Citations

Background: Ventricular tachycardia (VT) is a potentially life-threatening arrhythmia frequently observed in structural heart diseases, including cardiac laminopathy, a genetic cardiomyopathy associated with a high risk of sudden cardiac death (SCD) and progressive systolic dysfunction caused by pathogenic variants in LMNA -encoded lamin A/C. While catheter ablation is a key therapeutic strategy for VT management, its efficacy in cardiac laminopathy remains poorly defined. Objective: This systematic review and single-arm meta-analysis aims to synthesize the available evidence in the literature on the role of VT ablation for patients with cardiac laminopathy. Methods: A single-arm meta-analysis was conducted following PRISMA guidelines, systematically searching PubMed, Embase, and Cochrane databases for studies investigating VT ablation outcomes in patients with cardiac laminopathy. We applied an inverse variance random-effects model for a meta-analysis of proportions. Results: We included 6 cohort studies and 1 abstract comprising 62 patients with LMNA-related cardiomyopathy (mean age at 53.2 ± 9.7 years, 85% males, and 88% with an ICD). The predominant ablation strategy was endocardial/endo-epicardial in 93% of cases. Acute success rate following VT ablation was 37% (95% CI: 14 to 63%) and 28% of the patients required multiple procedures. Over a median follow-up of 26 (9-35) months, VT recurrence rate after ablation was 91% (95% CI: 76 to 100%; Figure A ). The all-cause mortality rate was 54% (95% CI: 39% to 70%; Figure B ), primarily driven by cardiac causes 51% (95% CI: 25 to 76%; Figure C ). There was an elevated rate of heart transplantation 14% (95% CI: 1 to 34%), highlighting overall poor outcomes in this patient population. Conclusion: Catheter ablation in cardiac laminopathy is associated with limited long-term efficacy, with high rates of VT recurrence, cardiovascular mortality and heart transplantation. These findings underscore the importance of ICD implantation for primary prevention and the pressing need to develop alternative treatment strategies. Further research is necessary to determine whether specific LMNA variants influence ablation outcomes and to explore emerging therapies targeting the underlying molecular mechanisms of cardiac laminopathy.

Background: Atrial arrhythmia recurrence after surgical ablation remains challenging to predict and integrating novel biomarkers may improve risk stratification. Objective: To evaluate whether combining preoperative transthoracic echocardiography (TTE) with artificial intelligence-enabled ECG (AI-ECG) scores enhances prediction of atrial fibrillation/flutter (AF/AFl) recurrence post surgical ablation. Methods: We retrospectively analyzed 1,696 patients undergoing Surgical AF/AFl Ablation between 2006 and 2025 with preoperative TTE and post-blanking ECGs. Clinical variables, TTE indices, and AI-ECG scores (AF probability, ECG-estimated age, HFpEF, LV dysfunction, and aortic stenosis scores) were assessed. The primary outcome was time to AF/AFl recurrence. Univariate/multivariable Cox models and a Random Survival Forest (RSF) model (80:20, training: testing) were developed to identify predictors. Results: Of 1,696 patients (mean age 67.3±10.2 years; 61.7% male) undergoing surgical AF/AFl ablation, 949 (56%) experienced AF/AFl recurrence during a median follow-up of 3.14 years. Patients with recurrence had larger left atria (mean LA area 30.4 vs 24.5 cm 2 , p < 0.001), more diastolic dysfunction (mitral inflow E-wave velocity 1.015 m/s vs 0.896 m/s , p < 0.001), and adverse AI-ECG biomarkers. In multivariable analysis, independent predictors of recurrence included a higher ECG-AF score (p < 1 x 10 -300 ), an older AI-ECG age (p = 0.0002), LA area (p = 0.046), body mass index (p = 0.036), and elevated diastolic blood pressure (HR 1.008 per mmHg, 95% CI 1.002 – 1.014; p = 0.010). The final Cox model achieved a C-index of ~0.67 and stratified patients into risk quartiles with 3-year freedom-from-arrhythmia rates of ~85% (lowest-risk) vs ~43% (highest-risk). An RSF model yielded a slightly higher test C-index (≈0.69), suggesting modest improvement with non-linear modeling. Conclusions: Preoperative AI-ECG biomarkers (AF probability, age discordance) and TTE markers of atrial remodeling independently predicted AF/AFl recurrence after surgical AF/AFl ablation and integration of these metrics improved risk stratification.

Abstract Disclosure: H. Ahmad: None. M. Kakakhel: None. A. Ullah: None. M. Saeed: None. J. Ikram: None. A. Qadeer: None. M. Khawar: None. H. Jawad: None. S. Haider: None. R. Haider: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of insulin-producing cells in the pancreas. It is a global health concern with regional variation in incidence and prevalence. This study aims to analyze the regional incidence and prevalence of T1DM among adolescents and young adults (15-39 years) from 1990 to 2021 in 26 regions. Methods: Global Burden of Disease (GBD) data for 2021 were analyzed to assess regional incidence and prevalence of T1DM among adolescents and young adults. The Annual Average Percentage Change (AAPC) was calculated to evaluate trends from 1990 to 2021, with statistical significance determined using p-values. Results: In 2021, middle socio-demographic index (SDI) has the highest incidence (54541) as well as prevalence (1.86 million), followed by Low-middle SDI (I: 48416, P: 1.80 million) and South Asia (I: 46310, P: 1.73 million). Oceania has the lowest incidence (356) as well as prevalence (12885), followed by Andean Latin America (I: 911, P: 31954) and Caribbean regions (I: 1214, P: 54610), respectively. The largest increase in AAPC of incidence was showed by Southern Latin America (2.23, CI: 2.11-2.30), High-income Asia Pacific (2.22, CI: 2.18-2.26), and Western Europe (1.80, CI: 1.73-1.84) regions, while Western Europe (1.72, CI: 1.66-1.75), Eastern Europe (1.64, CI: 1.63-1.66), and Australasia (1.38, CI: 1.36-1.40) showed largest increase in AAPC of prevalence. The Caribbean region had the greatest decline in AAPC of prevalence (-0.11, CI: -0.08 to -0.12) followed by Eastern Sub-Saharan Africa (-0.07, CI: -0.06 to -0.09) and Central Latin America (-0.04, CI: -0.02 to -0.07). There was no region with decline in incidence. All AAPC values were statistically significant (p &lt; 0.000001). Conclusion: Middle SDI region exhibited the highest incidence and prevalence, highlighting the vulnerability of these populations, while Oceania and Andean Latin America bore the least burden. Notably, several regions, particularly in Europe, experienced substantial increases in both incidence and prevalence, emphasizing the need for targeted interventions. Conversely, some regions, such as the Caribbean, showed encouraging declines in prevalence, suggesting that effective prevention and control strategies can be implemented. These findings underscore the importance of tailored approaches to address the evolving burden of T1DM. Presentation: Saturday, July 12, 2025

Abstract Disclosure: M. Kakakhel: None. S. Fatima: None. H. Ahmad: None. A. Ibrahim: None. W. Rahman: None. R. Haider: None. H. Jawad: None. A. Qadeer: None. M. Khawar: None. F. Ahmed: None. J. Ikram: None. R. Kirchoff: None. Background: Across the world, type 1 diabetes mellitus (T1DM) is a major health problem for teenagers and young people. This study aims to examine the incidence and prevalence of T1DM by gender in the 15-39 age range between 1990 and 2021. Methods: We analyzed data from the Global Burden of Disease (GBD) to evaluate incidence and prevalence rates of T1DM in each gender from 1990 to 2021. The Annual Percentage Change (APC) and The Annual Average Percentage Change (AAPC) was used to assess trends, with p-values determining the statistical significance. Results: From 1990 to 2021, the global prevalence of T1DM was found to be increased steadily for both genders, with the highest rates recorded in 2021: 247.32 per 100,000 for females and 246.47 per 100,000 for males. Incidence rates in 2021 showed a contrasting pattern, with males exhibiting higher rates (7.18 per 100,000) compared to females (5.98 per 100,000). AAPC analysis showed that males exhibit a faster rise in both prevalence and incidence compared to females over the study period. The difference in AAPC between males and females is more pronounced for prevalence (+0.3748%) compared to incidence (+0.1956%), with all AAPC values being statistically significant (p &lt; 0.000001). Following the APC analysis, other significant trends were revealed. Male incidence experienced the greatest increase during 2015-2021, with an APC of +1.9033% (p &lt; 0.000001), whereas female incidence increased most between 2011 and 2014 (APC = +1.3050%; p &lt; 0.000001). In contrast, the most significant decline in incidence was observed in females during 1990-1992, with an APC of +0.1665% (p = 0.006799), which was the lowest increase in the dataset. For prevalence, males exhibited the highest increase during 2015-2021, with an APC of +1.3938% (p &lt; 0.000001), whereas females had their peak increase during 2006-2009, with an APC of +0.8957% (p &lt; 0.000001). The slowest increase in prevalence for females occurred during 2014-2019, with an APC of +0.4591% (p &lt; 0.000001). Conclusion: The prevalence and incidence of T1DM among people aged 15-39 increased significantly between 1990 and 2021, with a greater increase in males. This highlights the need for gender-specific strategies in T1DM prevention and management, and research into the factors driving these disparities. Presentation: Sunday, July 13, 2025

Abstract Disclosure: M. Kakakhel: None. S. Fatima: None. H. Ahmad: None. M. Khan: None. A. Rai: None. A. Qadeer: None. R. Haider: None. M. Khawar: None. U. Habib: None. H. Jawad: None. J. Ikram: None. F. Ahmed: None. R. Kirchoff: None. Introduction: Type 1 Diabetes Mellitus (T1DM) is a disease that affects people all over the world. This condition causes significant morbidity, as measured by Disability-Adjusted Life Years (DALYs) and mortality rates, and its severity varies worldwide. The purpose of this study is to examine trends in T1DM-related death rates and DALYs across 26 geographical areas from 1990 to 2021 in order to provide a current picture of the disease's consequences and identify regional differences. Methods: This study examined DALYs and mortality rates per 100,000 people in individuals aged 15-39 years using data from the Global Burden of Disease Study from 1990 to 2021. Trends were assessed using the Average Annual Percentage Change (AAPC), with p-values used to define statistical significance. The study examined 26 regions with varied socioeconomic development indices (SDI). Using confidence intervals to account for data uncertainty, DALYs and mortality were examined to investigate the disease burden across time. Results: In 1990, the Middle SDI region had the highest DALYs at 298,352 (95% CI: 256,144 -349,670), which reached 382,857 (95% CI: 213,704-317,664) by 2021 (AAPC = 0.15, P-value &lt; 0.000001). The region with the highest DALYs in 2021 was the Low-Middle SDI, with 419,772 (95% CI: 344,307- 495,496) cases (AAPC = -2.93, P-value = &lt;0.000001). From 1990 to 2021, Oceania consistently had the lowest DALYs of 1,895 (95% CI: 1,264-2,577) and 4,210(95% CI: 3,011-5,724), respectively (AAPC= 0.15, P-value = 0.0004). Mortality rates in 1990 were highest in the Middle SDI area with 3,758 deaths (95% CI: 3,343-4,332) (AAPC= -1.23, P-value = &lt;0.000001), but by 2021, South Asia had the highest mortality rate at 5,189(95% CI: 4,272-6,087) (AAPC= -0.49). Oceania had the lowest mortality rate of 25 deaths (95% CI 145-35) (AAPC = 0.193, P-value = &lt;0.0004) in 1990, whereas Australasia had the lowest mortality rate of 28 deaths (95% CI 26-29) in 2021 (AAPC = -0.93, P-value = &lt;0.000001). Conclusion: From 1990 to 2021, the global burden of type 1 diabetes—as indicated by DALYs and death rates—underwent a substantial shift, with significant rises in several regions. DALYs were highest in the Middle SDI region in 1990 but have migrated to the Low-Middle SDI region by 2021, reflecting shifting healthcare issues and demographics. Mortality rates followed a similar pattern, with South Asia and the Low-Middle SDI regions experiencing the highest rates in 2021. Over both time periods, however, Oceania and Australasia consistently had the lowest DALYs and death rates. These findings emphasise the critical need for targeted interventions in high-burden areas. Addressing these differences is crucial for decreasing the global burden of T1DM. Presentation: Sunday, July 13, 2025

Abstract Disclosure: H. Ahmad: None. S. Fatima: None. M. Kakakhel: None. I. khan: None. A. Raza: None. Z. Khan: None. R. Haider: None. A. Qadeer: None. M. Khawar: None. F. Ullah: None. H. Jawad: None. J. Ikram: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Type 1 diabetes mellitus (T1DM) is an autoimmune condition, characterized by the destruction of pancreatic beta cells, resulting in lifelong dependency on insulin. It is a significant health burden in adolescents and young adults, with long-term complications affecting quality of life and survival. We aim to explore sex-stratified trends in mortality and disability-adjusted life years (DALYs) due to T1DM from 1990 to 2021. Methods: We obtained sex-stratified data for adolescents and young adults (15-39 years) with T1DM from the Global Burden of Disease (GBD) from 1990 to 2021. The mortality rates were age-standardized and expressed per 100,000 deaths. Trends were analyzed as annual percentage change (APC) and average APC (AAPC) using Joinpoint Regression. Results: From 1990 to 2021, deaths due to T1DM in adolescent and young adult males increased globally from 7,123 to 9,244 per annum, with age-standardized mortality rates (ASMRs) decreasing from 0.64 to 0.61 and standardized DALYs rising from 49.56 to 51. In females, deaths rose from 6,160 to 6,892, with ASMRs declining from 0.57 to 0.47 and DALYs declining from 47.12 to 43.11. Despite the apparent rise in deaths, ASMRs exhibited a significant decline in both sexes, with an AAPC of -0.16% (95% CI: -0.20 to -0.12) in males and -0.62% (-0.68 to -0.55) in females, four times that of in males. The DALYs showed a significant decline in females with an AAPC of -0.31% (-0.35 to -0.26) but a significant increase in males with an AAPC of 0.09% (0.04 to 0.12). Males showed the greatest APC increase in ASMRs of 1.34% from 1990 to 1994, while females showed the greatest APC increase of 0.45% from 1990 to 2000, three times less and over twice the period seen in males. This was followed by the greatest APC decline of -1.14% in females from 2001 to 2011, and a non-significant decline of -0.14% till 2021. Males experienced the greatest decline of -1.14% from 2000 to 2013. It then increased significantly from 2013 to 2018 (APC: 0.73%), followed by a significant decline of -0.62% till 2021, almost four times that in females. DALYs showed a similar trend in females with the greatest increase of 0.45% from 1990 to 2000, followed by the greatest decrease of -1.14% till 2011, and then a non-significant decline of -0.14 till 2021. Males showed the greatest increase of 1.24% from 1990 to 1994 and the greatest decrease of 0.63% from 2000 to 2013, followed by a much smaller decline. Conclusion: Although ASMRs declined, the recent decline in ASMRs in females is becoming less pronounced highlighting the importance of ongoing monitoring and improvement strategies. The disparity in DALYs between males and females also demands the need for targeted interventions addressing male-specific challenges to reduce the burden of T1DM. Presentation: Sunday, July 13, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. M.H. Alsaadi: None. M. Ikram: None. W. Ftih: None. H. Jawad: None. M.U. Rehman: None. R. Akhtar: None. A. Qadeer: None. M. Khawar: None. A. Ullah: None. H. Ahmad: None. F. Ahmed: None. R. Alcaraz: None. Introduction: Conditions that disrupt the adrenal glands' typical function are known as adrenal gland ailments or diseases. This study examines the distribution of adrenal disorders across various demographic and geographic groups in the United States, including gender, census region, race, age groups, and urbanization levels. Our objective was to identify disparities and trends to inform targeted interventions and resource allocation. Methods: From 1999 to 2020, mortality statistics for adrenal diseases were extracted from the CDC-WONDER database. Age, sex, race, location, urbanization status, and place of death were used to stratify the age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000. We calculated the average annual percentage change (APC) using Joinpoint regression software. Results: A total of 31,028 fatalities were reported due to adrenal disorders from 1999-2020 (AAPC: 1.277; 95% CI, -0.032 to 2.6032, p=0.055916). An initial rising trend was observed from 1999-2003 (APC: 2.4799), followed by a declining trend from 2003-2013 (APC: -3.0094), then a modest rise from 2013-2018 (APC: -0.9188), and finally a sharp increase from 2018-2020 (APC: 2.9445). Males had a higher AAMR (6.8) than females (6.4). The West census region had the highest AAMR (7.2), followed by the Midwest (7.1), South (6.3), and Northeast (5.6). The highest crude mortality rate was observed in individuals aged 85+ years (52.2). Several disparities were noted when stratified by urbanization and race, including the highest AAMR in Non Core (Nonmetro) regions (7.9) and among American Indian or Alaska Native populations (8.2). The highest percentage of deaths occurred in medical facilities. Conclusions: The findings underscore the need for tailored public health strategies to address disparities in adrenal disorders among vulnerable populations. Specific attention should be directed towards the male gender, West census region, American Indian or Alaska Native populations, and the geriatric population. Future research should explore underlying causes and interventions to mitigate these disparities. Presentation: Monday, July 14, 2025

Abstract Disclosure: M. Kakakhel: None. F. Saleem: None. A. Ullah: None. K. Abdul Rehman: None. M.H. Alsaadi: None. H. Ahmad: None. A. Qadeer: None. R. Haider: None. M. Khawar: None. H. Jawad: None. J. Ikram: None. M. Filal: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Thyroid disorders are common endocrine disorders including thyrotoxicosis, thyroiditis, hypothyroidism, and autoimmune thyroid diseases. Although it affects an estimated 200 million people globally, the epidemiology of this condition remains underexplored. Here we aimed to investigate mortality trends attributable to thyroid disorders in the US stratified by year, sex, race, and region. Methods: Using data from the CDC WONDER database, we calculated the crude and age-adjusted mortality rates (AAMRs) per 1,000,000 individuals (≥25 years) and used Joinpoint regression to determine annual and average annual percent change (AAPC) in the mortality trends. Results: Between 1999 and 2020, 561,089 deaths were recorded among patients with thyroid disorders in the United States, with an overall increasing trend in mortality (AAPC = 0.78). The age-adjusted mortality rate (AAMR) declined gradually from 1999 to 2018 (APC = -0.43, 95% CI: -0.65 to -0.22) before rising sharply from 2018 to 2020 (APC = 13.05, 95% CI: 6.39 to 20.12). Females had a higher AAMR (139.75) than males (81.99). Among racial and ethnic groups, Whites exhibited the highest AAMR (124.09), followed by American Indian or Alaskan Natives (121.36), Hispanics (89.13), Black or African Americans (88.44), and Asian or Pacific Islanders (59.36). Regional disparities showed the highest AAMR in the Midwest (130.45) and the lowest in the South (109.40). West Virginia (199.93) and North Dakota (198.82) reported the highest state-level AAMRs, while Nevada (60.18) and Florida (65.49) had the lowest. Non-metropolitan areas experienced higher mortality rates (141.04) than metropolitan areas (112.21), underscoring significant geographical and demographic variations in thyroid disorder-related mortality. Conclusion: Adults in the US have shown a rising trend in Thyroid-related deaths, with the highest mortality rates seen in females, Whites, and people living in the Midwest and Non-metropolitan areas. Our study also highlights the disparities across different demographics. Policy makers should focus on equitable access to healthcare to control this increasing mortality. Presentation: Monday, July 14, 2025

Background: Ventricular tachycardia (VT) is a life-threatening arrhythmia frequently observed in structural heart diseases, including LMNA-related cardiomyopathy, a genetic disorder associated with high risk of sudden cardiac death and progressive systolic dysfunction. While catheter ablation is an established therapeutic option for VT, its efficacy in cardiac laminopathy remains poorly defined. Objectives: To synthesize available evidence on the role and outcomes of VT ablation in patients with cardiac laminopathy. Methods: A systematic review and single-arm meta-analysis was performed in accordance with PRISMA guidelines. PubMed, Embase, and Cochrane databases were searched for studies reporting VT ablation outcomes in LMNA-related cardiomyopathy. An inverse variance random-effects model was applied for meta-analysis of proportions. Results: Seven studies (six cohorts, one abstract) comprising 62 patients (mean age 53.2 ± 9.7 years; 85% male; 88% with implantable cardioverter-defibrillator) were included. An endocardial/endo-epicardial approach was used in 93% of cases. Acute procedural success was achieved in 37% (95% CI: 14–63%; I 2 = 27.4%), and 28% required multiple procedures. Over a median follow-up of 26 (9–35) months, VT recurrence occurred in 91% (95% CI: 76–100%; I 2 = 37.2%). All-cause mortality was 54% (95% CI: 39–70%; I 2 = 28%), predominantly from cardiac causes (51%, 95% CI: 25–76%; I 2 = 53%), and 14% (95% CI: 1–34%; I 2 = 42%) underwent heart transplantation. Conclusions: In LMNA-related cardiomyopathy, catheter ablation is associated with high VT recurrence, limited long-term success, and substantial cardiovascular mortality and transplantation rates, underscoring the importance of ICD implantation and the need for alternative strategies, including variant-specific and molecularly targeted therapies.

ABSTRACT Introduction Lead‐related venous obstruction is a significant complication of chronic indwelling transvenous leads, which poses unique challenges during cardiac device upgrades. Background The anatomical sequelae of venous occlusion are variable and carry important procedural implications. Occlusions can develop in any part of the venous system, but they most often occur in the subclavian and innominate veins, while the superior vena cava is less frequently affected. Methods In this review, we describe approaches to lead‐related venous occlusion providing step‐by‐step procedural guidance. Results Venoplasty, neovascular channel creation are two main techniques for addressing lead‐related venous obstruction. Conclusion Venoplasty in the setting of an indwelling pacemaker or defibrillator leads can be performed safely and effectively. The difficulty of the procedure lies in crossing the obstruction. Familiarity with various tools is needed for a successful outcome.