A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.

Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest [UCA]; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia [CPVT]), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS (P < .001). The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination. Although the median change in QT interval was longer in CRDS cases (P = .002), an overlap between the cases and controls was present. The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.

The R-wave amplitude in V1 on baseline electrocardiogram correlates with the occurrence of high-degree atrioventricular block following left bundle branch block after transcatheter aortic valve replacement.

AIMS: Several procedural and electrocardiogram (ECG) parameters have been associated with the occurrence of high-degree atrioventricular block (AVB) requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR). We hereunder sought to assess if the baseline R-wave amplitude in V1 ECG lead of patients with normal QRS duration undergoing TAVR is associated with a higher patient's risk for developing high-degree AVB following left bundle branch block (LBBB). METHODS AND RESULTS: In this retrospective single-centre study in 720 consecutive patients who underwent TAVR, 141 (19.6%) patients with normal QRS duration developed a new LBBB after TAVR. The 24 (17%) patients who underwent PPI for reasons other than high-degree AVB were excluded from further analysis. In the remaining 117 study patients, 14 (12%) developed high-degree AVB requiring PPI (Group 1) while the remaining 103 (88%) patients did not (Group 2). There were no significant differences in baseline demographic or procedural characteristics nor in PR interval, QRS duration, and QRS axis between these two groups. The incidence of left anterior hemiblock was higher in Group 1 (3 of 14, 21.4%) than that in Group 2 (9 of 103, 8.7%), but the difference was not statistically significant (P = 0.156). The R-wave amplitude in V1 was smaller in Group 1 than that in Group 2 (0.029 ± 0.04 mV vs. 0.11 ± 0.14 mV, P = 0.0316). In the receiver-operating characteristics analysis, the cutoff for R-wave amplitude pre-TAVR was 0.03 mV, area under the curve = 0.7219 (P = 0.0002). CONCLUSION: The R-wave amplitude in lead V1 during baseline ECG in patients with normal QRS duration may predict the occurrence of high-degree AVB following new LBBB after TAVR.

Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia.

AIMS: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. METHODS AND RESULTS: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. CONCLUSIONS: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

The QRS frontal plane axis changes during left bundle branch block after transcatheter aortic valve replacement.

BACKGROUND AND AIMS: Left bundle branch block (LBBB) is common after transcatheter aortic valve replacement (TAVR) and associated with a left or normal QRS axis. We aim to assess the QRS frontal plane axis shift changes during LBBB after TAVR and determine if the risk of procedure-related high degree atrioventricular block (AVB) is affected by QRS axis shift changes. METHODS AND RESULTS: In a retrospective single-center study of 720 consecutive patients who underwent TAVR, 141 (19.6%) with normal baseline QRS duration developed a new LBBB after TAVR and constituted the study group. Most patients (59.6%) were females and the mean age of the cohort was 81.2 ± 6 years. RESULTS: As compared with the baseline QRS axis before TAVR, the occurrence of LBBB was associated with a leftward QRS axis shift (by 40 ± 28.3°) in 73% of the study patients and a rightward (by 18.6 ± 19.4°) or no change in QRS axis in 25.6% and 1.4% of the study patients, respectively. A left QRS axis (-30°) was observed in 14.9% and 38.3% of the study patients before and after TAVR, respectively. The group of patients exhibiting a rightward or no QRS axis shift had a greater incidence of high degree AVB than the group of patients exhibiting a leftward QRS axis shift (18.4% vs. 6.8%, p = .056). CONCLUSION: Although post TAVR-LBBB is associated with a leftward QRS axis shift in most patients, a non-negligible proportion of patients (27%) exhibited a rightward or no QRS axis shift. The latter group tend to have a higher risk of developing high degree AVB.

The prevalence of left and right bundle branch block morphology ventricular tachycardia amongst patients with arrhythmogenic cardiomyopathy and sustained ventricular tachycardia: insights from the European Survey on Arrhythmogenic Cardiomyopathy.

AIMS: In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. METHODS AND RESULTS: Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients' clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P < 0.001). Mutations in PKP2 predominated in the LBBB-VT (65.2%) and the LBBB + RBBB-VT (41.7%) groups while DSP mutations predominated in the RBBB-VT group (45.5%). By multivariable analysis, female sex was associated with LBBB + RBBB-VT (P = 0.011) while DSP mutations were associated with RBBB-VT (P < 0.001). After a median follow-up of 103 (51-185) months, death occurred in 106 (11.1%) patients with no intergroup difference (P = 0.176). CONCLUSION: RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

Quinidine-Responsive Polymorphic Ventricular Tachycardia in Patients With Coronary Heart Disease.

BACKGROUND: Polymorphic ventricular tachycardia (VT) without QT prolongation is well described in patients without structural heart disease (mainly idiopathic ventricular fibrillation and Brugada syndrome) and in patients with acute ST-elevation myocardial infarction. METHODS: Retrospective study of patients with polymorphic VT related to coronary artery disease, but without evidence of acute myocardial ischemia. RESULTS: The authors identified 43 patients in whom polymorphic VT developed within days of an otherwise uncomplicated myocardial infarction or coronary revascularization procedure. The polymorphic VT events were invariably triggered by extrasystoles with short (364±36 ms) coupling interval. Arrhythmic storms (4-16 events of polymorphic VT deteriorating to ventricular fibrillation) occurred in 23 (53%) patients. These arrhythmic storms were always refractory to conventional antiarrhythmic therapy, including intravenous amiodarone, but invariably responded to quinidine therapy. In-hospital mortality was 17% for patients with arrhythmic storm. Patients treated with quinidine invariably survived to hospital discharge. During long-term follow-up (of 5.6±6 years; range, 1 month to 18 years), 3 (16%) of patients discharged without quinidine developed recurrent polymorphic VT. There were no recurrent arrhythmias during quinidine therapy Conclusions: Arrhythmic storm with recurrent polymorphic VT in patients with coronary disease responds to quinidine therapy when other antiarrhythmic drugs (including intravenous amiodarone) fail.

Quinidine-responsive out-of-hospital polymorphic ventricular tachycardia in patients with coronary heart disease.

AIMS: We recently reported that patients with coronary artery disease (CAD) who develop polymorphic ventricular tachycardia (VT) during the healing phase of an acute coronary event, generally fail to respond to revascularization or standard antiarrhythmic therapy but respond immediately to quinidine therapy. Here, we describe that CAD patients presenting with out-of-hospital polymorphic VT without a recent coronary event or an obvious precipitating factor, also respond uniquely to quinidine therapy. METHODS AND RESULTS: Retrospective study of patients with unheralded, mainly out-of-hospital, polymorphic VT related to CAD but without evidence of acute myocardial ischaemia. We identified 20 patients who developed polymorphic VT without precipitating factors. The polymorphic VT events were triggered by extrasystoles with short (376 ± 49 ms) coupling interval. Arrhythmic storms occurred in 70% patients. These arrhythmic storms were generally refractory to conventional antiarrhythmic therapy but invariably responded to quinidine therapy. Revascularization was antiarrhythmic in 3 patients despite the absent clinical or ECG signs of ischaemia. During long-term follow-up (range 2 months to 11 years), 3 (15%) of patients not receiving quinidine developed recurrent polymorphic VT. There were no recurrent arrhythmias during long-term quinidine therapy. CONCLUSIONS: Patients with CAD may develop polymorphic VT in the absence of obvious acute ischaemia or apparent precipitating factors, presenting as out-of-hospital polymorphic VT with high risk of arrhythmic storms that respond uniquely to quinidine therapy.

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry.

AIMS: To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs). METHODS AND RESULTS: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03]. CONCLUSION: Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.

Time-to-first appropriate shock in patients implanted prophylactically with an implantable cardioverter-defibrillator: data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS).

AIMS: Data on predictors of time-to-first appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with Brugada Syndrome (BrS) and prophylactically implanted ICD's are scarce. METHODS AND RESULTS: SABRUS (Survey on Arrhythmic Events in BRUgada Syndrome) is an international survey on 678 BrS patients who experienced arrhythmic event (AE) including 252 patients in whom AE occurred after prophylactic ICD implantation. Analysis was performed on time-to-first appropriate ICD discharge regarding patients' characteristics. Multivariate logistic regression models were utilized to identify which parameters predicted time to arrhythmia ≤5 years. The median time-to-first appropriate ICD therapy was 24.8 ± 2.8 months. A shorter time was observed in patients from Asian ethnicity (P < 0.05), those with syncope (P = 0.001), and those with Class IIa indication for ICD (P = 0.001). A longer time was associated with a positive family history of sudden cardiac death (P < 0.05). Multivariate Cox regression revealed shorter time-to-ICD therapy in patients with syncope [odds ratio (OR) 1.65, P = 0.001]. In 193 patients (76.6%), therapy was delivered during the first 5 years. Factors associated with this time were syncope (OR 0.36, P = 0.001), spontaneous Type 1 Brugada electrocardiogram (ECG) (OR 0.5, P < 0.05), and Class IIa indication (OR 0.38, P < 0.01) as opposed to Class IIb (OR 2.41, P < 0.01). A near-significant trend for female gender was also noted (OR 0.13, P = 0.052). Two score models for prediction of <5 years to shock were built. CONCLUSION: First appropriate therapy in BrS patients with prophylactic ICD's occurred during the first 5 years in 76.6% of patients. Syncope and spontaneous Type 1 Brugada ECG correlated with a shorter time to ICD therapy.

New Insights on Verapamil-Sensitive Idiopathic Left Fascicular Tachycardia.

Verapamil-sensitive left fascicular monomorphic ventricular tachycardia (LF-VT) was first described ~4 decades ago. Our knowledge regarding this arrhythmia is evolving continuously. The current review aims to highlight up to date aspects of this arrhythmia focusing on its ECG recognition, new considerations of the reentrant circuit, ablation targets in inducible and non-inducible patients and the approach to LF-VT with multiform morphology.

Catheter Induced Mechanical Suppression of Outflow-tract Arrhythmias: Incidence, Characteristics, and Significance.

BACKGROUND: The incidence, characteristics, and clinical significance of catheter-induced mechanical suppression (trauma) of ventricular arrhythmias originating in the outflow tract (OT) area have not been thoroughly evaluated. OBJECTIVES: To determine these variables among our patient cohort. METHODS: All consecutive patients with right ventricular OT (RVOT) and left ventricular OT (LVOT) arrhythmias ablated at two medical centers from 1998 to 2014 were included. Patients were observed for catheter-induced trauma during ablation procedures. Procedural characteristics, as well as response to catheter-induced trauma and long term follow-up, were recorded. RESULTS: During 288 ablations of OT arrhythmias in 273 patients (RVOT n=238, LVOT n=50), we identified 8 RVOT cases (3.3%) and 1 LVOT (2%) case with catheter-induced trauma. Four cases of trauma were managed by immediate radiofrequency ablation (RFA), three were ablated after arrhythmia recurrence within a few minutes, and two were ablated after > 30 minutes without arrhythmia recurrence. Patients with catheter-induced trauma had higher rates of repeat ablations compared to patients without: 3/9 (33%) vs. 12/264 (0.45%), P = 0.009. The three patients with arrhythmia recurrence were managed differently during the first ablation procedure (immediate RFA, RFA following early recurrence, and delayed RFA). During the repeat procedure of these three patients, no catheter trauma occurred in two, and in one no arrhythmia was observed. CONCLUSIONS: Significant catheter-induced trauma occurred in 3.1% of OT arrhythmias ablations, both at the RVOT and LVOT. Arrhythmia suppression may last > 30 minutes and may interfere with procedural success. The optimal mode of management following trauma is undetermined.

Arrhythmic Events in Brugada Syndrome: A Nationwide Israeli Survey of the Clinical Characteristics, Treatment; and Long-Term Follow-up (ISRABRU-VF).

BACKGROUND: Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE). OBJECTIVES: To conduct the first nationwide survey focused on BrS patients with documented AE. METHODS: Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2). RESULTS: The cohort comprised 31 patients: 25 in group 1, 6 in group 2. Group 1: 96% male, mean CA age 38 years (range 13-84). Nine patients (36%) presented with arrhythmic storm and three had a lethal outcome; 17 (68%) had spontaneous type 1 Brugada electrocardiography (ECG). An electrophysiology study (EPS) was performed on 11 patients with inducible ventricular fibrillation (VF) in 10, which was prevented by quinidine in 9/10 patients. During follow-up (143 ± 119 months) eight patients experienced appropriate shocks, none while on quinidine. Group 2: all male, age 30-53 years; 4/6 patients had familial history of sudden death age < 50 years. Five patients had spontaneous type 1 Brugada ECG and four were asymptomatic at ICD implantation. EPS was performed in four patients with inducible VF in three. During long-term follow-up, five patients received ≥ 1 appropriate shocks, one had ATP for sustained VT (none taking quinidine). No AE recurred in patients subsequently treated with quinidine. CONCLUSIONS: CA from BrS is apparently a rare occurrence on a national scale and no AE occurred in any patient treated with quinidine.

Use of New Imaging CARTO® Segmentation Module Software to Facilitate Ablation of Ventricular Arrhythmias.

INTRODUCTION: A new imaging software (CARTO® Segmentation Module, Biosense Webster) allows preprocedural 3-D reconstruction of all heart chambers based on cardiac CT. We describe our initial experience with the new module during ablation of ventricular arrhythmias. METHODS AND RESULTS: Eighteen consecutive patients with idiopathic ventricular arrhythmias or ischemic ventricular tachycardia (VT) were studied. In the latter group, a combined endocardial and epicardial ablation was performed. Of the 14 patients with idiopathic arrhythmias, 12 were ablated in the outflow tract (OT), 1 in the midseptal left ventricle, and 1 at the left posterior fascicular area; acute successful ablation was achieved in 11 (78.6%) patients. The procedure was discontinued due to close proximity of the arrhythmia origin to the coronary arteries (CA) in 2 patients. Acute successful uncomplicated ablation was achieved in all 4 patients with ischemic VT. During ablation in the coronary cusps commissures, the CARTO® Segmentation Module accurately defined the cusps anatomy. The precise anatomic location provided by the module assisted in successfully ablating when information from activation mapping was not optimal, by ablating at the opposite side of the cusps. In addition, by demonstrating the precise location of the CA, it allowed safe ablation of arrhythmias that originated in close proximity to the CA both in the OT area and the epicardium, eliminating the need for repeat angiography. CONCLUSIONS: The CARTO® Segmentation Module is useful for accurate definition of the exact anatomic location of ventricular arrhythmias and for safely ablating them especially in close proximity to the CA.

Atrial Tachycardia Originating in the Vicinity of the Noncoronary Sinus of Valsalva: Report of a Series Including the First Case of Ablation-Related Complete Atrioventricular Block.

BACKGROUND: A few series of focal atrial tachycardia (AT) originating from the noncoronary sinus of Valsalva (NCSV) have been reported in the literature during the last decade. METHODS AND RESULTS: Of 147 patients with AT referred for radiofrequency ablation (RFA), we identified nine (6%) originating in the vicinity of the NCSV. Clinical AT was induced during electrophysiological study in all patients without (n = 6) and with (n = 3) isoproterenol infusion. Mean cycle length of the induced tachycardia was 399 ± 85 ms. Mapping of the right atrium and of the left atrium (LA) was initially performed in all nine patients and in four patients, respectively. Earliest tachycardia activation occurred at the His bundle area in all cases. Earliest activations in the LA were at the low paraseptal regions. In two patients with antegrade dual atrioventricular (AV) node physiology that rendered difficult accurate distinction between atrial and ventricular activation, slow pathway ablation was necessary. A retrograde aortic approach was used for mapping the aortic cusps. The earliest local atrial activation in the NCSV preceded the atrial activation in the His area in all patients by 27 ± 8 ms. RFA was performed in all nine patients and was acutely successful in eight. Two patients required radiofrequency (RF) energy outputs of 50 W in order to terminate the arrhythmia. In one patient, successful AT ablation was associated with complete AV block requiring implantation of permanent pacemaker. CONCLUSIONS: Focal AT can be successfully mapped and ablated in the NCSV. Higher than usual RF energy levels are sometimes required. Complete AV block is a possible complication.