSP (30% vs 13%, P < 0.001). In multivariable analyses, CSP was independently associated with 47% reduction of the primary outcome (adjusted hazard ratio [AHR]: 0.53; 95% CI: 0.29-0.97; P = 0.04) and HF hospitalization alone (AHR: 0.40; 95% CI: 0.17-0.95; P = 0.04), among only patients with Vp >20%. The incidence of the primary outcome was highest among RVP with Vp >20% and lowest in CSP with Vp >20% (35% vs 10%, P < 0.001). Compared with RVP with Vp >20%, both CSP with Vp >20% (AHR: 0.51; 95% CI: 0.28-0.91; P = 0.02) and all patients with Vp ≤20% (AHR: 0.73; 95% CI: 0.54-0.99; P = 0.04) were independently associated with reduced primary outcome, driven primarily by reductions in HF hospitalizations (P < 0.05). Event-free survival was similar between CSP with Vp >20% and those needing ≤20% Vp. CONCLUSIONS: CSP significantly reduced adverse clinical outcomes for bradycardic patients requiring ventricular pacing and should be the preferred pacing modality of choice.

Successful Ablation of Sustained Monomorphic Ventricular Tachycardia in a Patient With Mitral Annular Disjunction.

Mitral annular disjunction (MAD) with or without mitral valve prolapse is associated with sudden death. Observed arrhythmias are usually ventricular ectopic beats originating from the papillary muscles. We describe a successful ablation of sustained monomorphic ventricular tachycardia from an epicardial focus in a patient with MAD. (Level of Difficulty: Intermediate.).

Use of extendable helix leads for conduction system pacing: Differences in lead handling and performance lead design impacts conduction system pacing.

INTRODUCTION: Pacing leads with extendable-retractable helix (EHL) are alternatives to fixed-helix leads (FHL) for conduction system pacing (CSP), but data on handling characteristics are limited. This study evaluated a dual-center experience of lead handling and performance during CSP. METHODS AND RESULTS: Consecutive patients with His-bundle pacing (HBP) or left bundle branch pacing (LBBP) were evaluated for the primary outcome of lead failure, defined as structural damage to the lead necessitating lead replacement. Differences in pacing characteristics were compared. Among 280 patients (mean age 74 ± 11 years, 44% male, 50% LBBP), 246 (88%) received FHL and 34 (12%) received EHL. Of 299 leads used, lead failure occurred more frequently among patients with EHL than FHL (29% vs. 2%, p < .001), regardless of CSP modality. Majority of damaged leads (89%) in the form of helix deformation were successfully removed, with failure occurring in only two patients, both EHL, leading to helix fracture and retention within the septal myocardium. EHL, compared to FHL, was associated with 25-fold increased odds of lead failure (odds ratio: 25.21, 95% confidence interval: 7.35-86.51), and persisted after adjustment in turn for age, pacing modality and indication. CSP implant success rates did not differ by lead design (FHL 80% vs. EHL 71%, p = .18), with similar pacing thresholds at implant and follow-up. CONCLUSION: Helix deformation and fracture were more frequent with EHL in CSP despite similar implant success. These findings have significant implications for lead selection during CSP and raises concerns about the long-term extractability of EHL in CSP.

Acute suppression of epicardial left ventricular summit premature ventricular ectopy by occlusive venogram.

We describe the unique phenomenon of occlusive venogram-induced suppression of premature ventricular complexes (PVC) arising from the epicardial left ventricular summit (LVS). Prior to ablation through the coronary sinus, routine occlusive venogram performed at the focus of PVC origin led to localized myocardial staining and simultaneous, sustained PVC suppression. Pace-mapping adjacent to the area of myocardial staining revealed near-identical PVC morphology match (98%). Routine occlusive venogram prior to ablation within the coronary venous system is safe and contributed to localization of the PVC focus.

Outcomes of supraventricular tachycardia ablation: Results from the Singapore ablation and cardiac devices registry.

BACKGROUND: The Singapore Cardiac Databank was designed to monitor the performance and outcomes of catheter ablation. We investigated the outcomes of paroxysmal supraventricular tachycardia (PSVT)-ablation in a prospective, nationwide, cohort study. METHODS: Atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular re-entry tachycardia (AVRT), or atrial tachycardia (AT)-ablations in Singapore from 2010 to 2018 were studied. Outcomes include acute success, periprocedural-complications, postoperative pacing requirement, arrhythmic recurrence and 1-year all-cause mortality. RESULTS: Among 2260 patients (mean age 45 ± 18 years, 50% female, 57% AVNRT, 37% AVRT, 6% AT), overall acute success rates of PSVT-ablation was 98.4% and increased in order of AT, AVRT, and AVNRT (p < .001). Periprocedural cardiac tamponade occurred in two AVRT patients. A total of 15 pacemakers (6 within first 30-days, 9 after 30-days) were implanted (seven AV block, eight sinus node dysfunction [SND]), with the highest incidence of pacemaker implantation after AT-ablation (5% vs. 0.6% AVNRT vs. 0.1% AVRT, p < .001). Repeat ablations (0.9% AVNRT, 7% AVRT, 4% AT, p < .001) were performed in 78 (3.5%) patients and 13 (0.6%) patients died within a year of ablation. Among outcomes considered adjusting for age, sex, PSVT-type and procedure-time, AT was independently associated with 6-fold increased odds of total (adjusted odds ratio [AOR] 6.32, 95% confidence interval [CI] 1.95-20.53) and late (AOR 6.38, 95% CI 1.39-29.29) pacemaker implantation, while AVRT was associated with higher arrhythmic recurrence with repeat ablations (AOR 4.72, 95% CI 2.36-9.44) compared to AVNRT. CONCLUSIONS: Contemporary PSVT ablation is safe with high acute success rates. Long-term outcomes differed by nature of the PSVT.

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.

Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: Consensus Recommendations by the Asian Pacific Society of Cardiology on Strategies for Thrombotic and Bleeding Risk Management.

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed.