Noninvasive Identification of Ventricular Tachycardia-Related Anatomical Isthmuses in Repaired Tetralogy of Fallot: What Is the Role of the 12-Lead Ventricular Tachycardia Electrocardiogram.

OBJECTIVES: This study sought to evaluate the relation between 12-lead ventricular tachycardia (VT) electrocardiography (ECG) and VT-related anatomical isthmuses (AIs) in repaired tetralogy of Fallot (rTOF). BACKGROUND: Slow-conducting AIs are the dominant VT substrate in rTOF. Whether an AI is considered critical relies on pace mapping (PM) guided by the VT ECG. METHODS: VT ECGs, electroanatomical mapping data and PM results were analyzed in 25 rTOF patients (group 1) (age 57 ± 13 years). Selection of PM and ablation sites was guided by VT ECG. In 7 patients (group 2) (age 33 ± 14 years), PM was systematically performed within all AIs, irrespective of the VT ECG. RESULTS: In group 1, all 35 induced VTs (median VT cycle length 270 [interquartile range: 240 to 310] ms) were AI related. All 11 right bundle branch block (RBBB) VTs were related to AI3 (right ventricular septum if positive concordant [7 of 7]), coronary cusp if V2 transition break [3 of 4]). Left bundle branch block (LBBB) VTs with transition 

Slow Conducting Electroanatomic Isthmuses: An Important Link Between QRS Duration and Ventricular Tachycardia in Tetralogy of Fallot.

OBJECTIVES: This study sought to evaluate the influence of slow conducting anatomic isthmuses (SCAI) as dominant ventricular tachycardia (VT) substrate on QRS duration. BACKGROUND: QRS prolongation has been associated with VT in repaired tetralogy of Fallot. METHODS: Seventy-eight repaired tetralogy of Fallot patients (age 37 ± 15 years, 52 male, QRS duration 153 ± 29 ms, 67 right bundle branch blocks [RBBB]) underwent programmed stimulation and electroanatomic activation mapping during sinus rhythm. Right ventricular (RV) surface, RV activation pattern, RV activation time, conduction velocity at AI, and remote RV sites were determined. RESULTS: Twenty-four patients were inducible for VT (VT+); SCAI was present in 22 of 24 VT+ but only in 2 of 54 patients without inducible VT (VT-). Conduction velocity through AI was slower in VT+ patients (median of 0.3 [0.3 to 0.4] vs. 0.7 [0.6 to 0.9] m/s; p < 0.01) but conduction velocity in the remote RV did not differ between groups. In non-RBBB, QRS duration was similar in VT+ patients (n = 6) and VT- patients (n = 5), but RV activation within SCAI exceeded QRS offset in VT+ patients (37 ± 20 ms vs. -5 ± 9 ms, p < 0.01). In RBBB, both QRS duration and RV activation time were longer in VT+ patients (n = 18, 17 of 18 QRS > 150 ms) compared with VT- patients (n = 49, 27 of 49 QRS > 150 ms) (173 ± 22 ms vs. 156 ± 20 ms; p < 0.01; 141 ± 22 ms vs. 129 ± 21 ms; p = 0.04). In VT+ patients, QRS prolongation >150 ms (n = 17) was due to SCAI or blocked isthmus in 15 patients (88%) and 1 (6%). In contrast, in VT- patients, QRS prolongation >150 ms (n = 27) was due to enlarged RV or blocked isthmus in 10 patients (37%) and 8 (30%), but due to SCAI in only 1 (4%). After exclusion of a severely enlarged RV, a QRS duration >150 ms was highly predictive for SCAI/blocked AI (OR: 17; 95% CI: 3.3 to 84; p < 0.01). CONCLUSIONS: A narrow QRS interval does not exclude VT-related SCAI. In the presence of RBBB, SCAI further prolongs QRS duration. QRS duration >150 ms is highly suspicious for SCAI or isthmus block distinguishable by electroanatomic mapping.

Impact of surgery on presence and dimensions of anatomical isthmuses in tetralogy of Fallot.

OBJECTIVE: In tetralogy of Fallot (TOF), the dominant ventricular tachycardia substrates are slow-conducting anatomical isthmuses. Surgical correction has evolved, which might have influenced isthmus presence and dimensions. METHODS: One hundred and forty-two postmortem TOF specimens (84/58 corrected/uncorrected) were studied for isthmus presence. Isthmus 1 is located between the tricuspid annulus and right ventricular (RV) outflow tract (RVOT) patch/RV incision, isthmus 2 between RVOT patch/RV incision and pulmonary valve, isthmus 3 between pulmonary valve and ventricular septal defect (patch), isthmus 4 between ventricular septal defect (patch) and tricuspid annulus. Isthmus width and thickness were measured. RESULTS: Of 84 corrected postmortem TOF specimens (death: 6.6 years (4.0-11.5)), 83 demonstrated isthmus 1 (99%, width=25±10 mm, thickness=5±2 mm), 35 isthmus 2 (42%, width=10±9 mm, thickness=3±2 mm), 83 isthmus 3 (99%, width=10±6 mm, thickness=5±2 mm), and 5 isthmus 4 (6%, width=4±2 mm, thickness=2±1 mm). Transatrial-transpulmonary correction (n=49) as compared with transventricular correction (n=35) prevented isthmus 2 (0% vs 100%, P<0.001). Transatrial-transpulmonary correction at age <1 year (n=7) as compared with ≥1 year (n=42) required a smaller transannular RVOT patch (28±15 vs 45±14 mm, P<0.001). Mode and timing of correction did not influence presence and dimensions of isthmus 3. In corrected and uncorrected TOF specimens (death 1.8 years (0.5-6.6)), the range of isthmus 3 dimensions was broad (width: min=2 mm, max=32 mm; thickness: min=1, max 13 mm) across all ages. Isthmus 3 width and thickness were strongly correlated (r=0.65, P<0.001). CONCLUSIONS: In TOF, the current routine use of transatrial-transpulmonary correction prevents isthmus 2. Correction <1 year reduces transannular patch size, which may influence isthmus 1 width later in life. Mode and timing of correction did not change prevalence and dimensions of isthmus 3, in which dimensions varied widely in uncorrected and corrected TOF.

Unipolar Endocardial Voltage Mapping in the Right Ventricle: Optimal Cutoff Values Correcting for Computed Tomography-Derived Epicardial Fat Thickness and Their Clinical Value for Substrate Delineation.

BACKGROUND: Low endocardial unipolar voltage (UV) at sites with normal bipolar voltage (BV) may indicate epicardial scar. Currently applied UV cutoff values are based on studies that lacked epicardial fat information. This study aimed to define endocardial UV cutoff values using computed tomography-derived fat information and to analyze their clinical value for right ventricular substrate delineation. METHODS AND RESULTS: Thirty-three patients (50±14 years; 79% men) underwent combined endocardial-epicardial right ventricular electroanatomical mapping and ablation of right ventricular scar-related ventricular tachycardia with computed tomographic image integration, including computed tomography-derived fat thickness. Of 6889 endocardial-epicardial mapping point pairs, 547 (8%) pairs with distance <10 mm and fat thickness <1.0 mm were analyzed for voltage and abnormal (fragmented/late potential) electrogram characteristics. At sites with endocardial BV >1.50 mV, the optimal endocardial UV cutoff for identification of epicardial BV <1.50 mV was 3.9 mV (area under the curve, 0.75; sensitivity, 60%; specificity, 79%) and cutoff for identification of abnormal epicardial electrogram was 3.7 mV (area under the curve, 0.88; sensitivity, 100%; specificity, 67%). The majority of abnormal electrograms (130 of 151) were associated with transmural scar. Eighty-six percent of abnormal epicardial electrograms had corresponding endocardial sites with BV <1.50 mV, and the remaining could be identified by corresponding low endocardial UV <3.7 mV. CONCLUSIONS: For identification of epicardial right ventricular scar, an endocardial UV cutoff value of 3.9 mV is more accurate than previously reported cutoff values. Although the majority of epicardial abnormal electrograms are associated with transmural scar with low endocardial BV, the additional use of endocardial UV at normal BV sites improves the diagnostic accuracy resulting in identification of all epicardial abnormal electrograms at sites with <1.0 mm fat.

Isolated Subepicardial Right Ventricular Outflow Tract Scar in Athletes With Ventricular Tachycardia.

BACKGROUND: High-level endurance training has been associated with right ventricular pathological remodeling and ventricular tachycardia (VT). Although overlap with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been suggested, the arrhythmogenic substrate for VTs in athletes is unknown. OBJECTIVES: The goal of this study was to evaluate whether electroanatomic scar patterns related to sustained VT can distinguish exercise-induced arrhythmogenic remodeling from ARVC and post-inflammatory cardiomyopathies. METHODS: In 57 consecutive patients (mean age 48 ± 16 years; 83% male) undergoing catheter ablation for scar-related right ventricular VT, 2 distinct scar distributions were identified: 1) scars involving the subtricuspid right ventricle in 46 patients (group A); and 2) scars restricted to the anterior subepicardial right ventricular outflow tract in 11 patients (group B). RESULTS: Definite ARVC or post-inflammatory cardiomyopathy was diagnosed in 40 (87%) of 46 group A patients but was not diagnosed in any patients in group B. All group B patients underwent intensive endurance training for a median of 15 h/week (interquartile range [IQR]: 10 to 20 h/week) for a median of 13 years (IQR: 10 to 18 years). The cycle lengths of scar-related VTs were significantly faster in group B patients (257 ± 34 ms vs. 328 ± 72 ms in group A; p = 0.003). Catheter ablation resulted in complete procedural success in 10 (91%) of 11 group B patients compared with 26 (57%) of 46 group A patients (p = 0.034). During a median follow-up of 27 months (IQR: 6 to 62 months), 50% of group A patients but none of the group B patients had a VT recurrence. CONCLUSIONS: This study describes a novel clinical entity of an isolated subepicardial right ventricular outflow tract scar serving as a substrate for fast VT in high-level endurance athletes that can be successfully treated by ablation. This scar pattern may allow distinguishing exercise-induced arrhythmogenic remodeling from ARVC and post-inflammatory cardiomyopathy.

Detection of elevated pulmonary pressures by the ECG-derived ventricular gradient: A comparison of conversion matrices in patients with suspected pulmonary hypertension.

BACKGROUND: The aim was to assess the diagnostic value of the Inverse Dower (INVD)-derived vectorcardiogram (VCG) and the Kors-derived VCG to detect elevated systolic pulmonary artery pressure (SPAP) in suspected pulmonary hypertension (PH). METHODS: In 132 patients, morphologic variables were evaluated by comparing the VCG parameters synthesized by INVD and Kors matrix. Comparison of the diagnostic accuracy of detecting SPAP ≥50mmHg between the matrices was performed by ROC curve analysis and logistic regression analysis. RESULTS: Most VCG parameters differed significantly between INVD and Kors. ROC analysis for detection of SPAP ≥50mmHg by VG projected on the X-axis demonstrated no difference (p=0.99) between INVD (AUC=0.80) and Kors (AUC=0.80). Both the INVD- and Kors-derived VCG provided significant diagnostic information on the presence of SPAP ≥50mmHg (INVD, OR 1.05, 95%CI 1.03-1.07; P<0.001; Kors, OR 1.05, 95%CI 1.03-1.08; P<0.001). CONCLUSION: Although there were significant differences in measures of vector morphology, both INVD- and Kors-derived VCG demonstrated equal clinical performance in case of elevated SPAP.

QRS prolongation after premature stimulation is associated with polymorphic ventricular tachycardia in nonischemic cardiomyopathy: Results from the Leiden Nonischemic Cardiomyopathy Study.

BACKGROUND: Progressive activation delay after premature stimulation has been associated with ventricular fibrillation in nonischemic cardiomyopathy (NICM). OBJECTIVES: The objectives of this study were (1) to investigate prolongation of the paced QRS duration (QRSd) after premature stimulation as a marker of activation delay in NICM, (2) to assess its relation to induced ventricular arrhythmias, and (3) to analyze its underlying substrate by late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) and endomyocardial biopsy. METHODS: Patients with NICM were prospectively enrolled in the Leiden Nonischemic Cardiomyopathy Study and underwent a comprehensive evaluation including LGE-CMR, electrophysiology study, and endomyocardial biopsy. Patients without structural heart disease served as controls for electrophysiology study. RESULTS: Forty patients with NICM were included (mean age 57 ± 14 years; 33 men [83%]; left ventricular ejection fraction 30% ± 13%). After the 400-ms drive train and progressively premature stimulation, the maximum increase in QRSd was larger in patients with NICM than in controls (35 ± 18 ms vs. 23 ± 12 ms; P = .005) and the coupling interval window with QRSd prolongation was wider (47 ± 23 ms vs. 31 ± 14 ms; P = .005). The maximum paced QRSd exceeded the ventricular effective refractory period, allowing for pacing before the offset of the QRS complex in 20 of 39 patients with NICM vs. 1 of 20 controls (P < .001). In patients with NICM, QRSd prolongation was associated with the inducibility of polymorphic ventricular tachycardia (16 of 39 patients) and was related to long, thick strands of fibrosis in biopsies, but not to focal enhancement on LGE-CMR. CONCLUSION: QRSd is a simple parameter used to quantify activation delay after premature stimulation, and its prolongation is associated with the inducibility of polymorphic ventricular tachycardia and with the pattern of myocardial fibrosis in biopsies.

Re-entry using anatomically determined isthmuses: a curable ventricular tachycardia in repaired congenital heart disease.

BACKGROUND: Ventricular tachycardia (VT) is an important cause of late morbidity and mortality in repaired congenital heart disease. The substrate often includes anatomic isthmuses that can be transected by radiofrequency catheter ablation similar to isthmus block for atrial flutter. This study evaluates the long-term efficacy of isthmus block for treatment of re-entry VT in adults with repaired congenital heart disease. METHODS AND RESULTS: Thirty-four patients (49±13 years; 74% male) with repaired congenital heart disease who underwent radiofrequency catheter ablation of VT in 2 centers were included. Twenty-two (65%) had a preserved left and right ventricular function. Patients were inducible for 1 (interquartile range, 1-2) VT, median cycle length: 295 ms (interquartile range, 242-346). Ablation aimed to transect anatomic isthmuses containing VT re-entry circuit isthmuses. Procedural success was defined as noninducibility of any VT and transection of the anatomic isthmus and was achieved in 25 (74%) patients. During long-term follow-up (46±29 months), all patients with procedural success (18/25 with internal cardiac defibrillators) were free of VT recurrence but 7 of 18 experienced internal cardiac defibrillator-related complications. One patient with procedural success and depressed cardiac function received an internal cardiac defibrillator shock for ventricular fibrillation. None of the 18 patients (12/18 with internal cardiac defibrillators) with complete success and preserved cardiac function experienced any ventricular arrhythmia. In contrast, VT recurred in 4 of 9 patients without procedural success. Four patients died from nonarrhythmic causes. CONCLUSIONS: In patients with repaired congenital heart disease with preserved ventricular function and isthmus-dependent re-entry, VT isthmus ablation can be curative.

Left-sided ablation of ventricular tachycardia in adults with repaired tetralogy of Fallot: a case series.

BACKGROUND: Radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in repaired Tetralogy of Fallot focuses on isthmuses in the right ventricle but may be hampered by hypertrophied myocardium or prosthetic material. These patients may benefit from ablation at the left side of the ventricular septum. METHODS AND RESULTS: Records from 28 consecutive repaired Tetralogy of Fallot patients from 2 centers who underwent VT ablation were reviewed. Ablation targeted anatomic isthmuses containing VT re-entry circuits, which were identified by 3-dimensional substrate, pace, and entrainment mapping. A left-sided approach was considered beneficial if (1) right-sided RFCA failed, (2) part of the circuit was mapped to the left side, and (3) left-sided RFCA resulted in isthmus transection and prevention of VT induction. In 4 of 28 patients (52±13 years; 75% men), inducible for 1.5 (quartiles, 1.0 - 2.0) VTs (335±58 ms), left-sided RFCA was performed. In 3 patients, RFCA at aortic sites terminated VT related to a septal isthmus and prevented reinduction. In 1 patient, with prior biventricular implantable cardioverter-defibrillator, diastolic activity was recorded at the left side of the septum in proximity to the His-bundle. RFCA prevented VT reinduction with anticipated complete atrioventricular block. The left-sided approach resulted in complete procedural success (transection of anatomic isthmus and noninducibility) and freedom of VT recurrence during follow-up (20±15 months) in all patients. Right-sided RFCA failure was likely because of septal hypertrophy in 2, overlying pulmonary homograft in 1, and overlying ventricular septal defect patch in 1. CONCLUSIONS: Left-sided RFCA for VTs dependent on septal anatomic isthmuses improves ablation outcome in repaired Tetralogy of Fallot.

Endocardial or epicardial ventricular tachycardia in nonischemic cardiomyopathy? The role of 12-lead ECG criteria in clinical practice.

BACKGROUND: Specific 12-lead ECG criteria have been reported to predict an epicardial site of origin (SoO) of induced ventricular tachycardias (VTs) in left ventricular nonischemic cardiomyopathy. OBJECTIVE: The purpose of this study was to (1) determine the value of ECG criteria to predict an epicardial SoO of clinically documented VTs, (2) analyze the effect of VT cycle length (CL) and antiarrhythmic drugs on the accuracy of ECG criteria, and (3) assess interobserver variability. METHODS: In 36 consecutive patients with nonischemic left ventricular cardiomyopathy (age 58 ± 16 years, 75% male) who underwent combined endocardial/epicardial VT ablation, all clinically documented and induced right bundle branch block VTs were analyzed for previously reported ECG criteria to determine the SoO, as defined by ≥11/12 pace-map, concealed entrainment, and/or VT termination during ablation. RESULTS: In 21 patients with clinically documented (25 mm/s) right bundle branch block VT, none of the ECG criteria differentiated between patients with and those without an epicardial SoO. In induced VTs (100 mm/s), 2 of 4 interval criteria differentiated between an endocardial and epicardial SoO for slow VTs (CL >350 ms) and 2 of 4 criteria in patients on amiodarone, but none for fast VTs (CL ≤350 ms) or patients off amiodarone. The Q wave in lead I was the most accurate criterion for an epicardial SoO (sensitivity 88%, specificity 80%). In both clinically documented and induced VTs, interobserver agreement was poor for pseudodelta wave and moderate for other criteria. CONCLUSION: When applied to clinically documented VTs, no ECG criterion could differentiate between patients with and those without an epicardial SoO. Published interval-based ECG criteria do not apply to fast VTs and patients off amiodarone.