Journal: Circ Arrhythm Electrophysiol

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<div><h4>Reduction in Junctophilin 2 Expression in Cardiac Nodal Tissue Results in Intracellular Calcium-Driven Increase in Nodal Cell Automaticity.</h4><i>Landstrom AP, Yang Q, Sun B, Perelli RM, ... Kim JJ, Wehrens XHT</i><br /><b>Background</b><br />Spontaneously depolarizing nodal cells comprise the pacemaker of the heart. Intracellular calcium (Ca<sup>2+</sup>) plays a critical role in mediating nodal cell automaticity and understanding this so-called Ca<sup>2+</sup> clock is critical to understanding nodal arrhythmias. We previously demonstrated a role for Jph2 (junctophilin 2) in regulating Ca<sup>2+</sup>-signaling through inhibition of RyR2 (ryanodine receptor 2) Ca<sup>2+</sup> leak in cardiac myocytes; however, its role in pacemaker function and nodal arrhythmias remains unknown. We sought to determine whether nodal Jph2 expression silencing causes increased sinoatrial and atrioventricular nodal cell automaticity due to aberrant RyR2 Ca<sup>2+</sup> leak.<br /><b>Methods</b><br />A tamoxifen-inducible, nodal tissue-specific, knockdown mouse of Jph2 was achieved using a Cre-recombinase-triggered short RNA hairpin directed against Jph2 (Hcn4:shJph2). In vivo cardiac rhythm was monitored by surface ECG, implantable cardiac telemetry, and intracardiac electrophysiology studies. Intracellular Ca<sup>2+</sup> imaging was performed using confocal-based line scans of isolated nodal cells loaded with fluorescent Ca<sup>2+</sup> reporter Cal-520. Whole cell patch clamp was conducted on isolated nodal cells to determine action potential kinetics and sodium-calcium exchanger function.<br /><b>Results</b><br />Hcn4:shJph2 mice demonstrated a 40% reduction in nodal Jph2 expression, resting sinus tachycardia, and impaired heart rate response to pharmacologic stress. In vivo intracardiac electrophysiology studies and ex vivo optical mapping demonstrated accelerated junctional rhythm originating from the atrioventricular node. Hcn4:shJph2 nodal cells demonstrated increased and irregular Ca<sup>2+</sup> transient generation with increased Ca<sup>2+</sup> spark frequency and Ca<sup>2+</sup> leak from the sarcoplasmic reticulum. This was associated with increased nodal cell AP firing rate, faster diastolic repolarization rate, and reduced sodium-calcium exchanger activity during repolarized states compared to control. Phenome-wide association studies of the <i>JPH2</i> locus identified an association with sinoatrial nodal disease and atrioventricular nodal block.<br /><b>Conclusions</b><br />Nodal-specific Jph2 knockdown causes increased nodal automaticity through increased Ca<sup>2+</sup> leak from intracellular stores. Dysregulated intracellular Ca<sup>2+</sup> underlies nodal arrhythmogenesis in this mouse model.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 27 Jan 2023:e010858; epub ahead of print</small></div>
Landstrom AP, Yang Q, Sun B, Perelli RM, ... Kim JJ, Wehrens XHT
Circ Arrhythm Electrophysiol: 27 Jan 2023:e010858; epub ahead of print | PMID: 36706317
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<div><h4>Abnormal Conduction Zone Detected by Isochronal Late Activation Mapping Accurately Identifies the Potential Atrial Substrate and Predicts the Atrial Fibrillation Ablation Outcome After Pulmonary Vein Isolation.</h4><i>Kuo MJ, Ton AK, Lo LW, Lin YJ, ... Hsu CY, Chen SA</i><br /><b>Background</b><br />The presence of abnormal substrate of left atrium is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. We aimed to investigate the isochronal late activation mapping to access the abnormal conduction velocity for predicting AF ablation outcome.<br /><b>Methods</b><br />Forty-five paroxysmal AF patients (30 males, 57.8±8.7 years old) who underwent pulmonary vein isolation were enrolled. Isochronal late activation mapping was retrospectively constructed with 2 different windows of interest: from onset of P wave to onset of QRS wave on surface electrocardiography (W1) and 74 ms tracking back from the end of P wave (W2). Deceleration zone was defined as regions with 3 isochrones (DZa) or ≥4 isochrones (DZb) within a 1 cm radius on the isochronal late activation mapping, and the estimated conduction velocity (ECV) are 0.27 m/s and <0.20 m/s for DZa and DZb, respectively in W2. The distribution of deceleration zone was compared with the location of low-voltage zone (bipolar voltage ≤0.5 mV). Any recurrence of atrial arrhythmias was defined as the primary end point during follow ups after a 3-month blanking period.<br /><b>Results</b><br />Pulmonary vein isolation was performed in all patients, and there were 2 patients (4.4%) received additional extrapulmonary vein ablation. After a mean follow-up of 12.7±4.5 months, recurrence of AF occurred in 14 patients (31.1%). Patients with the presence of DZb in W2 had higher AF recurrence (Kaplan-Meier event rate estimates: HR, 9.41 [95% CI, 2.61-33.90]; log-rank <i>P</i><0.0001). 52.6% of the DZb locations in W2 were comparable to the distributions of low-voltage zone, and 47.4% DZb were distributed in the area without low-voltage zone.<br /><b>Conclusions</b><br />Deceleration zone detected by isochronal late activation mapping represents a critical AF substrate, it accurately predicts the AF recurrence following ablation in patients with paroxysmal AF.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 23 Jan 2023:e011149; epub ahead of print</small></div>
Kuo MJ, Ton AK, Lo LW, Lin YJ, ... Hsu CY, Chen SA
Circ Arrhythm Electrophysiol: 23 Jan 2023:e011149; epub ahead of print | PMID: 36688314
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<div><h4>Substrate Mapping Alters Ventricular Tachycardia Inducibility.</h4><i>Aboud AA, Davogustto G, Adeola O, Richardson TD, ... Stevenson WG, Kanagasundram A</i><br /><b>Background</b><br />Initiation of ventricular tachycardia (VT) by programmed electrical stimulation (PES) has an important role to allow mapping and assess ablation end points. We hypothesized that substrate mapping may alter VT inducibility by mechanical bumping of critical sites.<br /><b>Methods</b><br />Subjects with left ventricular scar-related VT that was inducible by PES who were undergoing ablation were included. PES was repeated after substrate mapping (Group I) or after time under sedation/anesthesia during which additional imaging and transeptal puncture were performed without substrate mapping (Group II). The response to the second PES was categorized as type I if the same VT was induced, type II if a different VT was induced, and type III if VT was not inducible.<br /><b>Results</b><br />Twenty-eight patients (median age 66 years, 61% ischemic cardiomyopathy), 14 in Group I and 14 in Group II, were included. Age, time between initial and second PES, type of cardiomyopathy, ejection fraction, and anesthesia methods were not different between the 2 groups. Initial VT cycle length, however, was shorter in Group I (305 millisecond [range, 235-600] versus 350 millisecond [range, 235-600], <i>P</i>=0.016). Also, Group I required more extrastimuli to induce VT in PES 1 (2 [1-4] versus 2 [1-3], <i>P</i>=0.022). In Group I, following substrate mapping, the second PES induced the same VT in 3 patients (21%), a different VT in 9 (64%), and no VT in 2 (14%) patients. In contrast, in Group II the same VT was induced in 10 (71%) patients, a different VT in 3 (21%) and no VT in 1 (7%) patient (<i>P</i>=0.017).<br /><b>Conclusions</b><br />Mechanical effects of substrate mapping commonly alter inducibility of VT. This has important implications for catheter ablation procedure planning and acute assessment of outcome and can potentially account for some recurrent VTs that are not recognized at the time of the procedure.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 05 Jan 2023:e010889; epub ahead of print</small></div>
Aboud AA, Davogustto G, Adeola O, Richardson TD, ... Stevenson WG, Kanagasundram A
Circ Arrhythm Electrophysiol: 05 Jan 2023:e010889; epub ahead of print | PMID: 36602818
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<div><h4>Pleomorphic Ventricular Tachycardia in Dilated Cardiomyopathy Predicts Ventricular Tachycardia Recurrence After Ablation Independent From Cardiac Function: Comparison With Patients With Ischemic Heart Disease.</h4><i>Kimura Y, de Riva M, Ebert M, Glashan C, ... Trines SA, Zeppenfeld K</i><br /><b>Background</b><br />In dilated cardiomyopathy (DCM), outcome after catheter ablation of ventricular tachycardia (VT) is modest, compared with ischemic heart disease (IHD). Pleomorphic VT (PL-VT) has been associated with fibrotic remodeling and end-stage heart failure in IHD. The prognostic role of PL-VT in DCM is unknown.<br /><b>Methods</b><br />Consecutive IHD (2009-2016) or DCM (2008-2018) patients undergoing ablation for monomorphic VT were included. PL-VT was defined as ≥1 spontaneous change of the 12-lead VT-morphology during the same induced VT episode. Patients were followed for VT recurrence and mortality.<br /><b>Results</b><br />A total of 247 patients (86% men; 63±13 years; IHD n=152; DCM n=95) underwent ablation for monomorphic VT. PL-VT was observed in 22 and 29 patients with IHD and DCM, respectively (14% versus 31%, <i>P</i>=0.003). In IHD, PL-VT was associated with lower LVEF (28±9% versus 34±12%, <i>P</i>=0.02) and only observed in those with LVEF<40%. In contrast, in DCM, PL-VT was not related to LVEF and induced in 27% of patients with LVEF>40%. During a median follow-up of 30 months, 79 (32%) patients died (IHD 48; DCM 31; <i>P</i>=0.88) and 120 (49%) had VT recurrence (IHD 59; DCM 61; <i>P</i><0.001). PL-VT was associated with mortality in IHD but not in DCM. In IHD, VT recurrence was independently associated with LVEF, number of induced VTs, and procedural noncomplete success. Of note, in DCM, PL-VT (HR, 2.62 [95% CI, 1.47-4.69]), pathogenic mutation (HR, 2.13 [95% CI, 1.16-3.91]), and anteroseptal VT substrate (HR, 1.75 [95% CI, 1.00-3.07]) independently predicted VT recurrence.<br /><b>Conclusions</b><br />In IHD, PL-VT was associated with low LVEF and mortality. In DCM, PL-VT was not associated with mortality but a predictor of VT recurrence independent from LVEF. PL-VT in DCM may indicate a specific arrhythmic substrate difficult to control by current ablation techniques.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 03 Jan 2023:e010826; epub ahead of print</small></div>
Kimura Y, de Riva M, Ebert M, Glashan C, ... Trines SA, Zeppenfeld K
Circ Arrhythm Electrophysiol: 03 Jan 2023:e010826; epub ahead of print | PMID: 36595629
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<div><h4>Alternating Early Afterdepolarizations Underlying Bradycardia-Dependent Macroscopic T Wave and Discordant Mechanical Alternans.</h4><i>Qi D, Li W, Quan XQ, Gao Y, ... Gao C, Yan GX</i><br /><b>Background</b><br />Macroscopic T wave alternans (macro-TWA) often heralds the onset of Torsades de Pointes in patients with QT prolongation. However, the mechanisms underlying macro-TWA remain unclear. We examined the cellular and ionic basis for macro-TWA in rabbits with left ventricular hypertrophy (LVH).<br /><b>Methods</b><br />The renovascular hypertension model was used to induce LVH in rabbits. Action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contractility in arterially perfused left ventricular wedges. Late sodium current (I<sub>Na</sub>-L) was recorded in single-isolated left ventricular myocytes with the whole cell patch-clamp technique.<br /><b>Results</b><br />Macro-TWA and accompanied mechanical alternans occurred spontaneously in 8 of 33 LVH rabbits (<i>P</i><0.05, versus 0/15 in controls) and were induced by an I<sub>Na</sub>-L enhancer ATX-II at 1 to 3 nM in additional 7. Macro-TWA and mechanical alternans occurred discordantly, that is, that longer QT interval and larger T wave were associated with weaker isometric contractility. Alternating early afterdepolarizations in the endocardium caused macro-TWA in 12 of 15 LVH rabbits and, therefore, early afterdepolarization-dependent R-from-T extrasystoles and Torsades de Pointes always originated from the beats with longer QT and larger T wave during macro-TWA. I<sub>Na</sub>-L density was significantly larger in LVH myocytes than that of control myocytes. Macro-TWA, mechanical alternans, R-from-T extrasystoles, and Torsades de Pointes were all abolished by I<sub>Na</sub>-L blocker ranolazine or mexiletine.<br /><b>Conclusions</b><br />LVH enhances I<sub>Na</sub>-L density and promotes alternating early afterdepolarizations in the left ventricular endocardium that manifest as macro-TWA with discordant mechanical alternans. I<sub>Na</sub>-L blockade abolishes macro-TWA, mechanical alternans, early afterdepolarization-dependent R-from-T extrasystoles, and Torsades de Pointes.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 03 Jan 2023:e011453; epub ahead of print</small></div>
Qi D, Li W, Quan XQ, Gao Y, ... Gao C, Yan GX
Circ Arrhythm Electrophysiol: 03 Jan 2023:e011453; epub ahead of print | PMID: 36595630
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<div><h4>Chronic Kidney Disease Induces Proarrhythmic Remodeling.</h4><i>King BMN, Mintz S, Lin X, Morley GE, ... Khodadadi-Jamayran A, Fishman GI</i><br /><b>Background</b><br />Patients with chronic kidney disease (CKD) are at increased risk of developing cardiac arrhythmogenesis and sudden cardiac death; however, the basis for this association is incompletely known.<br /><b>Methods</b><br />Here, using murine models of CKD, we examined interactions between kidney disease progression and structural, electrophysiological, and molecular cardiac remodeling.<br /><b>Results</b><br />C57BL/6 mice with adenine supplemented in their diet developed progressive CKD. Electrocardiographically, CKD mice developed significant QT prolongation and episodes of bradycardia. Optical mapping of isolated-perfused hearts using voltage-sensitive dyes revealed significant prolongation of action potential duration with no change in epicardial conduction velocity. Patch-clamp studies of isolated ventricular cardiomyocytes revealed changes in sodium and potassium currents consistent with action potential duration prolongation. Global transcriptional profiling identified dysregulated expression of cellular stress response proteins RBM3 (RNA-binding motif protein 3) and CIRP (cold-inducible RNA-binding protein) that may underlay the ion channel remodeling. Unexpectedly, we found that female sex is a protective factor in the progression of CKD and its cardiac sequelae.<br /><b>Conclusions</b><br />Our data provide novel insights into the association between CKD and pathologic proarrhythmic cardiac remodeling. Cardiac cellular stress response pathways represent potential targets for pharmacologic intervention for CKD-induced heart rhythm disorders.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 03 Jan 2023:e011466; epub ahead of print</small></div>
King BMN, Mintz S, Lin X, Morley GE, ... Khodadadi-Jamayran A, Fishman GI
Circ Arrhythm Electrophysiol: 03 Jan 2023:e011466; epub ahead of print | PMID: 36595632
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<div><h4>Electrophysiology, Pathology, and Imaging of Pulsed Field Ablation of Scarred and Healthy Ventricles in Swine.</h4><i>Kawamura I, Reddy VY, Santos-Gallego CG, Wang BJ, ... Dukkipati SR, Koruth JS</i><br /><b>Background</b><br />Pulsed field ablation (PFA) has recently been shown to penetrate ischemic scar, but details on its efficacy, risk of arrhythmias, and imaging insights are lacking. In a porcine model of myocardial scar, we studied the ability of ventricular PFA to penetrate scarred tissue, induce ventricular arrhythmias, and assess the influence of QRS gating during pulse delivery.<br /><b>Methods</b><br />Of a total of 6 swine, 5 underwent coronary occlusion and 1 underwent radiofrequency ablation to create infarct scar and iatrogenic scar models, respectively. Two additional swine served as healthy controls. An 8 Fr focal PFA catheter was used to deliver bipolar, biphasic PFA (2.0 kV) lesions guided by electroanatomical mapping, fluoroscopy, and intracardiac echocardiography over both scarred and healthy myocardium. Swine underwent magnetic resonance imaging 2-7 days post-PFA.<br /><b>Results</b><br />PFA successfully penetrated scar without significant difference in lesion depth between lesion at the infarct border (5.9±1.0 mm, n=41) and healthy myocardium (5.7±1.3 mm, n=26; <i>P</i>=0.53). PFA penetration of both infarct and iatrogenic radiofrequency abalation scar was observed in all examined sections. Sustained ventricular arrhythmias requiring defibrillation occurred in 4 of 187 (2.1%) ungated applications, whereas no ventricular arrhythmias occurred during gated PFA applications (0 of 64 [0%]). Dark-blood late-gadolinium-enhanced sequences allowed for improved endocardial border detection as well as lesion boundaries compared with conventional bright-blood late-gadolinium-enhanced sequences.<br /><b>Conclusions</b><br />PFA penetrates infarct and iatrogenic scar successfully to create deep lesions. Gated delivery eliminates the occurrence of ventricular arrhythmias observed with ungated porcine PFA. Optimized magnetic resonance imaging sequences can be helpful in detecting lesion boundaries.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 03 Jan 2023:e011369; epub ahead of print</small></div>
Kawamura I, Reddy VY, Santos-Gallego CG, Wang BJ, ... Dukkipati SR, Koruth JS
Circ Arrhythm Electrophysiol: 03 Jan 2023:e011369; epub ahead of print | PMID: 36595634
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<div><h4>Atrial Endocardial Unipolar Voltage Mapping for Detection of Viable Intramural Myocardium: A Proof-of-Concept Study.</h4><i>Yavin H, Younis A, Zilberman I, Krywanczyk A, ... Barkagan M, Anter E</i><br /><b>Background</b><br />Endocardial bipolar voltage amplitude is largely derived from endocardial and subendocardial wall layers. This may result in situations of low bipolar voltage amplitude despite the presence of mid-myocardial including epicardial (ie, intramural-epicardial) viable myocardium. This study examined the utility of endocardial unipolar voltage mapping for detection of viable intramural-epicardial atrial myocardium.<br /><b>Methods</b><br />In 15 swine, an atrial intercaval ablation line with an intentional gap was created. Animals survived for 6 to 8 weeks before electroanatomical mapping followed by sacrifice. Gaps were determined by the presence of electrical conduction and classified based on the histopathologiclly layer(s) of viable myocardium into the following: (1) transmural, (2) endocardial, and (3) intramural-epicardial. Voltage data from healthy, scar, and gap points were exported into excel. The sensitivity and specificity of bipolar and unipolar voltage amplitude to detect intramural-epicardial gaps were compared using receiver operating characteristic analysis.<br /><b>Results</b><br />In 9 of 15 (60%) swine, a focal ablation gap was detected in the intercaval line, while in the remainder 6 of 15 (40%), the line was complete without gaps. Gaps were classified into transmural (n=3), endocardial (n=3), or intramural-epicardial (n=3). Intramural-epicardial gaps were characterized by very low bipolar voltage amplitude that was similar to areas with transmural scar (<i>P</i>=0.91). In comparison, unipolar voltage amplitude in intramural-epicardial gaps was significantly higher compared to transmural scar (<i>P</i><0.001). Unipolar voltage amplitude had higher sensitivity (93% versus 14%, respectively) and similar specificity (95% versus 98%, respectively) to bipolar voltage for detection of intramural-epicardial gaps.<br /><b>Conclusions</b><br />Atrial unipolar voltage mapping may be a useful technique for identifying viable intramural-epicardial myocardium in patients with endocardial scar.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 03 Jan 2023:e011321; epub ahead of print</small></div>
Yavin H, Younis A, Zilberman I, Krywanczyk A, ... Barkagan M, Anter E
Circ Arrhythm Electrophysiol: 03 Jan 2023:e011321; epub ahead of print | PMID: 36595639
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<div><h4>First Randomized, Multicenter, Placebo-Controlled Study of Self-Administered Intranasal Etripamil for Acute Conversion of Spontaneous Paroxysmal Supraventricular Tachycardia (NODE-301).</h4><i>Stambler BS, Plat F, Sager PT, Shardonofsky S, ... Haberman R, Camm AJ</i><br /><b>Background</b><br />Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal-dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT.<br /><b>Methods</b><br />NODE-301, a phase 3, multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of etripamil nasal spray administered, unsupervised in patients with symptomatic sustained PSVT. After a medically supervised etripamil test dose while in sinus rhythm, patients were randomized 2:1 to receive etripamil 70 mg or placebo. When PSVT symptoms developed, patients applied a cardiac monitor and attempted a vagal maneuver; if symptoms persisted, they self-administered blinded treatment. An independent Adjudication Committee reviewed continuous electrocardiogram recordings. The primary efficacy endpoint was termination of adjudicated PSVT within 5 hours after study drug administration.<br /><b>Results</b><br />NODE-301 accrued 156 positively adjudicated PSVT events treated with etripamil (n=107) or placebo (n=49). The hazard ratio for the primary endpoint, time-to-conversion to sinus rhythm during the 5-hour observation period, was 1.086 (95% CI, 0.726-1.623; <i>P</i>=0.12). In predefined sensitivity analyses, etripamil effects (compared with placebo) occurred at 3, 5, 10, 20, and 30 minutes (<i>P</i><0.05). For example, at 30 minutes, there was a 53.7% of SVT conversion in the treatment arm compared to 34.7% in the placebo arm (hazard ratio, 1.87 [95% CI, 1.09-3.22]; <i>P</i>=0.02). Etripamil was well tolerated; adverse events were mainly related to transient nasal discomfort and congestion (19.6% and 8.0%, respectively, of randomized treatment-emergent adverse events.<br /><b>Conclusions</b><br />Although the primary 5-hour efficacy endpoint was not met, analyses at earlier time points indicated an etripamil treatment effect in terminating PSVT. Etripamil self-administration during PSVT was safe and well tolerated. These results support continued clinical development of etripamil nasal spray for self-administration during PSVT in a medically unsupervised setting.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT03464019.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 28 Nov 2022:e010915; epub ahead of print</small></div>
Stambler BS, Plat F, Sager PT, Shardonofsky S, ... Haberman R, Camm AJ
Circ Arrhythm Electrophysiol: 28 Nov 2022:e010915; epub ahead of print | PMID: 36441560
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<div><h4>The Utility of Sodium Channel Provocation in Unexplained Cardiac Arrest Survivors and Electrocardiographic Predictors of Ventricular Fibrillation Recurrence.</h4><i>Ensam B, Cheung CC, Almehmadi F, Gregers Winkel B, ... Krahn AD, Behr ER</i><br /><b>Background</b><br />The implications of a drug-induced type 1 Brugada ECG pattern following sodium channel blocker provocation (SCBP) are not fully understood.<br /><b>Methods</b><br />Baseline clinical and ECG data were obtained from consecutive unexplained cardiac arrest survivors undergoing SCBP at 3 centers. A further 15 SCBP positive (SCBP+) unexplained cardiac arrest survivors were recruited from 3 additional centers to explore ventricular fibrillation recurrence.<br /><b>Results</b><br />A total of 121 consecutive unexplained cardiac arrest survivors underwent SCBP. The yield of the drug-induced type 1 Brugada ECG pattern was 17%. A baseline type 2/3 Brugada pattern (T2/3BP) (adjusted odds ratio, 19.36 [2.74-136.61]; <i>P</i>=0.003) and PR interval (odds ratio, 1.03 [1.01-1.05] per ms; <i>P</i>=0.017) were independent predictors of SCBP+ response. A pathogenic <i>SCN5A</i> variant was identified in 36% of the SCBP+ group versus 0% in the SCBP- group (<i>P</i><0.001). Amongst SCBP+ patients, a spontaneous type 1 Brugada pattern was identified in 19% during follow up and in 24% a type 1 Brugada pattern was identified in a relative. Prior syncope (adjusted hazard ratio, 3.83 [1.36-10.78]; <i>P</i>=0.011) and the presence of global early repolarization (hazard ratio, 7.91 [3.22-19.44]; <i>P</i><0.001) were independent predictors of 5-year ventricular fibrillation recurrence. There was a nonsignificant trend toward greater 5-year ventricular fibrillation recurrence in the SCBP- group (23/95 [24%] versus 3/34 [9%]; <i>P</i>=0.055).<br /><b>Conclusions</b><br />The yield of the drug-induced type 1 Brugada ECG pattern in consecutive unexplained cardiac arrest survivors undergoing SCBP is 17%. A baseline T2/3BP and PR interval were independent predictors of the drug-induced type 1 Brugada ECG pattern. Greater heritability of BrS phenotype in this group was evidenced by a greater prevalence of pathogenic <i>SCN5A</i> variants and relatives with a type 1 Brugada pattern. A history of prior syncope and the presence of global early repolarization were independent predictors of ventricular fibrillation recurrence.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 28 Nov 2022:e011263; epub ahead of print</small></div>
Ensam B, Cheung CC, Almehmadi F, Gregers Winkel B, ... Krahn AD, Behr ER
Circ Arrhythm Electrophysiol: 28 Nov 2022:e011263; epub ahead of print | PMID: 36441561
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<div><h4>Advances in Cardiac Electrophysiology.</h4><i>Piccini JP, Russo AM, Sharma PS, Kron J, ... Zeitler EP, Wang PJ</i><br /><AbstractText>Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.</AbstractText><br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 28 Nov 2022:e009911; epub ahead of print</small></div>
Piccini JP, Russo AM, Sharma PS, Kron J, ... Zeitler EP, Wang PJ
Circ Arrhythm Electrophysiol: 28 Nov 2022:e009911; epub ahead of print | PMID: 36441565
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<div><h4>Early Catheter Ablation Versus Initial Medical Therapy for Ventricular Tachycardia Storm.</h4><i>Huang K, Bennett R, Campbell T, Lee V, ... Chow CK, Kumar S</i><br /><b>Background</b><br />Ventricular tachycardia (VT) storm is associated with significantly increased morbidity, mortality, and exponential healthcare utilization. Although catheter ablation (CA) may be curative, there are limited data directly comparing outcomes of early CA with initial medical therapy.<br /><b>Methods</b><br />We compared outcomes of patients presenting with VT storm treated with initial CA versus those treated with initial medical therapy during their first storm presentation in an observational study. Retrospective data from the host institution from January 2014 to April 2020 of 129 patients with their first VT storm presentation were analyzed (58 underwent initial CA, 71 underwent treatment with initial medical therapy). Outcomes were compared in follow-up.<br /><b>Results</b><br />Median time to initial CA was 6 days. Over a median follow-up of 702 days, patients who underwent initial CA compared with those treated with initial medical therapy had significantly less: (i) VA recurrence (43% versus 92%; <i>P</i>=0.002); (ii) VT storm recurrence (28% versus 73%; <i>P</i><0.001); (iii) composite end point of death, heart transplant, VT storm recurrence, and VT-related hospitalization (47% versus 89%; <i>P</i>=0.002); (iv) iatrogenic complications (at 12 months: 17% versus 45%; <i>P</i><0.001); (v) cardiovascular-related hospitalizations (50% versus 89%; <i>P</i>=0.01); (vi) total number of hospitalizations (median 1 versus 4; <i>P</i><0.001); and (vi) cumulative days in hospital (median 0.5 versus 18; <i>P</i><0.001). There were no intraprocedural deaths in patients treated with early CA.<br /><b>Conclusion</b><br />In an observational setting in which patients presenting with storm, early CA appears superior to initial medical therapy in terms of VT recurrence, storm recurrence, iatrogenic complications, cardiovascular hospitalizations, and cumulative days in hospital in follow-up.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 18 Nov 2022:e011129; epub ahead of print</small></div>
Huang K, Bennett R, Campbell T, Lee V, ... Chow CK, Kumar S
Circ Arrhythm Electrophysiol: 18 Nov 2022:e011129; epub ahead of print | PMID: 36399370
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<div><h4>Recurrent Out-of-Hospital Sudden Cardiac Arrest: Prevalence and Clinical Factors.</h4><i>Held EP, Reinier K, Chugh H, Uy-Evanado A, Jui J, Chugh SS</i><br /><b>Background</b><br />Despite improvements in management following survival from sudden cardiac arrest (SCA) and wide availability of implantable cardioverter defibrillators for secondary prevention, a subgroup of individuals will suffer multiple distinct episodes of SCA. The objective of this study was to characterize and evaluate the burden of recurrent out-of-hospital SCA among survivors of SCA in a single large US community.<br /><b>Methods</b><br />SCA cases were prospectively ascertained in the Oregon Sudden Unexpected Death Study. Individuals that experienced recurrent SCA were identified both prospectively and retrospectively.<br /><b>Results</b><br />We ascertained 6649 individuals with SCA (2002-2020) and 924 (14%) survived to hospital discharge. Of these, 88 survivors (10%) experienced recurrent SCA. Of the nonsurvivors (n=5725), 35 had suffered a recurrent SCA. Of the total 123 SCA cases with recurrent SCA, >60% occurred at least 1 year after the initial SCA (median 23 months, range: 6 days to 31 years). SCA occurred despite a secondary prevention implantable cardioverter defibrillator in 22% (n=26). Prevalence of coronary disease (36% versus 25%), hypertension (69% versus 43%), diabetes (44% versus 21%), and chronic kidney disease (35% versus 14%) was significantly higher in recurrent SCA versus single SCA survivors (n=80, <i>P</i>=0.01). Among individuals with no secondary prevention implantable cardioverter defibrillators before recurrent SCA, the majority had apparently reversible etiologies identified at initial SCA, with one-quarter undergoing coronary revascularization and over half diagnosed with noncoronary cardiac etiologies.<br /><b>Conclusions</b><br />At least 10% of SCA survivors had recurrent SCA, and a large subgroup suffered their repeat SCA despite treatment for an apparently reversible etiology. A renewed focus on careful assessment of cardiac substrate as well as management of coronary disease, hypertension, diabetes, and chronic kidney disease in SCA survivors could reduce recurrent SCA.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 16 Nov 2022:e011018; epub ahead of print</small></div>
Held EP, Reinier K, Chugh H, Uy-Evanado A, Jui J, Chugh SS
Circ Arrhythm Electrophysiol: 16 Nov 2022:e011018; epub ahead of print | PMID: 36383377
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Abstract
<div><h4>Longitudinal Prediction of Ventricular Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.</h4><i>Carrick RT, Te Riele ASJM, Gasperetti A, Bosman L, ... James CA, Wu KC</i><br /><b>Background</b><br />The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator stratifies risk for incident sustained ventricular arrhythmias (VA) at the time of ARVC diagnosis. However, included risk factors change over time, and how well the ARVC risk calculator performs at follow-up is unknown.<br /><b>Methods</b><br />This was a retrospective analysis of patients with definite ARVC and without prior sustained VA. Risk factors for VA including age, nonsustained ventricular tachycardia, premature ventricular complex burden, T-wave inversions on electrocardiogram, cardiac syncope, right ventricular function, therapeutic medication use, and exercise intensity were assessed at the time of 2010 Task Force Criteria based ARVC diagnosis and upon repeat evaluations. Changes in these risk factors were analyzed over 5-year follow-up. The 5-year risk of VA was predicted longitudinally using (1) the baseline ARVC risk calculator prediction, (2) the ARVC risk prediction calculated using updated risk factors, and (3) time-varying Cox regression. Discrimination and calibration were assessed in comparison to observed VA event rates.<br /><b>Results</b><br />Four hundred eight patients with ARVC experiencing 132 primary VA events were included. Matched comparison of risk factors at baseline versus at 5 years of follow-up revealed decreased burdens of premature ventricular complexes (-1200/day) and nonsustained ventricular tachycardia (-14%). Presence of significant right ventricular dysfunction and number of T-wave inversions on electrocardiogram were unchanged. Observed risk for VA decreased by 13% by 5 years follow-up. The baseline ARVC risk calculator\'s ability to predict 5-year VA risk worsened during follow-up (C statistics, 0.83 at diagnosis versus 0.68 at 5 years). Both the updated ARVC risk calculator (C statistics of 0.77) and time-varying Cox regression model (C statistics, 0.77) had strong discrimination. The updated ARVC risk calculator overestimated 5-year VA risk by an average of +6%.<br /><b>Conclusion</b><br />Risk factors for VA in ARVC are dynamic, and overall risk for incident sustained VA decreases during follow-up. Up-to-date risk factor assessment improves VA risk stratification.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 31 Oct 2022:e011207; epub ahead of print</small></div>
Carrick RT, Te Riele ASJM, Gasperetti A, Bosman L, ... James CA, Wu KC
Circ Arrhythm Electrophysiol: 31 Oct 2022:e011207; epub ahead of print | PMID: 36315818
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This program is still in alpha version.