Tan, Min Choon

Background Connective tissue disorders (CTDs) such as Marfan syndrome, Loeys-Dietz syndrome, and Ehlers-Danlos syndromes are traditionally defined by vascular fragility and aortic complications. Increasing evidence, however, demonstrates that CTDs also predispose to atrial and ventricular arrhythmias, often independent of overt cardiomyopathy or severe valvular disease. Content This review integrates emerging data on the arrhythmogenic substrates of CTDs. Four mechanistic bridges are emphasized: (1) diffuse myocardial fibrosis driven by dysregulated TGF-β signaling, (2) structural valve and annular abnormalities, particularly mitral valve prolapse and mitral annular disjunction, (3) altered mechanotransduction linking extracellular matrix instability to cytoskeletal and nuclear signaling pathways, and (4) downstream ion-channel and gap-junction remodeling as secondary amplifiers. We outline the genetic architecture underlying these processes, focusing on established CTD-implicated genes in the TGF-β/SMAD pathway, valve and annulus regulators, cytoskeletal and myocyte-coupling proteins, and extracellular matrix components, while incorporating emerging CTD modifiers that expand the spectrum of arrhythmia susceptibility. Summary Recognition of CTDs as both vascular and electrical disorders reframes clinical management. Imaging markers such as mitral annular disjunction and diffuse fibrosis, together with targeted ambulatory rhythm monitoring and consideration of genetic context, may improve recognition of higher-risk phenotypes. Therapeutic strategies must balance arrhythmia control with procedural risk in fragile connective tissue substrates. Conclusions By unifying genetic, mechanistic, and clinical insights, this review provides an integrated framework for understanding arrhythmias in CTDs. It underscores the need for prospective registries and genotype-phenotype studies to refine surveillance and prevention strategies.

Abstract Background Recurrence of symptomatic atrial fibrillation (AF) after catheter ablation (CA) is not uncommon. However, real-world long-term data on clinical outcomes of rhythm control strategies in patients with recurrent AF after CA remain limited. Methods Using the TriNetX database, we identified adult patients (≥18 years) with recurrent AF after index CA. A 3-month blanking period was applied, during which no rhythm-control therapy was received. Patients were classified into two groups: repeat CA or initiation of antiarrhythmic drug (AAD) therapy. Propensity score matching (PSM) was performed to balance baseline characteristics. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Outcomes included all-cause mortality, all-cause hospitalization, heart failure (HF) exacerbation, ischemic stroke, and major bleeding over 5 years. Results Among 4,056 patients with recurrent AF post-CA, 17.2% underwent repeat CA. After PSM, 697 patients in the repeat CA group (mean age 68.9 ± 9.6 years; 35.7% female) and 697 in the AAD group (mean age 68.4 ± 10.0 years; 37.6% female) were analyzed. Repeat CA was associated with lower all-cause mortality (3.3% vs 8.2%; HR 0.44; 95% CI, 0.27–0.72; P < 0.01), all-cause hospitalization (42.8% vs 56.4%; HR 0.71; 95% CI, 0.61–0.82; P < 0.01) and HF exacerbation (12.5% vs 24.8%; HR 0.50; 95% CI, 0.39–0.64; P < 0.01). No differences were observed in ischemic stroke (5.3% vs 4.7%; HR 1.22; 95% CI, 0.77–1.96; P = 0.40) or major bleeding (4.6% vs 6.2%; HR 0.82; 95% CI, 0.52–1.29; P = 0.39). Conclusions Repeat CA was associated with lower mortality, hospitalization, and HF exacerbation over 5 years.

ABSTRACT Background Atrial fibrillation (AF) is prevalent in cardiac amyloidosis (CA) and is associated with adverse clinical outcomes. Catheter ablation is increasingly used for rhythm control in this population, yet its clinical outcomes remain uncertain. We performed a systematic review and meta‐analysis to evaluate arrhythmia recurrence and clinical outcomes following catheter ablation compared with medical therapy in patients with CA. Methods We systematically searched MEDLINE, Embase, and Scopus from inception through December 2025 for studies evaluating catheter ablation of atrial arrhythmias in CA. Cohort studies reporting arrhythmia recurrence and/or clinical outcomes were included. The primary outcome was freedom from atrial arrhythmia (AA) following ablation. Secondary outcomes included all‐cause mortality, heart failure hospitalization, and stroke. Random‐effects models were used to pool event rates and odds ratios (ORs). Results Thirteen observational studies comprising 797 patients with CA and AF were included. The pooled rate of freedom from AA following catheter ablation was approximately 50% (95% CI 37%–63%; I 2 = 71.7%). The all‐cause mortality analysis included 4 observational studies comprising 616 patients. Catheter ablation was associated with lower odds of all‐cause mortality (OR 0.26, 95% CI 0.11–0.60; I 2 = 18.4%); however, this association should be interpreted with caution given the retrospective design and risk of bias. No statistically significant differences were observed for heart failure hospitalization or stroke. Conclusions In patients with CA, catheter ablation was associated with modest arrhythmia‐free survival and lower odds of all‐cause mortality. However, all contributing studies were observational cohorts. Randomized studies are needed to confirm these findings.

This cross-sectional study investigates the association between lipoprotein(a) levels and risk of ventricular arrhythmias among patients with heart failure with reduced ejection fraction receiving implantable cardioverter-defibrillator therapy.

Abstract Background Emerging evidence suggests that premature ventricular contractions (PVCs) may influence atrial electrophysiology and remodeling, potentially leading to higher rates of atrial fibrillation (AF) recurrence. However, existing data is limited to small-scale studies. Therefore, we conducted a retrospective study to evaluate the potential association between PVCs and AF ablation outcomes, which may suggest the need for more aggressive management of ventricular ectopy in this population. Objective This study aims to assess the 5-year outcomes of catheter ablation for AF in patients with and without a diagnosis of PVCs. Methods Using the TriNetX Analytics Research Network, we included patients aged ≥ 18 years who underwent AF catheter between January 1, 2014, and January 1, 2020. Patients were further categorized into two groups based on the presence of a diagnosis of PVCs. Propensity score matching (PSM) was performed using patient demographics, left ventricular ejection fraction (LVEF), cardiac comorbidities, and medications. Study outcomes included all-cause mortality & hospitalization, acute heart failure (HF), and rhythm control interventions during a 5-year follow-up. Results A total of 15,987 patients with PVCs and 40,605 patients without PVCs were identified. After PSM, 15,152 patients from each group were included for further analysis. Compared to control group, patients with PVCs had significantly higher odds of all-cause mortality (odds ratio [OR], 1.138; 95% confidence interval [CI], 1.034–1.253), all-cause hospitalization (OR, 1.300; 95% CI, 1.243–1.360), acute heart failure (HF) (OR, 1.223; 95% CI, 1.162–1.287), and cardiogenic shock (OR, 2.059; 95% CI, 1.751–2.420) following catheter ablation for AF at 5-year follow-up. Additionally, higher odds of AF requiring cardioversion (OR, 1.135; 95% CI, 1.074–1.199) or repeated ablation (OR, 1.164; 95% CI, 1.085–1.249) were observed in the PVCs group. Conclusion Premature ventricular contractions were associated with poorer clinical outcomes and a higher odds of requiring additional rhythm control intervention following catheter ablation for AF. These findings suggest that PVCs may be a marker for worse outcomes after AF ablation.

Abstract Background The incidence of type 2 diabetes mellitus among young adults has been increasing over the past few decades. There are limited data on contemporary national cardiovascular mortality rates in young adults with diabetes mellitus (DM). Methods We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database for patients aged 15 to 44 years from 1999 to 2019 in the primary analysis. A secondary analysis included data from 2020 to 2022 to examine the effect of the COVID‐19 pandemic. We analysed patients in whom cardiovascular diseases (CVD) were listed as the main cause of death and DM as a contributing cause of death. In calculating age‐adjusted mortality rates (AAMR) per 100 000 individuals, we used CVD mortality in young adults with comorbid diabetes as the numerator and the overall population as the denominator. We determined temporal trends by estimating the average annual percent change (AAPC) using the Joinpoint regression program. Results Among 3 309 079 individuals aged 15–44 years who died, 30 978 deaths were due to CVD with comorbid DM listed as a contributing cause. The overall AAMR increased from 1.08 per 100 000 individuals in 1999 to 1.23 per 100 000 individuals in 2019, with an average APC of 0.75 (95% CI, 0.31–1.20). Compared with 1999, the percentage increase in CVD deaths in 2019 among young adults with comorbid DM was +6.2%, whereas a decrease of 19.9% was observed among those without comorbid DM. Males had a higher AAMR than females (1.60 vs. 0.97). Non‐Hispanic Black individuals and non‐Hispanic American Indian/Alaska Native individuals had the highest AAMRs of 2.99 and 2.89, respectively. The AAMR was higher in rural regions compared to urban areas (1.63 vs. 1.23). The overall AAMR increased markedly from 1.23 in 2019 to 1.60 in 2022, with a similar pattern observed across demographic subgroups. Conclusion Our study reveals a rising trend in CVD mortality in young adults with DM as a contributing cause. Males, non‐Hispanic Black individuals, and individuals from rural regions had higher AAMR than their counterparts. This warrants the development of specific healthcare policies aimed at these at‐risk populations. Lay summary Our study shows that cardiovascular disease (CVD) deaths are increasing in young adults with diabetes mellitus listed as a contributing cause.

ABSTRACT Introduction Cardiac resynchronization therapy (CRT) improves clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, data on its efficacy in patients with sarcoidosis and HFrEF are limited. Methods Using the TriNetX network, we identified patients with sarcoidosis, heart failure with a left ventricular ejection fraction (LVEF) below 35%, and either left bundle branch block (LBBB) or prolonged QRS duration ( > 150 ms) between 2014 and 2019. Patients were categorized into two cohorts: (1) those who received CRT and (2) those who received an ICD‐only implant. Five‐year outcomes included all‐cause mortality, all‐cause hospitalization, heart failure exacerbation, and the proportion of patients with improvement in LVEF to greater than 40% and greater than 50%. Results Out of 245 eligible patients, we identified a cohort of 87 patients (mean age 62.6 ± 9.5 years) who received CRT and 87 patients (mean age 62.1 ± 11.1 years) who received ICD‐only implant, with similar propensity scores, and included them in a comparative analysis. At 5‐year follow‐up, the CRT group demonstrated outcomes comparable to the ICD‐only implant group for all‐cause mortality (14.9% vs. 20.7%; HR 0.63; 95% CI 0.31–1.28; p = 0.19), all‐cause hospitalization (83.9% vs. 77.0%; HR 1.24; 95% CI 0.89–1.73; p = 0.19), and heart failure exacerbation (28.7% vs. 28.7%; HR 0.90; 95% CI 0.52–1.57; p = 0.72). The proportion of patients with improvement in LVEF to greater than 40% and greater than 50% was also similar in both groups (LVEF > 40%, 43.7% vs. 33.3%; HR 1.30; 95% CI 0.80–2.10; p = 0.29; LVEF > 50%, 31.0% vs. 17.2%; HR 1.72; 95% CI 0.92–3.24; p = 0.09). Conclusion CRT implantation had similar long‐term outcomes compared to ICD‐only implantation in patients with sarcoidosis and HFrEF, particularly all‐cause mortality, all‐cause hospitalization, heart failure exacerbation, and the proportion of patients with improvement in LVEF to greater than 40% and greater than 50%.

Background: Ventricular tachycardia (VT) is a major contributor to death among ischemic heart disease (IHD) patients. In this systematic review and meta-analysis, we evaluate the efficacy of catheter ablation in patients with ischemic cardiomyopathy. Methods: We conducted a meta-analysis by searching the electronic database up to April 2025. Seven studies, including 1192 patients, were identified. A random-effect model was used to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Trial sequential analysis was conducted to assess sample size adequacy. Results: Among Ischemic heart disease patients with ICDs, VT ablation was associated with a significant reduction in ICD shocks (RR = 0.50, 95% CI [0.34–0.74]), a trend toward reduced VT storm (RR = 0.64, 95% CI [0.40–1.04], p = 0.07), and lower rates of cardiovascular hospitalization (RR = 0.73, 95% CI [0.53–1.01], p = 0.06) compared to ICD alone. However, no significant differences were observed when compared to patients receiving ICD plus antiarrhythmic drugs (AADs). Additionally, VT ablation showed no significant impact on mortality or VT/VF recurrence compared to either ICD alone or ICD with AADs. Trial Sequential Analysis provided conclusive evidence for VT/VF recurrence outcomes, while further data are required for other outcomes. Conclusion: Among ischemic heart disease patients with ICD, VT ablation reduces ICD shocks, VT storm, and cardiovascular hospitalizations compared to ICD-only, but offers no significant advantage over ICD combined with antiarrhythmic drugs. VT ablation does not impact mortality or the recurrence of VT/VF. Trial Sequential Analysis confirmed conclusive evidence for VT/VF recurrence, while additional data is needed for other outcomes.