Malignant arrhythmia risk assessment based on lead-I mobile ECG measurements using machine learning.

Objective. To evaluate the contribution of genetic variability in the proinflammatory cytokine system to the development of druginduced long QT syndrome (LQTS). Materials and methods. 129 patients with cardiac arrhythmias taking Class III antiarrhythmic drugs (amiodarone or sotalol) were examined. Depending on the presence or absence of drug-induced LQTS, patients were divided into 2 groups: group 1 (n = 64) – with QT interval prolongation; group 2 (n = 65) – without QT interval prolongation. Forty individuals without a history of cardiac arrhythmias served as a control group. All patients underwent polymerase chain reaction analysis for the T31C and C3953T polymorphisms in the IL-1b gene, C3872T in the CRP gene, G308A in the TNF-α gene, and G174C in the IL-6 gene. Statistical analysis was performed using Statistica 12.0. Results. The most pronounced effect was demonstrated by the combination of the CT genotype of the IL-1b gene C3953T polymorphism, the GC genotype of the IL-6 gene G174C polymorphism, and the GA genotype of the TNF-α gene G308A polymorphism. These genotypes increased the risk of developing LQTS by 5.26 times (95 % CI (1.42–19.50), p = 0.013). Using the Fruchterman – Reingold algorithm, the G308A polymorphism of the TNF-α gene (9.16 %), the C3953T polymorphism of the IL-1b gene (8.95 %), and the G174C polymorphism of the IL-6 gene (6.31 %) had the greatest predictive potential for the development of LQTS. The greatest genegene interaction effect was demonstrated by combinations of the G308A TNF-α gene and C3872 CRP gene polymorphisms (5.22 %), as well as the G308A TNF-α gene and T31C IL-1b gene polymorphisms (3.49 %). Conclusion. The obtained data support the possible involvement of the proinflammatory cytokine genetic polymorphism system in the regulation of drug-induced LQTS development. A putative mechanism for this association may be the varying degrees of activation of potassium and calcium ion channels in response to the causative drug, which depends, among other things, on the patient's blood cytokine concentration.

Background: Prolonged mechanical ventilation and tracheostomy in patients with COVID-19 is associated with longer hospital stays. Guidance on which patients are at risk for tracheostomy due to the progression of COVID-19 is limited. Objectives: This study aimed to identify risk factors associated with the need for tracheostomy in patients intubated for COVID-19 between 1 March and 31 December 2020. Methods: The methodology for this study involved a single-center retrospective analysis of 120 patients who were intubated due to COVID-19 infection between 1 March 2020 and 31 December 2020. A comparison of variables was performed using the Wilcoxon test, Chi-squared test, and Fisher's exact test alongside univariate analysis. Results: Several risk factors were found to be significantly associated with the need for tracheostomy, including age, P/F ratio, creatinine level, and history of arrhythmia. Conclusions: Initial exploration indicates the presence of certain factors that can help us understand future need for tracheostomy earlier in the patient's clinical course. Further analysis should be performed with a larger sample size to validate these findings and increase the generalizability of the present study.

We retrospectively analyzed data from the EBMT registry on patients with pretransplant comorbidities associated with cardiovascular risk. Patients who underwent first allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission between 2010 and 2022 from unrelated donors using post-transplant cyclophosphamide (ptCy) or anti-thymocyte globulin (ATG)-based graft-versus-host disease prophylaxis with a history of cardiac disease, arrhythmia, diabetes, obesity or cerebrovascular disease according to the HCT-specific comorbidity index were included. We performed a matched-pair analysis using a propensity score. After matching, 432 patients were included: 313 in the ATG group and 119 in the ptCy group. At 2 years, overall survival was 67.5% (95% CI 61-73.2) and 68.6% (95% CI 56.7-77.8); leukemia-free survival was 60.4% (95% CI 53.8-66.4) and 62.6% (95% CI 50.4-72.6); relapse incidence was 22.1% (95% CI 17-27.7) and 23.2% (95% CI 14.3-33.4); non-relapse mortality was 17.5% (95% CI 13.1-22.4) and 14.1% (95% CI 7.5-22.8), respectively. In conclusion, our study suggests that the use of ptCY for GVHD prophylaxis in patients with preexisting comorbidities associated with cardiovascular risk yields long-term outcomes comparable to those observed with ATG-based approaches.

Occurrence of paroxysmal supraventricular tachycardia accompanied by hemodynamic instability during anesthesia induction in patients with no previous history of arrhythmia

The association of right ventricular dysfunction, atrial tachyarrhythmias, and cardiac conduction system disease is rarely reported in literature. Previous case reports include right ventricular dysfunction associated with sudden cardiac death and ventricular arrhythmia. Other case reports with similar clinical presentation triad differ by either left ventricular involvement or having an abnormal presentation of systemic diseases. We report a case series of right ventricular dysfunction, atrial tachyarrhythmias, and cardiac conduction system disease in a single family. The proband in this case series is a 70-year-old Egyptian male who presented to our care for dual-chamber pacemaker generator replacement. He had the pacemaker for 10 years because of complete heart block. Device interrogation showed recorded paroxysmal atrial fibrillation episodes. Transthoracic echocardiography showed normal left ventricle internal dimensions and ejection fraction, dilated right ventricle with preserved systolic function, severe tricuspid regurgitation, and systolic pulmonary artery pressure of 40 mmHg. On reviewing his old records, there was no right ventricular affection 10 years ago; progressive right ventricular dysfunction occurred over the last decade. Despite guideline-directed medical therapy, the patient's clinical status deteriorated, and surgical tricuspid valve replacement was performed with a tissue valve. Since the surgical intervention, his clinical status and functional capacity improved, and repeated echocardiography showed no tricuspid regurgitation with persistence of the right ventricular dilatation but with normal right ventricular function. On reviewing his family history, the triad of right ventricular dysfunction, atrial tachyarrhythmias, and cardiac conduction system disease occurred in affected family members with various presentations. There was no left ventricular involvement, no history of ventricular arrhythmias in any of the affected members, and there was no history of sudden cardiac death across all three generations. Familial clustering of right ventricular dysfunction, atrial tachyarrhythmias, and cardiac conduction system disease do exist. This constellation of findings is not well described in literature. Further reporting of similar cases and investigating of genetic bases are required.

Objective: Atrial fibrillation (AF) is the most common type of arrhythmia and is responsible for a large proportion of hospitalizations. In this study, we aimed to investigate the presence of atrial fibrillation(AF) without developing thromboembolic complications in patients who applied to family medicine. Methods: The study included patients over 65 who applied to A University Training and Research Hospital and a State Hospital Family Medicine polyclinic. Those who had previously been diagnosed with AF were excluded from the study. Electrocardiography (ECG) was performed on patients over 65 who applied to our polyclinics to examine the frequency of AF. To assess the risk of thromboembolism, the CHA2DS2-VASc score was utilized. This score is a widely accepted and validated risk stratification system designed to predict stroke in patients with non-valvular AF. Results: In a study involving 146 participants with a mean age of 73.86±7.38 years (61.6% female, 38.4% male), AF incidence was 11%. Isolated hypertension was the most common diagnosis, affecting 58% of patients with chronic diseases linked to AF. While AF was more prevalent in men (14.3%), the difference was insignificant (p=0.310). Most patients with AF (87.5%) had a CHA2DS2-VASc score of 2 or higher. The mean systolic blood pressure was 132.59±22.03 mmHg in non-AF patients compared to 124.00±21.62 mmHg in AF patients. A history of cardiac surgery and arrhythmias was associated with a higher incidence of AF (p=0.010). Conclusion: The prevalence of AF in individuals over 65 years of age was found to be 11%, and the presence of comorbid disease was found to constitute the most important risk group. CHA2DS2-VASc score was two or above in 87.5% of patients and formed the high-risk group for stroke. In the study, patients with AF diagnosed before the development of thromboembolic complications were referred to the cardiology clinic for thromboembolic prophylaxis. This allowed the organization of cost-effective treatments based on bleeding risk scores and clinical indications. In primary health care services, every patient presentation should be evaluated effectively, and patients with symptoms and findings from a physical examination should be examined for AF.

Background/Objectives: Individuals with arrhythmia who survived COVID-19 could be susceptible to long-term cardiovascular complications and clinical outcomes. Methods: We performed a retrospective cohort study of adults with a history of arrhythmia in the Montefiore Health System (1 January 2016–17 August 2024). COVID-19 status was determined by a positive or negative polymerase-chain-reaction test. Outcomes included all-cause mortality, first-time myocardial infarction (MI), heart failure (HF), ischemic or hemorrhagic stroke, and major adverse cardiovascular events (MACE: defined as MI, HF, stroke, or death) > 30 days post-index date. Cox proportional hazards and Fine–Gray competing risk models, adjusted for demographic, clinical, socioeconomic, and COVID-19 vaccination variables, were employed. The association of outcomes with blood biomarkers taken at time of infection were also assessed in hospitalized COVID-19 patients. Results: Among the 6830 arrhythmia patients, 985 were hospitalized for COVID-19, 1591 were not hospitalized for COVID-19, and 4254 did not have COVID-19. Patients hospitalized for COVID-19 had a higher risk of all-cause mortality (adjusted hazard ratio = 2.90, 95% confidence-interval [2.08, 4.04]), first-time MI, HF, and MACE compared to controls without COVID-19. No increased risk was observed among non-hospitalized COVID-19-positive patients compared to controls, except for all-cause mortality. Older age, male sex, Medicaid, and significant comorbidities were associated with the risk of MACE. Elevated levels of creatinine, lactate dehydrogenase, D-dimer, neutrophil-to-lymphocyte ratio, low hemoglobin, and low left ventricular ejection fraction during infection were associated with higher future MACE risk. Conclusions. In individuals with arrhythmia, severe COVID-19 is associated with increased long-term risks of mortality and new-onset cardiovascular complications, while mild infection with mortality risk. These findings highlight the need for long-term cardiovascular monitoring in this population.

Background: Congenital kidney anomalies, such as horseshoe kidney and unilateral renal agenesis, are rare, occurring in 0.2% and 0.1% of live births, respectively. Vesicoureteral reflux, affecting 1-3% of children, is more common and often associated with recurrent urinary tract infections. Methods: During routine dissection of a whole-body donor, a rare case of a right-sided renal ectopia with suspected scrotal herniation was observed. The donor, a 108-year-old white male with a history of arrhythmia, lacked a left kidney with no evidence of nephrectomy. Results: The remaining kidney was ectopically located in the right iliac fossa, with its inferior pole terminating at the inguinal ligament. The parenchyma was embedded superiorly within the psoas major muscle and extended inferiorly into the scrotal sac. Fascial attachments to perinephric fat were observed, with the fat herniating into the scrotum. Within the scrotum, the perinephric fat and its fascial connections were fused with the right testicle, which had an elongated vas deferens. The kidney appeared to be fused, with evidence of a shared blood supply and ureter configuration consistent with a crossed fused renal ectopia. Conclusion: This study identifies a unique case of a pelvic kidney with perinephric fat herniation into the scrotum, immobilizing the kidney. It highlights the complex interplay between urinary and reproductive anatomy and underscores the importance of recognizing such variations. These can impact renal function, fertility and surgical outcomes. Greater awareness of these anomalies can improve diagnostic accuracy and inform clinical decision making.

Risk stratification for ventricular arrhythmia in adults with repaired tetralogy of Fallot (r-ToF) remains suboptimal. We investigated the relationships between left atrial reservoir strain (LAS) measured by cardiovascular magnetic resonance (CMR) and history of life-threatening ventricular arrhythmia (h-LTA) in r-ToF. We retrospectively analyzed 39 adults with r-ToF (mean age 39 ± 15 years; 69% male) undergoing routine CMR. LAS was quantified from four-chamber cine images. Patients with h-LTA, defined as a documented episode of any ventricular tachyarrhythmia, namely non-sustained ventricular tachycardia (≥ 3 consecutive ventricular beats for ≤ 30s duration), sustained ventricular tachycardia (lasting ≥ 30s), or ventricular fibrillation, were compared with those without. Ten patients (26%) had h-LTA. They tended to be older (46 ± 17 vs. 39 ± 13 years; p = 0.06), had longer QRS duration (167 ± 19 vs. 142 ± 25 ms; p < 0.001), and more often prior pulmonary valve replacement (40% vs. 24%; p = 0.03). LAS was significantly lower in the h-LTA group (12.9 ± 4.0% vs. 17.9 ± 4.6%; p = 0.01), while other ventricular and atrial indices, as well as late gadolinium enhancement, showed no difference. LAS correlated inversely with QRS duration (r = - 0.43; p = 0.005) and showed the strongest association with h-LTA (AUC = 0.838). Reproducibility for LAS was good (ICC = 0.84-0.97). In our study, CMR-derived LAS was markedly reduced in r-ToF patients with h-LTA. LAS demonstrated better discriminative performance in identifying patients with h-LTA. LAS may be a promising marker for arrhythmic risk stratification in r-ToF, complementing established CMR criteria, and warrants validation in larger prospective studies.

Abstract Background Septic shock is a life-threatening condition that can lead to multiorgan failure including cardiac dysfunction. Data remain limited on whether survivors of septic shock face a higher long-term risk of cardiovascular disease. Purpose To assess the long-term risk of heart failure, arrhythmia, and acute coronary syndrome in patients who have survived septic shock without a prior history of these conditions. Methods Using Danish nationwide registers, we identified all patients diagnosed with septic shock, defined by a hospital diagnosis code for septic shock or sepsis along with the use of vasopressors or inotropic agents. Patients who died during hospitalization or had a history of heart failure, arrhythmia, or acute coronary syndrome were excluded. Survivors were followed for up to five years, as we estimated the 5-year standardized absolute risk (SAR) of heart failure, arrhythmia, and acute coronary syndrome individually, as well as a composite outcome. For all outcomes, death was considered as competing risk. Finally, 5-year standardized risk ratios (SRR) were computed. For comparison, we identified patients with simple infections (urinary tract infections or erysipelas) or sepsis and estimated the risk of these cardiovascular outcomes within these groups. Results We identified 6,050 patients with septic shock (47% female, median age 67 years), 65,270 patients with simple infections (64% female, median age 70 years), and 32,687 patients with sepsis (45% female, median age 69 years). At 5.0% (95% CI 4.3%-5.7%), the 5-year SAR of heart failure was highest in the septic shock group, compared with 3.9% (95% CI 3.6%-4.1%) in the simple infection group (Figure 1). Using the simple infection group as a reference, this corresponded to a 5-year SRR of 1.3 (95% CI 1.1-1.5) (Figure 2). When compared with simple infections, the 5-year SAR of arrhythmia was higher for patients with septic shock at 10.1% (95% CI 9.1%-11.0%), while for acute coronary syndrome, it was similar at 1.7% (95% CI 1.3%-2.1%). Considering a composite outcome of heart failure, arrhythmia, and acute coronary syndrome, the 5-year SAR was 14.2% (95% CI 13.1%-15.3%) with a corresponding 5-year SRR of 1.1 (95% CI 1.0-1.2). Conclusions Survivors of septic shock face a significantly increased long-term risk of heart failure and clinically relevant arrhythmia, despite high overall mortality rates. These findings underscore the need for heightened awareness of cardiovascular symptoms in this patient population to enable early diagnosis and intervention, potentially improving long-term outcomes.

Abstract Introduction Cardiac sarcoidosis (CS) has been associated with an elevated risk of fatal ventricular arrhythmias (VAs) events. Current guidelines provide recommendations for the primary prevention of implantable cardioverter defibrillator (ICS) implantation in patients with CS. However, the prognostic factors for fatal VAs events in CS without a history of VAs have not been fully investigated. Purpose This study aims to investigate the prognostic factors in patients with CS and without a history of VAs. Methods A nationwide registry was retrospectively enrolled patients who were diagnosed with CS between 2012 and 2021 based on the 2016 Japanese Circulation Society criteria. Patients who had a history of sustained ventricular tachycardia or fibrillation were excluded. The primary endpoint was a composite of sudden cardiac death, sustained ventricular tachycardia, ventricular fibrillation, and appropriate ICD therapy. Results Among a total of 2,366 patients, we identified 1,552 patients with CS who had no prior history of VAs (median age 63 years; 66% female). During a median follow-up of 1922 days (interquartile range, 1103 to 3091 days), the primary endpoint was observed in 139 patients (9.0%). Patients who experienced the primary endpoint had a higher prevalence of non-sustained ventricular tachycardia, elevated b-type natriuretic peptide levels, worse New York Heart Association functional class, higher prevalence of late gadolinium enhancement of cardiac magnetic resonance, and lower left ventricular ejection fraction (LVEF). There were no significant differences in the history of advanced atrioventricular block or the positron emission tomography findings between the two groups. Kaplan-Meier analysis revealed that patients with LVEF &amp;lt; 35% or LVEF 35%-50% had a higher risk of the primary endpoint compared to those with LVEF ≧ 50% (P &amp;lt; 0.001). Multivariate Cox regression analysis demonstrated that LVEF &amp;lt; 35% [hazard ratio (HR) 2.33, 95% confidence interval (CI) 1.22–4.46, P = 0.001] or LVEF 35%-50% (HR 1.90, 95% CI 1.07–3.35, P = 0.028), and history of non-sustained ventricular tachycardia (HR 1.89, 95% CI 1.17–3.04, P = 0.010) were independently associated with the primary endpoint. Conclusions Impaired LVEF, even within the range of 35-50%, and a history of non-sustained ventricular tachycardia were independently associated with an increased risk of fatal arrhythmic events in patients with CS.Kaplan-Meier curve for primary endpoint

Abstract Introduction Malnutrition is frequently observed in patients with heart failure. It has been reported to be associated with poor clinical outcomes in patients with chronic heart failure (CHF). Previous studies demonstrated that patients with lower left ventricular ejection fraction (LVEF) were at increased absolute risk of death due to arrhythmia and worsening heart failure. However, the study investigating the association between malnutrition and adverse outcome including ventricular arrhythmia events is limited. Purpose This study aimed to investigate the association between malnutrition and adverse outcome in patients with CHF after cardiac resynchronization therapy (CRT). Methods This retrospective study evaluated 167 patients (112 male, mean age 70.9 ± 9.5 years; 32 (19.2%) ischemic cardiomyopathy, 70 (41.9%) dilated cardiomyopathy, 5 (3.0%) hypertrophic cardiomyopathy, 28 (16.8%) sarcoidosis, 10 (6.0%) valvular disease, 22 others) who underwent CRT implantation between 2004 and 2023. Mean follow-up period was 1310 ± 561 days. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT) score before the CRT implantation. Patients were divided into two groups as preserved nutrition (CONUT 0 - 4, n = 141; GNRI ≥ 92, n = 130) or malnutrition (CONUT 5 - 12, n = 26; GNRI &amp;lt; 92, n = 37) groups. Ventricular arrhythmia was defined as ventricular tachycardia or ventricular fibrillation requiring anti-tachycardia pacing or shock. The primary endpoint was a composite of ventricular arrhythmias and all-cause mortality. Secondary endpoints were ventricular arrhythmias and all-cause mortality. Results Ventricular arrhythmias occurred in 36 patients (21.6%), and all-cause mortality occurred in 38 patients (22.8%). Kaplan-Meier survival analyses revealed that malnutrition groups defined by both CONUT score and GNRI had a higher incidence of the primary composite endpoint (log-rank, p = 0.001 and p = 0.03, respectively). Regarding secondary endpoints, all-cause mortality was significantly higher in both malnutrition groups (p = 0.0005 and p = 0.008, respectively), while ventricular arrhythmias were significantly more frequent only in the CONUT-defined malnutrition group (p = 0.02) but not in the GNRI-defined group (p = 0.24). Cox proportional hazards regression analysis showed that malnutrition defined by CONUT score (hazard ratio 1.87, 95% CI: 1.01-3.45, p = 0.047), history of ventricular arrhythmias (hazard ratio 2.72, 95% CI: 1.59 – 4.65, p = 0.0003), and left bundle branch block (hazard ratio 0.54, 95% CI: 0.31 - 0.93, p = 0.03) were independent predictors of the primary endpoint, while malnutrition defined by GNRI was not significantly associated with the primary endpoint (hazard ratio 1.70, 95% CI: 0.99-2.92, p = 0.053). Conclusion Malnutrition defined by CONUT score could predict ventricular arrhythmias and all-cause mortality in patients with CHF who underwent CRT.

Background: The longitudinal burden of arrhythmias during the peripartum period among adults with congenital heart disease (ACHD) remains understudied. Objectives: To quantify arrhythmia subtype burden and identify associations with peripartum arrhythmias in the pregnancy and postpartum period in women ACHD. Methods: We analyzed Merative MarketScan data (2010-2016) to identify pregnancies among adults with and without ACHD using validated algorithms. Significant arrhythmias included ventricular tachycardia, atrial fibrillation/flutter, supraventricular tachycardia, and pathologic AV block. Regression models were adjusted for age, repeat pregnancies, cardiac and non-cardiac comorbidities. Results: Among 11,703 pregnancies, significant arrhythmias were more frequent in ACHD vs controls during pregnancy (severe ACHD 5.3%, non-severe 2.5%, controls 0.5%) and postpartum (severe ACHD 6.5%, non-severe 3.5%, controls 0.5%). Supraventricular tachycardia was the most common subtype, Table 1. For all patients, variables independently associated with arrhythmia during pregnancy included pre-pregnancy arrhythmia (odds ratio [OR] 8.86, 95% CI 6.80–11.54), presence of ACHD (severe ACHD: OR 10.12, 95% CI 7.45–13.76; moderate ACHD: OR 5.11 (4.00–6.52), heart failure (OR 3.45, 95% CI 1.98–6.01), pulmonary disease (OR 1.73, 95% CI 1.17–2.56), gestational hypertension (OR 1.65, 95% CI 1.21–2.25), and deep venous thrombosis (DVT) (OR 3.27, 95% CI 1.05–10.22), Figure 1 panel A. Variables independently associated with arrhythmia postpartum included pre-pregnancy arrhythmia, arrhythmia during pregnancy, and presence of ACHD , Figure 1 panel B. Among ACHD patients, pre-pregnancy arrhythmia, ACHD severity, heart failure, and DVT were independently associated with arrhythmia during pregnancy, while only pre-pregnancy and pregnancy arrhythmias were independently associated with arrhythmia during postpartum, Figure 1 panel D. Conclusions: Peripartum arrhythmia risk in ACHD extends through pregnancy and postpartum and spans the full spectrum of CHD severity. Prior arrhythmia and greater CHD severity are consistently associated with increased odds of arrhythmia during and after pregnancy, while heart failure demonstrates a significant association specifically during pregnancy. These findings underscore the importance of preconception counseling and expectation setting, particularly for women with a history of arrhythmia, to inform individualized risk stratification and management throughout pregnancy.

Background: Right ventricular (RV) dysfunction is an important determinant of outcomes in many forms of CHD. However, clinical and imaging biomarkers explain only 25% of the variability in long-term outcomes in patients with repaired tetralogy of Fallot (rTOF). The contribution of genetic factors to RV dysfunction in rTOF is a knowledge gap. Hypothesis: Genetic factors contribute to variation in RV function in patients with rTOF. Methods: We studied the relationship of rare damaging genetic variants (RDV) and RV function, assessed by cardiac MRI in a cohort of 223 rTOF patients with genome or exome sequencing, recruited under the auspices of the Pediatric Cardiac Genomics Consortium at Boston Children’s Hospital. We characterized demographics, genotypes, clinical and postoperative variables, and cardiac MRI measurements. Rare variants (gnomAD allele frequency &lt;10 -4 ) were considered damaging if predicted to be loss-of-function (nonsense, frameshift, or read-through), missense (REVEL score &gt;0.5), or splice altering (SpliceAI delta score &gt;0.8). Association was determined by comparing the proportion of participants with RV dysfunction (RV ejection fraction &lt;45%) and RDV in 70 genes associated with pediatric onset cardiomyopathy, as reported in ClinVar. We performed multivariable logistic regression to adjust for independent predictors of RV dysfunction. Results: Patients with rTOF and RV dysfunction were older at MRI (15.3 years vs. 12.6 years, p=0.01), and more likely to be male (71% vs. 49%, p=0.002), have a history of arrhythmia (26% vs. 11%, p=0.008), or repaired prior to 1985 (17% vs 6%, p = 0.01). 22q11 deletion syndrome was not associated with RV dysfunction. Heterozygous RDV in genes associated with pediatric cardiomyopathy were more common in patients with RV dysfunction (11% vs. 1%; OR 8.63, p =0.007). In a multivariable model (C statistic = 0.71), presence of a pediatric cardiomyopathy variant remained associated with RV dysfunction (OR 1.44, p=0.01). Conclusions: RDV in genes associated with pediatric cardiomyopathy are associated with RV dysfunction in patients with rTOF. These genes would not be expected to be causal for CHD but instead modify myocardial function. While future larger multicenter studies should validate these findings, these results suggest that pediatric cardiomyopathy variants may affect outcomes, improve risk-stratification, and provide more precise personalized therapies for CHD.

Background: Mutations in various genes encoding sarcomeric proteins account for 50–60% of familial hypertrophic cardiomyopathy (HCM) cases. However, the molecular pathogenesis underlying the disease in approximately one-third of patients remains unidentified. Case Summary: A 15-year-old Caucasian female with a history of Von Willebrand disease and anxiety presented with intermittent palpitations. Family history was notable for HCM and sudden cardiac arrest requiring implantable cardioverter-defibrillators (ICDs) in her father and uncle. Physical exam revealed a grade I systolic murmur. ECG showed left ventricular hypertrophy, left axis deviation, pathological Q waves, ST elevation in the inferior leads and T wave inversion in the anterolateral leads. Echocardiography revealed severe asymmetric septal hypertrophy (2.7 cm, Z score +9.7), preserved EF (68.5%), and moderate diastolic dysfunction. Genetic testing identified a variant of uncertain significance in exon 7 of the FHL1 gene (c.755G&gt;A, heterozygous), resulting in a cysteine-to-tyrosine substitution at codon 252 (p.Cys252Tyr); and exon 43 of the ANK2 gene (c.11454C&gt;A, heterozygous), leading to a serine-to-arginine substitution at codon 3818 (p.Ser3818Arg). Cardiac MRI confirmed HCM with a reverse curvature phenotype, 2.4 cm septal thickness, and 9.6% total fibrosis of the left ventricular mass. Ambulatory monitoring detected episodes of non-sustained ventricular tachycardia. Stress echo demonstrated a peak left ventricular outflow tract gradient of 15 mmHg. She was started on metoprolol for dyspnea and referred for electrophysiologic evaluation. Cardiac catheterization confirmed a non-obstructive HCM phenotype with elevated LV end-diastolic pressure. Given her arrhythmia history and family background, she is scheduled for ICD placement. Discussion: We identified a novel FHL1 variant in an adolescent with HCM, highlighting the evolving genetic landscape beyond core sarcomeric genes. This underscores the need for accurate phenotyping, vigilant reporting, and ongoing re-evaluation of variants to inform risk stratification, especially in pediatric populations. Take-home Messages: Detailed case reporting of novel genetic variants identified in HCM and longitudinal follow-up are key to improving genetic interpretation and guiding individualized care.

Background: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure (HF) patients that can be delivered either through a pacemaker (CRT-P) or a defibrillator (CRT-D). Despite significant differences between these two devices, current published guidelines do not separate recommendations for CRT-P versus CRT-D. We had conducted a pilot randomized controlled trial (RCT) of CRT-P versus CRT-D in eligible HF patients (age ≥75 years) and we here report their long-term mortality outcomes. Methods: Older HF patients (age=81±5 years, 27% women, LVEF=25±6%) indicated for CRT who had no prior history of ventricular arrhythmias were included. Patients who agreed to participate in the study but declined randomization received their device of choice and enrolled in an observational registry (OR) (Figure 1). All patients were followed to the primary endpoint of death from any cause, through May 1 st , 2025. Results: A total of 88 patients (36 RCT and 52 OR) were followed for a median of 3.4 years, during which time 49 (56%) patients died. There were no differences in overall survival between CRT-P and CRT-D recipients (adjusted hazard ratio (HR) 0.96, p=0.89, Figure 2). A majority (68%) of patients who refused randomization chose a CRT-D device. Patients who were enrolled in the RCT had better survival than those in the OR (adjusted HR 0.39, p=0.024, Figure 2). Importantly, the cause of death was cardiac in 16, non-cardiac in 25, and unknown in 8 patients. Of the known causes of death, only two were arrhythmic in nature, both in CRT-D recipients. Conclusions: In this long-term analysis, we identified no difference in survival between older CRT-P and CRT-D recipients. Most deaths were non-cardiac in origin and only 2 were arrhythmic in nature in CRT-D recipients. Our data support the use of the smaller and less expensive CRT-P device in older patients eligible for CRT therapy who have no prior history of ventricular arrhythmia. These findings should be tested in a larger pivotal trial.

Atrial fibrillation occurs in a growing number of adults with congenital heart disease (ACHD); however, recommendations for procedural considerations are lacking. A 43-year-old woman with surgical repair of sinus venosus ASD and partial anomalous pulmonary venous return and history of atrial arrhythmias and sinus node disease presents for repeat ablation procedure for persistent atrial fibrillation. Echocardiogram two days prior to ablation procedure demonstrated no SVC stenosis, known left SVC with dilated coronary sinus (CS), and moderate LV systolic dysfunction, presumed due to persistent atrial fibrillation with tachycardia. The AF ablation was performed with intracardiac echo guidance of trans-septal puncture. All four pulmonary veins were confirmed to be isolated from prior ablation. Right and left atria were mapped during atrial fibrillation using Volta Medical to identify dispersion areas, which identified areas of spatial dispersion in the posterior wall and coronary sinus, for which posterior wall isolation was performed with CS ablation set. AF was converted to AFL with ablation and patient was cardioverted to junctional rhythm, her known baseline rhythm. At conclusion of the study no pericardial effusion was noted by ICE. Post-procedure, the patient continued to have junctional rhythm and hypotension requiring vasoactive support; limited bedside echo demonstrated no effusion. Due to persistent hypotension, additional echo imaging was performed which demonstrated no pericardial effusion, normal LV systolic function; however, an echo lucency posterior to aorta with compression of left atria was seen. CT scan confirmed a hematoma surrounding LA, 7.2 x 3.3 cm, with compression on left superior vena cava. No surgical intervention was performed due to contained hematoma and clinical stability, as surgical evacuation of the hematoma would increase the risk of bleeding. Repeat CT at 7 days demonstrated stable mediastinal hematoma of 7.2 x 3.3 cm. The patient continues to be monitored clinically with serial imaging. In ACHD patients, ablation complicated by perforation may be underrecognized due to prior surgical scarring, which may contain bleeding and obscure findings on limited imaging due to lack of circumferential effusion. Heightened vigilance and tailored procedural and post-procedural imaging strategies are necessary for ablation procedure in ACHD patients, considering their unique anatomy and surgical history

Introduction: Intramyocardial fat and scar burden have been linked to mortality in cardiomyopathy (CM) patients. However, the prognostic value of advanced imaging features derived from cardiac CT remains underexplored. This study evaluated whether radiomic features from cardiac CT improve prediction of all-cause mortality in CM patients receiving a primary prevention implantable cardioverter-defibrillator (ICD). Methods: Patients enrolled in the PROSE-ICD study underwent cardiac CT and were followed for all-cause death. CTs were acquired on 64-slice scanners, and the left ventricle was segmented using 3D Slicer with TotalSegmentator. A total of 92 radiomic features were extracted (PyRadiomics 3.0.1) across four resampling grids (0.5–3 mm) and three bin widths (20–60 HU). The primary endpoint was all-cause mortality; ventricular arrhythmic events (n=6, 11%) were analyzed descriptively due to low counts. A clinical Cox model (age, CM etiology, diabetes) and four radiomics-based survival models were trained using 15×3-fold cross-validation. The best radiomics model (GBS, 0.5 mm grid, 20-HU bin) was combined with clinical variables in a second-stage Cox model. Model discrimination (c-index), calibration, and feature importance were assessed using Python 3.11 (lifelines, scikit-survival). Results: Among 55 patients (mean age 64 ± 9 years; 20% female; 76% White; 65.5% ischemic CM), 13 (24%) died over a median follow-up of 3,284 days (~9 years). Hypertension (89%), hyperlipidemia (95%), and diabetes (47%) were highly prevalent. Mean LVEF was 24 ± 13.7%, and 33% had a history of ventricular arrhythmia. Five-year survival was higher in non-ischemic vs. ischemic CM (89% vs. 74%, p=0.12). Diabetes was the only independent clinical predictor of mortality (HR 5.31, 95% CI 1.14–24.7, p=0.03); age and CM etiology were not significant. The clinical Cox model yielded a c-index of 0.70. The best radiomics model, based on myocardial texture heterogeneity, achieved a c-index of 0.80. Combining radiomics with clinical variables improved discrimination to 0.81 (Δ +0.02, p=0.08) with good five-year calibration (slope = 0.94). Conclusion: Radiomic features derived from high-resolution cardiac CT substantially enhance prediction of long-term mortality in cardiomyopathy patients receiving primary prevention ICDs, offering a promising non-invasive tool for personalized risk stratification.

Introduction: The AHA Cardiovascular-Kidney-Metabolic (CKM) framework outlines a continuum of risk, starting with metabolic dysfunction and leading to major cardiovascular events. However, the role and timing of arrhythmia onset within this trajectory remain poorly understood, and the impact of major arrhythmias has not been reported. This real-world evidence (RWE) study is the first to examine arrhythmias onset across the CKM continuum, offering new insights with potential implications for earlier detection, risk stratification, and intervention. Methods: We conducted a retrospective real-world evidence study using the Symphony Integrated Dataverse (2018–2024) to analyze adults with obesity. Patients were stratified into two cohorts based on cardiovascular-kidney-metabolic (CKM) risk at baseline. Cohort A (Non-Arrhythmia) included individuals with obesity but without any prior CKM risk factors, while Cohort B (Arrhythmia) comprised patients with obesity and a documented history of arrhythmia, in the absence of other CKM risk factors. CKM progression was specifically analyzed within Cohort A (Fig 1). Key outcomes included the incidence of new-onset arrhythmias, time to progression across CKM stages, and the occurrence of major adverse cardiovascular events (MACE). Results: Cohort A included 3,382,510 patients, while Cohort B comprised 269,867 (Fig 2). In Cohort A, arrhythmia incidence increased with CKM progression, rising from 6.3% after Stage 1 to 9.3% after Stage 2 and 12.5% after Stage 3. When stratified by age, younger patients showed higher arrhythmia rates at earlier CKM stages, with 41% in those aged 18–34 after Stage 1, 44% in those 35–54 after Stage 2, and 42% in those over 65 after Stage 3 (Fig 3). In Cohort B, arrhythmia onset typically occurred four months before the obesity index date. In Cohort A, MACE events followed CKM progression rapidly, with a median of 65 days after Stage 3, and atrial fibrillation appeared at a median of 49 days post–Stage 3 (Fig 4). Conclusions: In this large RWE study, arrhythmia frequently emerged early in the CKM disease continuum. These findings highlight the potential value of incorporating arrhythmia surveillance into risk stratification for patients at risk of CKM progression. Further research is needed to determine whether early arrhythmia represents a modifiable inflection point on the path to major adverse cardiovascular events