Ablation of the epicardial substrate in patients with long-QT syndrome at risk of sudden death.

Sudden cardiac death remains a critical public health concern globally, affecting millions annually. Recent advances in cardiac arrhythmia mapping have demonstrated that the ventricular epicardial region has a critical arrhythmogenic role in some inherited cardiogenetic diseases. Among these, long-QT syndrome (LQTS) exposes patients to the risk of life-threatening arrhythmic events. Despite advancements, there is a need for more effective therapeutic strategies. A recent study has uncovered a noteworthy connection between LQTS and epicardial structural abnormalities, challenging the traditional view of LQTS as purely an electrical disorder. High-density mapping revealed electroanatomic abnormalities in the right ventricular epicardium, presenting a potential target for catheter ablation, to finally suppress ventricular fibrillation recurrences in high-risk LQTS patients.

Right ventricular epicardial arrhythmogenic substrate in long-QT syndrome patients at risk of sudden death.

AIMS: The long-QT syndrome (LQTS) represents a leading cause of sudden cardiac death (SCD). The aim of this study was to assess the presence of an underlying electroanatomical arrhythmogenic substrate in high-risk LQTS patients. METHODS AND RESULTS: The present study enrolled 11 consecutive LQTS patients who had experienced frequent implantable cardioverter-defibrillator (ICD discharges triggered by ventricular fibrillation (VF). We acquired electroanatomical biventricular maps of both endo and epicardial regions for all patients and analyzed electrograms sampled from several myocardial regions. Abnormal electrical activities were targeted and eliminated by the means of radiofrequency catheter ablation. VF episodes caused a median of four ICD discharges in eleven patients (6 male, 54.5%; mean age 44.0 ± 7.8 years, range 22-53) prior to our mapping and ablation procedures. The average QTc interval was 500.0 ± 30.2 ms. Endo-epicardial biventricular maps displayed abnormally fragmented, low-voltage (0.9 ± 0.2 mV) and prolonged electrograms (89.9 ± 24.1 ms) exclusively localized in the right ventricular epicardium. We found electrical abnormalities extending over a mean epicardial area of 15.7 ± 3.1 cm2. Catheter ablation of the abnormal epicardial area completely suppressed malignant arrhythmias over a mean 12 months of follow-up (median VF episodes before vs. after ablation, 4 vs. 0; P = 0.003). After the procedure, the QTc interval measured in a 12-lead ECG analysis shortened to a mean of 461.8 ± 23.6 ms (P = 0.004). CONCLUSION: This study reveals that, among high-risk LQTS patients, regions localized in the epicardium of the right ventricle harbour structural electrophysiological abnormalities. Elimination of these abnormal electrical activities successfully prevented malignant ventricular arrhythmia recurrences.

Recurrences of ventricular tachycardia after stereotactic arrhythmia radioablation arise outside the treated volume: analysis of the Swiss cohort.

AIMS: Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of therapy-refractory ventricular tachycardia (VT). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. We analysed recurrences in our patients after STAR. METHODS AND RESULTS: From 09.2017 to 01.2020, 20 patients (68 ± 8 y, LVEF 37 ± 15%) suffering from refractory VT were enrolled, 16/20 with a history of at least one electrical storm. Before STAR, an invasive electroanatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23 ± 2 Gy was delivered to the planning target volume (PTV). The median ablation volume was 26 mL (range 14-115) and involved the interventricular septum in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester). After a median follow-up of 25 months, 12/20 (60%) developed a recurrence and underwent a redo ablation. VT recurrence was located in the proximity of the treated substrate in nine cases, remote from the PTV in three cases and involved a larger substrate over ≥3 LV segments in two cases. No recurrences occurred inside the PTV. Voltage measurements showed a significant decrease in both bipolar and unipolar signal amplitude after STAR. CONCLUSION: STAR is a new tool available for the treatment of VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude.

Cardiovascular magnetic resonance determinants of ventricular arrhythmic events after myocardial infarction.

AIMS: To non-invasively characterize, by means of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), scar differences, and potential variables associated with ventricular tachycardia (VT) occurrence in chronic post-myocardial infarction (MI) patients. METHODS AND RESULTS: A case-control study was designed through retrospective LGE-CMR data analysis of chronic post-MI patients (i) consecutively referred for VT substrate ablation after a first VT episode (n = 66) and (ii) from a control group (n = 84) with no arrhythmia evidence. The myocardium was characterized differentiating core, border zone (BZ), and BZ channels (BZCs) using the ADAS 3D post-processing imaging platform. Clinical and scar characteristics, including a novel parameter, the BZC mass, were compared between both groups. One hundred and fifty post-MI patients were included. Four multivariable Cox proportional hazards regression models were created for total scar mass, BZ mass, core mass, and BZC mass, adjusting them by age, sex, and left ventricular ejection fraction (LVEF). A cut-off of 5.15 g of BZC mass identified the cases with 92.4% sensitivity and 86.9% specificity [area under the ROC curve (AUC) 0.93 (0.89-0.97); P < 0.001], with a significant increase in the AUC compared to other scar parameters (P < 0.001 for all pairwise comparisons). Adding BZC mass to LVEF allowed to reclassify 33.3% of the cases and 39.3% of the controls [net reclassification improvement = 0.73 (0.71-0.74)]. CONCLUSIONS: The mass of BZC is the strongest independent variable associated with the occurrence of sustained monomorphic ventricular tachycardia in post-MI patients after adjustment for age, sex, and LVEF. Border zone channel mass measurement could permit a more accurate VT risk stratification than LVEF in chronic post-MI patients.

Distinct spectral dynamics of implanted cardiac defibrillator signals in spontaneous termination of polymorphic ventricular tachycardia and fibrillation in patients with electrical and structural diseases.

AIMS: To determine the spectral dynamics of early spontaneous polymorphic ventricular tachycardia and ventricular fibrillation (PVT/VF) in humans. METHODS AND RESULTS: Fifty-eight self-terminated and 173 shock-terminated episodes of spontaneously initiated PVT/VF recorded by Medtronic implanted cardiac defibrillators (ICDs) in 87 patients with various cardiac pathologies were analyzed by short fast Fourier transform of shifting segments to determine the dynamics of dominant frequency (DF) and regularity index (RI). The progression in the intensity of DF and RI accumulations further quantified the time course of spectral characteristics of the episodes. Episodes of self-terminated PVT/VF lasted 8.6 s [95% confidence interval (CI): 8.1-9.1] and shock-terminated lasted 13.9 s (13.6-14.3) (P < 0.001). Recordings from patients with primarily electrical pathologies displayed higher DF and RI values than those from patients with primarily structural pathologies (P < 0.05) independently of ventricular function or antiarrhythmic drug therapy. Regardless of the underlying pathology, the average DF and RI intensities were lower in self-terminated than shock-terminated episodes [DF: 3.67 (4.04-4.58) vs. 4.32 (3.46-3.93) Hz, P < 0.001; RI: 0.53 (0.48-0.56) vs. 0.63 (0.60-0.65), P < 0.001]. In a multivariate analysis controlled by the type of pathology and clinical variables, regularity remained an independent predictor of self-termination [hazard ratio: 0.954 (0.928-0.980)]. Receiver operating characteristic (ROC) curve analysis of DF and RI intensities demonstrated increased predictability for self-termination in time with 95% CI above the 0.5 cut-off limit at about t = 8.6 s and t = 6.95 s, respectively. CONCLUSION: Consistent with the notion that fast organized sources maintain PVT/VF in humans, reduction of frequency and regularity correlates with early self-termination. Our findings might help generate ICD methods aiming to reduce inappropriate shock deliveries.

Catheter ablation of ventricular tachycardia in dilated-phase hypertrophic cardiomyopathy: Substrate characterization and ablation outcome.

INTRODUCTION: Catheter ablation is a therapeutic option to suppress ventricular tachycardia (VT) in the setting of dilated-phase hypertrophic cardiomyopathy (DHCM). However, the characteristics of the arrhythmogenic substrate and the ablation outcome are not fully illustrated. METHOD: A total of 23 ablation procedures for drug-refractory sustained monomorphic VTs in 13 DHCM patients (60 ± 11 years, one female, the left ventricular [LV] ejection fraction 39% ± 9%, the LV mass index 156 ± 39 g/m2 ) were performed. The distribution of VT substrate as endocardial or epicardial/intramural was based on detailed mapping and ablation response during VT. RESULT: Two patients underwent ablation of sustained monomorphic VT that was not scar-mediated tachycardia. Of the remaining 11 patients, eight (73%) patients had VT substrate in the basal regions, most frequently at the epicardial and/or intramural basal antero-septum. None of the patients had VT substrate located at the LV inferolateral region. Ablation at the right ventricular septum and the aortic cusps was done in four and five patients, respectively. Other approaches including bipolar and chemical ablations, were done in three and two patients, respectively. Six (55%) out of 11 patients (two patients lost follow-up) had VT recurrence. All the six patients had basal substrate. However, anti-tachycardia pacing was sufficient for VT termination except in one patient. CONCLUSION: Catheter ablation of VT in patients with DHCM is challenging because of the predominant basal anteroseptal epicardial/intramural location of arrhythmogenic substrate. An ablation approach from multiple sites and/or adjunctive interventional techniques are often required.

Brugada syndrome genetics is associated with phenotype severity.

AIMS: Brugada syndrome (BrS) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia/fibrillation (VT/VF) in young, otherwise healthy individuals. Despite SCN5A being the most commonly known mutated gene to date, the genotype-phenotype relationship is poorly understood and remains uncertain. This study aimed to elucidate the genotype-phenotype correlation in BrS. METHODS AND RESULTS: Brugada syndrome probands deemed at high risk of future arrhythmic events underwent genetic testing and phenotype characterization by the means of epicardial arrhythmogenic substrate (AS) mapping, and were divided into two groups according to the presence or absence of SCN5A mutation. Two-hundred probands (160 males, 80%; mean age 42.6 ± 12.2 years) were included in this study. Patients harbouring SCN5A mutations exhibited a spontaneous type 1 pattern and experienced aborted cardiac arrest or spontaneous VT/VF more frequently than the other subjects. SCN5A-positive patients exhibited a larger epicardial AS area, more prolonged electrograms and more frequently observed non-invasive late potentials. The presence of an SCN5A mutation explained >26% of the variation in the epicardial AS area and was the strongest predictor of a large epicardial area. CONCLUSION: In BrS, the genetic background is the main determinant for the extent of the electrophysiological abnormalities. SCN5A mutation carriers exhibit more pronounced epicardial electrical abnormalities and a more aggressive clinical presentation. These results contribute to the understanding of the genetic determinants of the BrS phenotypic expression and provide possible explanations for the varying degrees of disease expression.

Easily available ECG and echocardiographic parameters for prediction of left atrial remodeling and atrial fibrillation recurrence after pulmonary vein isolation: A multicenter study.

BACKGROUND: The assessment of noninvasive markers of left atrial (LA) low-voltage substrate (LVS) enables the identification of atrial fibrillation (AF) patients at risk for arrhythmia recurrence after pulmonary vein isolation (PVI). METHODS: In this prospective multicenter study, 292 consecutive AF patients (72% male, 62 ± 11 years, 65% persistent AF) underwent high-density LA voltage mapping in sinus rhythm. LA-LVS (<0.5 mV) was considered as significant at 2 cm2  or above. Preprocedural clinical electrocardiogram and echocardiographic data were assessed to identify predictors of LA-LVS. The role of the identified LA-LVS markers in predicting 1-year arrhythmia freedom after PVI was assessed in 245 patients. RESULTS: Significant LA-LVS was identified in 123 (42%) patients. The amplified sinus P-wave duration (APWD) best predicted LA-LVS, with a 148-ms value providing the best-balanced sensitivity (0.81) and specificity (0.88). An APWD over 160 ms was associated with LA-LVS in 96% of patients, whereas an APWD under 145 ms in 15%. Remaining gray zones improved their accuracy by introduction of systolic pulmonary artery pressure (sPAP) of 35 mmHg or above, age, and sex. According to COX regression, the risk of arrhythmia recurrence 12 months following PVI was twofold and threefold higher in patients with APWD 145-160 and over 160 ms, compared to APWD under 145 ms. Integration of pulmonary hypertension further improved the outcome prediction in the intermediate APWD group: Patients with APWD 145-160 ms and normal sPAP had similar outcome than patients with APWD under 145 ms (hazard ratio [HR] 1.62, p = .14), whereas high sPAP implied worse outcome (HR 2.56, p < .001). CONCLUSIONS: The APWD identifies LA-LVS and risk for arrhythmia recurrence after PVI. Our prediction model becomes optimized by means of integration of the pulmonary artery pressure.

Arrhythmogenic substrate detection in chronic ischaemic patients undergoing ventricular tachycardia ablation using multidetector cardiac computed tomography: compared evaluation with cardiac magnetic resonance.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) permits characterizing ischaemic scars, detecting heterogeneous tissue channels (HTCs) which constitute the arrhythmogenic substrate (AS). Late gadolinium enhancement cardiac magnetic resonance also improves the arrhythmia-free survival when used to guide ventricular tachycardia (VT) substrate ablation. However, its availability may be limited. We sought to evaluate the performance of multidetector cardiac computed tomography (MDCT) imaging in identifying HTCs detected by LGE-CMR in ischaemic patients undergoing VT substrate ablation. METHODS AND RESULTS: Thirty ischaemic patients undergoing both LGE-CMR and MDCT before VT substrate ablation were included. Using a dedicated post-processing software, two blinded operators, assigned either to LGE-CMR or MDCT analysis, characterized the presence of CMR and computed tomography (CT) channels, respectively. Cardiac magnetic resonance channels were classified as endocardial (layers < 50%), epicardial (layers ≥ 50%), or transmural. Cardiac magnetic resonance- vs. CT-channel concordance was considered when showing the same orientation and American Heart Association (AHA) segment. Mean age was 69 ± 10 years; 90% were male. Mean left ventricular ejection fraction was 35 ± 10%. All patients had CMR channels (n = 76), whereas only 26/30 (86.7%) had CT channels (n = 91). Global sensitivity (Se) and positive predictive values for detecting CMR channels were 61.8% and 51.6%, respectively. MDCT performance improved in patients with epicardial CMR channels (Se 80.5%) and transmural scars (Se 72.2%). In 4/11 (36%) patients with subendocardial myocardial infarction (MI), MDCT was unable to identify the AS. CONCLUSIONS: Compared to LGE-CMR, myocardial wall thickness assessment using MDCT fails to detect the presence of AS in 36% of patients with subendocardial MI, showing modest sensitivity identifying HTCs but a better performance in patients with transmural scars.

The role of imaging in catheter ablation of ventricular arrhythmias.

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) and multidetector cardiac computed tomography (MDCT) have emerged as novel, fascinating imaging tools for arrhythmogenic substrate identification and characterization. The role of these techniques for aiding and guiding the catheter ablation of ventricular tachycardia, either as a complement or a surrogate of the electroanatomic map, has been rising in recent years. Integrating pixel signal intensity maps or wall thickness maps delivered from LGE-CMR or MDCT, respectively, into the navigation system has become a cornerstone for VT ablation procedures in a few centers of excellence around the world. The pre-procedure scar characterization offers some advantages, helping decide for the best procedure planning and approach; complete substrate identification and characterization, helping to focus electroanatomical mapping in regions of interest and also has a positive impact in procedure efficiency and outcomes. In the present article, we perform a review of the most practical aspects for using LGE-CMR or MDCT when a VT ablation procedure is planned, from the image acquisition to the integration into the navigation system, analyzing the current role of the LGE-CMR and MDCT for arrhythmogenic substrate characterization as well as for guiding VT ablation.

Non-invasive assessment of the arrhythmogenic substrate in Brugada syndrome using signal-averaged electrocardiogram: clinical implications from a prospective clinical trial.

AIMS: Brugada syndrome (BrS) represents a major cause of sudden cardiac death in young individuals. The risk stratification to forecast future life-threatening events is still controversial. Non-invasive assessment of late potentials (LPs) has been proposed as a risk stratification tool. However, their nature in BrS is still undetermined. The purpose of this study is to assess the electrophysiological determinants of non-invasive LPs. METHODS AND RESULTS: Two hundred and fifty consecutive patients with (Group 1, n = 96) and without (Group 2, n = 154) BrS-related symptoms were prospectively enrolled in the registry. Signal-averaged electrocardiogram (SAECG) was performed in all subjects before undergoing epicardial mapping. Group 1 patients exhibited larger arrhythmogenic substrates (AS; 5.8 ± 2.8 vs. 2.6 ± 2.1 cm2, P < 0.001) with more delayed potentials (220.4 ± 46.0 vs. 186.7 ± 42.3 ms, P < 0.001). Late potentials were present in 82/96 (85.4%) Group 1 and in 31/154 (20.1%) Group 2 individuals (P < 0.001). Patients exhibiting LPs had more frequently a spontaneous Type 1 pattern (30.1% vs. 10.9%, P < 0.001), SCN5A mutation (34.5% vs. 21.2%, P = 0.02), and exhibited a larger AS with longer potentials (5.8 ± 2.7 vs. 2.2 ± 1.7 cm2; 231.2 ± 37.3 vs. 213.8 ± 39.0 ms; P < 0.001, respectively). Arrhythmogenic substrate dimension was the strongest predictor of the presence of LPs (odds ratio 1.9; P < 0.001). An AS area of at least 3.5 cm2 identified patients with LPs (area under the curve 0.88, 95% confidence interval 0.843-0.931; P < 0.001) with a sensitivity of 86%, specificity 88%, positive predictive value 85%, and negative predictive value 89%. CONCLUSION: The results of this study support the role of the epicardial AS as an electrophysiological determinant of non-invasive LPs, which may serve as a tool in the non-invasive assessment of the BrS substrate, as SAECG-LPs could be considered an expression of the abnormal epicardial electrical activity.ClinicalTrials.gov number (NCT02641431; NCT03106701).

Long-term outcome and mode of recurrence following noninducibility during noninvasive programmed stimulation after ventricular tachycardia ablation.

BACKGROUND: Noninducibility of ventricular tachycardia (VT) at noninvasive programmed stimulation performed shortly following ablation (negative NIPS) predicts low risk of the medium-term recurrence. This study aimed to evaluate long-term rate and mode of recurrence following negative NIPS. METHODS: We extended follow-up on patients in whom no VT could be induced at NIPS following ablation between 2008 and 2010. Recurrent VTs were categorized as "Original clinical" if they matched VT that had occurred spontaneously prior to the index ablation; "Original nonclinical" if they matched VT that was induced during the index ablation but had not occurred spontaneously; or "New." Among those undergoing repeat ablation, the area ablated to treat the recurrent VT was categorized as "Targeted initial scar" if it was targeted during the index procedure; "Untargeted initial scar" if it was present but not targeted during the index procedure; or "New scar" if it was not present during the index procedure. RESULTS: Of 60 patients with negative NIPS, 18 (30%) had recurrent VT and nine underwent repeat ablation over (4.1 ± 3.2) years follow-up. Of 23 recurrent VTs, 18 (78%) were "New." During repeat ablations, six (46%) of the 13 recurrent VTs were ablated in "untargeted initial scar" and four (31%) in "new scar." CONCLUSIONS: When spontaneous or inducible VTs are eliminated with ablation and no longer inducible during NIPS, these VTs are unlikely to recur during long-term follow-up. More commonly, new VTs occur, which are either associated with areas of scar not present or not targeted during the initial ablation.

[Sudden Cardiac Death in Patients With Ischemic Heart Disease: From Mechanisms to Clinical Practice].

Ischemic heart disease (IHD) and acute coronary syndrome are the main cause of sudden cardiac death (SCD). Incidence of SCD in patients after myocardial infarction (MI) is 4-6-fold higher than in general population. The review focuses on electrophysiological changes during acute myocardial ischemia and mechanisms of myocardial electromechanical remodeling in remote period after MI. Current data on arrhythmia substrates and triggers are presented. Nowadays, the main guide for implantable cardioverter-defibrillator (ICD) use for primary prevention of SCD is reduced left ventricular ejection fraction. The significance of this parameter has been repeatedly demonstrated in large randomized studies. However, the use of a single indicator cannot solve the problem. In this review we present analysis of modern additional predictors of fatal arrhythmias which are available in clinical practice, as well as the perspective for further research of this highly important scientific, clinical, and social problem.

[Current state of treatment strategies for atrial fibrillation]. / Aktueller Stand der Differenzialtherapie des Vorhofflimmerns.

Atrial fibrillation is the most common form of persistent cardiac arrhythmia with a greatly increasing prevalence due to an aging population and increasing cardiovascular risk factors. Apart from impairment of the quality of life atrial fibrillation is associated with a high morbidity, most importantly stroke and heart failure. The therapy is complex and aims at improving symptoms as well as the prevention of thromboembolic complications, heart failure and aggravating comorbidities. Based on individual patient characteristics and symptoms therapy is mainly based on heart rate control by pharmacological means or therapy for maintaining sinus rhythm. This treatment includes antiarrhythmic drugs and catheter ablation. Current research is aimed at the investigation of the electrophysiological mechanisms of recurrent therapy refractive atrial fibrillation and the question whether the maintenance of sinus rhythm can improve the prognosis of atrial fibrillation.

Electrophysiologic characteristics of ventricular arrhythmias arising from the aortic mitral continuity-potential role of the conduction system.

INTRODUCTION: Catheter ablation of ventricular arrhythmia (VA) at the fibrous aortic mitral continuity (AMC) has been described, yet the nature of the arrhythmogenic substrate remains unknown. METHODS: Procedural records of 528 consecutive patients undergoing ablation of VA at Mayo Clinic, Rochester, MN, were reviewed. The electrocardiographic and electrophysiologic characteristics of patients with successful ablation at the AMC were analyzed to characterize the underlying arrhythmogenic substrate. RESULTS: Of the 21 patients (mean age 53.2 ± 13.4 years, 47.6% male) who underwent ablation of VA at the AMC with acute success, prepotentials (PPs) were found at the ablation sites preceding the ventricular electrogram (VEGM) during arrhythmias in 13 (61.9%) patients and during sinus rhythm in 7 (53.8%) patients. VAs with PPs were associated with a significantly higher burden of premature ventricular complexes (PVCs; 26.1 ± 10.9% vs. 14.9 ± 10.1%, P = 0.03), shorter VEGM to QRS intervals (9.0 ± 28.5 milliseconds vs. 33.1 ± 8.8 milliseconds, P = 0.03), lower pace map scores (8.7 ± 1.6 vs. 11.4 ± 0.8, P = 0.001), and a trend toward shorter V-H intervals during VA (32.1 ± 38.6 milliseconds vs. 76.3 ± 11.1 milliseconds, P = 0.06) as compared to those without PP. A strong and positive correlation was found between V-H interval and QRS duration during arrhythmia in those with PPs (B = 2.11, R(2) = 0.97, t = 13.7, P < 0.001) but not in those without PPs. CONCLUSION: Local EGM characteristics and relative activation time of the His bundle suggest the possibility of conduction tissue as the origin for VA arising from the fibrous AMC. Specific identification and targeting of PPs when ablating VAs at this location may improve procedural success.

Regional conduction velocities determined by noninvasive mapping are associated with arrhythmia-free survival after atrial fibrillation ablation.

BACKGROUND: Atrial arrhythmogenic substrate is a key determinant of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI), and reduced conduction velocities have been linked to adverse outcome. However, a noninvasive method to assess such electrophysiologic substrate is not available to date. OBJECTIVE: This study aimed to noninvasively assess regional conduction velocities and their association with arrhythmia-free survival after PVI. METHODS: A consecutive 52 patients scheduled for AF ablation (PVI only) and 19 healthy controls were prospectively included and received electrocardiographic imaging (ECGi) to noninvasively determine regional atrial conduction velocities in sinus rhythm. A novel ECGi technology obviating the need of additional computed tomography or cardiac magnetic resonance imaging was applied and validated by invasive mapping. RESULTS: Mean ECGi-determined atrial conduction velocities were significantly lower in AF patients than in healthy controls (1.45 ± 0.15 m/s vs 1.64 ± 0.15 m/s; P < .0001). Differences were particularly pronounced in a regional analysis considering only the segment with the lowest average conduction velocity in each patient (0.8 ± 0.22 m/s vs 1.08 ± 0.26 m/s; P < .0001). This average conduction velocity of the "slowest" segment was independently associated with arrhythmia recurrence and better discriminated between PVI responders and nonresponders than previously proposed predictors, including left atrial size and late gadolinium enhancement (magnetic resonance imaging). Patients without slow-conduction areas (mean conduction velocity <0.78 m/s) showed significantly higher 12-month arrhythmia-free survival than those with 1 or more slow-conduction areas (88.9% vs 48.0%; P = .002). CONCLUSION: This is the first study to investigate regional atrial conduction velocities noninvasively. The absence of ECGi-determined slow-conduction areas well discriminates PVI responders from nonresponders. Such noninvasive assessment of electrical arrhythmogenic substrate may guide treatment strategies and be a step toward personalized AF therapy.

Incidence and risk factors for very late recurrence of atrial fibrillation after radiofrequency catheter ablation.

AIMS: Although several prognostic factors for atrial fibrillation (AF) recurrence after catheter ablation (CA) have been reported, predictors of very late recurrence (VLR; initial recurrence >12 months after ablation) remain unidentified. This study investigated clinical variables predictive of VLR after CA for AF. METHODS AND RESULTS: This retrospective single-centre cohort study evaluated data from 1016 consecutive drug-refractory AF patients who underwent single CA for AF from July 2004 to May 2010. After excluding 324 patients with a short follow-up period (<1 year) and 300 patients with recurrence within a year of CA, 392 patients were included. Study subjects were divided into two groups on the basis of VLR presence. Preoperative clinical variables were evaluated as predictors of VLR using the Cox proportional hazards model. The annual rate of VLR was 7.6% after single CA. Univariate analysis revealed that hypertension [hazard ratio (HR) 1.77, 95% confidence interval (CI) 0.93-3.37, P = 0.08], obesity (HR 1.84, 95% CI 0.98-3.45, P = 0.06), long-standing persistent AF (HR 2.35, 95% CI 1.08-5.11, P = 0.03), and abnormally high preoperative C-reactive protein (CRP) levels >0.5 mg/dL (HR 4.28, 95% CI 2.03-9.03, P < 0.0001) were associated with VLR. In the multivariate model, only abnormally high preoperative CRP level was an independent predictor of VLR (HR 4.9, 95% CI 2.3-10.7, P < 0.0001). CONCLUSION: Even after a year without AF, VLR occurred annually in 7.6% cases. Continued vigilance for VLR after CA is clinically desirable, especially for patients with abnormally high preoperative CRP levels.

Comparison of the arrhythmogenic substrate for ventricular tachycardia in patients with ischemic vs non-ischemic cardiomyopathy - insights from high-density, multi-electrode catheter mapping.

PURPOSE: The purpose of this study was to compare the differences of arrhythmogenic substrate using high-density mapping in ventricular tachycardia (VT) patients with ischemic (ICM) vs non-ischemic cardiomyopathy (NICM). METHODS: Data from patients presenting for VT ablation from December 2016 to December 2020 at Westmead Hospital were reviewed. RESULTS: Sixty consecutive patients with structural heart disease (ICM 57%, NICM 43%, mean age 66 years) having catheter ablation of scar-related VT with pre-dominant left ventricular involvement were included. ICM was associated with larger proportion of dense scar area (bipolar; 19 [12-29]% vs 6 [3-10]%, P < 0.001, unipolar; 20 [12-32]% vs 11 [7-19]%, P = 0.01) compared with NICM. However, the scar ratio (unipolar dense scar [%]/bipolar dense scar [%]) was significantly higher in NICM patients (1.2 [0.8-1.7] vs 1.7 [1.3-2.3], P = 0.003). Larger scar area in ICM was paralleled by higher proportion of complex electrograms (6 [2-13] % vs 3 [1-5] %, P = 0.01), longer and wider voltage based conducting channels, higher incidence of late potential-based conducting channels, longer VT cycle-length (399 ± 80 ms vs 359 ± 68 ms, P = 0.04) and greater maximal stimulation-QRS interval among sites with good pace-map correlation (75 [51-99]ms vs 48 [31-73]ms, P = 0.02). Ventricular arrhythmia (VA) storm was more highly prevalent in ICM than NICM (50% vs 23%, P = 0.03). During the follow-up period, NICM had a significantly higher cumulative incidence for the VA recurrence than ICM (P = 0.03). CONCLUSIONS: High-density multi-electrode catheter mapping of left ventricular arrhythmogenic substrate of NICM tends to show smaller dense scar area and higher scar ratio, compared with ICM, suggestive the extent of epicardial/intramural substrate, with paucity of substrate targets for ablation, which results in the worse outcomes with ablation.

Increased vulnerability to atrial and ventricular arrhythmias caused by different types of inhaled tobacco or marijuana products.

BACKGROUND: The emergence of a plethora of new tobacco products marketed as being less harmful than smoking, such as electronic cigarettes and heated tobacco products, and the increased popularity of recreational marijuana have raised concerns about the potential cardiovascular risk associated with their use. OBJECTIVE: The purpose of this study was to investigate whether the use of novel tobacco products or marijuana can cause the development of proarrhythmic substrate and eventually lead to arrhythmias. METHODS: Rats were exposed to smoke from tobacco, marijuana, or cannabinoid-depleted marijuana, to aerosol from electronic cigarettes or heated tobacco products, or to clean air once per day for 8 weeks, following by assays for blood pressure, cardiac function, ex vivo electrophysiology, and histochemistry. RESULTS: The rats exposed to tobacco or marijuana products exhibited progressively increased systolic blood pressure, decreased cardiac systolic function with chamber dilation, and reduced overall heart rate variability, relative to the clean air negative control group. Atrial fibrillation and ventricular tachycardia testing by ex vivo optical mapping revealed a significantly higher susceptibility to each, with a shortened effective refractory period and prolonged calcium transient duration. Histological analysis indicated that in all exposure conditions except for air, exposure to smoke or aerosol from tobacco or marijuana products caused severe fibrosis with decreased microvessel density and higher level of sympathetic nerve innervation. CONCLUSION: These pathophysiological results indicate that tobacco and marijuana products can induce arrhythmogenic substrates involved in cardiac electrical, structural, and neural remodeling, facilitating the development of arrhythmias.