Congenital Heart And Pediatric Electrophysiology

The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy. Conway J, Min S, Villa C, Weintraub RG, Nakano S, Godown J, Tatangelo M, Armstrong K, Richmond M, Kaufman B, Lal AK, Balaji S, Power A, Baez Hernandez N, Gardin L, Kantor PF, Parent JJ, Aziz PF, Jefferies JL, Dragulescu A, Jeewa A, Benson L, Russell MW, Whitehill R, Rossano J, Howard T, Mital S. Take Home Points: Children with HCM are at increased risk for lower transplant-free survival and SCD. Exercise testing is commonly performed but rarely utilized for risk assessment. Of exercise test-related abnormalities, an ischemic response was independently associated with adverse cardiovascular outcomes, including worse transplant free survival and SCD. Abnormal BP response predicted worse transplant-free survival but not SCD in this study cohort. Commentary by Dr. Jeremy Moore (Los Angeles) Congenital and Pediatric Cardiac EP section editor:  Pediatric patients with HCM are at risk for sudden cardiac death and mortality related to progressive heart failure. Although exercise stress testing has been used in adults for risk stratification, there are few data in children with HCM. This study from the international PRiMaCY cohort evaluated the results of exercise stress testing in a subgroup of 630 children 8 years of age. Of these, 175 (28%) exercise tests were classified as abnormal (due to either blunted BP response, ischemia or complex ventricular ectopy) and was more frequently observed among those with prior septal myectomy, higher mean LV septal z score, LA diameter z score, LVEF and greater LVOTO (p=0.001). Patients with an abnormal exercise stress test were more likely to receive an ICD and were more likely to receive ICD shocks; although they were not at greater risk of SCD, they experienced worse transplant free survival (HR  2.97, p=0.007) during follow up. When examining the specific type of exercise test abnormality and all-cause mortality, those with abnormal BP response were at greatest risk (rate 4.6 per 100 pt-years) followed by ischemia (2.9 per 100 pt-years). Those with complex ventricular arrhythmia did not experience any events. Compared with those with normal exercise testing, there was a significantly higher hazard of all-cause mortality or transplant in those with an abnormal BP response (HR, 3.2, p=0.010) and in those with an ischemic response (HR, 4.86, p=0.003) both of which persisted in multivariate analysis that included echocardiographic indices. For SCD, the greatest risk was observed for those with ischemia (rate 5.9 per 100 pt-years) followed by abnormal BP response (1.7 per 100 pt-years); again no events were observed among those with complex ventricular ectopy. On multivariable analysis, only exercise-induced ischemia remained independently associated with SCD (HR, 3.3, p=0.014). When compared by exercise response category, there was a greater risk for appropriate ICD shocks among those with exercise-induced ischemia (HR, 5.8, p=0.054) and in those with ectopy (HR, 5.7, p=0.056) compared with those with a normal exercise test result, but these differences were not statistically significant The authors conclude that exercise testing is valuable for pediatric patients with HCM and that an ischemic response predicts both worse transplant-free survival and SCD risk.

Value of genetic testing in the diagnosis and risk stratification of arrhythmogenic right ventricular cardiomyopathy. de Brouwer R, Bosman LP, Gripenstedt S, Wilde AAM, van den Berg MP, Peter van Tintelen J, de Boer RA, Te Riele ASJM; Netherlands ACM Registry.Heart Rhythm. 2022 Oct;19(10):1659-1665. doi: 10.1016/j.hrthm.2022.05.038. Epub 2022 Jun 7.PMID: 35688345 Take Home points: Arrhythmogenic right ventricular cardiomyopathy (ARVC), the right dominant subform of arrhythmogenic cardiomyopathy (ACM), is characterized by fibrofatty replacement of cardiomyocytes leading to ventricular dysfunction and an increased risk of malignant ventricular arrhythmia (MVA). ARVC is often familial with incomplete penetrance and variable expressivity; diagnostic value of genetic testing is disappointing. Comments by EP section editor Dr. Khyati Pandya, Children’s Hospital of Georgia, Augusta, GA  The current study was one of the largest studies - 402 subjects – of individuals with ARVC, from Netherlands Arrhythmogenic Cardiomyopathy Registry. The investigators sought to determine the incremental value of genetic testing on the diagnostic yield for ARVC and the clinical impact of the testing on patient outcomes. Of the 216 probands, 121 (56%) harbored a pathogenic or likely pathogenic ARVC gene variant, most commonly PKP2. Without genetic testing, 5% of probands would have lost their ARVC diagnosis and 10% would have experienced a delay in diagnosis 30 days. Over a follow up period of 13 years, none of the undiagnosed patients would have experienced a malignant ventricular arrhythmia during follow-up and 3% of the patients with diagnostic delay would have experienced a malignant ventricular arrhythmia during the period of delay. Similarly, for the 186 relatives, 60% harbored a (likely) pathogenic variant. Removal of genetic testing from the diagnostic criteria would have led to a loss of diagnosis in 4% and delay in diagnosis of 0.5%. None of these patients would have experienced a malignant ventricular arrhythmia as a result of the lack of genetic testing. Figure 2 Survival curve of patients with arrhythmogenic right ventricular cardiomyopathy: pathogenic variant carriers vs noncarriers, showing no significant difference in time from the initial diagnosis to the first malignant ventricular arrhythmia. TFC -Task Force Criteria; VA - ventricular arrhythmia Discussion As mentioned by the authors, a focused analysis on the relationship between genetic testing results and MVA may shed light on the clinical value of genetic testing results in the management of patients with ARVC. The overall yield for genetic testing was good, however the clinical impact of the genetic testing was questioned by the authors of this study. The current study comprised of a Dutch population, however, studies conducted at various centers across the world have described a similar incidence of ARVC in individuals with various ethnic backgrounds. Findings such as age at presentation, preponderance of male gender, genetic yield, preponderance of PKP2 gene etc are comparable with studies across other populations. Although malignant ventricular arrhythmias occurred only in 1% of the patients with a delayed diagnosis of ARVC and although these were not fatal, this finding underscores the importance of continuing to include genetic findings in the TFC. A biomarker for ARVC may help identify disease in its initial stages, thereby overcoming the suboptimal genetic yield and identifying a greater number of individuals at risk for developing the disease. This may overcome the problems related to a low genetic yield and also help identify individuals with ARVC in the concealed phase of disease who may still be at risk for development of malignant ventricular arrhythmias. Until such time, inclusion of genetic findings in the TFC is likely expedite cascade testing and prevent onset of malignant ventricular arrhythmias in the vast majority, albeit at the cost of psychosocial well being in those that may never develop the disease. Future directions and limitations The 2010 Task Force Criteria are still used to establish a clinical diagnosis of ARVC, however, these criteria do not incorporate other arrhythmogenic cardiomyopathies, leading to a potential underdiagnosis. It remains to be seen if the Padua Criteria, recently being developed by an international expert panel for arrhythmogenic cardiomyopathies, will offer a higher diagnostic accuracy for ARVC as well. There are ongoing studies to evaluate the proposed Padua Criteria in larger cohorts. Multicenter studies conducted simultaneously in various centers across the world and presented as pooled data may help identify genetic heterogeneity in relation to disease causation in patients with ARVC with varying ethnic backgrounds. As highlighted by the authors a selection bias may have affected the findings owing to the retrospective nature of the study. Of note, tissue criteria are not available for comment in the primary cohort. Further, details of cardiac MRI if included, would have provided better correlation between severity of disease and onset of malignant ventricular arrhythmias in a background of genetic. As such, larger and prospective studies are required to address limitations related to the current study.

Value of genetic testing in the diagnosis and risk stratification of arrhythmogenic right ventricular cardiomyopathy. de Brouwer R, Bosman LP, Gripenstedt S, Wilde AAM, van den Berg MP, Peter van Tintelen J, de Boer RA, Te Riele ASJM; Netherlands ACM Registry. Heart Rhythm. 2022 Oct;19(10):1659-1665. doi: 10.1016/j.hrthm.2022.05.038. Epub 2022 Jun 7.PMID: 35688345 Take Home points: Arrhythmogenic right ventricular cardiomyopathy (ARVC), the right dominant subform of arrhythmogenic cardiomyopathy (ACM), is characterized by fibrofatty replacement of cardiomyocytes leading to ventricular dysfunction and an increased risk of malignant ventricular arrhythmia (MVA). ARVC is often familial with incomplete penetrance and variable expressivity; diagnostic value of genetic testing is disappointing. Commentary by Dr. Khyati Pandya (Augusta, GA, USA) Congenital and Pediatric Cardiac EP section editor:    The current study was one of the largest studies - 402 subjects – of individuals with ARVC, from Netherlands Arrhythmogenic Cardiomyopathy Registry. The investigators sought to determine the incremental value of genetic testing on the diagnostic yield for ARVC and the clinical impact of the testing on patient outcomes. Of the 216 probands, 121 (56%) harbored a pathogenic or likely pathogenic ARVC gene variant, most commonly PKP2. Without genetic testing, 5% of probands would have lost their ARVC diagnosis and 10% would have experienced a delay in diagnosis 30 days. Over a follow up period of 13 years, none of the undiagnosed patients would have experienced a malignant ventricular arrhythmia during follow-up and 3% of the patients with diagnostic delay would have experienced a malignant ventricular arrhythmia during the period of delay. Similarly, for the 186 relatives, 60% harbored a (likely) pathogenic variant. Removal of genetic testing from the diagnostic criteria would have led to a loss of diagnosis in 4% and delay in diagnosis of 0.5%. None of these patients would have experienced a malignant ventricular arrhythmia as a result of the lack of genetic testing. Figure 2 Survival curve of patients with arrhythmogenic right ventricular cardiomyopathy: pathogenic variant carriers vs noncarriers, showing no significant difference in time from the initial diagnosis to the first malignant ventricular arrhythmia. TFC -Task Force Criteria; VA - ventricular arrhythmia Discussion As mentioned by the authors, a focused analysis on the relationship between genetic testing results and MVA may shed light on the clinical value of genetic testing results in the management of patients with ARVC. The overall yield for genetic testing was good, however the clinical impact of the genetic testing was questioned by the authors of this study. The current study comprised of a Dutch population, however, studies conducted at various centers across the world have described a similar incidence of ARVC in individuals with various ethnic backgrounds. Findings such as age at presentation, preponderance of male gender, genetic yield, preponderance of PKP2 gene etc. are comparable with studies across other populations. Although malignant ventricular arrhythmias occurred only in 1% of the patients with a delayed diagnosis of ARVC and although these were not fatal, this finding underscores the importance of continuing to include genetic findings in the TFC. A biomarker for ARVC may help identify disease in its initial stages, thereby overcoming the suboptimal genetic yield and identifying a greater number of individuals at risk for developing the disease. This may overcome the problems related to a low genetic yield and also help identify individuals with ARVC in the concealed phase of disease who may still be at risk for development of malignant ventricular arrhythmias. Until such time, inclusion of genetic findings in the TFC is likely expedite cascade testing and prevent onset of malignant ventricular arrhythmias in the vast majority, albeit at the cost of psychosocial well-being in those that may never develop the disease. Future directions and limitations The 2010 Task Force Criteria are still used to establish a clinical diagnosis of ARVC; however, these criteria do not incorporate other arrhythmogenic cardiomyopathies, leading to a potential underdiagnosis. It remains to be seen if the Padua Criteria, recently being developed by an international expert panel for arrhythmogenic cardiomyopathies, will offer a higher diagnostic accuracy for ARVC as well. There are ongoing studies to evaluate the proposed Padua Criteria in larger cohorts. Multicenter studies conducted simultaneously in various centers across the world and presented as pooled data may help identify genetic heterogeneity in relation to disease causation in patients with ARVC with varying ethnic backgrounds. As highlighted by the authors a selection bias may have affected the findings owing to the retrospective nature of the study. Of note, tissue criteria are not available for comment in the primary cohort. Further, details of cardiac MRI if included, would have provided better correlation between severity of disease and onset of malignant ventricular arrhythmias in a background of genetic. As such, larger and prospective studies are required to address limitations related to the current study.

 Impact and Modifiers of Ventricular Pacing in Patients With Single Ventricle Circulation   Chubb H, Bulic A, Mah D, Moore JP, Janousek J, Fumanelli J, Asaki SY, Pflaumer A, Hill AC, Escudero C, Kwok SY, Mangat J, Ochoa Nunez LA, Balaji S, Rosenthal E, Regan W, Horndasch M, Asakai H, Tanel R, Czosek RJ, Young ML, Bradley DJ, Paul T, Fischbach P, Malloy-Walton L, McElhinney DB, Dubin AM.J Am Coll Cardiol. 2022 Aug 30;80(9):902-914. doi: 10.1016/j.jacc.2022.05.053.PMID: 36007989 PMID: 36007989   Take Home Points: The risk for heart transplantation or death was significantly higher in the functionally univentricular patients with a permanent ventricular pacemaker system. (HR 3.8) The risk of single ventricle failure was significantly higher in the functionally univentricular patients with permanent ventricular pacemaker system. (HR 4.7) Patients with permanent ventricular pacemaker systems had a higher rate of decline in ventricular function (HR 3.5) Higher amount of ventricular pacing resulted in a higher risk for death or transplantation (HR 2.0) and Fontan-failure (HR1.8) Type of pacing system (single chamber, dual chamber, CRT) did not impact outcomes. Increased ventricular pacing, higher QRS z-score, higher heart rate, and non-apical ventricular lead position were associated with heart transplantation or death. Potential considerations to mitigate the deleterious effects of ventricular pacing in univentricular hearts include apical pacing, minimizing ventricular pacing, and targeting lead location to provide shorter paced QRS duration z-scores.   Comment from Dr. Akash Patel (Cleveland), section editor of Congenital Electrophysiology Journal Watch.     A significant portion of patients with functionally univentricular hearts have shown over time to require pacemaker therapy for sinus node dysfunction, tachy-brady syndrome, and AV block with data ranging from 8 to 45%. Previous studies have shown that ventricular pacing in this population is associated with increased morbidity (poor functional status, depressed ventricular function) and mortality (death or transplant).  The objectives of this study were to establish a clear profile of pacemaker-attributable risk and identify risk factors that may be modified to alleviate the detrimental impact of ventricular pacing.   This was retrospective multi-center matched control study of functionally univentricular patients with an epicardial pacemaker and functional ventricular pacing lead (PPMv).  It included those patients after Jan 1, 2000, with an implant done before 30 years of age.  Cases were matched based on ventricular morphology (left vs right), sex, most recent palliative surgical procedure (maximum 1 year discrepancy), and age.  All single ventricle palliative surgical procedures were included.   The primary outcome was heart transplantation or death. The secondary outcome was death alone and single ventricle failure, which was defined as identification of PLE, plastic bronchitis, listing for heart transplant, VAD, heart transplantation, or death.   Baseline characteristics at time of enrollment showed a total of 449 patients with 213 matched permanent pacemaker patients with ventricular pacing (PPMv) and 213 controls from 22 centers and 9 countries. 5% of patients with ventricular pacing were unmatched and included only in the analysis of risk factors for PPMv alone.  The median year of birth was 2002 [1995-2008] and the median age at enrollment was 5.3 years [IQR: 1.5-13.2].  There was no difference between cases and controls regarding year of birth, age of enrollment, sex, systemic ventricle morphology, presence of heterotaxy, total cardiac medications, number of bypass procedures, age at Fontan, and presence of aortic stenosis or arch obstruction. The PPMv group were different than the matched controls with regards to the following: 1) higher inotropic support, antiarrhythmic medication use, total number of surgical procedures 2) less extracardiac and more fenestrated Fontan procedures and 3) worse ventricular function, atrioventricular valve regurgitation, and aortic regurgitation. Overall, the PPMv group was “sicker” than the control group. See figure below.     The specific cardiac anatomies included HLHS (24%), DILV (20%), Tricuspid Atresia (13%), DORV (11%), Unbalanced AV Canal (10%), PA/IVS (3%), Ebstein (1%), and Other (18%).   The PPMv matched patients included significantly more DILV (24% vs 16%) and less PA/IVS (1% vs 6%).  See figure below.     The median follow-up was 7.0 years [IQR: 3.5 – 11.6] with no difference between the cases and controls. The primary outcome of heart transplantation or death occurred in 47 (22.1%) of the 213 matched subjects with PPMv vs. 14 (6.6%) of the 213 matched controls. The risk for heart transplantation or death was significantly higher in the PPMv group (univariable: 4.6; 95% CI: 2.4-8.7; P < 0.001, multivariable HR: 3.8; 95% CI: 1.9-7.6; P < 0.001).  Factors significantly associated with primary outcome based on multivariate analysis included heart failure medications (HR 1.545), toral cardiac medications (HR 1.135), qualitative function on echo (HR 1.59), and aortic arch obstruction (HR 5.675).  The secondary outcome of death alone (censored at heart transplantation) and single ventricle failure occurred in 31 (14.5%) and 61 (28.6%) patients with PPMv, respectively; in control patients, the figures were 8 (3.8%) and 19 (8.9%), respectively.  (HR: 6.0; 95% CI: 2.5-14.0; P < 0.001 and HR: 4.7; 95% CI: 2.6-8.4; P < 0.001, respectively). See Figure and Table Below.       Of note, the PPMv group had a higher rate of decline in ventricular function (to first-time identification of at least moderate dysfunction. (HR: 3.52; 95% CI: 2.4-5.2; P < 0.0001), but no difference in progression of systemic AVVR. In addition, PPMv patients had significant lengthening in the QRS duration from baseline intrinsic QRS by 18 ± 2 ms (z-score: 1.6 ± 0.2) following pacemaker implantation. This prolongation in QRS during remained constant at least 10 years. See Figure below.     Analysis of the 236 patients with PPMv showed heart transplantation or death occurred in 51 (21.7%) with a median follow-up 6.3 years [IQR: 3.0-11.3].  On multivariate analysis, the primary outcome was associated with increased Vp (weighted average Vp), higher heart rate (weighted average), non-apical lead position, and higher QRS z-score (weighted average). Of note, note average QRS duration was not associated with primary outcome.     Average percent ventricular pacing was noted to be 90.8% [IQR: 4.3 – 100] in this cohort.  The higher amount of ventricular pacing was shown to result in a higher risk for death or transplantation. Of note, the average Vp was similar in those with single-chamber vs multi-chamber pacing systems (84% [IQR: 13 -100] vs 86% [IQR: 3-100]; p= 0.57). See below.     The impact of pacing strategy was not shown to be associated with the primary or secondary outcomes. ed. 200 (85%) had dual chamber devices, 28 (12%) had single chamber devices, and 8(3%) had multisite/CRT systems.   This study provides additional insight into our understanding of the impact of ventricular pacing in patients with univentricular hearts.  As has been described, ventricular pacing is “bad” for these patients resulting in a higher risk for death, transplantation, and single ventricle failure. This study demonstrates a more rapid decline in ventricular function with ventricular pacing and the deleterious effects of non-apical pacing location, higher burden of ventricular pacing, and wider paced QRS complexes (z-score duration).   Univentricular patients requiring ventricular pacing are often more complex and sicker as demonstrated by the higher need for inotropic support, antiarrhythmic medications, fenestrated Fontan procedures, worse function and atrioventricular valve regurgitation, and more surgeries.  Therefore, an individualized approach balancing risks and benefits is needed in these patients.  This study provides a thoughtful framework of modifiable pacing strategies (apical pacing location, minimize ventricular pacing, and shorter paced QRS duration z-score) that can be used to potentially mitigate the deleterious effects of chronic ventricular pacing.  See Figure below.  

A New Score for Life-threatening Ventricular Arrhythmias and Sudden Cardiac Death in Adults with Transposition of the Great Arteries and a System Right Ventricle. Ladouceur M et al, Eur Heart J. 2022 Jul 21;43(28):2685-2694. doi: 10.1093/eurheartj/ehac288. PMID: 35673927   Take-home points: 1) Ventricular arrhythmic sudden death remains a concerning long-term risk in patients with D- or L-TGA with systemic right ventricles, though event rates remain proportionately low in comparison to other conventional cardiovascular substrates in adult patients, making risk stratification challenging 2) Risk factors can be identified and combined to help predict higher or lower risk of arrhythmic death among TGA/systemic RV patients 3) Determining candidates that will benefit most from primary prevention ICD implantation in TGA/systemic RV remains challenging despite identification of contributing risk factors, with most primary prevention ICD recipients not receiving appropriate shocks         Commentary by Dr. Philip Chang (Gainesville, FL, USA) Congenital and Pediatric Cardiac EP section editor:   Sudden cardiac death remains a challenging and devastating end point for older patients surviving with congenital heart disease.  Factors that contribute to risk of sudden death have been identified, though stratification schemes and prediction of who may carry higher/highest risk (and therefore benefit from primary prevention ICD implantation) remain limited given the significant heterogeneity between CHD substrates, intra-substrate variability, and proportionately low event rates overall.  A subpopulation that particularly highlights all of these is the CHD subgroup of patients with TGA and systemic RV. Ladouceur et al performed a multi-center retrospective study including all patients >16 years old with TGA substrates and systemic RV followed over time across several European ACHD programs, specifically looking at incidence of Major Adverse ventricular arrhythmias and Related Events (MAREs).  Patients encountered between 2000-2018 with at least 2 years of follow-up were included.  Demographic and clinical data were gathered to identify risk factors for MAREs and then used to derive a risk calculator and scoring system to facilitate the identification and categorization of patients at lower vs. higher risk. A total of 1184 patients were identified and met inclusion criteria (median age 27.1 years, 59% male, 70% D-TGA).  Among D-TGA patients, there were nearly twice as many Mustard atrial switch procedures performed compared to Senning operations.  Over a median follow-up duration of 9.4 years, 59 patients (5%) experienced MAREs yielding an overall incidence of 6.3 per 1000 patient-years.  There were 79 patient deaths (6.7%), of which MAREs accounted for 13.  Nearly a quarter of patients during the study period experienced new cardiovascular events including atrial arrhythmias (12%), symptomatic heart failure (10%), and pacemaker implant (9%). While multiple risk factors were identified and considered significant based on univariate analysis, increasing age, history of heart failure, syncope, wider QRS duration, severe systemic RV dysfunction, and at least moderate subpulmonary LV outflow obstruction were significant risk factors by multivariate analysis. Among patients with ICDs during the study period, 121 had an ICD for primary prevention, with recipients being older and more likely to have L-TGA.  Nearly 12% experienced inappropriate shocks and appropriate shocks occurred in only 8/121 patient. The MAREs risk calculator was derived from the 6 risk factors identified as significant by multivariate analysis.  Each risk factor was weighted and integrated into a prognostic index value that was then incorporated into an equation to calculate a score for risk of MAREs over 5 years.  The authors then applied the model to the study population for basic validation, noting the comparison between prediction of MAREs risk by the calculator and the observed MAREs incidence.  Using cutoffs of <5%, 5 to <10%, and >10% for risk of MAREs over 5 years of follow-up, the authors were able to determine a percentage of patients who would have qualified for primary prevention ICDs by risk calculation and how many would receive appropriate ICD therapies based on the incidence of events over the study period.  From these calculations, they determined that 1 patient could potentially be saved from MAREs at 5 years for every 10 primary prevention ICDs implanted using a risk cutoff of >5% and 1 patient for every 5 ICDs implanted using a risk cutoff of >10%. Reviewer perspective: Sudden death in aging survivors with palliated D-TGA or L-TGA with systemic RV remains an ongoing concern.  Given this concern, many patients undergo primary prevention ICD using basic risk assessment, yet many do not experience any shock therapy benefit over extended periods of follow-up but carry risks and experiences of inappropriate shocks and hardware-related complications.  This study further refines our understanding of sudden death risk in TGA patients with systemic RV, noting the influence of increasing age, myocardial fibrosis, and atrial arrhythmias contributing to substrate and triggers for potentially lethal ventricular arrhythmias. Interestingly, the study investigators found a risk of at least moderate subpulmonary LV outflow obstruction to be an independent risk factor for MAREs.  Historically, the presence of subpulmonary LV outflow obstruction was felt to control and even reduce the degree of systemic tricuspid regurgitation by way of ventricular septal shift.  While this may still be true, moderate or greater degrees of obstruction may give rise to adverse myocardial remodeling and fibrotic substrate for arrhythmias.  This finding also highlights that attention must be paid to the “opposite” ventricle from the one that appears to pose the primary and dominant concern, as is also the case with tetralogy of Fallot with significant RV derangements as well as LV involvement (with high EDPs and/or systolic dysfunction). The study also demonstrated that, while a higher rate of sudden arrhythmic death was calculated in this contemporary study, overall event rates remain proportionately low in comparison to other adult acquired cardiovascular disease states and substrates.   For example, recent risk models in post-MI patients have derived sudden arrhythmic death rates of 3.3 per 100 person-years over a median 2-year follow-up period compared to the 6.3 per 1000 over 9 years of follow-up reported in the current study.  This only further serves to highlight the challenges of developing risk stratification schemes in CHD patients.  The authors noted that their higher reported rate of sudden death may reflect the aging and older ACHD population studied in this contemporary era. The risk calculator that was derived appears to carry some utility in predicting risk, particularly those with high risk of MAREs >10% at 5 years.  Furthermore, the application of this risk scoring tool prospectively holds some promise of refining candidacy for primary prevention ICDs and sparing some patients who may not derive the desired survival benefit.  The authors acknowledged some limitations to the risk score, given that certain variables that were either considered significant risk factors or potentially useful predictors were excluded from the risk model either due to limited numbers of events involving those factors or missing data across the study cohort.  The incorporation of certain biomarkers and advanced imaging data may help to further differentiate patients with similar risk profiles. Though thoughtful overall, the study primarily reinforces what we currently know and frequently integrate into even basic risk assessment of TGA/systemic RV patients.  Increasing age, worsening systemic RV function, and associated atrial arrhythmias remain recognized dominant risk factors.  The incorporation of a quantified risk value may help to better group patients into those who should proceed with primary prevention ICD sooner and those who should undergo serial risk scoring assessments over time to trend quantifiable changes that may drive a change in management in the future.

Diagnostic accuracy of the 12-lead electrocardiogram in the first 48 hours of life for newborns of a parent with congenital long QT syndrome. Perez Y, Tobert K, Saunders M, Sorensen K, Bos M, Ackerman M. Heart Rhythm. 2022 June; 19(6): 969-974. doi: 10.1016/j.hrthm.2022.01.041.   Take Home Points: This study looked at the accuracy of ECGs in the first 48 hours of life in diagnosing LQTS in neonates born to a parent with LQTS. Using a recommended QTc threshold of ≥ 440 ms, the ECG is 88% sensitive but only 29% specific, resulting in significant overdiagnosis. Confirmatory variant-specific, cascade genetic testing should be initiated before discharge to ensure the most accurate diagnosis in this at-risk population. Commentary by Dr. Roberto G. Gallotti (Seattle, USA), Congenital and Pediatric Cardiac EP section editor   Congenital long QT syndrome (LQTS) affects ~ 1 in 2000 persons, with the majority of LQTS caused by pathogenic variants in KNCQ1, KCNH2, and SCN5A. The pattern of inheritance is typically autosomal dominant, where a single variant is inherited from one of the parents, meaning there is a 50% probability of inheriting a disease-causative variant.   The optimal timing for ECG screening in newborn infants remains contested with differing opinions with regards to when it should occur. This study sought to elucidate the diagnostic accuracy of ECGs obtained in the first 48 hours of life to correctly identify LQTS in neonates born to a genotype-positive parent.   This was a retrospective review that included infants with at least one LQTS genotype-positive parent, ECG performed within the first 48 hours of life, and LQTS genetic testing results available. A total of 74 newborns (36 female [49%]) were included, among whom 23 (46%) had LQT1 (KCNQ1), 15 (30%) had LQT2 (KCNH2), 8 (16%) had LQT3 (SCN5A) and 4 had multiple LQTS-associated pathogenic variants. The remaining 24 (32%) had negative genetic testing for the parent’s LQTS variant.   Among the genotype-positive newborns, the QTc mean was 506 ± 52 ms versus 455 ± 41 ms in the genotype-negative cohort (see distribution table below). The large overlap in QTc values highlights the challenge of making the diagnosis of LQTS by ECG alone in this population.     Analysis using a QTc cutoff of 440, 450, 460 and 470 ms was performed (see below). The most notable finding was that using a standard cutoff of 440 ms (previously validated as the 97.5th percentile in 4-day old newborns), ECG alone to diagnose LQTS had a positive-predictive value of 72% and negative-predictive value of 54%. In other words, among 50 genotype positive newborns, 6 (12%) would have been missed (underdiagnosed; false-negative), and among 24 genotype negative newborns, 17 (71%) would have been wrongly diagnosed with LQTS (overdiagnosed; false positive).     Conclusions The present study demonstrates the challenge of using the ECG alone to diagnose LQTS in a cohort of newborns who have a 50% pretest probability of having a disease-causative genetic variant. The QTc interval varies significantly in the first week of life and regardless of the adopted QTc cutoff, the newborn ECG will have a relatively high sensitivity but low specificity.   The authors highlight the importance of confirmatory variant-specific, cascade genetic testing to ensure the most accurate diagnosis in this at-risk population. They also emphasize that universal ECG screening is not recommended and would only lead to a higher number of misdiagnoses given the low prevalence of disease.   Lastly, the authors propose the below alogithm for the evaluation of newborns suspected for long QT syndrome. In their experienced practice, they allow the newborn to bond with their mother and do no transfer to a monitored unit unless there are other obstetrical or medical indications to do so.   

Repeat radiofrequency catheter ablation of atrial tachycardias in patients with congenital heart disease Ulrich Krause et al J Cardiovasc Electrophysiol. 2022;33:943–952   Take Home Points: Atrial tachycardias (AT) in patients with congenital heart disease (CHD) have a significant impact on morbidity and mortality. Radiofrequency catheter ablation (RFA) of the tachycardia substrates has improved outcome and is recommended by current consensus statements of the United States and European societies with satisfactory rates of acute success. Repeat ablation procedures are frequent but effective during a mean follow up of more than 4 years after the last procedure; 73% of the patients stayed in SR and 27% did not require further ablation procedures Factors associated with a greater likelihood of repeat ablations comprised: Complex atrial anatomy after Fontan palliation and atrial switch procedures Induction of multiple unstable IART during EPS Noninducibility of AT during programmed atrial stimulation after AT ablation has been described to be sufficient proof for a favorable outcome. Promising longterm success could be achieved after repeat ablation procedure. Commentary by Dr. Khyati Pandya (Augusta, GA, USA) Congenital and Pediatric Cardiac EP section editor:   The current study was aimed at evaluating the long‐term course of 144 patients with CHD requiring repeat ablation procedures (RAP) of AT between January 2003 and October 2018. Patients were classified according to the complexity of CHD: complex CHD (cCHD), moderate CHD (mCHD), and simple CHD (sCHD).   Atrial tachycardias (AT) in patients with congenital heart disease (CHD) have a significant impact on morbidity and mortality. Radiofrequency catheter ablation (RFA) of the tachycardia substrates has improved outcome and is recommended by current consensus statements of the United States and European societies and satisfying acute success rates have been reported. During mid and long‐term follow‐up, however, recurrence rates of AT ranging from 34% to 54% necessitating repeat ablation have been reported. Reports on mid and long‐term outcome after RFA of AT in patients with CHD are sparse covering only a limited number of patients and limited number of repeat procedures.   The purpose of the current study was to evaluate the mid and long‐term outcome of CHD patients requiring repeat ablation procedures of AT at University Medical Center, Georg‐August‐University Göttingen, Göttingen, Germany focusing (1) on a potential impact of the complexity of CHD on AT recurrence, (2) the role of tachycardia mechanism and ablation substrates with respect to AT recurrence, and (3) identification of potential factors associated with AT recurrence with impact on repeat ablation outcome.   RFA was performed with various 7F and 8F open‐irrigated radiofrequency ablation catheters as point‐by‐point applications (45°C, 30–50 W, 45 s/point). Since June 2012 real‐time contact force monitoring during ablation was used in all procedures (TactiCathTM, goal force 10–40g). Conduction gaps in previous ablation lines were sought and targeted.   Confirmation of acute procedural success and noninducibility after ablation were in accordance with conventional EP testing methods. Ablation endpoints were not changed over time.   In 62% of the patients, repeat RFA was performed at a single site, in 38% more than one substrate was targeted. A substrate within the CTI was targeted in 73%, a right atrial (RA)/SVA substrate other than CTI was targeted in 49%. A substrate within the left atrium (LA)/PVA was targeted in 22% procedures (22%). In 24% patients, RFA at a site different from the site targeted in the preceding procedure was performed. In 31% procedures, previous and additional substrates were targeted. In about half of those procedures, a new AT different from the initially targeted tachycardia was induced and targeted and in about the remaining half of those procedures, the same AT as targeted previously was induced and targeted again. In about 50% of the patients with dTGA post Mustard procedure, substrates other than CTI were targeted. The frequency of scars in the superior and the inferior baffles was comparable. Because of the heterogeneity of underlying CHDs details of main tachycardia mechanisms were not further analyzed for other types of CHD.     The original study population is outlined in the image above in a study published by the same group in 2017. Radiofrequency Catheter Ablation of Atrial Tachycardias in Congenital Heart Disease: Results With Special Reference to Complexity of Underlying Anatomy Ulrich Krause et al. Originally published15 Dec 2017https://doi.org/10.1161/CIRCEP.117.005451Circulation: Arrhythmia and Electrophysiology. 2017;10:e005451   Image from the original study outlining the patient demographics     FI GURE 1 The outcome of all 144 patients including all procedures. After 116 successful primary procedures (n = 116), six patients had NFU (blue box) and were excluded from further analysis; 46 patients stayed in SR (including SR, atrial rhythm (AR), and atrial paced rhythm (APR) while 64 patients had AT recurrence. Of those 64 patients, nine patients had recurrence of a single AT episode, lacking the need for re‐ablation (NR); six patients developed AF requiring pulmonary vein isolation (AF‐PVI; excluded from follow‐up [blue box]) while 49 of those 64 patients underwent a second procedure together with 15/28 patients having an unsuccessful primary procedure; 6/28 of the primary failure patients stayed in SR/AR/APR while another six patients needed NR after a single AT‐recurrence. After primary procedures 52/132 patients (39%) stayed in SR, 16/132 patients needed NR, and 64/132 patients underwent a second procedure. At final assessment 91/125 patients (patients with NFU, EPS extern, and AF‐PVI excluded) stayed in SR/AR/APR and 34/125 patients did not require re‐ablation after AT recurrence (see also Figure 3). AF‐PVI, pulmonary vein isolation for atrial fibrillation treatment; APR, atrial paced rhythm; AR, atrial rhythm; EPS, electrophysiological study; NFU, no follow‐up; NR, no re‐ablation; SR, sinus rhythm with or without antiarrhythmic drug therapy; *NR after sustained self‐limiting atrial tachycardia, **NR after sustained atrial tachycardia necessitating cardioversion), ‡already published data in Klehs et al.   TA BL E 1 Patients' and procedural characteristics with reference to the severity of CHD All reprocedures (n = 101)Simple CHD (n = 6)Moderate CHD (n = 38)Complex CHD (n = 57)p for overall comparisonp for pairwise comparisonMean age (year)37 ± 1332 ± 1244 ± 1433 ± 10p < .001p < .001aMedian body weight (kg)76 (IQR 63–88)65 (57–72)77 (67–85)77 (62–88)p = .16Median procedure duration (min)241 (IQR 203–300)145 (116–263)231 (182–280)251 (212–310)p = .008p = .03bMedian fluoroscopy time (min)16 (IQR 7.6–25)5.5 (2.9–17)10 (6.3–24)17 (12–26)p = .01p = .042bAblation site LA/PVA22 (22%)1 (17%)2 (5%)19 (33%)p = .002p = .001aAblation site CTI74 (73%)4 (67%)32 (84%)38 (66%)p = .13More than one ablation site38 (38%)013 (34%)25 (44%)p = .1New ablation site55 (54%)2 (33%)18 (47%)35 (61%)p = .22Acute success83 (82%)5 (83%)31 (82%)47 (82%)p= 1.0Recurrences after successful45/82 (55%)2/4 (50%)15/31 (48%)28/47 (59%)p= .6procedure (n = 82c) Timing of recurrences (months) 12 ± 18 6 ± 6 11 ± 12 12 ± 21 p= .32   Abbreviations: cCHD, complex congenital heart disease; CTI, cavotricuspid isthmus; LA, left atrium; mCHD, moderate congenital heart disease; PVA, pulmonary venous atrium; sCHD, simple congenital heart disease.   TABLE 2 Procedural characteristics with reference to primary procedures6 and repeat procedures All procedures (n = 245)Primary procedures (n = 144)Repeat procedures (n = 101)p ValueMore than one ablation site71 (29%)33 (23%)38 (38%)p = .01Ablation site LA/PVA31 (13%)9 (6%)22 (22%)p < .001Ablation site CTI175 (71%)101 (70%)74 (73%)p = .6Median fluoroscopy time (min)19 (IQR 11–29)22 (IQR 15–34)16 (IQR 7.6–25)p < .001Median procedure duration (min)250 (IQR 199–315)260 (IQR 197–334)241 (IQR 203–300)p = .04Acute success199 (81%)116 (81%)83 (82%)p = .7 Abbreviations: CTI, cavotricuspid isthmus; LA, left atrium; PVA, pulmonary venous atrium.   As described by the authors, ablation of more than one substrate and ablation within the LA/ PVA was significantly more frequent in repeat ablations compared with primary procedures (Table 2; 38 of 101 reprocedures [38%] vs. 33/144 procedures [23%], p=.01, and 22/101 [22%] vs. 9/144 [6%], p < .001).   FI GUR E 2 Kaplan–Meier curve of freedom from atrial tachycardia recurrence after each procedure. Log‐rank test showed no significant difference in timing of recurrence (p = .34). 12 months survival rates were after first procedure 59%, after second procedure 54%, after third procedure 55%, and after fourth procedure 88%   TABLE 3 Total number of procedures with reference to complexity of CHD Total numberAllSimpleModerateComplexofpatientsCHDCHDCHDprocedures(n = 144)(n = 18)(n = 53)(n = 73)180 (55%)13 (72%)28 (53%)39 (53%)240 (28%)4 (22%)17 (32%)19 (26%)313 (9%)1 (6%)3 (6%)9 (12%)410 (7%05 (9%)5 (7%)61 (1%)001 (1%)   Abbreviations: cCHD, complex congenital heart disease; mCHD, moderate congenital heart disease; sCHD, simple congenital heart disease.     FI GURE 4 Number of procedures for all patients with follow‐up. Number of procedures was not different in the overall comparison of the three groups, however, patients with sCHD needed significantly less procedures than patients with mCHD and cCHD (p = .04). Patients after Fontan palliation or atrial switch procedures for D‐transposition of the great arteries and patients with induction of multiple unstable IART during primary and/or repeat procedures required more procedures than the rest of the cohort. cCHD, complex congenital heart disease; mCHD, moderate congenital heart disease; sCHD, simple congenital heart disease   As described in literature, the mechanisms by which atrial arrhythmias potentially cause morbidity and mortality in CHD are multiple, including 1:1 conduction throughout atrio-ventricular node or accessory pathways, ischemia, preload reduction, embolism, systemic ventricle remodeling and consequent heart failure or ventricular arrhythmias.   The current study was a great attempt at defining factors related to recurrence of atrial arrhythmias in the population with adult congenital heart disease.   The study data has successfully demonstrated that increasing complexity of the underlying congenital heart disease correlates with an increase in the number of ablation procedures required. The higher frequency of IART in the presence of complex congenital heart disease with significant atrial stretch is somewhat intuitive.   As pointed out by the authors, the study limitations comprise of the following factors:   This study was based on retrospective data derived from a single center. A possible association of hemodynamic deterioration and AT recurrence could not reliably be assessed as hemodynamic data at the time of AT recurrence were incomplete. Patients with AF without evidence for macroreentrant tachycardia undergoing only PVI were excluded from further follow‐up. The study analyzes procedures over a time period of 15 years thereby being potentially influenced by operator skills and technical equipment. All operators, however, had the same high level of clinical experience in catheter ablation of ATs in patients with CHD and all procedures were supervised by a single senior operator.   Future prospective multicenter assessments of the results of AT ablation in CHD patients may overcome these limitations. Incorporation of cardiac MRI findings to better define areas of scarring and amalgamating the same into 3D mapping during the EP study maybe beneficial in further defining the arrhythmia substrates.   Further analysis with regards to influence of patient’s age and comorbidities on the risk of arrhythmia recurrence would be helpful as also inclusion of a broader age group. Future studies need to study the coexistence of ventricular arrhythmias and its impact on recurrence rates of atrial arrhythmias in the population of adults with congenital heart disease.   In addition, longer term follow up of these patient subgroups is required alongwith analysis of their hemodynamic data in order to better define the impact of the underlying congenital heart disease on arrhythmias.   A more thorough understanding of underlying mechanisms and substrates carries the potential to further improve outcomes as does use of novel arrhythmia mapping techniques.   

Arrhythmias Requiring ECMO in Infants Without Structural Congenital Heart Disease Andrew Well1,2 · Arnold Fenrich1,3 · Daniel Shmorhun1,3 · Daniel Stromberg1,3 · Preston Lavinghousez1,3 · Ziv Beckerman1,2 · Charles D. Fraser Jr.1,2 · Carlos M. Mery1,2 Received: 9 July 2021 / Accepted: 6 December 2021 / Published online: 17 January 2022   Commentary by Dr. Daniel Cortez (Sacramento, CA, USA), Congenital and Pediatric Cardiac EP section editor. Introduction Discussion of incidence of pediatric arrhythmias in emergency room notes a fairly low number of 55/100000, however the next line is slightly misleading, to clarify, the quoted abstract (reference 1) discusses that sinus tachycardia makes up most of the arrhythmia emergency room visits, while SVT is diagnosed 13% of the time in the pediatric emergency room visits. Two smaller studies have demonstrated 6/6 infants survived to discharge after ECMO for SVT, while in those under 21 years ofg age, with ECMO due to SVT, only 65% survived, with decreased survival in congenital structural heart disease. The need exists to further evaluate ECMO survival for neonatal SVT.   Methods Fairly sound methods here with congenital heart disease patients not included (this might be worth a second thought, however, but perhaps they are planning a second manuscript). Data is from the Extracorporal Life Support Organization Registry from 2008 through 2019 of patients less than 1 year of age using ICD-9 and ICD-10 codes. Appropriate statistical analyses were employed.   Results One hundred and forty patients were evaluated including based on ICD codes for SVT, unspecified arrhythmia (23.6%) and cardiac arrest. Sixty two percent had SVT, 12.5% had VT, and unspecified arrhythmias noted in 22.5%, with VF in3.3% and atrial flutter/fibrillation in 1.7% (2 patients) with “neonatal tachycardia” noted in 1.7% as well and one patient (0.8%) with supraventricular premature beats. Most patients were Caucasian and none were black.   One hundred and twenty survived (85.7%). Median time on ECMO support was 94 hours (interquartile range 69 to 158.5). Inotropic support prior to ECMO (12.1% vs 37.7%, p-value 0.005) and narcotic use (30.3% vs 57.5%, p-value -0.006) were associated with incidence of ECMO complication. Of those that did not survive, 65% (13/20) occurred while on ECMO and the other 7 (35%) were successfully separated but did not survive to discharge. Interestingly enough all VF patients survived and 10/15 (66.7%) of the VT patients survived and one of the two atrial fibrillation/flutter patients survived. Increased narcotic use (and neuromuscular blockade were associated with non-survival, as well as potentially use of norepinephrine (but small numbers used).   Central cannulation complications occurred in 12.9% of patients (36.9%) in non-survivors. Central ECMO cannulation had a high odds ratio for in-hospital mortality of 50.2 (95% CI 2.96 to 1,651.93). Out of patients with just SVT pacemaker pre-operatively, bicarb administration and central ECMO cannulation were associated with non-survival.   Overall, this paper discusses Infant ECMO survival in the setting of arrhythmias and looks partially at those with SVT. And although the driving point of the manuscript is that survival of 85.7% is better than prior reports of ECMO in older patients in the setting of SVT, I think there are a few points that would have been helpful, that are likely limited due to the nature of the study (registry study). The first is that the demographics of the SVT population (and how they differ from all comers with arrhythmias) would have been helpful. Secondly, what was used to control the arrhythmias and was urgent ablation performed in any of these patients? With smaller catheters available such as 5F Livewire mapping and with the advent of Cryoablation and it’s proven safety in smaller patients, were any of these modalities attempted to prevent or curb ECMO time. The answer is likely no, but perhaps type of antiarrhythmic used would help determine most effective to limit ECMO time (especially with IV sotalol now at more centers).  

Left Cardiac Sympathetic Denervation for Long QT Syndrome: 50 Years' Experience Provides Guidance for Management. Dusi V, Pugliese L, De Ferrari GM, Odero A, Crotti L, Dagradi F, Castelletti S, Vicentini A, Rordorf R, Li C, Shkolnikova M, Spazzolini C, Schwartz PJ. JACC Clin Electrophysiol. 2022 Mar;8(3):281-294. doi: 10.1016/j.jacep.2021.09.002. Epub 2021 Oct 27. PMID: 35331422   Take Home Points: Left stellate cardiac sympathetic denervation (LCSD) is an effective and safe adjunct to beta-blocker therapy LSCD in addition to increasing the ventricular fibrillation threshold can shorten the QTc interval providing another mode of risk reduction. LCSD can reduce the yearly cardiac event rate by 86% in symptomatic patients. LCSD has durable long-term efficacy during the follow-up of 12.9 ± 10.3 years A new algorithmic approach for the use of LCSD in the management of LQTS in those not protected by beta-blocker therapy is proposed by the authors. Comment from Dr. Akash Patel (Cleveland), section editor of Congenital Electrophysiology Journal Watch. Management of Long QT syndrome (LQTS) has been relatively unchanged over the last several decades. Beta-blockers have been the mainstay in treatment to prevent cardiac events, but breakthroughs still can occur. Pioneering work in 1973 by Dr. Arthur Moss and Dr. Peter Schwartz showed the efficacy of left stellate cardiac sympathetic denervation (LCSD) as an adjunctive therapy. Due to efficacy of beta-blocker therapy, lack of expertise to perform the LCSD procedure, and limited long term data, LCSD has seen limited use. In 2005, Dr. Ackerman and colleagues introduced a minimally invasive thoracoscopic approach which reinvigorated interest in LCSD for the management of LQTS. There continues to be limited long term data and lack of consensus about timing and patient selection for LCSD and ICD. This single center study aimed to review their 50-year experience of LCSD in LQTS. This was retrospective single center study of all consecutive patients with LQTS who underwent a LCSD from 1973 to 2020. Follow-up was obtained on all but 1 patient. The study analyzed the population in 4 groups: 1) very high risk with either symptoms in the first year of life or high-risk features including CALM, CACNA1C, JLN, and recurrences on beta-blockers (n=18); 2) patients with previous aborted cardiac arrest (n=31); 3) patients with previous syncope and/or ICD shock on beta-blocker or previous syncope and intolerance/refusal to beta-blocker (n = 45); and 4) patients with LCSD in primary prevention such as patients still asymptomatic or with syncope off treatment but deemed to be at high risk based on a combination of factors such as QT interval corrected for frequency [QTc] >500 ms at resting ECG and/or on Holter ECG recordings, T wave alternans, intolerance to beta-blockers, prolonged sinus pauses, or bizarre repolarization recognized as dangerous pattern by clinical experience (n=31). Clinical characteristics and outcomes were analyzed. Cardiac events were classified as at least 1 arrhythmic syncope, aborted cardiac arrest (ACA), or ICD appropriate shocks. Major cardiac event was classified as sudden death (SD), ACA, and ICD shocks. Baseline characteristics showed a total of 125 patients that consisted of LQT1 (26%), LQT2 (44%), LQT3 (10%), other mutations (9%), and genotype unknown (21%). The mean age at LCSD was 20 ± 15 years. The median age of first symptom was 7 (IQR: 2- 14) years. The mean time from first major cardiac event to LCSD was 8.0± 8.1 years. 82% were symptomatic before LCSD with aborted cardiac arrest in 34%. The first symptom was aborted cardiac arrest in 13% and syncope in 69%. A QTc ≥ 500 msec was seen in 66%. The majority were on treatment, beta-blockers (90%) and mexiletine (10%). In addition, a pacemaker or ICD was present in 17%. Of importance, recurrence of cardiac events was seen in 81% with a median of 5 (IQR: 1 – 13.5) events. See Table 1.     Surgical LCSD was conducted by 3 surgeons over 43 years. The surgical approach consisted of resection of the lower half of the left stellate ganglion, together with the thoracic ganglia from T2 to T4. A sub clavicular approach (n=94) was used before 2014 and a thorascopic approach (n=31) after 2014. After LCSD, there was a cardiac event seen in 44% with mean follow-up of 12.9 ± 10.3 years. The cardiac events included sudden death (4%), aborted cardiac arrest (10%), ICD shock only (11%), and syncope (18%). The most common first cardiac event was syncope seen in 84%. Aborted cardiac arrest was the first symptom in 16%. There was no sudden death seen as the first event after LCSD. See Table 2.     After LCSD, 56% were totally asymptomatic. Syncope was seen in 18%. Major cardiac event in 26% including 4% with sudden death and 11% with aborted cardiac arrest. The median time from LCSD to first cardiac event was 20 months (IQR: 7-52 months), major cardiac event was 129 months (IQR: 24 – 205), and 103 months (IQR: 36 – 160) for sudden death. Based on the subgroups analysis, 97% of the primary prevention group, 49% of the syncope group, 67% of ICD shock group, and 52% of the aborted cardiac arrest group remained asymptomatic. See Figure 1 which excludes the very high risk.     Overall, there were 5 sudden deaths of which 2 were in the very high-risk group and 3 in the previous syncope/ICD shock. 2 had stopped taking beta-blockers. Of note, the sudden death episode was always preceded by at least 2 cardiac events after LCSD (median 3, IQR 2-9). Right cardiac sympathetic denervation was done in 5 patients because of a major cardiac event after LCSD with 3 patients having improvement. On-treatment analysis of event free survival at 10 and 15 years for cardiac event was 97% for both in the primary prevention group, 49% and 42% in the syncope/ICD shock group, 60% and 45% in the aborted cardiac arrest group, and 15% and 8 % in the very high-risk group (p<0.0001). On-treatment analysis of event free survival at 10 and 15 years for major cardiac event was 100% for both in the primary prevention group, 87% and 74% in the syncope/ICD shock group, 78% and 69% in the aborted cardiac arrest group, and 35% and 9% in the very high-risk group (p<0.0001). See Figure 2.     Survival from cardiac events after LCSD in those without ICD shock in follow-up or ICD at first major cardiac event was 79% at 10 and 15 years in those with previous syncope on beta-blocker or previous aborted cardiac arrest. See Figure 3.     Cardiac events in the secondary prevention group reduced by 86% after LCSD from 1.66 (IQR: 1.57 – 1.75) events/year to 0.26 (IQR: 0.23 – 0.28) (p<0.001). Among those with aborted cardiac arrest the major cardiac event rate decreased by 80% after LCSD from 0.63 to 0.13. (p=0.03) Among those with very high risk the cardiac event rate decreased by 75% after LCSD from 2.1 to 0.48. (p=0.03) LCSD was done as monotherapy due to beta-blocker intolerance/refusal in 12 patients (4 primary prevention, 4 syncope, and 4 prior aborted cardiac arrest). During a follow-up of 18±12 years, there were no major cardiac events and only 2 with syncope. LCSD did show a significant reduction in the QTc duration after LCSD which persisted at 6 months in most patients. The mean QTc at baseline was 527 ± 60 msec which reduced by 16 ± 24 msec at discharge (p<0.0001) and 26 ± 35 msec at 6 months (P<0.0001) In those patients with QTc>500 msec, 33% had a reduction to <500 msec QTc. See Figure 4.     As expected, a QTc >500 before LCSD (HR 3.17) and at discharge from LCSD (HR 2.54) were significant predictors of cardiac events. In those with prior syncope or ICD shock, a QTc at 6 months after LCSD of <500 msec compared to >500msec was associated with 15-year survival from cardiac events of 80 vs 9%, p=0.0001. LCSD efficacy did not shows any difference across genotypes. See Below.     Finally, LCSD was safe with no major complications. There was permanent ptosis seen in 2.4% and transient neuropathic pain in 35% of VATS procedure. This study provides a unique review of a single center’s 50-year experience using LCSD to manage LQTS. It showed that LCSD was safe and durable. It resulted in an overall reduction in cardiac event rates by 86%. In addition, this study showed LSCD resulted in QTc shortening and conferred additional benefit when the QTc was shortened to <500 msec. Based on their data, the authors developed a practice algorithm (Central illustration below) which provides a logical but not prospectively validated approach to the management of LQTS. The authors favor the use of LCSD, mexiletine, RSCD, and pacing before ICD consideration in primary prevention and syncope on beta-blocker patients. The authors advocate for LCSD with ICD placement in high and very high-risk patients due to the marked reduction in event rates. This study highlights the importance of LCSD and the need to individualize patient care management in LQTS.      

Identifying an appropriate endpoint for cryoablation in children with atrioventricular nodal reentrant tachycardia: Is residual slow pathway conduction associated with recurrence? Zook N, DeBruler K, Ceresnak S, Motonaga K, Goodyer W, Trela A, Dubin A, Chubb H.Heart Rhythm. 2022 Feb;19(2):262-269. doi: 10.1016/j.hrthm.2021.09.031. Epub 2021 Sep 30.PMID: 34601128   Take Home Points Cryoablation for acute slow pathway modification or elimination can be accomplished safely and with very high acute success Recurrence of SVT following cryoablation for AVNRT remains a measurable mid-term outcome despite procedural refinements and high initial success rates In this study, the degree of pre-ablation SVT inducibility and post-ablation slow pathway activity were not predictive of post-ablation SVT recurrence               Commentary by Dr. Philip Chang (Gainesville, FL, USA) Congenital and Pediatric Cardiac EP section editor:   Catheter ablation is considered a safe and effective treatment for SVT in otherwise healthy individuals with low risk of complications as well as reasonably low incidence of recurrence. In the case of AVNRT, cryoablation has widely been adopted given its favorable safety profile in pediatric patients, however SVT recurrence has historically been higher than what has been seen following radiofrequency ablation for slow pathway modification or elimination. Efforts to further refine the procedure remain an active area of interest.   Zook et al examined their experience with cryoablation for slow pathway modification in pediatric AVNRT. This study is retrospective in design with review of procedural experiences and data from a single pediatric EP center. Patients <21yo were included if they underwent first-time cryoablation for the treatment of typical AVNRT with acute success between 2011-2019. Data and findings from ablation procedures were reviewed to identify factors that were associated with SVT recurrence following initial ablation success. The authors noted and included the incorporation of low voltage bridge mapping and ablation beginning in 2013. Subjects were further classified and studied based on pre-ablation SVT inducibility characteristics and degree of residual slow pathway activity, both being numerically designated (see Tables 1 and 2). A scale was developed to quantify the degree of change in AVNRT inducibility following ablation by subtracting the pre-ablation inducibility value from the post-ablation residual slow pathway value.     A total of 256 patients were included. There were no significant differences in general demographic characteristics between those with and without AVNRT recurrence. AVNRT recurrence occurred in 5% of patients (14 patients) with 64% of the recurrences occurring within the first year after ablation. A total of 44 cases were performed prior to the incorporation of low voltage bridge mapping and 5 of the 14 total recurrences were noted in this subgroup of patients. Among all included patients, a majority received isoproterenol before ablation (57%). There was no correlation between degree of inducibility pre-ablation and post-ablation recurrence. Most patients fell into either of the 2 extremes for post-ablation residual slow pathway activity – 152 patients (59%) without any identifiable slow pathway activity and 76 patients (30%) with some slow pathway activity defined as an echo beat without isoproterenol. Those without post-ablation slow pathway activity received significantly less cryoablation time/treatment compared to those who had some post-ablation slow pathway activity. Recurrence of SVT occurred in all 4 post-ablation slow pathway activity categories with the highest absolute number of recurrences among those with the lowest degree of residual slow pathway conduction after ablation. However, there was no statistically significant difference in recurrence rates between each of the 4 post-ablation endpoint groups. (see Figure 3) Furthermore, on multi-variate analysis looking at procedure duration, total cryolesion time, use of low voltage bridging, cryocatheter tip size, pre-ablation inducibility, and post-ablation slow pathway activity, there were no factors that were clearly predictive of future recurrence. Using the scale derived from pre-ablation inducibility and post-ablation slow pathway activity (ie. degree of change in AVNRT inducibility post-ablation), no association was seen between level of inducibility and actual recurrence.     Reviewer Perspective: This single center retrospective experience with exclusive cryoablation treatment for AVNRT demonstrates the midterm outcomes for this approach to ablation therapy in the hands of experienced operators at a well-established and moderate-to-large volume center. As with previously published data, acute success rates of ablation for AVNRT are very high. However, recurrences remain an observed outcome and have remained a perceived limitation of cryoablation vs. radiofrequency ablation for AVNRT. Zook et al have shown that cryoablation can achieve excellent outcomes without post-ablation heart block in pediatric patients, with a recurrence rate that falls toward the lower range of recurrence rates that have been reported in the literature.   There are multiple limitations to this study. First, the endpoint criteria evaluated are rather narrow, focusing primarily on pre-ablation inducibility vs. post-ablation slow pathway activity. Further definition of slow pathway activity before and after ablation, such as the presence or absence of sustained slow pathway conduction, was not incorporated as an endpoint. There was inconsistency in the performance of EP testing and ablation delivery as evidenced by the variable use of isoproterenol before and after ablation and the varying durations of cryolesions ranging between 4-8 minutes, which are not trivial differences. Follow-up duration was carried out to an upper limit of 3.7 years, though late recurrences beyond this timeframe are known to occur (which the authors do acknowledge as well) but were not included in this study.   The authors also noted that achieving an ablation goal of complete slow pathway elimination can lead to longer ablation times and longer procedure times. Yet, from their data, the shortest ablation times were in patients who achieved acute slow pathway elimination. The assumption is that further ablation was not delivered once slow pathway elimination was observed. However, the authors reported the highest absolute number of recurrences among patients that initially had elimination of slow pathway conduction. This brings into question the durability of lesions in these cases and, while lesions may have been placed in the critical sites, tissue damage and injury may have been insufficient to result in long-term elimination. As such, the issue may be less about acute post-ablation slow pathway activity and more an issue of long-term lesion durability.   The authors mentioned the vastly different cryoablation times between published pediatric vs. adult studies on AVNRT ablation but provided no suggestions from their findings as to how to understand this difference or potentially reduce cryoablation times in pediatric cases. Finally, a comparison to radiofrequency ablation using similar endpoint measures was not performed, which could potentially have been useful to determine if lesion durability may be a more dominant contributor to recurrence risk versus functional slow pathway behavior following ablation.   Endpoints following ablation for slow pathway modification or elimination for AVNRT can be viewed as either well established and predictive or debatable depending on practice patterns and experience and results from formal investigation. Both the location of ablation therapy and durability of lesions likely contribute to early and late findings following slow pathway ablation and likely impact the incidence of recurrence.    

Lead Extraction at a Pediatric/Congenital Heart Disease Center: The Importance of Patient Age at Implant.   Pham TDN, Cecchin F, O'Leary E, Fynn-Thompson F, Triedman JK, Gauvreau K, Mah DY.JACC Clin Electrophysiol. 2022 Mar;8(3):343-353. doi: 10.1016/j.jacep.2021.11.008. Epub 2022 Jan 31.PMID: 35331429   Take Home Points: This was a large contemporary single center study involving transvenous lead extraction (TLE) in 113 pediatric and congenital heart disease patients TLE was successful in 97% patients and 98% leads with 5 major complications, most commonly tricuspid valve regurgitation Risk factors for complex TLE (requiring advanced extraction tools) included younger age at implant, older lead age, RV location and multiple leads. Commentary by Dr. Jeremy Moore (Los Angeles) Congenital and Pediatric Cardiac EP section editor: Pediatric patients with cardiac implantable electronic devices may require transvenous lead extraction (TLE) due to a variety of factors that include most commonly lead dysfunction and infection. TLE in this group is not well understood, thus the present study attempted to examine the outcomes of TLE and risk factors for procedures that required specialized lead extraction equipment (“complex TLE”).   This study examined the outcomes of TLE In 113 patients and 162 leads that were classified as pediatric or congenital heart disease at a single center over a period spanning 2008 to 2019. All TLE were performed by one of 2 operators in the pediatric catheterization laboratory with surgical back up. Of the procedures, successful extraction was achieved in 110 (97%) patients and 159 (98%) leads. Overall, simple extraction was attempted in all leads and was successful in 41 leads (25%). Complex extraction was required in the remaining 120 leads (75%).   Independent risk factors for complex extraction in this study were 2leads extracted, lead location in the RV, and the combined variable of age 12 years at implant + lead age 7 years. The authors noted that of the combined variable of age at implant and lead age, lead age was the more important of the two. Interesting, extraction of a high voltage coil (associated with an ICD) was not identified as a risk factor for complex TLE in this study, likely related to the fact that age at implant and lead age were both much greater in patients with pacemaker leads as opposed to high voltage leads. There were 5 major complications that included 1) incomplete TLE resulting in operative extraction, 2) tamponade requiring urgent operative repair and 3) severe tricuspid regurgitation requiring valve repair within 6 months of the procedure in 3 patients.     The authors concluded that TLE can be performed successfully and safely in pediatric and congenital heart disease patients. Risk factors include younger age at implant, older lead age, RV location and multiple leads.