Matsuoka Y, Sunaga A, Sakamoto D
… +21 more, Hasegawa H, Nakatani D, Okada K, Kida H, Kitamura T, Tanaka N, Masuda M, Watanabe T, Minamiguchi H, Egami Y, Oka T, Miyoshi M, Okada M, Matsuda Y, Kawasaki M, Inoue K, Hikoso S, Dohi T, Sotomi Y, Sakata Y, OCVC-Arrhythmia Investigators
El-Assaad I, Hammond BH, Clark BC
… +10 more, Tanel RE, Dubin AM, Law I, Marino BS, Cassedy A, Vickers Saarel E, Shah MJ, Kannankeril PJ, Dasgupta S, Mah DY
Cano-Valls A, Martinez Monblan MA, Carro-Fernández E
… +12 more, Niebla M, Domingo R, Hevia-Puyo S, Venturas-Nieto M, Borras R, Tolosana JM, Porta-Sánchez A, Guichard JB, Althoff TF, Roca-Luque I, Mont L, Guasch E
BACKGROUND: Atrial fibrillation (AF) is associated with reduced quality of life and frequent hospitalizations. Integrated nurse-led care (NLC) has proven beneficial in unselected AF patients, but evidence specific to pat...BACKGROUND: Atrial fibrillation (AF) is associated with reduced quality of life and frequent hospitalizations. Integrated nurse-led care (NLC) has proven beneficial in unselected AF patients, but evidence specific to patients undergoing catheter ablation is limited. We aimed to assess the impact of a structured nurse-led intervention in patients undergoing first-time AF ablation. METHODS: NURSECAT-AF was a single-center prospective randomized clinical trial comparing usual care with NLC, which incorporated an AF educational program, peri-procedural support, and risk factor management. Consecutive patients without heart failure referred for first-time AF ablation were randomized to NLC or usual care. NLC visits were scheduled at 15 days preablation, 15 days, and 6 months postablation. The primary end point was quality of life at 12 months postablation using the arrhythmia-specific scale in tachycardia and arrhythmia. Secondary outcomes included arrhythmia recurrence, readmissions and emergency visits, and symptom burden at 1 year and AF knowledge and satisfaction at 3 months. RESULTS: Of 116 patients screened, 66 were randomized (33 per group; mean age 63±10 years; 67% male). At 12 months, the NLC group showed statistically significant better quality of life (baseline-adjusted arrhythmia-specific scale in tachycardia and arrhythmia difference +4 points [95% CI, 1.8-6.3]; =0.0007) than usual care, and presented with less arrhythmia recurrences (odds ratio, 0.2 [95% CI, 0.05-0.78]) and emergency visits (odds ratio, 0.2 [95% CI, 0.06-0.66]). Patients assigned to NLC also presented with a lower symptom burden, higher satisfaction, and greater disease knowledge. Risk factor profile was improved in the NLC group, with higher rates of smoking cessation, engagement in regular physical activity, and weight optimization. Nurse-led management enabled more frequently diagnosing obstructive sleep apnea. CONCLUSIONS: Nurse-led, integrated care for patients undergoing AF ablation improves the quality of life, clinical outcomes, and risk factor management at 1 year postprocedure. These findings support the incorporation of structured nurse-led interventions in the peri-ablation care pathway. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05333445.
Yogeswaran V, Brody JA, Sitlani CM
… +8 more, Wiggins KL, Prutkin JM, C Bis J, Yang E, Shah AM, Akoum N, Ye T, Floyd JS
Circ Arrhythm Electrophysiol
· 2026 Mar · PMID 41744085
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BACKGROUND: Atrial cardiopathy often precedes atrial fibrillation (AF) and has emerged as an independent risk factor for cardiovascular outcomes. However, previous studies have been limited in size and have overlooked th...BACKGROUND: Atrial cardiopathy often precedes atrial fibrillation (AF) and has emerged as an independent risk factor for cardiovascular outcomes. However, previous studies have been limited in size and have overlooked the right atrium. METHODS: In 51 693 UK Biobank participants without prevalent AF, we assessed biatrial volumes and emptying fraction from cardiac magnetic resonance imaging using deep learning segmentation. We evaluated associations with new-onset AF, ischemic stroke, heart failure, and dementia, conducted a genome-wide association study, and evaluated causal associations using Mendelian randomization. RESULTS: Among 51 693 adults, the mean (SD) age was 65 (7.7) years, and 24 584 (48%) were male. During the 4-year follow-up, 964 (1.9%) developed AF, 266 (0.5%) developed ischemic stroke, 365 (0.7%) developed heart failure, and 72 (0.1%) developed dementia. After adjustment for clinical risk factors, both left and right atrial measures were associated with new-onset AF (left atrial minimal volume; hazard ratio, 1.55 [95% CI, 1.48-1.62]), ischemic stroke, and heart failure, with stronger associations in women. Left atrial minimal volume was also associated with dementia. Our genome-wide association study identified 51 (27 novel) genetic associations with atrial measures, many of which do not overlap with established AF loci. Genetic correlations revealed that each atrium had varying correlations with cardiometabolic risk factors, and Mendelian randomization demonstrated that left atrial measures had direct causal effects on AF and stroke risk. However, the stroke associations were attenuated after accounting for AF variants. CONCLUSIONS: In this largest assessment of biatrial structure and function to date, both left and right atrial cardiopathies were independently associated with increased risk of adverse cardiovascular events. We identified several novel genetic loci for atrial traits and observed unique genetic correlations between left and right atrial traits and cardiovascular phenotypes, providing insight into chamber-specific remodeling. Several of these measures are likely to be causal determinants of cardiovascular complications previously attributed to AF.
Rodrigo M, Ruipérez-Campillo S, Ganesan P
… +2 more, Feng R, Narayan SM
Circ Arrhythm Electrophysiol
· 2026 Mar · PMID 41744082
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BACKGROUND: Mapping of heart rhythms is influenced by the size and configuration of the mapping electrodes. Whether a recorded electrogram represents near (local) or remote activity influences diagnosis and treatment, ye...BACKGROUND: Mapping of heart rhythms is influenced by the size and configuration of the mapping electrodes. Whether a recorded electrogram represents near (local) or remote activity influences diagnosis and treatment, yet is affected by mapping characteristics that are often undefined. METHODS: We developed biophysical computational models to predict interactions between the recording tool and cardiac tissue in coherent and disorganized rhythms, which we validated in clinical recordings. RESULTS: Biophysical computational models demonstrated the ability to quantify and visualize the recording antennae for different electrode configurations. Our results show that unipolar electrograms reflected a recording antenna within 3-dimensional ellipsoids of radius 8 mm across-tissue and 2.7 mm transmurally. Bipolar electrogram antennae align with propagation direction in ellipsoids of long axis radius 1.7, 5.7, and 8.3 mm for 2, 5, and 10 mm spacing, respectively, and often extend beyond the physical extent of electrodes. Notably, omnipolar electrograms, constructed from orthogonal bipoles in a triangular configuration, retained some directional preferences of bipolar electrograms, with a complex relationship between electrode orientation and wave direction. When tested clinically on high-resolution, narrow field (grid) catheters and moderate-to-low resolution, global (basket) catheters, antennae varied more with electrode type (correlation coefficient of 0.43 unipolar, 0.05 bipolar, and 0.26 omnipolar; <0.001) and spacing (correlation coefficient of 0.36 versus 0.42; =0.002) than the precise electrode size. CONCLUSIONS: This novel computational-clinical system approach enabled us to systematically compare electrode configurations. This work may help interpret signals in complex biological rhythms, such as atrial fibrillation, and may influence the design of novel catheter configurations and signal processing approaches to identify local tissue signals.
Ukita K, Popescu SS, Schmidt V
… +81 more, Pürerfellner H, Sommer P, Sohns C, Veltmann C, Steven D, Chun KRJ, Maury P, Gandjbakhch E, Willems S, Beiert T, Iden L, Füting A, Spittler R, Richter S, Schade A, Kuniss M, Wunderlich C, Shin DI, Grosse Meininghaus D, Bonsels M, Reek D, Wiegand U, Bauer A, Metzner A, Eckardt L, Krahnefeld O, Sticherling C, Kühne M, Nguyen DQ, Roten L, Linz D, van der Voort P, Mulder BA, Vijgen J, Almorad A, Guenancia C, Fauchier L, Boveda S, De Greef Y, Da Costa A, Jais P, Milhem A, Jesel L, Garcia R, Poty H, Khoueiry Z, Seitz J, Laborderie J, Mechulan A, Brigadeau F, Zhao A, Saludas Y, Piot O, Ahluwalia N, Martin CA, Chen J, Antolic B, Leventopoulos G, Özcan EE, Yorgun H, Cay S, Yalin K, Botros MS, Jędrzejczyk-Patej E, Inaba O, Okumura K, Ejima K, Khakpour H, Catanzaro JN, Reddy V, Natale A, Blessberger H, Yang B, Vogler J, Kuck KH, Merino JL, Saguner AM, Keelani A, Heeger CH, Tilz RR, POTTER-AF Investigators
The current guidelines contraindicate intravenous amiodarone in patients with Wolff-Parkinson-White syndrome presenting with preexcited atrial fibrillation (AF) due to the risk of degeneration into ventricular fibrillati...The current guidelines contraindicate intravenous amiodarone in patients with Wolff-Parkinson-White syndrome presenting with preexcited atrial fibrillation (AF) due to the risk of degeneration into ventricular fibrillation (VF). However, these recommendations are based predominantly on isolated case reports, which is concerning given the drug's widespread global use as a first-line antiarrhythmic in resource-limited settings. To evaluate the safety of intravenous amiodarone in this context, we conducted a systematic review of (1) studies enrolling patients with electrocardiographically confirmed preexcited AF who received intravenous amiodarone and (2) studies quantifying antegrade accessory-pathway effective refractory period during intravenous amiodarone administration. All observational and interventional studies assessing patients with preexcited AF were pooled under a conjugate β-binomial model with prespecified weak priors to estimate the risk of VF during or following infusion. Concomitantly, to assess real-world access to alternative class IIa/IIb European Society of Cardiology-recommended antiarrhythmic agents for preexcited AF, we performed a multinational survey of Latin American emergency departments. Twelve studies comprising 177 patients were included in the review (7 case reports, 2 cohorts, 3 before-and-after interventional studies). Four case reports described transient ventricular rate acceleration or VF following intravenous amiodarone. However, across the observational and interventional cohorts assessing patients with preexcited AF (n=146), no acceleration or VF was observed. The posterior mean estimates of VF risk ranged 0.12% to 0.68% over priors. Across 3 interventional before-and-after studies, there was a significant increase in the anterograde effective refractory period of the atrioventricular node and AP following amiodarone administration. The survey responses from 10 emergency centers indicated that none had access to class IIa/IIb indicated agents, while all had intravenous amiodarone available. Taken together, population-level evidence suggests that the risk of VF in preexcited AF following intravenous amiodarone administration is rare. In settings where guideline-recommended drugs are inaccessible, intravenous amiodarone may represent a clinically reasonable alternative for rhythm or rate control.
Li Y, Pan NC, Xu C
… +5 more, Qiao L, Wang X, Shu W, Yu T, Wang Y
Circ Arrhythm Electrophysiol
· 2026 Mar · PMID 41725548
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BACKGROUND: The cingulo-insular region is crucial for modulating cardiac activity. However, the distinct roles of its anatomic subdivisions in modulating sympathetic-parasympathetic balance remain poorly defined. We aime...BACKGROUND: The cingulo-insular region is crucial for modulating cardiac activity. However, the distinct roles of its anatomic subdivisions in modulating sympathetic-parasympathetic balance remain poorly defined. We aimed to explore the distinct contributions of subdivisions within the cingulo-insular region to modulating cardio-autonomic balance. METHODS: In this prospective observational study, patients with drug-resistant epilepsy undergoing stereo-electroencephalography with electrical cortical stimulation of the cingulo-insular region were enrolled. Stereo-electroencephalography and ECG signals were synchronously recorded during electrical cortical stimulation of the cingulo-insular region. Heart rate variability and R-R interval analyses were conducted to assess cardiac sympathetic-parasympathetic balance. The correlation coefficient between heart rate variability and the strength of phase-amplitude coupling in stereo-electroencephalography was calculated before and after stimulation. RESULTS: Data from 33 patients (70 electrode contacts, 287 trials) were analyzed. Stimulation of the anterior cingulate gyrus enhanced parasympathetic activity, correlated with increased local phase-amplitude coupling strength. The left anterior cingulate gyrus stimulation increased pNN50 (median difference, -5.00% [95% CI, -17.99 to -0.16]; =0.044); right anterior cingulate gyrus stimulation increased the SD of all normal-to-normal intervals (median difference, -14.22 ms [95% CI, -26.68 to -1.63]; =0.019) and SD2 (median difference, -19.49 ms [95% CI, -33.26 to -3.22]; =0.013). Meanwhile, stimulation of the posterior insula significantly reduced the parasympathetic component of heart rate variability and short-term R-R interval. The left posterior insula decreased the SD1/SD2 ratio (median difference, 0.08 [95% CI, 0.03-0.15]; =0.005); right posterior insula decreased power in the high-frequency range (median difference, 25.30 ms [95% CI, 3.98-49.35]; =0.013) and the approximate entropy (median difference, 0.15 [95% CI, 0.04-0.29]; =0.004). CONCLUSIONS: Within the cingulo-insular region, the anterior cingulate gyrus is associated with a relative cardio-parasympathetic dominance, while the posterior insula is linked to a relative cardio-sympathetic dominance. These findings provide a deeper understanding of the neural modulation of cardio-autonomic balance, and may have implications for the prevention and treatment of cardio-autonomic dysfunction in neurological disorders.
BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. We sought to investigate the predictive value of serum metabolomics for 5-year incident AF in the context of clinical and polyg...BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. We sought to investigate the predictive value of serum metabolomics for 5-year incident AF in the context of clinical and polygenic risk score (PRS) stratification tools. METHODS: We studied a cohort of 240 628 patients UK Biobank participants with proton nuclear magnetic resonance spectroscopy measurements of 170 serum metabolites at enrollment. Five-year incidence of AF was assessed using Cox proportional hazards models. Cohorts for Heart and Aging Research in Genomic Epidemiology-AF (CHARGE-AF) and AF polygenic risk score (AF-PRS) scores were used as benchmark risk models for comparison. Models were trained on 80% of the cohort, and performances were validated on the remaining 20% cohort. Performance of clinical, AF-PRS, and combined metabolomics models was evaluated using time-dependent area under the receiver operating characteristic curve, net reclassification improvement, and relative integrated discrimination improvement analysis. RESULTS: During follow-up, 4174 (1.7%) participants developed AF. After training a model on the full metabolomics panel in addition to Cohorts for Heart and Aging Research in Genomic Epidemiology-AF and AF-PRS, the final model retained 8 metabolites. Creatinine level was associated with increased risk (hazard ratio, 1.01 per 1 SD log-transformed value [95% CI, 1.00-1.03]) while linoleic acid level (hazard ratio, 0.985 [0.979-0.994]) was associated with decreased risk of AF. The addition of metabolomics to the CHARGE-AF+AF-PRS model improved risk prediction (5-year time-dependent area under the receiver operating characteristic curve, 0.789 [0.776-0.802] versus 0.755 [0.738-0.772]; <0.05) and stratification on the validation set (NRI: 11.1%, NRI: 3.1%, IDI: 11.6%). A model using only age, sex, metabolomics, and AF-PRS had fair risk prediction on the validation set (5-year time-dependent area under the receiver operating characteristic curve, 0.787 [0.773-0.801]). CONCLUSIONS: The addition of metabolomics to clinical and genomic risk scores improves the prediction of 5-year incident AF. A risk stratification tool using age, sex, and serum metabolomics and AF-PRS provides excellent AF risk prediction. Mechanisms by which specific metabolites reflect AF risk require further exploration.
BACKGROUND: Nanosecond pulsed field ablation, which offers potential benefits, such as reduced muscle contraction, may enable procedures to be performed under local anesthesia.To evaluate the 12-month safety and efficacy...BACKGROUND: Nanosecond pulsed field ablation, which offers potential benefits, such as reduced muscle contraction, may enable procedures to be performed under local anesthesia.To evaluate the 12-month safety and efficacy of a novel high-repetition frequency nanosecond pulsed field ablation for treating paroxysmal atrial fibrillation. METHODS: The prospective, multicenter, single-arm trial SCENA-AF study (Safety-and-effectiveness Clinical Evaluation of Nanosecond-pulse Ablation for Atrial Fibrillation) was conducted across 11 Chinese centers. Symptomatic drug-refractory patients with paroxysmal atrial fibrillation aged 18 to 80 years underwent pulmonary vein isolation using a commercial nanosecond pulsed field ablation system. The primary efficacy end point was freedom from documented atrial fibrillation, atrial flutter, or atrial tachycardia ≥30 seconds from 91 to 365 days postablation without use of class I and III antiarrhythmic drugs. The primary safety end point was freedom from device- or procedure-related death, stroke, transient ischemic attacks, or other major complications during the procedure and 12-month follow-up. RESULTS: Of the 166 enrolled patients who underwent the PFA procedures, 162 completed follow-up. Acute pulmonary vein isolation success was 100% for targeted veins. At 12 months, 88.49% (95% CI, 82.54%-92.50%) met the primary efficacy end point. No device- or procedure-related death, stroke, or transient ischemic attacks occurred. Notably, 92.77% of procedures were performed under local anesthesia and conscious sedation. Procedure-specific serious adverse events occurred in 2.41% of patients and were limited to access-site hematomas or pseudoaneurysms that resolved. No clinical hemolysis signs or symptoms were observed. CONCLUSIONS: The novel high-repetition-frequency nanosecond pulsed field ablation demonstrated high 12-month efficacy and a favorable safety profile for paroxysmal atrial fibrillation treatment. The ability to perform most procedures under local anesthesia with conscious sedation, with general anesthesia rarely needed, highlights a potential advantage of this technology. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov; Unique identifier: NCT06039722.
Cespón-Fernández M, Nakasone K, Pannone L
… +13 more, Sieira J, Della Rocca DG, Almorad A, Overeinder I, Bala G, Ströker E, Eltsov I, Padisák A, Vetta G, Brugada P, Chierchia GB, de Asmundis C, Sarkozy A
BACKGROUND: Reversible pulsed field ablation (PF) can temporarily block cardiomyocyte conduction, potentially identifying critical target sites before creating definitive lesions. However, PF local capture might interfer...BACKGROUND: Reversible pulsed field ablation (PF) can temporarily block cardiomyocyte conduction, potentially identifying critical target sites before creating definitive lesions. However, PF local capture might interfere with the tachycardia mechanism. The aim of the study was to characterize the responses of nontriggered PF pulses to serve as a novel clinical mapping tool in reentrant atrial flutter. METHODS: PF pulses were delivered in and outside of the circuit using a 9-mm lattice-tip catheter in 30 reentrant atrial tachycardias in 26 patients. The presence of local capture and responses to PF pulses was characterized. RESULTS: Out of 163 PF pulses analyzed, 56 (34.4%) showed atrial capture and propagation. Propagated versus Nonpropagated PF cohorts were compared. The coupling interval of propagated PF pulses was significantly longer (195.3±69.2 msec versus 98.9±77.2 msec; <0.001). Globally, 4 responses were observed: tachycardia termination (11.0%), stable tachycardia cycle length (TCL) prolongation (9.8%), transient irregular TCL variations (3.1%), and no change in activation sequence and TCL (76.1%). Propagation was only associated with irregular TCL variations (8.9% versus 0%, =0.002). Tachycardia termination or TCL prolongation occurred only when PF was delivered in the reentry circuit (100% specificity). Termination occurred exclusively in the critical isthmus (100% specificity regardless of propagation), and stable TCL prolongation occurred in 93.8% and 6.2% of the cases in the isthmus and outer loop, respectively (100% specificity for nonpropagated and 83.3% specificity for propagated PF to localize the isthmus). Sensitivity of termination or stable TCL prolongation for identifying the critical isthmus was moderate (38.8%) and influenced by isthmus width (11.7±1.7 mm versus 22.9±2.1 mm; <0.001). Reproducibility of PF pulses, determined by consecutive pulses delivered at the same site producing identical responses, was high (82.9%). CONCLUSIONS: PF mapping is a novel, feasible, and reproducible tool for identifying critical sites in reentrant atrial tachycardia with narrow isthmuses that may be improved through optimized triggering and dose titration.
BACKGROUND: A limitation of ablation for scar-related ventricular tachycardia (VT) is insufficient lesion depth to address nonendocardial substrate. Ultra-low temperature cryoablation (ULTC) at -196°C has been shown to c...BACKGROUND: A limitation of ablation for scar-related ventricular tachycardia (VT) is insufficient lesion depth to address nonendocardial substrate. Ultra-low temperature cryoablation (ULTC) at -196°C has been shown to create transmural lesions in preclinical models. Early human studies in Europe have shown safety and efficacy. METHODS: An EFS (Early Feasibility Study) was designed in collaboration with the Food and Drug Administration as a prospective, nonrandomized evaluation of the acute safety and effectiveness of ULTC ablation for scar-related VT. RESULTS: Twenty patients (age 63±14 years; 5% women; LVEF 36±13%; 45% ischemic and 55% nonischemic) underwent VT ablation with ULTC from September to December 2023 at 4 clinical sites. Ablation strategies included substrate modification during sinus rhythm, as well as activation and entrainment mapping when hemodynamics permitted. Mean ULTC lesions were 9.9±3.6, with a total freeze duration of 47±22 minutes. Noninducibility of the targeted VTs was observed in 13 of 14 patients with inducibility tested both pre- and postablation. There were no procedural strokes, tamponades, or deaths. One suspected cardiac perforation without tamponade was conservatively managed. One patient was excluded from the follow-up efficacy analysis due to RF use, and another lacked postacute follow-up due to death from heart failure 1 month post-procedure. Among surviving per-protocol patients, 23.7±4.3 weeks of freedom from VT and implantable cardioverter defibrillator shock were 61.1% (11/18) and 83.3% (15/18), respectively. CONCLUSIONS: In a US EFS, ULTC therapy was safe and effective for the treatment of scar-related VT. The EFS design, in collaboration with the Food and Drug Administration, represents an important initiative to accelerate the evaluation of new medical technologies in the United States. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05675865.
BACKGROUND: In the presence of sustained monomorphic ventricular tachycardia (VT), catheter ablation may be an option in congenital heart disease. However, the heterogeneity of underlying congenital heart disease and pre...BACKGROUND: In the presence of sustained monomorphic ventricular tachycardia (VT), catheter ablation may be an option in congenital heart disease. However, the heterogeneity of underlying congenital heart disease and previous cardiac surgeries is associated with a unique and particularly complex substrate. The aim of the study was to investigate whether preprocedural 3-dimensional anatomic and substrate reconstruction based on cardiac computed tomography scan or magnetic resonance imaging could reliably identify VT substrate and ablation targets. METHODS: Consecutive patients with cardiac computed tomography or magnetic resonance imaging referred for VT ablation in 5 congenital electrophysiology centers were included. Three observers, electrophysiologists, blinded to the ablation procedure and each other, annotated potential ablation targets on 3-dimensional imaging reconstructions with a dedicated software (InHeart). Once completed, the annotations were compared between observers and with the ablation target(s) on the electroanatomical mapping generated during the procedures. RESULTS: Forty patients (mean age, 38±12 years; 67.5% male) underwent VT ablation, including 28 with a history of spontaneous sustained VT. VT was inducible in 97.5% of cases, with an acute success rate of ablation of 92.5%. Preprocedural imaging identified VT substrate in concordance with electroanatomical mapping in 87.5% of cases. There was a high degree of agreement between the observers. Positive interobserver agreement was complete in 65.0% of cases, moderate in 22.5%, and poor in 5.0%. Considering the total number of isthmuses identified by imaging in comparison with electroanatomical mapping, the sensitivity of imaging was 87.0%, and its positive predictive value was 77.0%. CONCLUSIONS: In our series, 3-dimensional anatomic reconstruction enabled identification of the critical VT substrate in most patients with complex congenital heart disease, particularly those with anatomically based reentrant circuits. Substrate target can be identified by operators with good interobserver reproducibility. This approach may guide VT ablation in these challenging cases.
De Marco C, Asatryan B, Te Riele ASJM
… +32 more, Di Marco A, Gasperetti A, Delinière A, Roberts JD, Jensen HK, Davies B, Krahn AD, Tadros R, Svensson A, Castelletti S, Crotti L, Platonov PG, Borowiec K, Biernacka EK, Arbelo E, David LP, Saguner AM, Healey JS, Brunckhorst C, Cappelletto C, Stolfo D, Merlo M, Rootwelt-Norberg C, Haugaa KH, Duru F, van Tintelen JP, Velthuis BK, Calkins H, Zimmerman SL, James CA, Bosman LP, Cadrin-Tourigny J
BACKGROUND: The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator estimates the risk of incident sustained ventricular arrhythmia (VA) and performs well in ARVC populations meeting 2010 Task Force Cr...BACKGROUND: The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator estimates the risk of incident sustained ventricular arrhythmia (VA) and performs well in ARVC populations meeting 2010 Task Force Criteria. However, the calculator includes no measure of left ventricular (LV) structure and function, while late gadolinium enhancement (LGE) on cardiac magnetic resonance shows promise in arrhythmic risk prediction. This study aims to evaluate whether LV LGE on cardiac magnetic resonance can further refine ARVC VA risk stratification. METHODS: Patients with definite ARVC, no prior sustained VA, and contrast-enhanced cardiac magnetic resonance at baseline were followed at 17 centers. Survival analyses were performed to assess LV LGE effect on VA prediction, and its incremental prognostic value on the risk calculator was evaluated using Cox proportional hazard models. The presence of high-risk LGE, defined as LV epicardial, transmural, or combined septal and free-wall LGE, was studied as a sensitivity analysis. RESULTS: Of 385 patients (39.6±15.4 years, 39.7% male, 54.0% probands), 132 (34.3%) had LV LGE on cardiac magnetic resonance, with 98 (25.5%) having a high-risk pattern. Over 3.1 [1.2-5.8] years of follow-up, 67 (17.4%) patients experienced VA. In univariable analysis, both LV LGE (hazard ratio, 1.82; =0.014) and high-risk LV LGE (hazard ratio, 1.85; =0.017) were associated with higher risk for VA. However, after adjusting for the ARVC calculator-estimated risk, the presence of neither LV LGE (=0.85) nor high-risk LV LGE (=0.87) independently predicted sustained VA. (graphic abstract). CONCLUSIONS: While associated with the risk of VA in ARVC, LV LGE did not provide incremental prognostic value for incident VA risk prediction compared with the ARVC risk calculator.
Song Z, Sui F, Huang X
… +4 more, Liu MB, Gao W, Weiss JN, Qu Z
Circ Arrhythm Electrophysiol
· 2026 Feb · PMID 41603028
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BACKGROUND: Cardiovascular disease is the number 1 killer in industrialized countries, with sudden cardiac death due to ventricular arrhythmias representing a major component. To reduce sudden cardiac death, accurate ris...BACKGROUND: Cardiovascular disease is the number 1 killer in industrialized countries, with sudden cardiac death due to ventricular arrhythmias representing a major component. To reduce sudden cardiac death, accurate risk prediction and development of effective preventive treatments remain major challenges. In this study, we explored the possibility of using a population-based computational modeling approach to perform virtual clinical trials for antiarrhythmic drug discovery and drug safety testing. METHODS: We developed genetically diverse populations of 1-dimensional cardiac tissue models for both normal hearts and hearts with long QT syndromes (LQT1, LQT2, and LQT3) based on matching the models to the clinically measured distributions of corrected QT intervals for each condition. RESULTS: Using a doubling of the L-type calcium current to mimic sympathetic stress, the population models exhibited a similar incidence of arrhythmias as observed in corresponding clinical studies for each condition. We demonstrated that the model populations (1) accurately predicted arrhythmia risk under normal and diseased conditions; (2) could be used to assess the effectiveness of a therapeutic strategy, namely shifting the steady-state inactivation curve of the L-type calcium current; and (3) accurately predicted the cardiotoxicity of a series of drugs when compared with their known clinical profiles. CONCLUSIONS: The population-based modeling approach outlined here shows promise as a computational platform that can directly take advantage of data from human clinical studies to improve arrhythmia risk prediction, test antiarrhythmic therapies, and assess cardiotoxicity of drugs.