BACKGROUND: Inappropriate sinus tachycardia (IST) is an arrhythmia characterized by rapid sinus rates of over 100 bpm at rest. The mechanisms underlying this often-debilitating condition are not fully understood. The dif...BACKGROUND: Inappropriate sinus tachycardia (IST) is an arrhythmia characterized by rapid sinus rates of over 100 bpm at rest. The mechanisms underlying this often-debilitating condition are not fully understood. The differential diagnosis for this persistent observation is broad, including medication side effects or serendipitous use of chronotropic stimulating drugs. Genetic causes of IST are seldom considered. Only 2 mutations have been linked to this condition, both of which affect the gene encoding channels, which play an important role in generating pacemaker activity of the sinoatrial node. METHODS: Standard clinical genetic testing was performed on a child with IST, her affected mother, and 2 healthy siblings. A novel channel variant identified in the family was studied by whole-cell patch clamp analysis. Three-dimensional protein structures of mutant and wild-type channels were generated and subjected to 200 ns of unrestricted molecular dynamics simulation. RESULTS: A heterozygous, missense variant was identified in the gene (p.N299S) in the affected child and mother, while absent in 2 healthy siblings of the child. Patch clamp analysis revealed significantly increased current density and a rightward-shifted activation curve in cells expressing p.N299S- versus wild-type channels, suggesting constitutive activity of the mutant channel. In molecular dynamics simulations, the voltage sensor of p.N299S- channels adopted a resting conformation mimicking that of cAMP-bound wild-type , providing a structural basis for the functional observations. Ivabradine application returned the gain-of-function properties of mutant channels to baseline levels. CONCLUSIONS: We identified a gain-of-function variant in a family with IST that displays constitutive activity and structurally mimics the effects of cAMP activation. This study furthers our understanding of the mechanisms underlying IST and provides data supporting the efficacious effect of ivabradine in genetically based IST.
Xie A, Kang GJ, Liu H
… +4 more, Kim EJ, Feng F, Dobrev D, Dudley SC
Circ Arrhythm Electrophysiol
· 2025 Nov · PMID 41084803
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BACKGROUND: In nonischemic cardiomyopathy, mitochondrial Ca handling is involved in arrhythmogenesis by modulating diastolic sarcoplasmic reticulum (SR) Ca release. Recently, it has been reported that lysosomal Ca releas...BACKGROUND: In nonischemic cardiomyopathy, mitochondrial Ca handling is involved in arrhythmogenesis by modulating diastolic sarcoplasmic reticulum (SR) Ca release. Recently, it has been reported that lysosomal Ca release can trigger an SR Ca release. We investigated whether lysosomal Ca flux through the TRPML1 (transient receptor potential mucolipin 1) channel could contribute to ischemic cardiomyopathy-related arrhythmia by causing diastolic SR Ca release. METHODS: Ischemic cardiomyopathy was induced in wild-type C57BL/6J and TRPML1 heterozygous knockdown (TRPML1±) mice by ligating the left anterior descending coronary artery. Mice were studied at 3 weeks after myocardial infarction (MI). RESULTS: After MI, the lysosomal-restricted TRPML1 Ca release channel was significantly increased in human patients with ischemic or nonischemic cardiomyopathy. TRPML1, but not the TPC2 (2-pore channel 2), was significantly upregulated by 85% in the mouse MI border zone and by 55% in a remote zone. Lysosomal number and approximation to the SR were increased after MI. Lysosomal Ca release was substantially upregulated in MI mouse cardiomyocytes compared with sham cardiomyocytes. The action potential duration was prolonged, and arrhythmogenic diastolic SR Ca release was increased in the cardiomyocytes isolated from MI mice. Blocking TRPML1 reduced action potential duration prolongation and depressed early and delayed afterdepolarizations in cardiomyocytes isolated from MI mice, while the TRPML1 agonist increased TRPML1-dependent cellular triggered activity. A TRPML1 antagonist could inhibit induced ventricular fibrillation in MI mice. Consistent with that result, genetic knockdown of TRPML1 could inhibit arrhythmic risk after MI. The effects of TRPML1-targeted drugs were not seen in control cardiomyocytes. CONCLUSIONS: Lysosomes contribute to arrhythmic risk after MI because of increased number, proximity to the SR, and induction of diastolic SR Ca release mediated by TRPML1-dependent lysosomal Ca release.
Alahwany SH, Uetake S, Jiménez-Jáimez J
… +10 more, Cabrera-Borrego E, Dalal A, Kannankeril PJ, Shoemaker MB, Togashi D, Katsume Y, Richardson TD, Kanagasundram A, Stevenson WG, Tandri H
Circ Arrhythm Electrophysiol
· 2025 Nov · PMID 41078126
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BACKGROUND: Radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy is safe and reduces ventricular arrhythmia burden. Previous studies included adult pa...BACKGROUND: Radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy is safe and reduces ventricular arrhythmia burden. Previous studies included adult patients, and data on pediatric patients are scarce. The objective of our study was to report on the safety and efficacy of RFCA in pediatric arrhythmogenic right ventricular cardiomyopathy. METHODS: Fifteen patients who fulfilled the 2010 arrhythmogenic right ventricular cardiomyopathy task force criteria, clinically presented before the age of 18, and underwent VT RFCA procedures at ≤21 years old were included. Baseline characteristics, genotypic and phenotypic data, and ablation outcomes were collected. RESULTS: The mean age at symptom onset was 15.5±1.6 years, and at the index procedure was 18.1±2 years, with 73% of the patients being male. Pathogenic mutation in desmosomal genes was detected in 87%. First presentation symptoms included palpitations (33%), syncope (27%), sustained VT (27%), and sudden cardiac arrest (13%). ECG repolarization abnormalities were present in 93% and 40% were reported to be athletes. In the index RFCA procedure, sustained monomorphic VT was induced in 60%. Electroanatomic mapping showed 100% basal RV epicardial substrate and 54% endocardial low voltage/scar. Repeat VT ablation was required in 80% over a mean follow-up of 16.4 months. The median number of procedures was 2 (interquartile range, 2-4), with sustained VT-free survival of 73% over a mean follow-up duration of 21.4 months. No acute periprocedural complications occurred. Bilateral cardiac sympathetic denervation due to recurrent ventricular arrhythmia was performed in 27%. Eventually, 2 patients (13%) developed advanced heart failure and underwent heart transplantation. CONCLUSIONS: Pediatric arrhythmogenic right ventricular cardiomyopathy RFCA is safe, but early recurrences are common, requiring repeat ablations and sometimes bilateral cardiac sympathetic denervation. The substrate is mostly epicardial with preserved endocardial voltage. VT free survival is 73% after multiple procedures. Progressive heart failure requiring transplantation occurred in 13% within 2 decades of initial presentation.
BACKGROUND: Recurrence of atrial arrhythmias remains a significant challenge following catheter ablation for atrial fibrillation. The potential role of semaglutide in reducing atrial arrhythmia recurrence postablation is...BACKGROUND: Recurrence of atrial arrhythmias remains a significant challenge following catheter ablation for atrial fibrillation. The potential role of semaglutide in reducing atrial arrhythmia recurrence postablation is unclear. METHODS: A consecutive sample of 437 patients with a body mass index ≥24 kg/m² and type 2 diabetes who underwent their first atrial fibrillation ablation procedure between January 2022 and March 2024 were enrolled. Participants were divided into a semaglutide group and a control group based on patient preference. The primary outcome was the freedom from atrial arrhythmia recurrence during the 12-month follow-up period after the 3-month blanking period postablation. RESULTS: Of the 437 enrolled patients, 158 opted for semaglutide therapy and 279 declined. At baseline, the semaglutide group had higher body mass index (27.5 [2.2] versus 27.0 [2.4]; =0.038) and glycated hemoglobin levels (8.0 [1.0] versus 7.6 [1.1]; <0.001) compared with controls. During the 12-month follow-up, the semaglutide group showed a higher event-free rate for recurrent atrial arrhythmias (hazard ratio, 0.68 [95% CI, 0.49-0.95]; =0.030), greater weight loss (-8.2% [3.2] versus -4.6% [2.9]; <0.001), and larger reductions in glycated hemoglobin (-1.3% [0.8] versus -0.6% [0.8]; <0.001). CONCLUSIONS: Semaglutide treatment following catheter ablation for atrial fibrillation is associated with a lower rate of atrial arrhythmia recurrence over 12 months and may lead to improvements in weight and glycated hemoglobin levels.
Terricabras M, Lombergar P, Escartin T
… +12 more, Kos B, Krahn P, Barry J, Wright G, Jarm T, Štublar J, Kranjc M, Coulombe N, Mattison L, Sigg DC, Miklavčič D, Verma A
Circ Arrhythm Electrophysiol
· 2025 Oct · PMID 41031398
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BACKGROUND: Various pulsed field ablation (PFA) parameters have been proposed to improve lesion depth. This study evaluated a modified unipolar return PFA system to create deep lesions in healthy and infarcted ventricula...BACKGROUND: Various pulsed field ablation (PFA) parameters have been proposed to improve lesion depth. This study evaluated a modified unipolar return PFA system to create deep lesions in healthy and infarcted ventricular myocardia. METHODS: Numerical modeling was used to compare a modified unipolar return PFA system configuration with a conventional unipolar return (skin patch). We then performed ablation in 14 swine (5 with chronic myocardial infarction and 9 healthy). PFA lesions were created in the left ventricle using a focal catheter (4-mm tip) with a return electrode positioned in the inferior vena cava (biphasic, microsecond pulses of 1300 and 1500 V, 1-16 trains). Electroanatomical mapping guided ablation and lesion localization on magnetic resonance imaging were performed 48 hours post-ablation in the infarcted group and at 1 day, 7 days, and 6 weeks post-ablation in the healthy group. RESULTS: Numerical modeling demonstrated that the modified unipolar return PFA system produced deeper lesions with reduced variability compared with the skin patch. In healthy pigs (n=35 lesions), depths of 6.8±1.8 mm and widths of 11.5±4.7 mm were achieved with 8 pulse trains. Depths of 8.2±2.8 mm and widths of 14.0±4.7 mm were achieved with 16 trains. The maximum lesion depths were 8.8 and 11.6 mm for 8 and 16 trains, respectively. In the infarcted cohort (n=22 lesions), all lesions applied to scar tissue penetrated through fibrotic regions, with epicardial involvement observed in 57% of lesions. CONCLUSIONS: The modified unipolar return PFA system effectively creates large lesions and can achieve transmurality in healthy and infarcted animals. Compared with conventional unipolar, it may offer greater lesion depth, width, and consistency.
BACKGROUND: The incidence of postural orthostatic tachycardia syndrome (POTS) in long COVID has been a growing concern since the first cases were reported in 2021. The aim of this study was to assess the prevalence and c...BACKGROUND: The incidence of postural orthostatic tachycardia syndrome (POTS) in long COVID has been a growing concern since the first cases were reported in 2021. The aim of this study was to assess the prevalence and clinical impact of POTS in a series of well-characterized patients with long COVID. METHODS: We prospectively analyzed 467 nonhospitalized, highly symptomatic (sick leave ≥50%) patients with long COVID, and studied differences in demographics and clinical assessment outcomes between those diagnosed with POTS and the remaining long COVID patients. Examinations were performed at a median of 12 months after acute COVID-19, followed by a cardiologist evaluation with 48-hour ECG, head-up tilt test, and Active Stand Test for those with clinically suspected POTS. RESULTS: Of all long COVID patients, 143 (31%) were diagnosed with POTS, 128 (27%) did not fulfill POTS criteria, while 196 (42%) had no clinical signs of POTS. Patients with POTS were younger (mean age, 40.0 versus 44.0 versus 47.0 years, respectively; ≤0.001) and predominantly female (91%). They had significantly lower physical activity compared with the other 2 groups, as measured with the Frändin-Grimby scale (=0.001). Heart rates during the 6-minute walk test were significantly higher in the POTS group, both during walking and at rest afterward, with a significantly shorter walking distance (448 m versus 472 m versus 509 m, respectively; ≤0.001). However, the distribution of symptoms showed no significant differences between the groups. CONCLUSIONS: In this cohort of predominantly younger women with highly symptomatic long COVID, POTS is common and presents with overlapping symptoms between POTS and non-POTS patients. Long COVID POTS confers lower physical activity and capacity compared with non-POTS long COVID and should be systematically assessed in this condition.
Brant LCC, Ribeiro AH, Eromosele OB
… +7 more, Pinto-Filho MM, Barreto SM, Duncan BB, Larson MG, Benjamin EJ, Ribeiro ALP, Lin H
Circ Arrhythm Electrophysiol
· 2025 Oct · PMID 41025252
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BACKGROUND: We aimed to refine and validate a deep neural network model from the ECG to predict atrial fibrillation (AF) risk, using samples from diverse backgrounds: the Framingham Heart Study (FHS), UK Biobank, and Est...BACKGROUND: We aimed to refine and validate a deep neural network model from the ECG to predict atrial fibrillation (AF) risk, using samples from diverse backgrounds: the Framingham Heart Study (FHS), UK Biobank, and Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil). We compared the model's performance to the clinical Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE-AF) risk score and evaluated the association with other cardiovascular outcomes. METHODS: The ECG-derived deep-learning prediction of AF (ECG-AF) model was refined using 60% of FHS samples free of AF. Its performance was then tested in the remaining FHS samples, UK Biobank, and ELSA-Brasil, with discrimination assessed by the area under the receiver operating characteristic curve. The association of ECG-AF with cardiovascular outcomes was assessed using Cox proportional hazards models. RESULTS: The study sample included 10 097 FHS participants (mean age 53±12 years; 54.9% women), 49 280 participants from the UK Biobank (mean age 64±8 years, 47.9% women), and 12 284 participants from ELSA-Brasil (mean age 53±8 years, 54.7% women). The ECG-AF model showed moderate discrimination for incident AF (area under the curve, 0.82 [95% CI, 0.80-0.84]) in the FHS, comparable to the CHARGE-AF score (area under the curve, 0.83 [95% CI, 0.81-0.85]), and incremental when combined (area under the curve, 0.85 [95% CI, 0.83-0.87]). In UK Biobank and ELSA-Brasil, combining ECG-AF and CHARGE also improved prediction. Higher ECG-AF scores were associated with increased risks of heart failure, myocardial infarction, stroke, and all-cause mortality in all 3 cohorts. CONCLUSIONS: In multinational cohort studies, the single-input ECG-AF deep neural network model demonstrated good performance in predicting AF and other cardiovascular outcomes, comparable to a multivariable clinical risk score, with improved performance when combined.
BACKGROUND: Hyperactivity of sympathetic neurons in the stellate ganglia (SG) contributes to ventricular arrhythmias and remodeling postmyocardial infarction (MI). However, the role of satellite glial cells (SGCs) surrou...BACKGROUND: Hyperactivity of sympathetic neurons in the stellate ganglia (SG) contributes to ventricular arrhythmias and remodeling postmyocardial infarction (MI). However, the role of satellite glial cells (SGCs) surrounding the neurons in this process remains unknown. METHODS: SGC-specific chemogenetic manipulation was locally applied to modulate SG-SGC activity dual-directionally in the rats with naïve or infarcted hearts. Subsequently, cardiac sympathetic neural activity and ventricular electrophysiological stability in response to stimulation were evaluated, as well as cardiac neural and structural remodeling post-MI. SG bulk RNA sequencing and the interaction between SGCs and sympathetic neurons isolated from SG were used to explore the underpinning mechanisms. RESULTS: SG-SGC excitation increased SG neural activity and ventricular electrophysiological instability in rats with naïve hearts, whereas its inhibition influenced none of the above under physiological conditions. Of note, 2-hour-MI provoked SG-SGC activation that positively correlated with cardiac sympathetic neurotransmitter (norepinephrine) release. Accordingly, SGC activation in the SG enhanced cardiac sympathetic hyperactivity 2 hours post-MI, whereas SG-SGC inhibition suppressed MI-induced cardiac sympathetic hyperexcitability. Moreover, the persistent inhibition of SG-SGCs improved ventricular remodeling and dysfunction, alleviated SG and ventricular sympathetic nerve sprouting 7 days post-MI. In addition, the bulk RNA sequencing with SG and pharmacological purinergic P2Y1R (P2Y1 receptor) blockage indicated that P2Y1R/IGFBP2 (insulin-like growth factor-binding protein 2) signaling mediated the effects of SG-SGC activation on cardiac sympathetic hyperexcitability post-MI, and IGFBP2 bridged the interaction between the neurons and surrounding SGCs. CONCLUSIONS: SGC inhibition in SG rectifies cardiac sympathetic hyperactivity, stabilizes ventricular electrophysiological properties, and alleviates cardiac structural and neural remodeling post-MI, thereby preventing ventricular arrhythmias and cardiac dysfunction. Neuromodulation targeting SG-SGCs exhibits a safe and fruitful strategy for the treatment of MI.
Ellenbogen KA, Khoynezhad A, La Meir M
… +32 more, de Asmundis C, Koneru JN, Johnkoski J, Rist K, Mumtaz M, Link MG, de Groot JR, Driessen AHG, Lee MY, Hoff SJ, Bello D, Dunnington G, Eisenberg S, Vloka M, Taylor BJ, Jones SD, Philpott JM, Beaver TM, Miles WM, Khan JH, Kang S, Gandhi GD, Okum EJ, Badhwar N, Baykaner T, Lee AM, Vesco PA, Smith JM, Gaynor S, Frazier K, Lee RJ, Kasirajan V
BACKGROUND: Despite advances in endocardial catheter ablation (ECA) for persistent atrial fibrillation (PersAF), undertreatment persists, especially in ECA nonresponders and in longstanding PersAF (LSPersAF), with disapp...BACKGROUND: Despite advances in endocardial catheter ablation (ECA) for persistent atrial fibrillation (PersAF), undertreatment persists, especially in ECA nonresponders and in longstanding PersAF (LSPersAF), with disappointing ablation results. These patients need effective clinical treatment options. METHODS: The DEEP (Dual Epicardial and Endocardial Procedure) was a prospective, multicenter, single-arm, investigational device exemption trial to establish the safety and effectiveness of a combined epicardial/endocardial ablation procedure with left atrial appendage exclusion for PersAF/LSPersAF. Eligibility included age 18 to 75 years; symptomatic PersAF/LSPersAF refractory to ≥1 Class I/III antiarrhythmic drug; and ≤2 previous failed ECAs. Two-stage hybrid ablation included ECA performed at 91 to 121 days after the epicardial first stage (including left atrial appendage exclusion), followed by a 90-day blanking and 90-day antiarrhythmic drug optimization period. Primary effectiveness was defined as freedom from documented atrial fibrillation/atrial flutter/atrial tachycardia episodes >30 seconds through the 12-month follow-up, absent Class I/III antiarrhythmic drugs, except previously failed antiarrhythmic drugs at doses not exceeding those previously failed. Primary safety was defined as a composite of device/procedure-related serious adverse events within 30 days of epicardial ablation and 7 days of ECA. RESULTS: Ninety patients enrolled from February 2015 to December 2020; 83.3% (75/90) were male and mean±SD age was 63.4±7.7 years. AF classification was 83.3% (75/90) PersAF/16.7% (15/90) LSPersAF, and 47.8% (43/90) had prior ECA. The composite serious adverse events rate was 6.7% (6/90 [95% CI, 2.5%-13.9%]; <0.001 versus safety goal), including 3 patients experiencing serious adverse events within 30 days of the epicardial procedure and 3 patients within 7 days of the endocardial procedure, all of whom were anticoagulated at the time of the event. Primary effectiveness through 12 months was 71.8% (61/85 [95% CI, 62.2%-81.3%]; =0.0134 versus performance goal) and was 62.4% (53/85 [95% CI, 52.1%-72.7%]) through 2 years. CONCLUSIONS: A collaborative hybrid ablation approach to treating PersAF/LSPersAF is safe and effective. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02393885.
Miyake CY, Kallas D, Stephens SB
… +38 more, Moore OM, Wehrens XHT, Fischbach PS, LaPage MJ, Landstrom AP, Law IH, Hill AC, Kannankeril PJ, Fish FA, Howard TS, Valdes SO, Pham TDN, Kim JJ, Dhillon SS, Johnsrude CL, Krause U, Sarquella-Brugada G, Kubuš P, Tavacova T, Kwok SY, Etheridge SP, Tisma-Dupanovic S, Kean AC, Krahn AD, Ebrahim MA, Atallah J, Fournier A, Batra AS, Young ML, Perry J, Kovach JR, Kamp AN, Clark BC, Jimenez E, Charafeddine F, Hamilton RM, Balaji S, Sanatani S
BACKGROUND: Marked intellectual and neurodevelopmental delay (INDD) was noted in 6 unrelated patients diagnosed with -related catecholaminergic polymorphic ventricular tachycardia (CPVT) from a single center. Patients ex...BACKGROUND: Marked intellectual and neurodevelopmental delay (INDD) was noted in 6 unrelated patients diagnosed with -related catecholaminergic polymorphic ventricular tachycardia (CPVT) from a single center. Patients exhibited similar distinct phenotypic features not previously described. We aimed to determine the prevalence of INDD in CPVT, compare clinical characteristics between patients with CPVT with and without INDD, and investigate the possibility of a unique neurocardiac CPVT phenotype. METHODS: Retrospective combined review of patients with -related CPVT diagnosed ≤18 years with and without INDD from a single center and the International Pediatric CPVT Registry. Patients with hypoxic ischemic insult were excluded unless INDD preceded injury. RESULTS: Among a total of 168 patients, INDD was reported in 19 (11.3% [95% CI, 7.0%-17.1%]). When compared with cases without INDD, patients with INDD exhibited distinct features including (1) younger age at onset of symptoms (median 7.0 versus 10.0 years; =0.04); (2) higher frequency of atrial tachyarrhythmias (84.2% versus 16.3%, <0.001); (3) atrial or ventricular tachycardia without adrenergic stimulation (81.3% versus 2.2%, <0.001, 31.6% versus 4.5%, =0.001 respectively); (4) cardiac structural changes or systolic dysfunction (36.8% versus 1.3%, <0.001); and (5) higher incidence of cardiac arrest or sudden death after diagnosis (26.3% versus 2.7%, =0.001). INDD-related genetic variants clustered within the central and channel domains and may be specific to certain variants. CONCLUSIONS: This study demonstrates a wider spectrum of -related disease, with a subset associated with extracardiac manifestations. Certain variants may lead to a neurocardiac phenotype with distinct features that are important to recognize, as these patients may be at higher risk.
Masuda M, Matsuda Y, Uematsu H
… +23 more, Ooka H, Kudo S, Ochi M, Mano T, Sunaga A, Tanaka N, Watanabe T, Minamiguchi H, Egami Y, Oka T, Minamisaka T, Kanda T, Okada M, Kawasaki M, Tanaka K, Makino N, Kida H, Hikoso S, Dohi T, Inoue K, Sotomi Y, Sakata Y, OCVC-SUPPRESS-AF Investigators
Circ Arrhythm Electrophysiol
· 2025 Oct · PMID 41000017
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BACKGROUND: In the randomized controlled SUPPRESS-AF trial (Efficacy and Safety of Left Atrial Low-voltage Area Guided Ablation for Recurrence Prevention Compared to Pulmonary Vein Isolation Alone in Patients with Persis...BACKGROUND: In the randomized controlled SUPPRESS-AF trial (Efficacy and Safety of Left Atrial Low-voltage Area Guided Ablation for Recurrence Prevention Compared to Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation), the efficacy of low-voltage-area (LVA) ablation was highly dependent on the degree of atrial remodeling, while the efficacy was not statistically significant in total patients. This subanalysis of the SUPPRESS-AF trial aimed to compare the efficacy of LVA ablation in patient groups classified by left atrial diameter (LAD), which is a commonly used atrial remodeling index. METHODS: The SUPPRESS-AF trial included patients with persistent AF and left atrial LVAs, and compared rhythm outcomes between patients randomized to undergo pulmonary vein isolation (PVI) followed by left atrial LVA ablation group (n=170) or PVI-alone group (n=172). In this post hoc subanalysis, patients in each of the 2 randomly allocated groups were further divided into 2 groups using a median LAD of 44 mm. RESULTS: Atrial fibrillation or atrial tachycardia recurrence-free rates did not differ between patients with LAD>44 mm and ≤44 mm (60.1% versus 53.7%; =0.261). Among patients with a LAD>44 mm, the LVA ablation group demonstrated a higher atrial fibrillation or atrial tachycardia-recurrence-free rate than the PVI-alone group (62.5% versus 43.4%; =0.016). In contrast, no difference in atrial fibrillation or atrial tachycardia recurrence-free rate was found between the 2 groups of patients with a LAD≤44 mm (60.8% versus 59.6%; =0.986). CONCLUSIONS: The efficacy of LVA ablation in addition to PVI for the treatment of persistent AF was more pronounced in patients with a large left atrium. REGISTRATION:URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000035940.
Izda A, Sonig A, Brown A
… +21 more, Capodanno E, Matteo M, Baranowski B, Bhargava M, Callahan TD, Dresing TJ, Higuchi K, Hussein A, Kanj M, Kochar A, Koeth RA, Lee JZ, Martin DO, Nakhla S, Saliba WI, Taigen T, Varma N, Wazni O, Santangeli P, Chung MK, Sroubek J
Bhaskaran A, Deshmukh T, Selvakumar D
… +10 more, Bennett R, Turnbull S, Campbell TG, Kotake Y, Barry MA, Lu J, Pearson L, Kizana E, Chong JJH, Kumar S
BACKGROUND: Multiple extrastimulus (ES) pacing protocols exist for ventricular substrate mapping. Despite being increasingly adopted in clinical practice, direct protocol comparisons have been limited. This study aims to...BACKGROUND: Multiple extrastimulus (ES) pacing protocols exist for ventricular substrate mapping. Despite being increasingly adopted in clinical practice, direct protocol comparisons have been limited. This study aims to compare the substrate delineation and mapping efficiency of right ventricular pacing+ES (RVp+ES) and sensed ES pacing strategies in a large animal ischemia-reperfusion injury model. METHODS: Four swine underwent 90-minute balloon occlusion of the mid-left anterior descending artery, followed by late gadolinium-enhanced cardiac magnetic resonance between days 30 and 58 and invasive electroanatomic mapping. Late gadolinium-enhanced cardiac magnetic resonances were segmented for scar topography and border zone channel geometry. RESULTS: Sensed ES substrate maps had greater point density (12.90±4.20 pts/cm versus 5.75±0.52 pts/cm; =0.032) and faster acquisition (113.71±22.38 s/pt per cm versus 228.57±77.30 s/pt per cm; =0.027) than RVp+ES. Despite this, RVp+ES substrate maps had greater uncovering of split potentials within border zone channels (76.5% [15.4%-95.5%] versus 16.7% [0%-52.9%]; =0.028), higher sensitivity (53% versus 30%), and similarly high specificity (91% versus 93%) than sensed ES, as well as better visual correlation on decrement-evoked potential maps. Bipolar voltage in sinus rhythm and RVp did not reliably predict tissue response to ES, with 46% to 57% of split potentials within border zone channels arising from seemingly normal voltage (≥1.5 mV). CONCLUSIONS: RVp+ES is more sensitive than sensed ES and highly specific for the detection of late gadolinium-enhanced cardiac magnetic resonance border zone channels postmyocardial infarct.
Chivers S, Pini N, Chowdhury S
… +16 more, Cicci L, Vigneswaran T, Zidere V, Maxwell S, Moriarty G, Regan W, Rosenthal E, Lloyd DFA, Day TG, Miller OI, Sharland GK, Hayes-Gill B, Niederer S, Fifer WP, Williamson C, Simpson JM
Circ Arrhythm Electrophysiol
· 2025 Sep · PMID 40931811
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BACKGROUND: Fetal tachycardias can cause adverse fetal outcomes including ventricular dysfunction, hydrops, and fetal demise. Postnatally, ECG is the gold standard, but, in fetal practice, echocardiography is used most f...BACKGROUND: Fetal tachycardias can cause adverse fetal outcomes including ventricular dysfunction, hydrops, and fetal demise. Postnatally, ECG is the gold standard, but, in fetal practice, echocardiography is used most frequently to diagnose and monitor fetal arrhythmias. Noninvasive extraction of the fetal ECG (fECG) may provide additional information about the electrophysiological mechanism and monitoring of intermittent arrhythmias. Signal processing advances could provide improved data quality impacting clinical translation. The aim of this study was to assess the fetus with known or suspected tachycardia using noninvasive abdominal fECG and correlate results with fetal echocardiography and postnatal ECG. METHODS: Prospective recruitment of pregnant participants with known or suspected fetal tachycardia in a tertiary fetal cardiology unit. Overnight fECG recording at home using the MonicaAN24 monitor was performed. Data processing using bespoke MATLAB scripts was undertaken to produce fetal heart rate and beat-to-beat rhythm strips. Comparison of fECG data with clinical data obtained using echocardiography and postnatal findings. Data are presented as median (interquartile range; range). RESULTS: Fifteen participants undertook 1 to 4 fECG recordings, giving a total of 23 recordings. Gestational age was 28.9 (23.9-34.3; 21-39.1) weeks. Duration of recording was 512 (380-609; 5-1259) minutes. Intermittent tachycardia was demonstrated on fetal heart rate graphs. Rhythm strips correctly identified short-ventriculoatrial and long-ventriculoatrial tachycardia, atrial flutter, and sinus rhythm with findings correlating with echocardiography. Postnatal ECG correlation was possible in 3. CONCLUSIONS: We have shown that rhythm strips of fECG signals can be extracted and correctly identify the electrical mechanism of arrhythmia in cases of fetal tachycardia. The potential to monitor fetal heart rate over a prolonged period is an advantage over current monitoring strategies for documentation of intermittent arrhythmias and gauging the response to medical therapy. These data will enable research to focus on improvement in signal quality, assessment of other arrhythmia subtypes, and real-time ambulatory monitoring of the fetal rhythm.
Chang A, Beqaj H, Sittenfeld L
… +12 more, Miotto MC, Dridi H, Willson G, Martinez Jorge C, Altosaar Li J, Reiken S, Liu Y, Dai Z, Tchagou C, Elsayed S, Marx SO, Marks AR
Circ Arrhythm Electrophysiol
· 2025 Sep · PMID 40875405
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BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia, with pathogenic variants in the gene responsible for 60% of clinically well-defined CPVT cases. Diagnosis of CPVT...BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia, with pathogenic variants in the gene responsible for 60% of clinically well-defined CPVT cases. Diagnosis of CPVT often occurs after a major cardiac event, posing a severe threat to the patient's life. A data set of patients with CPVT would improve the diagnosis and treatment of patients with CPVT. METHODS: This review cataloged clinical data on patients with -related CPVT variants from articles published up to October 2020 from PubMed, Scopus, and Embase. Variants were mapped to the structural domains of RYR2. Differences in the age of onset based on variant location and incidence of CPVT symptoms, and differences in treatment strategies were analyzed. RESULTS: In 221 publications analyzed, 964 patients with CPVT (351 male, 463 female) were identified with 263 protein-coding variants and a median age of onset of CPVT of 11 years (interquartile range, 7-14 years). A web app was developed to allow users to query the database and is available at https://markslab-cpvtdb.org. The proportion of patients requiring treatments in addition to β-blockers varied between variants. The age of onset of CPVT differed significantly between variants located in different exons, domains, and subdomains. Patients with variants in the core solenoid at the domain level, and the core solenoid (exEF-hand) and channel pore at the subdomain level, tended to have a lower age of onset compared with other regions. CONCLUSIONS: This study compiled a comprehensive data set of CPVT-associated variants and their clinical phenotypes. The age of onset in certain domains (core solenoid) and subdomains (core solenoid[exEF-hand], channel pore) tended to be lower compared with other regions. Variability in patient phenotypes, such as age of onset and treatment efficacy, along with structural information on variants, suggests that patients may benefit from personalized interventions based on their variant.
Miyazaki S, Nitta J, Nakamura K
… +17 more, Kobori A, Inaba O, Murakami M, Yamauchi Y, Sekiguchi Y, Sasaki T, Sasaki Y, Inamura Y, Mizuno S, Sagawa Y, Asano S, Naito S, Ooka J, Ohya H, Nishimura T, Hirakawa A, Sasano T