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Circulation. Arrhythmia And Electrophysiology[JOURNAL]

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Phenotypic Severity of -Related Bradycardia Is Independent of Dominant-Negative and Coupled Gating Effects.

Tano A, Kato K, Yamauchi K … +9 more , Jinzai H, Iguchi T, Toyoda F, Baba Y, Kubo T, Ohno S, Makiyama T, Nakagawa Y, Horie M

Circ Arrhythm Electrophysiol · 2026 Feb · PMID 41582807 · Full text

BACKGROUND: Pathogenic variants are associated with inherited arrhythmias such as long-QT syndrome, Brugada syndrome, and sick sinus syndrome. While Na1.5, an α-subunit of the cardiac sodium channel encoded by , has bee... BACKGROUND: Pathogenic variants are associated with inherited arrhythmias such as long-QT syndrome, Brugada syndrome, and sick sinus syndrome. While Na1.5, an α-subunit of the cardiac sodium channel encoded by , has been considered to function as a monomer, recent studies reveal that a reduction of sodium current in wild-type Na1.5 can be caused by dimerization with loss-of-function mutated Na1.5 through dominant-negative effects. However, the clinical significance of the dominant-negative effect remains unclear. METHOD: We genetically screened a family who presented with sick sinus syndrome and sudden cardiac death. Whole-cell patch-clamp study using HEK293 (human embryonic kidney) cells coexpressing wild-type and variant was performed. Channel dimerization was assessed by coimmunoprecipitation and proximity ligation assays. Also, the effects of difopein, a high-affinity inhibitor of Na1.5 interaction via 14-3-3 proteins, were evaluated. RESULTS: The proband carried compound heterozygous variants p.T1396P and p.G833R. The whole-cell mode patch-clamp techniques demonstrated that the p.T1396P showed a dominant-negative effect on the peak sodium currents (37% decrease in I) and altered gating properties (5.6-mV shift in steady-state inactivation) when expressed with wild-type . These effects were abolished by difopein. p.G833R showed no dominant-negative or coupled gating effect but still formed dimers. The proband developed earlier and more severe bradycardia than the mother, who only carries p.T1396P, suggesting that loss of coupled gating effect contributed to the severe phenotype. CONCLUSIONS: Our findings suggest that coupled gating may be physiologically important for normal Na1.5 function, and its loss can exacerbate disease severity.

ECG-Based Prediction of Shock-Refractory Ventricular Fibrillation During Resuscitation Without Interrupting CPR.

Coult J, King JA, Kwok H … +8 more , Kutz JN, Blackwood J, Boyle PM, Hsu CH, Daya MR, Johnson NJ, Kudenchuk PJ, Rea TD

Circ Arrhythm Electrophysiol · 2026 Feb · PMID 41582806 · Full text

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Arctic Front Advance Versus POLARx Cryoablation System for Pulmonary Vein Isolation in Patients With Atrial Fibrillation: A Single-Center Randomized Controlled Trial.

Ferreira D, Dwivedi J, Brienesse S … +10 more , Malaty MM, Govender K, Trevaskis N, Hughes B, Sverdlov AL, Collins N, Boyle A, Morris GM, Barlow M, Jackson N

Circ Arrhythm Electrophysiol · 2026 Feb · PMID 41574428 · Publisher ↗

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Editors and Editorial Board.

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41557767 · Publisher ↗

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High Burden of Premature Ventricular Contractions Upregulates Transcriptional Markers of Inflammation and Promotes Adverse Cardiac Remodeling Linked to Cardiomyopathy.

Medina-Contreras JML, Balderas-Villalobos J, Gomez-Arroyo J … +6 more , Hayles J, Kaszala K, Tan AY, Samsó M, Huizar JF, Eltit JM

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41527819 · Full text

BACKGROUND: Premature ventricular contractions (PVCs) are the most prevalent ventricular arrhythmia in adults. High PVC burden can lead to left ventricular systolic dysfunction, eccentric hypertrophy, and an increased ri... BACKGROUND: Premature ventricular contractions (PVCs) are the most prevalent ventricular arrhythmia in adults. High PVC burden can lead to left ventricular systolic dysfunction, eccentric hypertrophy, and an increased risk of heart failure and sudden cardiac death. Inadequate angiogenesis is a key determinant in the transition from adaptive to maladaptive cardiac hypertrophy, and fibrosis is a risk factor for arrhythmia and sudden cardiac death. We quantitatively assessed structural remodeling and transcriptional alterations in PVC-induced cardiomyopathy (PVC-CM). METHODS: Animals were implanted with modified pacemakers to deliver bigeminal PVCs (200-220 ms coupling interval) for 12 weeks. Collagen deposition and interstitial ultrastructure of left ventricular samples were analyzed using light and transmission electron microscopy, respectively. Pericytes, fibroblasts, myocytes, smooth muscle, and endothelial cells were imaged using confocal microscopy, quantified with an artificial intelligence-based segmentation analysis, and compared using hierarchical statistics. Transcriptional changes were assessed via RNAseq, and protein expression was assessed using western blot. RESULTS: Although cardiomyocytes hypertrophied in PVC-CM, capillary rarefaction was overcome by an increase in the capillary-to-myocyte ratio. Additionally, thicker blood vessels were more abundant in PVC-CM. Fibroblast-to-myocyte ratio more than doubled, interstitial collagen fibers increased, and interstitial space thickened in PVC-CM. Transcripts involved in interstitial remodeling, inflammatory response, and alarmins were strongly elevated in PVC-CM, showing enrichment of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) transcriptional signature. These results coincide with elevated levels of the proinflammatory cytokine IL (interleukin)‑1β, the inflammasome component NLRP3 (nucleotide-binding domain, leucine-rich repeat family, pyrin domain containing 3), and increased expression of NF‑κB p65 (RelA). CONCLUSIONS: Although the angiogenic response meets the metabolic demands of cardiac hypertrophy, upregulated markers of inflammation and cardiomyopathy linked to reactive fibrosis collectively represent an adverse left ventricular remodeling in PVC-CM that could provide the substrate for heart failure, arrhythmias, and sudden cardiac death in PVC-CM.

Association of Race, Ethnicity, and Area Deprivation With the Prevalence of Atrial Fibrillation in a Large US Population.

Alonso A, Najarro G, Shah AJ … +2 more , Li L, Lewis TT

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41473962 · Full text

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Loss-of-Function Mutation RyR2-A4860G Confers an Arrhythmia Phenotype in Mice Inconsistent With Calcium Release Deficiency Syndrome.

Pattridge HK, Ponce-Balbuena D, Ríos Pérez EB … +3 more , Eckhardt LL, Valdivia HH, Alvarado FJ

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41473951 · Full text

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Initial Experience With a Dual-Energy Lattice-Tip Catheter for Ventricular Tachycardia Ablation: Procedural Feasibility and Emerging Safety Warning.

Ventrella N, Sabatino M, Bianchini L … +7 more , Schiavone M, Dell'Aquila A, Tundo F, Mancini ME, Pontone G, Tondo C, Carbucicchio C

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41451700 · Publisher ↗

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Factors Influencing Lesion Titration in a Monopolar Pulsed-Field Ablation Point Catheter: A Preclinical Study.

Younis A, Demian J, Bifulco S … +16 more , Lehn L, Liuba I, Hinds S, Santangeli P, Hussein AA, Mdaihly M, Taigen TL, Tabaja C, Nakagawa H, Farwati M, Kleve R, Mora Ramirez M, Saliba WI, Kanj M, Garrott K, Wazni OM

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41451505 · Publisher ↗

BACKGROUND: Despite the rise of pulsed-field ablation (PFA), predicting and titrating lesion geometry remains challenging. This study aimed to find modifiable parameters that can accurately and repeatedly predict focal P... BACKGROUND: Despite the rise of pulsed-field ablation (PFA), predicting and titrating lesion geometry remains challenging. This study aimed to find modifiable parameters that can accurately and repeatedly predict focal PFA lesions across a range of dimensions and to develop a model to predict lesion geometry. METHODS: An in vivo study was performed in 9 swine using an investigational dual-energy contact-force focal catheter with local impedance. Ablations were performed endocardially in the right and left ventricles using settings specifically selected to provide a wide range of lesion dimensions. Predefined PFA applications (1, 2, or 4) were delivered while maintaining different contact-force values (5-45 g). Four different voltages were used (1.0, 1.4, 2.0, and 2.2 kV). Following a 1-week survival period, the animals were euthanized for histopathologic examination. RESULTS: In the study characterization data set, a total of 78 PFA lesions were analyzed. Lesion depth ranged from 1.4 mm to 12.3 mm, while lesion width ranged from 3.3 mm to 21.2 mm. All 3 tested parameters-contact force, number of applications, and voltage-demonstrated a positive linear correlation with lesion depth (<0.01). The proposed formula (Focal FARAPULSE Index Model) showed a strong positive correlation with lesion depth (=0.83; <0.0001) and lesion width (=0.76; <0.0001). A perpendicular catheter orientation was correlated with deeper lesions than a parallel orientation. No ST-segment elevations or sustained ventricular arrhythmias were observed. CONCLUSIONS: Our findings demonstrate that PFA can be effectively titrated and predicted using the Focal FARAPULSE Index Model to create lesions of varying depths (1-12 mm), with these results being specific to the proprietary waveform and catheter used.

Interatrial Synchronized Pacing at the Posterosuperior Bundle: Feasibility, Mechanism, and Mid-Term Outcomes.

Qiu Z, Wu X, Hu W … +7 more , Tang Y, Xu Z, Ou Z, Zhou Y, Ren Z, Shi T, Lu H

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41446938 · Publisher ↗

BACKGROUND: Conventional atrial pacing at the right atrial appendage may impair interatrial synchrony. Posterosuperior bundle (PSB) pacing has been observed to offer anatomic accessibility by targeting the interatrial mu... BACKGROUND: Conventional atrial pacing at the right atrial appendage may impair interatrial synchrony. Posterosuperior bundle (PSB) pacing has been observed to offer anatomic accessibility by targeting the interatrial muscular connection within the superior vena cava. The study aimed to further validate the feasibility of PSB pacing and to observe mid-term outcomes through a retrospective cohort analysis. METHODS: This cohort enrolled 33 consecutive patients with pacing indications. PSB pacing was performed using a pacing lead delivered via a catheter to the medial wall of the superior vena cava, ≈1.5 cm superior to the junction of superior vena cava and right atrium. Electrophysiological and echocardiographic parameters were assessed before the procedure (baseline), acute phase, and at least 3 months after implantation. RESULTS: The mean follow-up period was 7.6±3.6 months, and PSB pacing was successful in all patients (100%), with stable lead fixation and no procedural complications, such as increased atrial capture threshold, atrial lead perforation, or atrial lead dislodgement. P-wave duration significantly shortened from baseline (120±15 ms) to follow-up (104±18 ms; <0.05), particularly in patients with interatrial conduction delay (indicated by intrinsic P-wave duration ≥120 ms; baseline: 130±10 ms, follow-up: 111±17 ms; <0.05). Atrial capture threshold (1.0±0.4 V) and sensing amplitudes (2.0±1.4 mV) remained stable. Structural and functional echocardiography showed maintained parameters in this study. Clinical events were minimal (1 heart failure hospitalization, 1 atrial fibrillation recurrence hospitalization, 1 syncope unrelated to pacing). CONCLUSIONS: PSB pacing is a feasible, safe, and effective strategy for atrial pacing. It maintains interatrial electrical synchrony, offers stable pacing parameters, and may provide potential functional benefits, especially in interatrial conduction delay, offering a new option for atrial physiological pacing. Further research is necessary to validate long-term outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06995027.

Impact of GLP-1 Receptor Agonist Therapy on Atrial Fibrillation Recurrence After Catheter Ablation in Obese Patients: A Real-World Data Analysis.

Venier S, Defaye P, Lochon L … +6 more , Benali R, Bisson A, Carabelli A, Diouf Y, Jacon P, Fauchier L

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41446932 · Full text

BACKGROUND: GLP-1 (glucagon-like peptide-1) receptor agonists (GLP-1RAs), initially developed for glycemic control in type 2 diabetes, have shown cardiometabolic benefits including weight loss, improved endothelial funct... BACKGROUND: GLP-1 (glucagon-like peptide-1) receptor agonists (GLP-1RAs), initially developed for glycemic control in type 2 diabetes, have shown cardiometabolic benefits including weight loss, improved endothelial function, and reduced inflammation. Recent data suggest potential anti-arrhythmic effects via modulation of atrial substrate and autonomic tone. Their impact on obese, nondiabetic patients remains underexplored. This study examines whether GLP-1RA use is associated with reduced atrial fibrillation recurrence after catheter ablation in obese patients, using real-world data from a large multicenter database. METHODS: We conducted a retrospective cohort study using the TriNetX research network, which contains de-identified electronic health records from >100 million patients. Adult patients (age ≥18 years) with obesity (body mass index >30 kg/m²) who underwent atrial fibrillation (AF) ablation between January 2015 and January 2025 were eligible. The cohort was divided into GLP-1RA users (n=3350) and nonusers (n=3350), with 1:1 propensity score matching performed across 82 clinical and demographic variables, including age, sex, race, AF subtype, cardiovascular comorbidities, and baseline medications. RESULTS: During a median follow-up of 2 years (interquartile range, 0.8-3.2) AF recurrence was significantly lower in GLP-1RA users versus non users (6.66% versus 7.72%; hazard ratio [HR], 0.82 [95% CI, 0.76-0.88]; <0.0001) Progression to permanent AF occurred less frequently in GLP-1RA users (3.16% versus 3.38%; HR, 0.77 [95% CI, 0.63-0.93]; =0.01). Risk of all-cause mortality was lower in the GLP-1RA group (HR, 0.73 [95% CI, 0.59-0.91]; =0.01) HF hospitalization (HR, 0.80 [95% CI, 0.71-0.90]; <0.0001) and cardiovascular hospitalizations (HR, 0.85 [95% CI, 0.77-0.93]; =0.001) were also significantly lower with GLP-1RA use. No significant difference was found for redo ablation. CONCLUSIONS: In a large real-world cohort of obese patients undergoing catheter ablation for AF, GLP-1RA therapy was associated with lower risks of AF recurrence, progression to permanent AF, cardiovascular hospitalizations, and mortality.

4D Digital Heart Model-Guided Left and Right Ventricular Lead Placement for Cardiac Resynchronization Therapy: Results of MAPIT-CRT Trial.

Chew DS, Vandenberk B, Exner DV … +15 more , Labib D, Flewitt J, Mikami Y, Rivest S, Chan D, Manlucu J, Leong-Sit P, Rinne C, Birnie DH, Nery PB, Sumner G, Ayala-Paredes F, Philippon F, Yee R, White JA

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41446931 · Publisher ↗

BACKGROUND: Suboptimal left ventricular (LV) and right ventricular lead positioning has been associated with a lesser response to cardiac resynchronization therapy. The MAPIT-CRT (MRI Allocation of Pacing Targets in Card... BACKGROUND: Suboptimal left ventricular (LV) and right ventricular lead positioning has been associated with a lesser response to cardiac resynchronization therapy. The MAPIT-CRT (MRI Allocation of Pacing Targets in Cardiac Resynchronization Therapy) randomized controlled trial evaluated a novel, cardiac magnetic resonance-generated 4-dimensional phenomics cardiac magnetic resonance imaging (4DPcmr) lead placement strategy. METHODS: A total of 202 participants with New York Heart Association class II to IV heart failure on optimal medical therapy, LV ejection fraction ≤35%, and QRS duration ≥120 ms were analyzed from 7 Canadian sites. Participants were randomized to 4DPcmr-guided lead placement using a web-based application or standard lead placement. 4DPcmr-recommended LV and right ventricular (RV) lead locations were generated using the combined consideration of (1) regional scar distribution and burden, (2) maximal regional delay in LV peak systolic strain, and (3) maximal interlead distance. RESULTS: The primary end point, an increase in LV ejection fraction ≥5% at 6 months, was reached in 69 of 105 4DPcmr-guided participants (65.7%) versus 50 of 96 control participants (52.1%; risk ratio, 1.80 [95% CI, 1.02-3.17]; =0.04). The absolute increases in LV ejection fraction observed for the respective study arms were 10.8% versus 5.8% (=0.01). No differences were identified in the secondary end points of all-cause mortality or heart failure hospitalization at 12 months, rate of adverse outcomes, or procedural times between the 2 study arms. CONCLUSIONS: 4DPcmr-guided LV/RV cardiac resynchronization therapy lead implantation using a practical web application was clinically feasible, safe, and was associated with greater LV ejection fraction improvement at 6 months versus standard of care with no increase in procedural times or complications. REGISTRATION: URL: https://clinicaltrials.gov/study/NCT01640769; Unique identifier: NCT01640769.

Dose-Dependent Effects of Radiation on the Coronary Arteries: Results From a Preclinical Model of Single-Fraction Proton Beam Cardiac Radioablation.

Hirao T, Rettmann ME, Deisher AJ … +10 more , Koya T, Newman LK, Gades NM, Lerman A, Asirvatham SJ, Kruse JJ, Merrell KW, Shumway DA, Packer DL, Siontis KC

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41446918 · Publisher ↗

BACKGROUND: Cardiac radioablation is emerging as a treatment modality for refractory ventricular tachycardia. This study aimed to evaluate the effects of radiation on the coronary arteries in a swine model of proton beam... BACKGROUND: Cardiac radioablation is emerging as a treatment modality for refractory ventricular tachycardia. This study aimed to evaluate the effects of radiation on the coronary arteries in a swine model of proton beam cardiac radioablation. METHODS: Eighteen swine underwent single-fraction 30 to 40 Gy pencil-beam scanning proton therapy targeting the left ventricle and were euthanized 12 to 40 weeks later. Treatment planning was performed without restricting the dose to the coronary arteries. The maximum point dose (D) to the epicardial coronary arteries was calculated. In secondary analyses, the mean (D) and minimum dose received by the highest irradiated 0.01 cm (D) of each coronary artery were also calculated. Coronary artery segments were harvested from the D sites for histological analysis, and the D was correlated with stenosis severity. RESULTS: Ninety-six coronary arteries were analyzed. No stenoses were observed by computed tomography imaging preirradiation. By histological analysis posteuthanasia, 25/96 (26%) coronaries sampled at their D sites had ≥75% stenosis. The median D was 4.7 Gy for the <75% stenosis group and 29.7 Gy for the ≥75% stenosis group (<0.001). The AUC-ROC for the association between D and stenosis ≥75% was 92.2%. A D value of 20.1 Gy best predicted stenosis ≥75%, with sensitivity 92.3% and specificity 87.1%. The AUC-ROCs for the associations of D and D with stenosis ≥75% were 84.8% and 91.6%, respectively. In histopathologic analysis, intimal hyperplasia was the most common coronary artery abnormality at the D sites, and it was present in 61.5% of all arteries and in 93.9% of arteries with D ≥20 Gy. CONCLUSIONS: In this preclinical model of proton beam cardiac radioablation, coronary stenoses occurred in a dose-dependent manner, with D showing the closest correlation with stenosis ≥75%. These data provide for the first time a framework for dose constraint considerations for the coronary arteries during treatment planning for cardiac radioablation and thoracic malignancy radiation.

Convolutional Neural Network Models Leverage Morphological Rather Than Temporal Features to Detect Myocardial Diseases From 12-Lead Electrocardiograms.

Nakayama M, Yagi R, Katsumata Y … +4 more , Oki M, Deo RC, MacRae CA, Goto S

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41431897 · Full text

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Athlete's Heart or Heart at Risk? Cardiac Remodeling and Exercise-Induced Ventricular Arrhythmias in Elite Athletes.

Di Gioia G, Squeo MR, Ferrera A … +8 more , Spera FR, Maestrini V, Monosilio S, Mango F, Paoletti G, Serdoz A, Bernardi M, Pelliccia A

Circ Arrhythm Electrophysiol · 2026 Jan · PMID 41424268 · Publisher ↗

BACKGROUND: Ventricular ectopic beats (VEBs) are frequently observed in athletes, but their clinical significance remains debated. We aimed to assess the prevalence, pattern of exercise-induced VEBs, and their associatio... BACKGROUND: Ventricular ectopic beats (VEBs) are frequently observed in athletes, but their clinical significance remains debated. We aimed to assess the prevalence, pattern of exercise-induced VEBs, and their association with exercise-induced cardiac remodeling (EICR) in elite athletes. METHODS: We analyzed a large cohort of Olympic athletes who underwent comprehensive preparticipation screening, including exercise-electrocardiography test and echocardiography. VEB morphology was classified as common (left bundle branch block, with inferior axis, and fascicular) or uncommon, including polymorphic. RESULTS: We enrolled 2525 athletes (mean age, 25.7±5.2 years; 45.1% women); 14.8% of athletes had exercise-induced VEBs, more frequently men (16.7% versus 12.4%; =0.002), with no differences between sport disciplines (=0.295). The VEB pattern was defined in 283 (ie, 76%), including 135 (48%) common and 148 (52%) uncommon, including polymorphic. Prevalence of common VEBs increased proportionally with the functional capacity (as W/kg), ranging from 16.3.% in I quartile to 40% in IV quartile (<0.0001), while no differences existed in those with uncommon VEBs (=0.140). Moreover, athletes with common VEBs showed a greater EICR, including a larger right ventricle (with wider right ventricular outflow tract; =0.014; right ventricular end-diastolic area; =0.016) and left ventricle (greater left ventricular mass indexed; =0.037; a higher prevalence of eccentric remodeling; =0.019). On the contrary, no relationship with cardiac remodeling or exercise capacity was seen in athletes with uncommon VEBs and in those without VEBs. CONCLUSIONS: Exercise-induced common VEBs in athletes seem to be associated with EICR and superior exercise performance and may represent a benign phenomenon, expression of the pathophysiologic consequences of EICR. Instead, uncommon VEBs were not related to the extent of EICR or the level of exercise performance, suggesting a nonphysiological nature.

Thyrotropin Directly Affects Cardiac Electrophysiology and Is Associated With AF Prevalence.

Rahm AK, Wunsch MN, Seibold D … +23 more , Kramp XC, Schöffel A, Syren P, Rivinius R, Mages C, Pfeiffer J, Gampp H, Caspari T, Wen X, Hund H, Akin I, Zhou X, Fan X, Meng Z, Yan C, Li Y, Sticht C, Ullrich ND, Kender Z, Heijman J, Frey N, Thomas D, Lugenbiel P

Circ Arrhythm Electrophysiol · 2025 Dec · PMID 41332396 · Full text

BACKGROUND: Although hyperthyroidism is known to increase the risk of atrial fibrillation (AF), subclinical hypothyroidism (SH) is an often-underreported condition characterized by elevated thyroid-stimulating hormone (T... BACKGROUND: Although hyperthyroidism is known to increase the risk of atrial fibrillation (AF), subclinical hypothyroidism (SH) is an often-underreported condition characterized by elevated thyroid-stimulating hormone (TSH) levels and normal free triiodothyronine/free thyroxine (fT/fT) levels. This study aimed to clarify the association between SH and AF and to identify potential direct electrophysiological effects of TSH. METHODS: We retrospectively included 2311 patients diagnosed with SH between 2007 and 2020 who had an ECG within 7 days of diagnosis. Logistic regression analysis identified factors independently associated with AF in patients with SH. Effects of different TSH doses on ion channel mRNA and protein levels were analyzed in HL-1 and neonatal rat cardiomyocytes. Video analysis with MYOCYTER, patch-clamp, optical mapping, and computational modeling were used to study automaticity and action potential characteristics after TSH application. RESULTS: AF was documented more often with higher TSH levels (4-10 mU/L TSH: 32.1% versus >10 mU/L TSH: 44.6%; <0.0001). Multivariable regression identified elevated TSH levels as an independent risk factor for AF. TSHR (TSH receptors) were confirmed in cardiomyocytes, and exposure to TSH led to changes in ion channel expression levels that promoted action potential prolongation. TSH also increased the beating rate in neonatal rat cardiomyocytes. We identified a TSHR-mediated cascade involving cAMP, PKA (protein kinase A), and CREB (cAMP-responsive element-binding protein) as a potential regulator of cardiomyocyte electrical remodeling leading to the proarrhythmic effects that promote the development of AF. CONCLUSIONS: Individuals with SH exhibit an increased prevalence of AF, which is likely in part due to a direct effect of TSH on ion channel expression in cardiomyocytes via the TSHR/cAMP/PKA pathway.

Demonstration of Coronary Sinus Reentry by Ultrahigh-Resolution Mapping in Adults With Congenital Heart Disease.

Moore JP, Newlon CA, Shannon KM

Circ Arrhythm Electrophysiol · 2025 Dec · PMID 41328584 · Full text

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Cautionary Tales in LQTS 2: Reassuring History With Life-Threatening Arrhythmias.

El Assaad I, Patel A, Aziz PF

Circ Arrhythm Electrophysiol · 2025 Dec · PMID 41328581 · Full text

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Predictors of Response to Cardiac Resynchronization Therapy in Pediatric Patients and Patients With Congenital Heart Disease.

Chubb H, Mah D, Shah M … +12 more , Lin KY, Peng D, Hale BW, May L, Etheridge S, Goodyer W, Ceresnak SR, Motonaga KS, Rosenthal DN, Almond CS, McElhinney DB, Dubin AM

Circ Arrhythm Electrophysiol · 2025 Dec · PMID 41328579 · Full text

BACKGROUND: Cardiac resynchronization therapy (CRT) is an important therapeutic option in selected pediatric patients and patients with congenital heart disease with reduced systemic ventricular ejection fraction (SVEF).... BACKGROUND: Cardiac resynchronization therapy (CRT) is an important therapeutic option in selected pediatric patients and patients with congenital heart disease with reduced systemic ventricular ejection fraction (SVEF). However, the identification of optimal responders is challenging. This study aimed to identify predictors of response to CRT in children and patients with congenital heart disease at 5 large quaternary referral centers. METHODS: Patients were aged <21 or had congenital heart disease and had SVEF <45%, symptomatic heart failure, and significant electrical dyssynchrony before CRT. Primary outcome was defined as an ordinal response at 6 or 12 months: (1) improved SVEF (≥5%), (2) unchanged SVEF, and (3) worse SVEF. Secondary outcome utilized a propensity score-matched control cohort. Response to CRT was defined using the longitudinal trajectory of SVEF up to the latest follow-up. RESULTS: In total, 167 eligible CRT recipients were identified across the 5 centers; 150 had comprehensive data at 6 or 12 months: 96 (64%) with improved SVEF, 26 (17%) unchanged, and 28 (19%) worsened. Mean increase in SVEF was 11% (interquartile range, 3%-21%). On univariable ordinal regression, lower SVEF (=0.013), biventricular circulation (=0.022), systemic left ventricle (=0.021), and conduction delay to the lateral wall of the systemic ventricle (=0.01) were associated with a positive response. For the assessment of the secondary outcome, 324 controls were identified. Median follow-up is 5.1 (interquartile range, 2.0-8.6) years. Almost all subgroups demonstrated improved SVEF trend with CRT, except those with systemic right ventricle (=0.69) or without prior single-site pacemaker (=0.20). CONCLUSIONS: CRT in children and patients with congenital heart disease frequently results in an improvement in SVEF. Those with lower SVEF, conduction delay to the lateral wall of the systemic ventricle, and those with a systemic left ventricle are most likely to respond.

Pulsed Field Ablation-Related Hemolysis: Comparison Between Technologies.

Gianni C, Al-Ahmad A, Elchouemi M … +12 more , La Fazia VM, Mohanty S, Allison JD, Bassiouny MA, Bode WD, Burkhardt JD, Coffeen PC, Gallinghouse GJ, Horton RP, Kessler DJ, Sanchez JE, Natale A

Circ Arrhythm Electrophysiol · 2025 Dec · PMID 41328578 · Full text

BACKGROUND: Hemolysis is a recognized side effect of pulsed field ablation (PFA). Severe hemolysis can lead to acute kidney injury, affecting the morbidity of patients undergoing PFA for atrial fibrillation. Here, we aim... BACKGROUND: Hemolysis is a recognized side effect of pulsed field ablation (PFA). Severe hemolysis can lead to acute kidney injury, affecting the morbidity of patients undergoing PFA for atrial fibrillation. Here, we aimed to characterize the degree of hemolysis across different PFA technologies. METHODS: This is a retrospective cohort study of 552 PFA procedures performed in our center, where Hp (haptoglobin) was measured both at baseline and on postoperative day 1. The PFA catheters used were Farawave (59%), Sphere-9 (19%), Pulseselect (16%), and Varipulse (5.8%). RESULTS: Hemolysis (ie, reduction in Hp >10 mg/dL) was observed in the majority of cases (95%), with the lowest incidence observed in patients undergoing PFA with Sphere-9 (88%) compared with Farawave (97%), Varipulse (97%), and Pulseselect (100%). Significant and severe hemolysis (ie, Hp-postoperative day 1 ≤25 mg/mL and Hp-postoperative day 1 ≤10 mg/mL) occurred in 34% and 13%, with a different distribution across catheter types: Farawave 46% and 21%, Varipulse 29% and 9.7%, Pulseselect 23% and 1.2%, and Sphere-9 5.5% and 0%. Hp decreased by a mean of 76±40 mg/dL from baseline, with a significantly greater degree of reduction seen with Farawave (94±40 mg/dL) and Varipulse (85±32 mg/dL) compared with Pulseselect (62±25 mg/dL) or Sphere-9 (39±23 mg/dL). There is a linear relationship between Hp reduction and number of PFA applications, with a decrease of Hp per application of 0.47 mg/dL (95% CI, 0.22-0.71 mg/dL) for Farawave, 0.40 mg/dL (95% CI, 0.09-0.73 mg/dL) for Pulseselect, and 0.10 mg/dL (95% CI, 0.02-0.19 mg/dL) for Sphere-9. CONCLUSIONS: PFA-induced hemolysis is common, with different PFA technologies exhibiting variable degrees of hemolysis, lower with the focal PFA catheter Sphere-9 when compared with single-shot PFA catheters.
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