Multidetector Computed Tomography Assessment of Anatomical Ventricular Tachycardia Isthmuses in Repaired Tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (TOF) is associated with risk for sustained monomorphic ventricular tachycardia (VT). Preemptive electrophysiology study before transcatheter pulmonary valve placement is increasing, but the value of MDCT for anatomical VT isthmus assessment is unknown. OBJECTIVES: The purpose of this study was to determine the impact of multidetector computed tomography (MDCT) in the evaluation of sustained monomorphic VT for repaired TOF. METHODS: Consecutive pre-transcatheter pulmonary valve MDCT studies were identified, and anatomical isthmus dimensions were measured. For a subset of patients with preemptive electrophysiology study, MDCT features were compared with electroanatomical maps. RESULTS: A total of 61 repaired TOFs with MDCT were identified (mean 35 ± 14 years, 58% men) with MDCT electroanatomical map pairs in 35 (57%). Calcification corresponding to patch material was present in 46 (75%) and was used to measure anatomical VT isthmuses. MDCT wall thickness correlated positively with number of ablation lesions and varied with functional isthmus properties (blocked isthmus 2.6 mm [Q1, Q3: 2.1, 4.0 mm], slow conduction 4.8 mm [Q1, Q3: 3.3, 6.0 mm], and normal conduction 5.6 mm [Q1, Q3: 3.9, 8.3 mm]; P < 0.001). A large conal branch was present in 6 (10%) and a major coronary anomaly was discovered in 3 (5%). Median ablation lesion distance was closer to the right vs the left coronary artery (10 mm vs 15 mm; P = 0.01) with lesion-to-coronary distance <5 mm in 3 patients. CONCLUSIONS: MDCT identifies anatomical structures relevant to catheter ablation for repaired TOF. Wall thickness at commonly targeted anatomical VT isthmuses is associated with functional isthmus properties and increased thermal energy delivery.

Sinus rhythm QRS morphology reflects right ventricular activation and anatomical ventricular tachycardia isthmus conduction in repaired tetralogy of Fallot.

BACKGROUND: Patients with repaired tetralogy of Fallot (TOF) are at risk for ventricular tachycardia (VT) related to well-described anatomical isthmuses. OBJECTIVE: The purpose of this study was to explore QRS morphology as an indicator of anatomical isthmus conduction. METHODS: Patients with repaired TOF and complete right bundle branch block referred for transcatheter pulmonary valve replacement (PVR) or presenting with sustained VT underwent comprehensive 3-dimensional mapping in sinus rhythm. Electrocardiographic characteristics were compared to right ventricular (RV) activation and anatomical isthmus conduction properties. RESULTS: Twenty-two patients (19 pre-pulmonary valve replacement and 3 clinical VT) underwent comprehensive 3-dimensional mapping (median 39 years; interquartile range [IQR] 27-48 years; 12 [55%] male). Septal RV activation (median 40 ms; IQR 34-46 ms) corresponded to the nadir in lead V1 and free wall activation (median 71 ms; IQR 64-81 ms) to the transition point in the upstroke of the R' wave. Patients with isthmus block between the pulmonary annulus and the ventricular septal defect patch and between the ventricular septal defect patch and the tricuspid annulus (when present), were more likely to demonstrate lower amplitude R' waves in lead V1 (5.8 mV vs 9.4 mV; P = .005), QRS fragmentation in lead V1 (15 [94%] vs 2 [13%]; P < .001), and terminal S waves in lead aVF (15 [94%] vs 6 [40%]; P < .001) than those with intact conduction. During catheter ablation, these QRS changes developed during isthmus block. CONCLUSION: For patients with repaired TOF, the status of septal isthmus conduction was evident from sinus rhythm QRS morphology. Low-amplitude, fragmented R' waves in lead V1 and terminal S waves in the inferior leads were related to septal isthmus conduction abnormalities, providing a mechanistic link between RV activation and common electrocardiographic findings.

Conduction System Pacing Versus Conventional Cardiac Resynchronization Therapy in Congenital Heart Disease.

BACKGROUND: Dyssynchrony-associated left ventricular systolic dysfunction is a major contributor to heart failure in congenital heart disease (CHD). Although conventional cardiac resynchronization therapy (CRT) has shown benefit, the comparative efficacy of cardiac conduction system pacing (CSP) is unknown. OBJECTIVES: The purpose of this study was compare the clinical outcomes of CSP vs conventional CRT in CHD with biventricular, systemic left ventricular anatomy. METHODS: Retrospective CSP data from 7 centers were compared with propensity score-matched conventional CRT control subjects. Outcomes were lead performance, change in left ventricular ejection fraction (LVEF), and QRS duration at 12 months. RESULTS: A total of 65 CSP cases were identified (mean age 37 ± 21 years, 46% men). The most common CHDs were tetralogy of Fallot (n = 12 [19%]) and ventricular septal defect (n = 12 [19%]). CSP was achieved after a mean of 2.5 ± 1.6 attempts per procedure (38 patients with left bundle branch pacing, 17 with HBP, 10 with left ventricular septal myocardial). Left bundle branch area pacing [LBBAP] vs HBP was associated with a smaller increase in pacing threshold (Δ pacing threshold 0.2 V vs 0.8 V; P = 0.05) and similar sensing parameters at follow-up. For 25 CSP cases and control subjects with baseline left ventricular systolic dysfunction, improvement in LVEF was non-inferior (Δ LVEF 9.0% vs 6.0%; P = 0.30; 95% confidence limits: -2.9% to 10.0%) and narrowing of QRS duration was more pronounced for CSP (Δ QRS duration 35 ms vs 14 ms; P = 0.04). Complications were similar (3 [12%] CSP, 4 [16%] conventional CRT; P = 1.00). CONCLUSIONS: CSP can be reliably achieved in biventricular, systemic left ventricular CHD patients with similar improvement in LVEF and greater QRS narrowing for CSP vs conventional CRT at 1 year. Among CSP patients, pacing electrical parameters were superior for LBBAP vs HBP.

Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis.

BACKGROUND: Up to one-third of patients hospitalized for acute severe colitis secondary to inflammatory bowel diseases (IBD) do not adequately respond to intravenous steroids. There is an unmet need to identify a useful predictor for rescue treatment in this cohort of patients. AIMS: The aim of this study was to assess the predictive efficacy of fecal calprotectin in identifying the need for medical or surgical therapy in patients with acute severe colitis. METHODS: We conducted a multicenter retrospective cohort study including patients with ulcerative colitis (UC) who were hospitalized for severe exacerbation of colitis. The primary outcome was the need for in-hospital medical or surgical rescue therapy. Univariate and multivariate logistic regression was performed to identify predictors of rescue therapy. RESULTS: Our study included 147 patients with UC. One-third (33%) required rescue therapy, and 13% underwent colectomy. Patients requiring rescue therapy had significantly higher fecal calprotectin (mean 1748 mcg/g vs 1353 mcg/g, P = .02) compared with those who did not. A fecal calprotectin >800 mcg/g independently predicted the need for inpatient medical rescue therapy (odds ratio, 2.61; 95% CI, 1.12-6.12). An admission calprotectin >800 mcg/g independently predicted surgery within 3 months (odds ratio, 2.88; 95% CI, 1.01-8.17). CONCLUSIONS: Fecal calprotectin levels may serve as a useful noninvasive predictor of medical and surgical risk in individuals with UC presenting with acute severe colitis. This approach can facilitate earlier therapeutic interventions and improve outcomes.

Multicenter Outcomes of Catheter Ablation for Atrioventricular Reciprocating Tachycardia Mediated by Twin Atrioventricular Nodes.

OBJECTIVES: This study sought to describe the electrophysiologic properties and catheter ablation outcomes for atrioventricular reciprocating tacchycardia via twin atrioventricular nodes (T-AVRT). BACKGROUND: Although catheter ablation for T-AVRT is an established entity, there are few data on the electrophysiological properties and outcomes of this procedure. METHODS: An international, multicenter study was conducted to collect retrospective procedural and outcomes data for catheter ablation of T-AVRT. RESULTS: Fifty-nine patients with T-AVRT were identified (median age at procedure, 8 years [interquartile range: 4.4-17.0 years]; 49% male). Of these, 55 (93%) were diagnosed with heterotaxy syndrome (right atrial isomerism in 39, left atrial isomerism in 8, and indeterminate in 8). Twenty-three (39%) had undergone Fontan operation (12 extracardiac, 11 lateral tunnel). After the Fontan operation, atrial access was conduit or baffle puncture in 15 (65%), fenestration in 5 (22%), and retrograde in 3 (13%). Acute success was achieved in 43 (91%) of 47 attempts (targeting an anterior node in 23 and posterior node in 24). There was no high-grade AV block or change in QRS duration. Over a median of 3.8 years, there were 3 recurrences. Of 7 patients with failed index procedure or recurrent T-AVRT, 6 (86%) were associated with anatomical hurdles such as prior Fontan or catheter course through an interrupted inferior vena cava-to-azygous vein continuation (P = 0.11). CONCLUSIONS: T-AVRT can be targeted successfully with low risk for recurrence. Complications were rare in this population. Anatomical challenges were common among patients with reduced short and long-term efficacy, representing opportunities for improvement in procedural timing and planning.

Epicardial atrial pacing after the extracardiac Fontan operation: Feasibility of an entirely transvenous approach.

This series describes an innovative technique for pacing in patients with sinus node dysfunction after extracardiac Fontan surgery. This transpulmonary approach to the left atrial epi-myocardium has been successfully applied to three patients at two centers and resulted in excellent acute and midterm pacing characteristics without known complications. The principal advantage of this procedure in comparison to prior iterations is the absence of pacing material within the pulmonary venous atrium, so that future systemic thromboembolism risk is minimized. The transpulmonary approach for permanent atrial pacing offers a novel solution to the unique challenges for patients after extracardiac Fontan operation.

Electrophysiological characteristics of atrial tachycardia recurrence: Relevance to catheter ablation strategies in adults with congenital heart disease.

BACKGROUND: Catheter ablation outcomes for adults with congenital heart disease (ACHD) are described, but recurrence mechanisms remain largely unknown. OBJECTIVE: The purpose of this study was to identify the electrophysiological characteristics of atrial tachycardia (AT) recurrence in ACHD. METHODS: ACHD atrial tachycardia procedures over a 10-year period were explored for AT or atrial fibrillation (AF) recurrence. RESULTS: At 299 procedures in 250 ACHD (mean age 39 ± 15 years; 130 [52%] male), 464 ATs (360 intra-atrial reentrant tachycardia, 104 focal AT; median 2 [IQR 1-3] ATs per procedure) were targeted. Complete (n = 256 [86%]) or partial (n = 37 [12%]) success was achieved in 98% of procedures. Over a median of 3.0 (IQR 1.4-5.3) years of follow-up, 67 patients (27%) developed AT/AF recurrence after the index procedure. Repeat vs index tachycardias were more often focal AT (26/69 [38%] vs 73/378 [19%]; P < .001), demonstrated longer cycle length (325 ms vs 280 ms; P = .003), required isoproterenol (34/69 [50%] vs 121/378 [32%]; P = .03), and involved the pulmonary venous atrium (PVA)/septum (26/69 [38%] vs 67/378 [18%]; P < .001). AF history (hazard ratio [HR] 2.0; interquartile range [IQR] 1.2-3.4; P = .01), incomplete success (HR 3.6; IQR 2.1-6.4; P < .001), and PVA substrate (HR 2.1; IQR 1.2-3.5; P = .006) were independently associated with AT/AF recurrence. With complete index procedure success and no AF history, 5-year actuarial freedom from AT/AF and AT alone were 77% and 80%. CONCLUSION: After catheter ablation in ACHD, repeat ATs were more frequently focal, required isoproterenol administration, or involved intra-atrial reentrant tachycardia within the PVA or atrial septum. Negative factors were partial success, index PVA substrate, and remote history of AF. These data support aggressive pharmacological provocation to eliminate all inducible tachycardias and coexisting PVA substrates at index procedures for ACHD.

Utilising electroanatomic mapping during ablation in patients with CHD to reduce radiation exposure.

BACKGROUND: Patients with CHD can be exposed to high levels of cumulative ionising radiation. Utilisation of electroanatomic mapping during catheter ablation leads to reduced radiation exposure in the general population but has not been well studied in patients with CHD. This study evaluated the radiation sparing benefit of using three-dimensional mapping in patients with CHD. METHODS: Data were retrospectively collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy multi-institutional registry. Patients with CHD were selected. Those with previous ablations, concurrent diagnostic or interventional catheterisation and unknown arrhythmogenic foci were excluded. The control cohort was matched for operating physician, arrhythmia mechanism, arrhythmia location, weight and age. The procedure time, rate of fluoroscopy use, fluoroscopy time, procedural success, complications, and distribution of procedures per year were compared between the two groups. RESULTS: Fifty-six patients with congenital heart disease and 56 matched patients without CHD were included. The mean total procedure time was significantly higher in patients with CHD (212.6 versus 169.5 minutes, p = 0.003). Their median total fluoroscopy time was 4.4 minutes (compared to 1.8 minutes), and their rate of fluoroscopy use was 23% (compared to 13%). The acute success and minor complication rates were similar and no major complications occurred. CONCLUSIONS: With the use of electroanatomic mapping during catheter ablation, fluoroscopy use can be reduced in patients with CHD. The majority of patients with CHD received zero fluoroscopy.

Mechanisms and outcomes of catheter ablation for biatrial tachycardia in adults with congenital heart disease.

BACKGROUND: Biatrial tachycardia (BiAT) is a rare form of macroreentry not previously characterized in adults with congenital heart disease (ACHD). OBJECTIVE: The purpose of this study was to determine the prevalence, mechanisms, and outcomes of catheter ablation for BiAT in ACHD. METHODS: All ACHD undergoing catheter ablation for macroreentrant atrial tachycardia over a 10-year period were evaluated for evidence of BiAT. Patients were categorized as prior Senning, Fontan, or other biventricular operation. A novel biatrial global activation histogram (GAH) analysis was used to demonstrate the presence of interatrial connections (IACs). RESULTS: Among 263 ACHD, BiAT was identified at 11 procedures in 10 patients (4.2%; median age 35 years; 30% male). The congenital category was Fontan in 6, Senning in 3, and biventricular in 2. Diagnosis of BiAT was associated with ablation era and mapping technology (P <.001) and could be confirmed with a novel GAH mapping approach for normally septated atrial connections. Catheter ablation targeted an IAC in 5 cases (Bjork Fontan and biventricular operations), a posterior isthmus in 3 (Senning operation), and the cavotricuspid isthmus or equivalent in 3 (lateral tunnel [LT] Fontan). Recurrence was isolated to ablation to sites at the expected location of the Bachmann bundle, and durable success could be achieved after repeat ablation. CONCLUSION: BiAT occurs in approximately 4% of ACHD but is likely underrecognized. BiAT could be targeted at an IAC for normally septated atria and at a conventional critical isthmus after Senning and LT Fontan operations.

Acute outcomes of three-dimensional mapping for fluoroscopy reduction in paediatric catheter ablation for supraventricular tachycardia.

BACKGROUND: Catheter ablation is a safe and effective therapy for the treatment of supraventricular tachycardia in children. Current improvements in technology have allowed progressive reduction in radiation exposure associated with the procedure. To assess the impact of three-dimensional mapping, we compared acute procedural results collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to published results from the Prospective Assessment after Pediatric Cardiac Ablation study. METHODS: Inclusion and exclusion criteria from the Prospective Assessment after Pediatric Cardiac Ablation study were used as guidelines to select patient data from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to compare acute procedural outcomes between cohorts. Outcomes assessed include procedural and fluoroscopy exposure times, success rates of procedure, and complications. RESULTS: In 786 ablation procedures, targeting 498 accessory pathways and 288 atrioventricular nodal reentrant tachycardia substrates, average procedural time (156.5 versus 206.7 minutes, p < 0.01), and fluoroscopy time (1.2 versus 38.3 minutes, p < 0.01) were significantly shorter in the study group. Success rates for the various substrates were similar except for manifest accessory pathways which had a significantly higher success rate in the study group (96.4% versus 93.0%, p < 0.01). Major complication rates were significantly lower in the study group (0.3% versus 1.6%, p < 0.01). CONCLUSIONS: In a large, multicentre study, three-dimensional systems show favourable improvements in clinical outcomes in children undergoing catheter ablation of supraventricular tachycardia compared to the traditional fluoroscopic approach. Further improvements are anticipated as technology advances.

Cardiac implantable device outcomes and lead survival in adult congenital heart disease.

BACKGROUND: Long-term outcomes of cardiac implantable electronic devices (CIEDs) are ill-defined in adult congenital heart disease (ACHD). OBJECTIVE: To assess outcomes of transvenous (TV) and epicardial (EPI) CIEDs in ACHD. METHODS: A retrospective review of CIEDs implanted in patients >18 yrs. followed at the Ahmanson/UCLA ACHD Center was performed. Patients were grouped by implant approach. Primary outcomes included time to CIED dysfunction, lead dysfunction and unplanned CIED reintervention. RESULTS: Over a 27-year period, 283 CIEDs (208 TV, 75 EPI) were implanted in 260 ACHD patients. Dysfunction developed in 77 CIEDs (50 TV, 27 EPI) for which 62 underwent unplanned reintervention (47 TV, 15 EPI). Time to CIED dysfunction and unplanned reintervention did not differ by implant approach; however lead dysfunction was greater for EPI vs TV (HR 2.0, 95% CI 1.2-3.2, p = 0.01). Independent predictors of lead failure included cyanosis (HR 2.6, 95% CI 1.1-6.3; p = 0.03), implant indication other than bradycardia (HR 3.3, 95% CI 1.6-6.5; p < 0.01), right-sided Maze operation (HR 2.5, 95% CI 1.3-5.0; p = 0.01), and unipolar lead design (HR 4.5, 95% CI 1.8-11.5; p < 0.01). Importantly, EPI vs TV approach was not associated with lead dysfunction after adjusting for baseline covariates (HR 0.6, 95% CI 0.6-4.3; p = 0.3). CONCLUSION: Overall CIED system dysfunction and reinterventions are similar, whereas lead dysfunction is greater among EPI than TV devices. Patient and procedural differences, rather than EPI vs TV implant approach alone, appear to drive CIED lead outcomes in the ACHD population.

Genotype Predicts Outcomes in Fetuses and Neonates With Severe Congenital Long QT Syndrome.

OBJECTIVES: This study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs). BACKGROUND: LQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown. METHODS: A retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death. RESULTS: A total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p < 0.001), and LQT3, relative to LQT2, genotype predicted death and/or cardiac transplant (p < 0.001). CONCLUSIONS: In this large multicenter study, fetuses and/or neonates with LQT3 but not those with LQT1 or LQT2 presenting with severe arrhythmias were at high risk of not only frequent, but lethal CEs.

Ten-year outcomes of transcaval cardiac puncture for catheter ablation after extracardiac Fontan surgery.

BACKGROUND: Although they are at lower risk, patients with previous extracardiac conduit (EC) Fontan still may require catheter ablation for supraventricular arrhythmia. OBJECTIVE: The purpose of this study was to determine the optimal approach to pulmonary venous atrium (PVA) access after EC Fontan operation. METHODS: All electrophysiological procedures requiring PVA over a 10-year period at the UCLA Medical Center were reviewed. PVA was grouped by transcaval cardiac puncture (TCP) or direct conduit puncture. Procedural characteristics and outcomes were compared. RESULTS: Between June 2009 and November 2019, 23 electrophysiological procedures requiring PVA access were performed in 17 EC Fontan patients (53% male; median age 25 years; interquartile range 11-34). Cavoatrial overlap was identified in 14 patients by preprocedural imaging (10 cardiac computed tomography, 4 cardiac magnetic resonance). PVA access was obtained via TCP in 11, direct conduit puncture in 6, pre-existing fenestration in 5, and pulmonary artery puncture in 1. Time to PVA was significantly shorter for TCP vs direct conduit puncture (0.2 vs 1.1 hours, respectively; P = .03). The only predictor of successful TCP was the length of cavoatrial overlap by preprocedural imaging (14 vs 3 mm; P = .02). No procedural complications occurred. No change in oxygen saturation was noted, and no evidence of residual shunting was detected by follow-up echocardiography. CONCLUSION: TCP is feasible in most patients after EC Fontan surgery and can be predicted by preprocedural advanced imaging. TCP is associated with shorter time to PVA and was uncomplicated in this single-center study. Preoperative assessment of cavoatrial overlap should be considered before catheter ablation for EC Fontan.

Permanent conduction system pacing for congenitally corrected transposition of the great arteries: A Pediatric and Congenital Electrophysiology Society (PACES)/International Society for Adult Congenital Heart Disease (ISACHD) Collaborative Study.

BACKGROUND: Congenitally corrected transposition of the great arteries (CCTGA) is associated with spontaneous atrioventricular block and pacing-induced cardiomyopathy. Conduction system pacing is a potential alternative to conventional cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to determine the outcomes of conduction system pacing for CCTGA. METHODS: Retrospective data were collected from 10 international centers. RESULTS: His bundle (HBP) or left bundle branch pacing (LBBP) was attempted in 15 CCTGA patients (median age 23 years; 87% male). Previous surgery had been performed in 8 and chronic ventricular pacing in 7. Conduction system pacing (11 HBP, 2 LBBP 2; nonselective in 10, selective in 3) was acutely successful in 13 (86%) without complication. In 9 cases, electroanatomic mapping was available and identified the distal His bundle and proximal left bundle branches within the morphologic left ventricle below the pulmonary valve separate from the mitral annulus. Median implant HV interval was 42 ms (interquartile range [IQR] 35-48), R wave 6 mV (IQR 5-18), and threshold 0.5 V (IQR 0.5-1.2) at median 0.5 ms. QRSd was unchanged compared to junctional escape rhythm (124 vs 110 ms; P = .17) and decreased significantly compared to baseline ventricular pacing (112 vs 164 ms; P <.01). At a median of 8 months, all patients were alive without significant change in pacing threshold or lead dysfunction. New York Heart Association functional class improved in 5 patients. CONCLUSION: Permanent conduction system pacing is feasible in CCTGA by either HBP or proximal LBBP. Narrow paced QRS and stable lead thresholds were observed at intermediate follow-up. Unique anatomic characteristics may favor this approach over conventional CRT.

Catheter ablation of supraventricular tachycardia after tricuspid valve surgery in patients with congenital heart disease: A multicenter comparative study.

BACKGROUND: Tricuspid valve (TV) surgery is often required for adult congenital heart disease (ACHD), but may hinder catheter ablation when an artificial material or imbricated tissue covers the tricuspid annulus. OBJECTIVE: The purpose of this study was to determine the outcomes of catheter ablation after TV surgery in a large ACHD cohort. METHODS: An international retrospective study involving 7 centers was conducted. Patients who did and did not undergo TV surgery were matched for age, lesion classification, and postsurgical duration. TV operations were classified as valve ring/replacement vs repair. RESULTS: One hundred thirty-six patients (42 ring/replacement, 39 repair, and 55 no TV surgery; median 32 years [IQR 20 - 46]) underwent 180 procedures targeting 239 tachycardias (cavotricuspid-isthmus dependent intraatrial reentrant tachycardia 36%, other intraatrial reentrant tachycardia 29%, focal atrial tachycardia 18%, and other supraventricular tachyarrhythmia 17%). Post-TV surgery, procedures were longer (4.3 hours vs 3.3 hours; P = .003) and required longer fluoroscopy time (31 minutes vs 18 minutes; P = .001). At least partial acute success was achieved in 81% of procedures in the TV ring/replacement group vs 94% in both TV repair and no TV surgery groups (P = .03). The difference was driven mainly by ablation of annular substrates, with acute success in 73% of TV ring/replacement, 92% of TV repair, and 94% of no TV surgery groups (P = .01). Over a median of 3.0 years, tachycardia recurred after 26% of procedures. TV ring/replacement predicted recurrence in the multivariable analysis (hazard ratio 2.4; 95% confidence interval 1.2-5.2; P = .009). CONCLUSION: After surgery for ACHD, catheter ablation success was lower and tachycardia recurrence was higher after TV valve ring/replacement surgery. The findings of this retrospective report support future larger multicenter series and prospective evaluation to determine the role of empirical annular substrate ablation.

Glucocorticoids paradoxically facilitate steroid resistance in T cell acute lymphoblastic leukemias and thymocytes.

Glucocorticoids (GCs) are a central component of therapy for patients with T cell acute lymphoblastic leukemia (T-ALL), and although resistance to GCs is a strong negative prognostic indicator in T-ALL, the mechanisms of GC resistance remain poorly understood. Using diagnostic samples from patients enrolled in the frontline Children's Oncology Group (COG) T-ALL clinical trial AALL1231, we demonstrated that one-third of primary T-ALLs were resistant to GCs when cells were cultured in the presence of IL-7, a cytokine that is critical for normal T cell function and that plays a well-established role in leukemogenesis. We demonstrated that in these T-ALLs and in distinct populations of normal developing thymocytes, GCs paradoxically induced their own resistance by promoting upregulation of IL-7 receptor (IL-7R) expression. In the presence of IL-7, this augmented downstream signal transduction, resulting in increased STAT5 transcriptional output and upregulation of the prosurvival protein BCL-2. Taken together, we showed that IL-7 mediates an intrinsic and physiologic mechanism of GC resistance in normal thymocyte development that is retained during leukemogenesis in a subset of T-ALLs and is reversible with targeted inhibition of the IL-7R/JAK/STAT5/BCL-2 axis.

Ultrahigh-density mapping supplemented with global chamber activation identifies noncavotricuspid-dependent intra-atrial re-entry conduction isthmuses in adult congenital heart disease.

OBJECTIVE: To evaluate the role of ultrahigh-density mapping for conduction isthmus (CI) characterization in adult congenital heart disease (ACHD). BACKGROUND: Catheter ablation remains suboptimal for ACHD with atypical intra-atrial reentrant tachycardias (IART) that can be challenging to define using existing mapping technology. METHODS: An ultrahigh-density mapping system was selectively employed over a 1-year period for procedures involving noncavotricuspid isthmus-dependent-IART. A global activation histogram (GAH) was assessed for the ability to predict ablation targets. Procedural characteristics were compared to a group of matched controls. RESULTS: Twenty patients (mean age 43 ± 15, 70% male) underwent 20 procedures targeting 34 tachycardias during the study period. Diagnoses included single ventricle (8), tetralogy of Fallot (2), left heart obstruction (3), Ebstein's anomaly (2) atrial septal defect (2), Mustard operation (2), and Rasteilli operation (1). Prior catheter ablation/Maze operation had been performed in 12 (60%). The median time per map was 21 minutes (interquartile range [IQR], 16-32), representing 14 834 points per map (IQR 9499-43 191; P < .001 vs controls). Review of GAH maps showed lower trough values were associated with more favorable IART CI characteristics (P ≤ =.001 for all). Acute success was achieved in 19/20 (95%) procedures, with tachycardia termination during the first lesion in eight cases (P = .02 vs controls). There was one recurrence during 0.6 years follow-up. CONCLUSIONS: Ultrahigh-density mapping supplemented with the GAH tool was effective for CI identification in a cohort of complex ACHD patients. Catheter ablation was more efficient compared to controls, suggesting precise CI characterization using this technology.

Postoperative and short-term atrial tachyarrhythmia burdens after transcatheter vs surgical pulmonary valve replacement among congenital heart disease patients.

OBJECTIVE: We examined the atrial tachyarrhythmia (AT) burden among patients with congenital heart disease (CHD) following transcatheter (TC-) or surgical (S-) pulmonary valve replacement (PVR). DESIGN/SETTING: This was a retrospective observational study of patients who underwent PVR from 2010 to 2016 at UCLA Medical Center. PATIENTS: Patients of all ages who had prior surgical repair for CHD were included. Patients with a history of congenitally corrected transposition of the great arteries, underwent a hybrid PVR procedure, or had permanent atrial fibrillation (AF) without a concomitant ablation were excluded. OUTCOME MEASURES: The primary outcome was a time-to-event analysis of sustained AT. Sustained ATs were defined as focal AT, intra-atrial reentrant tachycardia/atrial flutter, or AF lasting at least 30 seconds or terminating with cardioversion or antitachycardia pacing. RESULTS: Two hundred ninety-seven patients (TC-PVR, n = 168 and S-PVR, n = 129) were included. During a median follow-up of 1.2 years, nine events occurred in TC-PVR group (5%) vs 23 events in S-PVR group (18%). In the propensity adjusted models, the following factors were associated with significant risk of AT after PVR: history of AT, age at valve implantation, severe right atrial enlargement, and S-PVR. In the secondary analysis, TC-PVR was associated with lower adjusted risk of AT events in the postoperative epoch (first 30 days), adjusted IRR 0.31 (0.14-0.97), P = .03, but similar risk in the short-term epoch, adjusted IRR 0.64 (0.14-2.94), P = .57. CONCLUSION: There was an increased risk of AT in the first 30 days following S-PVR compared to TC-PVR. Additional factors associated with risk of AT events after PVR were a history of AT, age at valve implantation, and severe right atrial enlargement.

CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition.

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a genetically heterogeneous subtype of B-cell ALL characterized by chromosomal rearrangements and mutations that result in aberrant cytokine receptor and kinase signaling. In particular, chromosomal rearrangements resulting in the overexpression of cytokine receptor-like factor 2 (CRLF2) occur in 50% of Ph-like ALL cases. CRLF2 overexpression is associated with particularly poor clinical outcomes, though the molecular basis for this is currently unknown. Glucocorticoids (GCs) are integral to the treatment of ALL and GC resistance at diagnosis is an important negative prognostic factor. Given the importance of GCs in ALL therapy and the poor outcomes for patients with CRLF2 overexpression, we hypothesized that the aberrant signal transduction associated with CRLF2 overexpression might mediate intrinsic GC insensitivity. To test this hypothesis, we exposed Ph-like ALL cells from patient-derived xenografts to GCs and found that CRLF2 rearranged (CRLF2R) leukemias uniformly demonstrated reduced GC sensitivity in vitro. Furthermore, targeted inhibition of signal transduction with the MEK inhibitor trametinib and the Akt inhibitor MK2206, but not the JAK inhibitor ruxolitinib, was sufficient to augment GC sensitivity. These data suggest that suboptimal GC responses may in part underlie the poor clinical outcomes for patients with CRLF2 overexpression and provide rationale for combination therapy involving GCs and signal transduction inhibitors as a means of enhancing GC efficacy.

Monomorphic Ventricular Arrhythmias in Athletes.

Ventricular arrhythmias are challenging to manage in athletes with concern for an elevated risk of sudden cardiac death (SCD) during sports competition. Monomorphic ventricular arrhythmias (MMVA), while often benign in athletes with a structurally normal heart, are also associated with a unique subset of idiopathic and malignant substrates that must be clearly defined. A comprehensive evaluation for structural and/or electrical heart disease is required in order to exclude cardiac conditions that increase risk of SCD with exercise, such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Unique issues for physicians who manage this population include navigating athletes through the decision of whether they can safely continue their chosen sport. In the absence of structural heart disease, therapies such as radiofrequency catheter ablation are very effective for certain arrhythmias and may allow for return to competitive sports participation. In this comprehensive review, we summarise the recommendations for evaluating and managing athletes with MMVA.