Trongtorsak A, De La Rosa Martinez J, Crawford TC
… +36 more, Bogun FM, Gu X, Puroll E, Ellenbogen KA, Chicos AB, Roukoz H, Zimetbaum PJ, Kalbfleisch SJ, Murgatroyd FD, Steckman DA, Rosenfeld LE, Soejima K, Bhan AK, Vedantham V, Dickfeld TL, DeLurgio DB, Platonov PG, Zipse MM, Nishiuchi S, Ortman ML, Narasimhan C, Patton KK, Rosenthal DG, Mukerji SS, Hoogendoorn JC, Zeppenfeld K, Torosoff M, Judson MA, Martin K, Madias C, Hermel M, Nour K, Torbey E, Sauer WH, Kron J, Cardiac Sarcoidosis Consortium
Circ Arrhythm Electrophysiol
· 2025 Jul · PMID 40557494
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BACKGROUND: Differences in cardiac sarcoidosis between racial groups remain understudied. Therefore, this study aims to explore race differences in patients with cardiac sarcoidosis. METHODS: We analyzed data from the Ca...BACKGROUND: Differences in cardiac sarcoidosis between racial groups remain understudied. Therefore, this study aims to explore race differences in patients with cardiac sarcoidosis. METHODS: We analyzed data from the Cardiac Sarcoidosis Consortium, an international registry including over 25 centers. The primary clinical outcome was a composite end point of all-cause mortality, left ventricular assist device implantation, heart transplantation, or implantable cardioverter defibrillator therapy. RESULTS: A total of 619 patients were included in the study (362 White, 193 Black, and 64 other races). Black patients were diagnosed with cardiac sarcoidosis at a younger age (50.5±11.8 versus 53.7±10.5 years old; =0.010) compared with White patients. Left ventricular ejection fraction was significantly lower in Black patients (44.6±15.4 versus 48.3±14.0; =0.008). In addition, extracardiac involvement in the lungs (80.3% versus 72.7%; =0.046), skin (22.8% versus 12.4%; =0.002), and eyes (13.5% versus 5.5%; =0.001) was more prevalent in Black patients. Patients had significantly higher rates of hypertension (69.9% versus 50.6%; <0.001), diabetes (37.8% versus 21.0%; <0.001), smoking (40.9% versus 26.8%; <0.001), chronic obstructive pulmonary disease or emphysema (15.5% versus 4.1%; <0.001), and chronic kidney disease (25.9% versus 12.4%; <0.001). The treatment patterns including glucocorticoid (71% versus 74.3%; =0.4), glucocorticoid-sparing (53.4% versus 59.9%; =0.14), and implantable cardioverter defibrillator or cardiac resynchronization implantation (75.6% versus 73.8%; =0.63), were similar. No significant differences were found in the primary outcome (29.5% in Black versus 28.5% in White; =0.79). Subgroup analysis of the primary outcome also revealed no significant differences in both the left ventricular ejection fraction >35% group (24.1% in Black versus 25.9% in White; =0.72) and the left ventricular ejection fraction ≤35% group (51% versus 42.5%; =0.35). CONCLUSIONS: Black patients with cardiac sarcoidosis exhibited significantly higher rates of lung, skin, and eye involvement and comorbidities, but had similar cardiac clinical outcomes and all-cause mortality compared with White patients. Nonetheless, ascertainment bias cannot be excluded.
Roy A, O'Shea C, Dasí A
… +18 more, Patel L, Cumberland MJ, Nieves D, Canagarajah HS, Thompson S, Azad A, Price AM, Hall C, Alvior AMB, Rath P, Davies B, Rodriguez B, Holmes AP, Pavlovic D, Townend JN, Geberhiwot T, Gehmlich K, Steeds RP
Circ Arrhythm Electrophysiol
· 2025 Jul · PMID 40557493
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BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by α-Gal A (α-galactosidase A) deficiency, resulting in multiorgan accumulation of sphingolipid, namely globotriaosylceramide. This triggers...BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by α-Gal A (α-galactosidase A) deficiency, resulting in multiorgan accumulation of sphingolipid, namely globotriaosylceramide. This triggers ventricular myocardial hypertrophy, fibrosis, and inflammation, driving arrhythmia and sudden death. Atrial fibrillation is common, yet the cellular mechanisms accounting for this are unknown. METHODS: To address this, we conducted ECG analysis from a large cohort of 115 adults with FD at varying cardiomyopathy stages. ECG P-wave characteristics were compared with non-FD controls. Cellular contractile and electrophysiological function were examined in a novel atrial cellular FD model developed and imputed into in silico atrial models to provide insight into mechanisms of arrhythmia. Induced pluripotent stem cells were genome-edited using Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 to introduce the p. variant and differentiated into induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-CMs). Contraction, calcium handling, and electrophysiology experiments were conducted. Bi-atrial in silico models were developed with cellular changes as in p. iPSC-CMs. RESULTS: ECG analysis demonstrated P-wave duration and PQ interval shortening in FD adults before the onset of cardiomyopathy. Patients with FD exhibited a higher incidence of premature atrial contractions and increased risk of atrial fibrillation compared with healthy controls. p. iPSC-CMs were deficient in α-Gal A and exhibited globotriaosylceramide accumulation. Atrial p. iPSC-CMs demonstrated a more positive diastolic membrane potential, faster action potential upstroke velocity, greater incidence of delayed afterdepolarizations, greater contraction force, and alterations in calcium handling compared with wild-type iPSC-CMs. Simulations with these changes in the in silico models resulted in similar P-wave morphology changes to those seen in early FD cardiomyopathy and increased atrial fibrillation vulnerability. CONCLUSIONS: These findings provide novel insights into underpinning mechanisms for atrial arrhythmia and a rationale for early P-wave changes in FD. These may be targeted to develop therapeutic strategies to reduce the arrhythmic burden in FD.
Lubitz SA, McConnell MV, Selvaggi C
… +8 more, Krishnamoorthy A, Atlas SJ, McManus DD, Pagoto S, Singer DE, Pantelopoulos A, Foulkes AS, Faranesh AZ
Circ Arrhythm Electrophysiol
· 2025 Jul · PMID 40557492
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BACKGROUND: Wrist-worn wearables can detect irregular heart rhythms using photoplethysmography, but ECGs are required to confirm atrial fibrillation (AF). We sought to determine the frequency of a recurrent irregular hea...BACKGROUND: Wrist-worn wearables can detect irregular heart rhythms using photoplethysmography, but ECGs are required to confirm atrial fibrillation (AF). We sought to determine the frequency of a recurrent irregular heart rhythm detection (IHRD; ≥30 minutes of an irregular rhythm), estimate the potential diagnostic yield of different electrocardiographic monitoring strategies for confirming AF, and identify predictors of recurrent IHRDs. METHODS: The Fitbit Heart Study enrolled wrist-worn photoplethysmography device users without diagnosed AF. Of 455 699 participants, 1057 who wore and returned a 1-week ECG patch monitor after receiving an IHRD were analyzed. Baseline clinical data, device-derived metrics, IHRDs during follow-up, and electrocardiographic patch data were used for analysis. RESULTS: A total of 570 (53.9%) participants were aged 40 to 64 years, 422 (39.9%) were aged ≥65 years, and 510 (48.2%) were women. Median follow-up after ECG patch initiation was 80 days (interquartile range, 45-122 days). The frequency of another IHRD was 57.2% (95% CI, 53.1%-60.9%) at 3 months. After an initial IHRD, the estimated diagnostic yield for AF with a 10-second ECG was 7.6% (95% CI, 6.2%-9.0%), twice-daily 30-second ECGs over 1 week 19.0% (95% CI, 16.7%-21.2%), 24-hour monitor 17.4% (95% CI, 15.5%-19.3%), 1-week monitor 32.2% (95% CI, 29.4%-35.0%), 2-week monitor 46.8% (95% CI, 42.7%-50.8%), and 4-week monitor 60.8% (95% CI, 56.5%-65.1%). The risk of a recurrent IHRD was greater with older age (<0.001), male sex (=0.001), vascular disease (=0.03), longer initial runs of consecutive IHRDs at detection (=0.02), and less nightly sleep (=0.03). CONCLUSIONS: Irregular heart rhythms are common after initial detection using a wrist-worn wearable device. Longer electrocardiographic monitoring periods increase the likelihood of confirming AF. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04380415.
Duytschaever M, De Smet M, Martens J
… +9 more, El Haddad M, De Becker B, Francois C, Tavernier R, Van den Abeele R, Hendrickx S, Vandersickel N, Le Polain de Waroux JB, Knecht S
BACKGROUND: Reentry (macro or localized) is historically described as multiple pathways that are separated by barriers (either anatomic or functional) and involve active and passive loops (identified by electro-anatomic...BACKGROUND: Reentry (macro or localized) is historically described as multiple pathways that are separated by barriers (either anatomic or functional) and involve active and passive loops (identified by electro-anatomic and entrainment mapping, EAM/ETM). Some reentrant atrial tachycardia (AT) cases are characterized by challenging activation patterns and unexpected ablation responses. A recent translational study, focusing on topology (TOP) and the role of boundaries, suggests that thinking topology within EAM/ETM might offer extra control during mapping and ablation of reentrant AT. We aimed to propose and prospectively validate a workflow (EAM/ETM+TOP) in which we integrate topological thinking within an EAM/ETM workflow for mapping and ablation of left-sided (left atrium) AT. METHODS: The integrated workflow was performed in 88 left atrium reentrant AT cases. After EAM/ETM, the number of loops and potential ablation strategy were verified against the number of critical and noncritical boundaries (critical boundary [CB], non-CB). Linear radiofrequency lesions were deployed to connect both CBs, preferably by one direct CB-CB line. RESULTS: EAM/ETM+TOP-based mapping was feasible in all cases and led to a diagnosis of a 2B topology with single-loop activation in 33 cases and a≥3B topology with dual-loop activation in 55 cases. In 87 out of 88 cases, subsequent ablation via a direct CB-CB approach (n=75), an indirect CB-non-CB-CB (n=9), or an indirect CB-non-CB-non-CB-CB approach (n=3) led to successful termination of AT. No unexpected changes in tachycardia cycle length occurred. After a median follow-up of 356 (inter-quartile range, 228-537) days, 16 patients experienced recurrence of AT (18%). CONCLUSIONS: Thinking topology within an EAM/ETM workflow may offer extra control during mapping and ablation of left-sided reentrant AT.
De Silva K, Campbell TG, Bennett RG
… +12 more, Turnbull S, Bhaskaran A, Anderson RD, Davey C, O'Donohue AK, Schindeler A, Selvakumar D, Kotake Y, Hsu CJ, Chong JJH, Kizana E, Kumar S
BACKGROUND: Accurate delineation of scar patterns is valuable for guiding catheter ablation of ventricular tachycardia. We hypothesized that scar and its pattern of distribution can be determined from intracardiac electr...BACKGROUND: Accurate delineation of scar patterns is valuable for guiding catheter ablation of ventricular tachycardia. We hypothesized that scar and its pattern of distribution can be determined from intracardiac electrograms using computational signal processing and that further improvements in classification can be achieved with a convolutional neural network. METHODS: A total of 5 sheep underwent anteroseptal infarction (plus 1 healthy control) with electroanatomic mapping (129±12 days post-infarct). A whole-heart histological model of the postinfarction scar was created and coregistered to ventricular electrograms. Electrograms were matched to scar pattern categories; no scar, at least endocardial scar: at least intramural scar (intramural scar sparing the endocardium), or epicardial-only scar (epicardial scar sparing the endocardium/intramural space). A suite of signal-processing features was extracted from bipolar electrograms. Furthermore, bipolar and unipolar electrograms were used to train a time series convolutional neural network (InceptionTime). RESULTS: A total of 11 551 electrograms were matched to 451 biopsies. Bipolar and unipolar voltage alone were poor classifiers of scar patterns. For each of the scar labels, 20 bipolar electrogram features (predominantly within the frequency domain) yielded an area under the curve of 0.815, 0.810, 0.704, and 0.681 to predict no scar, at least endocardial scar, at least intramural scar, and epicardial-only scar, respectively. Substantial improvement was achieved with a convolutional neural network trained on unipolar electrograms: areas under the curve and accuracy (averaged across wavefronts) were 0.977 and 0.929 for no scar, 0.970 and 0.919 for at least endocardial scar, 0.909 and 0.959 for at least intramural scar and 0.926 and 0.958 for epicardial-only scar. CONCLUSIONS: Convolutional neural network-derived analysis of unipolar electrogram data has excellent predictive value for determination of scar patterns. Computational analyses of electrogram data beyond voltage and other time-domain features are necessary to improve the identification of arrhythmogenic sites in the ventricle.
BACKGROUND: Mitral isthmus (MI) gap conduction is common despite ethanol infusion into the vein of Marshall (EI-VOM) and endocardial ablation of the MI. This study aimed to investigate the characteristics of electrograms...BACKGROUND: Mitral isthmus (MI) gap conduction is common despite ethanol infusion into the vein of Marshall (EI-VOM) and endocardial ablation of the MI. This study aimed to investigate the characteristics of electrograms of the distal coronary sinus (CSd) to guide the identification of the gap location in the MI. METHODS: A total of 187 patients who underwent EI-VOM and MI ablation were included in the study. After routine completion of EI-VOM and endocardial MI ablation, the characteristics of the electrogram in the CSd during left atrial appendage pacing were analyzed in unblocked MI conduction. RESULTS: Among the 187 patients, 43.3% (81/187) had unblocked MI following EI-VOM and linear lesion creation in the endocardium. In patients with unblocked MI, 84.0% (68/81) showed double potentials in the CSd during left atrial appendage pacing, among whom 80.9% (55/68) presented with an earlier high-frequency near-field potential followed by a low-frequency far-field potential, suggesting an epicardial gap, whereas 19.1% (13/68) presented with a far-field potential followed by a near-field potential, suggesting an endocardial gap. In patients with single potentials in the CSd (16.0%, n=13), simple activation mapping of the endocardium and CSd revealed the gap location. Intracoronary sinus ablation was necessary in 77.8% (63/81) of the patients, with a mean of 1.3±1.7 sites and 1.1±0.4 minutes of ablation. Eventually, 95.7% (179/187) of the patients achieved MI block. These findings were confirmed in an external validation cohort, which demonstrated the effectiveness and efficiency of CSd potential-guided gap identification. CONCLUSIONS: The characteristics of the electrograms in the CSd could aid in the prompt identification of the gap location(s) in the MI in patients with unblocked MI conduction.
Okada M, Inoue K, Tanaka N
… +20 more, Masuda M, Watanabe T, Makino N, Egami Y, Oka T, Minamiguchi H, Miyoshi M, Kanda T, Matsuda Y, Kawasaki M, Tanaka K, Hirao Y, Hikoso S, Sunaga A, Dohi T, Nakatani D, Okada K, Sotomi Y, Sakata Y, Osaka Cardiovascular Conference (OCVC)-Arrhythmia Investigators*
BACKGROUND: The efficacy of extensive linear ablation strategies, in addition to pulmonary vein (PV) isolation, remains controversial in persistent atrial fibrillation (AF) ablation. Gaps in previously ablated lesions ca...BACKGROUND: The efficacy of extensive linear ablation strategies, in addition to pulmonary vein (PV) isolation, remains controversial in persistent atrial fibrillation (AF) ablation. Gaps in previously ablated lesions can induce arrhythmias and potentially decrease the effectiveness of extensive ablation. This study evaluated the incidence of conduction gaps, gap-related reentry, and subsequent recurrence following redo AF ablation in the EARNEST-PVI trial (Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation; REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03514693). METHODS: The EARNEST-PVI trial is a randomized controlled study evaluating index ablation strategies for persistent AF. Of the 512 trial participants, 115 who underwent redo AF ablation (pulmonary vein isolation [PVI]-alone redo [n=69] and PVI-plus linear redo [n=46]) were included in the present study. Left atrial conduction gaps, the occurrence of left atrial tachycardias during redo procedures, and subsequent recurrences were compared between the PVI-alone redo group and the PVI-plus linear ablation redo group. RESULTS: In the PVI-alone redo group, electrical PV gaps were observed in 38 (57%) patients. In the PVI-plus redo group, 19 (41%) had PV gaps, 10 (22%) had gaps in left atrial linear lines, and 11 (24%) had gaps in both. During the redo session, 19 left atrial tachycardias were observed or induced in 15 patients. Atrial tachycardias were more frequently observed in the PVI-plus group than in the PVI-alone group (23.9% versus 5.8%; =0.005). The occurrence of left atrial tachycardias was associated with gaps in linear lesions, whereas PV gaps alone were associated with subsequent recurrence after redo (hazard ratio, 0.54 [95% CI, 0.31-0.95]; =0.033). CONCLUSIONS: In the redo AF ablation of the EARNEST-PVI trial, left atrial conduction gaps were more frequent in patients who underwent extensive linear ablation during the index procedure. While all gaps during redo were potentially arrhythmogenic, PV gaps alone were associated with recurrence after redo AF ablation. REGISTRATION:URL: https://www.umin.ac.jp/ctr/index-j.htm; Unique identifier: UMIN000019449.
Compagnucci P, Casella M, Narducci ML
… +15 more, Conte E, Cammarano M, Pelargonio G, Andreini D, Palmieri V, Stronati G, Lo Russo GV, Brusamolino M, Pontone G, Guerra F, Natale A, Tondo C, Crea F, Zeppilli P, Dello Russo A
BACKGROUND: Ventricular arrhythmias (VAs) are a major concern in athletes. We sought to determine the prognostic role of noninvasive and invasive assessments in athletes with complex VAs. METHODS: One-hundred-ninety athl...BACKGROUND: Ventricular arrhythmias (VAs) are a major concern in athletes. We sought to determine the prognostic role of noninvasive and invasive assessments in athletes with complex VAs. METHODS: One-hundred-ninety athletes (82% men; 28 [19-43] years; 148 [78%] competitive athletes) with frequent or exercise-induced premature ventricular complexes or nonsustained ventricular tachycardia were included in a multicenter cohort study and categorized based on VA ECG morphology into common (n=99) and uncommon (n=91) VA groups. Each athlete underwent a comprehensive diagnostic workup, including cardiac magnetic resonance in 94% (n=178) and electrophysiology study/electroanatomical mapping in 87% (n=166). The primary end point was the occurrence of sudden death or sustained VAs during long-term follow-up. RESULTS: Athletes with uncommon VA morphology had higher rates of abnormal findings at multimodality assessment and more final diagnoses of structural heart disease. Over a median follow-up of 6.2 (4.3-8.1) years, 7 (4%) athletes experienced a primary outcome event, including 1 sudden death. Interestingly, no events occurred in athletes with common morphology VAs. In univariable Cox models, factors associated with the primary end point included uncommon VA morphology (=0.003), lack of VA suppression (=0.049), and nonsustained ventricular tachycardia/ventricular tachycardia induction (=0.010) during stress testing, late gadolinium enhancement (=0.045), electroanatomical scar regions (=0.022), and sustained VA inducibility by electrophysiology study (<0.001). Incorporating findings of invasive tests improved prediction of primary outcome events over clinical/noninvasive findings in isolation (log-likelihood ratio for nested models, =0.004). A survival tree model based on VA morphology, late gadolinium enhancement, VA response to exercise testing, and electroanatomical mapping allowed risk stratification, identifying subgroups of athletes without primary outcome events during follow-up. Among 148 competitive athletes, 101 (68%) regained eligibility after 3 months of detraining, but only 42 (28%) continued long-term. CONCLUSIONS: A comprehensive diagnostic assessment integrating ECG, stress testing, and imaging findings, along with the selective use of invasive electrophysiology assessments, may help refine the prognostic evaluation of athletes with complex VAs.
BACKGROUND: Sinoatrial node (SAN) dysfunction is commonly associated with atrial dysrhythmia (tachy-brady syndrome) and is a particularly important feature of inherited atrial cardiomyopathies leading to artificial pacem...BACKGROUND: Sinoatrial node (SAN) dysfunction is commonly associated with atrial dysrhythmia (tachy-brady syndrome) and is a particularly important feature of inherited atrial cardiomyopathies leading to artificial pacemaker implantation. Essential MYL4 (myosin light chain-4) is an atrial-selective protein that associates with the myosin light chain and participates importantly in cardiacmuscle contraction. gene variants encoding dysfunctional versions of MYL4 cause familial atrial cardiomyopathy with a high incidence of early SAN dysfunction (SND) and pacemaker requirement. In this study, we used a rat line, genetically modified to express an gene mutation responsible for familial atrial cardiomyopathy, to address the mechanisms underlying SND. METHODS: Cardiac structure and function were assessed by echocardiography and in vivo telemetry recording. SAN function was studied in vivo with intracardiac electrophysiology and ex vivo with optical mapping. Mechanisms underlying SND were interrogated in vitro with the use of voltage and current clamp with tight-seal patch-clamp and Ca imaging of isolated SAN cardiomyocytes. Gene expression was assessed by quantitative polymerase chain reaction, and fibrosis was determined with Masson's trichrome stain. RESULTS: Mutant rats exhibited worse SAN function compared with wild-type controls. In vivo, SND was demonstrated by ≈63% increase in sinus node recovery time compared with wild type. In vitro, SAN conduction velocity was reduced by ≈ 50% for compared with wild type. Isolated SAN cells showed ≈50% reduction in funny current and L-type Ca-current densities. Dysregulation of Ca homeostasis was observed in , with ≈30% slower time to peak and Ca decay. Masson's trichrome staining showed ≈45% increase in SAN region collagen deposition in CONCLUSIONS: mutation causes progressive SND with aging, as a result of extensive abnormalities in the underlying determinants of SAN function, including ion-channel properties, Ca-homeostasis, and SAN structure. These observations provide new insights into the mechanisms of SAN abnormality in atrial cardiomyopathy.
Derval N, Tixier R, Duchateau J
… +15 more, Bouteiller X, Loock T, Denis A, Chauvel R, Bouyer B, Arnaud M, Yokoyama M, Kowalewski C, Monaco C, Ascione C, Sacher F, Hocini M, Jaïs P, Haïssaguerre M, Pambrun T
Circ Arrhythm Electrophysiol
· 2025 May · PMID 40392905
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BACKGROUND: Beyond pulmonary vein (PV) isolation, the optimal ablation strategy for persistent atrial fibrillation (AF) remains poorly defined. The purpose of this study was to compare 2 ablation strategies in the treatm...BACKGROUND: Beyond pulmonary vein (PV) isolation, the optimal ablation strategy for persistent atrial fibrillation (AF) remains poorly defined. The purpose of this study was to compare 2 ablation strategies in the treatment of patients with persistent AF: a comprehensive ablation strategy based on anatomic considerations versus PV isolation alone. METHODS: The Marshall-Plan trial is a prospective, randomized, parallel-group, controlled clinical trial of superiority conducted at the Bordeaux University Hospital. Consecutive patients with symptomatic, documented persistent AF were included and randomized into 2 arms: Marshall-Plan consisting of PV isolation with additional ablation including vein of Marshall ethanol infusion, and lines of block at the mitral, dome, and cavotricuspid isthmuses versus PV isolation alone. The main outcome was the 1-year freedom from any arrhythmia (atrial fibrillation/atrial tachycardia >30 seconds) after a single ablation procedure with or without any antiarrhythmic medication at 12 months. RESULTS: A total of 120 patients were included (age 65±8 years; 21 women). Two patients were excluded from analysis. All PVs were successfully isolated in both groups. In the Marshall-Plan group, vein of Marshall ethanol infusion was completed in 57 (97%) patients. Conduction block across linear lesions was obtained in 93%, 92%, and 93% of the mitral, dome, and cavotricuspid isthmuses, respectively. The full lesion set was successfully completed in 52 (88%) patients in the Marshall-Plan group and 59 (100%) patients in the PV isolation group. At 12 months, freedom from recurrence of atrial arrhythmia >30 seconds after 1 ablation procedure, with or without antiarrhythmic medication, had occurred in 51 of the 59 (86.4%) patients assigned to the Marshall-Plan approach, and 39 of the 59 (66.1%) patients assigned to PV isolation only (=0.012). CONCLUSIONS: In this prospective randomized controlled trial, the Marshall-Plan strategy was significantly superior to a PV isolation strategy at 12 months. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04206982.
Truyen TTTT, Lin H, Mathias M
… +4 more, Chugh H, Reinier K, Benjamin EJ, Chugh SS
Circ Arrhythm Electrophysiol
· 2025 Jun · PMID 40391444
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BACKGROUND: We have previously reported a novel clinical risk score (risk prediction score for shockable sudden cardiac arrest [VFRisk]) for the prediction of shockable sudden cardiac arrest, discovered and validated in...BACKGROUND: We have previously reported a novel clinical risk score (risk prediction score for shockable sudden cardiac arrest [VFRisk]) for the prediction of shockable sudden cardiac arrest, discovered and validated in 2 US west coast communities. We hypothesized that VFRisk predicts sudden cardiac death (SCD) risk in the geographically distinct FHS (Framingham Heart Study). METHODS: We performed a nested case-referents study in the FHS to test VFRisk. Cases were participants who experienced SCD among the original and offspring FHS cohorts. Referents were randomly selected from FHS participants frequency-matched (ratio of 1:3) to cases on age, sex, cohort, and exam. VFRisk was the sum of 12 risk factors, each multiplied by its respective points. RESULTS: Among 312 cases and 935 referents, mean ages were 69.5 and 69.7 years with 70.8% men in both groups. SCD cases had significantly higher prevalence of diabetes, heart failure, stroke, atrial fibrillation, and myocardial infarction compared with the referents group. The VFRisk score was validated with good discrimination (C-statistic, 0.71 [95% CI, 0.66-0.77]) for SCD. Cases had higher VFRisk scores than referents (3.8±2.8 versus 1.8±1.7; <0.001). A 1-unit increase in VFRisk score was associated with a 48% increase in odds of SCD (odds ratio, 1.48 [95% CI, 1.34-1.64]). The highest VFRisk quartile had 7.8-fold higher odds of SCD than the lowest quartile. CONCLUSIONS: The VFRisk score successfully predicted SCD in the FHS. The differences in discrimination between the 2 studies could partially be explained by the inability to distinguish shockable versus nonshockable events in the FHS.
Zenger B, Smith TW, Hicks S
… +23 more, Ng S, Pavek T, Knutson N, Samson PP, Zheng J, Berberet C, Ibrahim EH, Jani V, Tabor J, Wilson LD, Jordan SD, Marut LC, Kumar A, Manikandan S, Javaheri A, Bergom C, Schwarz JK, Boyle PM, Hugo GD, Cuculich PS, Robinson C, Zemlin C, Rentschler SL
Circ Arrhythm Electrophysiol
· 2025 Jun · PMID 40391432
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BACKGROUND: Stereotactic arrhythmia radiotherapy (STAR) has emerged as a potential therapy for treatment-refractory ventricular tachycardia (VT). However, the mechanisms underlying STAR efficacy, such as scar or other el...BACKGROUND: Stereotactic arrhythmia radiotherapy (STAR) has emerged as a potential therapy for treatment-refractory ventricular tachycardia (VT). However, the mechanisms underlying STAR efficacy, such as scar or other electromechanical changes, are still unclear. The goal of this study was to develop a translational porcine model of ischemic monomorphic VT treated with STAR to examine the physiological changes after a typical clinical STAR treatment. METHODS: We treated a previously validated porcine model of monomorphic VT after myocardial infarction with a clinically derived STAR protocol. A dose of 25 Gy was prescribed to the planning target volume and 35 Gy to the clinical target volume (regions of scar), while controls underwent a sham STAR treatment. All investigators in the study were blinded except the treating investigator. The primary study outcome was VT inducibility at 6 weeks post-STAR. Animals underwent pre- and post-STAR cardiac magnetic resonance imaging to quantify myocardial scar and function, as well as body surface mapping. Six weeks post-STAR, animals underwent a VT induction study, and tissue was harvested for optical mapping and histological analysis. RESULTS: Six animals completed the study, which ended before finishing enrollment because all animals had inducible VT. We found a significantly longer local effective refractory period in the left ventricular apex and longer VT cycle lengths in STAR-treated animals compared with controls (<0.05). We found no difference in myocardial scar burden, mechanical function, or body surface recordings when comparing pre- and post-STAR. CONCLUSIONS: Our data suggest a novel therapeutic mechanism of STAR driven by increasing the effective refractory period in locally treated areas, corresponding to increased tissue wavelength. Our results corroborate clinical case reports and anecdotal evidence that STAR increases VT cycle length. Importantly, these effects were not mediated by an increase in myocardial scar burden. However, our studies do not examine the long-term effects of STAR.
De Potter TJR, Grimaldi M, Duytschaever M
… +12 more, Anic A, Vijgen J, Neuzil P, Van Herendael H, Verma A, Skanes A, Scherr D, Pürerfellner H, Rackauskas G, Jais P, Reddy VY, inspIRE Trial Investigators
Circ Arrhythm Electrophysiol
· 2025 May · PMID 40276859
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