PJRT Spring 2021 Edition(Pediatric Journal Review by Trainees)

Fellows Participants:• Benjamin Hale, MD (C.S. Mott Children’s Hospital, Ann Arbor, MI)• Thomas Carberry, MD (Lurie Children’s Hospital, Chicago, IL)• Muhammad Mohsin, MD (Stollery Children’s Hospital, Edmonton, AB)• Ellis Rochelson, MD (Texas Children’s Hospital, Houston, TX)

Faculty Editor: William Goodyer, MD/PhD (Lucile Packard Children’s Hospital at Stanford, CA)

Education Committee Chairs:

Kara Motonaga, MD (Lucile Packard Children’s Hospital at Stanford, CA)

Eric Silver, MD (Columbia NewYork-Presbyterian Morgan Stanley Children's Hospital, NY)

PJRT Fellow Authors (Spring 2021): Benjamin (Ben) Hale, MD Ben is the pediatric electrophysiology fellow at the University of Michigan C.S. Mott Children’s Hospital Congenital Heart Center. He did med/peds residency and pediatric cardiology fellowship in Ann Arbor, and will be joining the faculty at University of Michigan after graduation in July. He has a particular interest in Adult Congenital electrophysiology and CIED innovations. Thomas Carberry, MD Tom is currently in the beginning of an 18 month EP fellowship at Lurie Children’s Hospital in Chicago. He grew up in the Chicago area. His previous training was at UC San Diego for pediatrics residency and Northwestern University for medical school. Muhammad Mohsin, MD Mohsin is a pediatric cardiologist from Pakistan and has recently completed a pediatric and congenital EP fellowship at the Stollery Children Hospital, University of Alberta, Canada. He is excited to start working as the first pediatric electrophysiologist of Pakistan. Ellis Rochelson, MD Ellis is the pediatric EP fellow at Texas Children’s Hospital. This summer he will join the faculty at Children’s Hospital at Montefiore in NYC. Check out his free app, the Peds Cardiology Handbook, on the iOS App Store!

Section # 1: ACHDBen Hale, MD

C.S. Mott Children’s Hospital

Background:- Determining risk of sudden death in ACHD remains challenging- The PREVENTION-ACHD risk score was developed from

multicenter retrospective case-control study of 25,790 patients- One point assigned for each of 7 risk factors:

- (1) coronary artery disease, - (2) heart failure symptoms (New York Heart Association class II/III)- (3) supraventricular tachycardia- (4) impaired systemic ventricular function (ejection fraction < 40%)- (5) impaired subpulmonary ventricular function (ejection fraction <40%)- (6) QRS duration > 120 ms- (7) QT dispersion > 70 ms

- Risk stratified by CHD diagnosis and risk factors per Table 1 à

Identification of patients at risk of sudden cardiac death in congenital heart disease: The PRospEctiVE study on implaNTablecardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD)

Study Objective:- Prospectively evaluate the performance of PREVENTION-

ACHD risk score, and compare 2014 PACES/HRS Guideline ICD indication

Methods:- 783 consecutive ACHD patients (>18 yo) at a single center

were assigned risk score at enrollment. Divided cohort into high and low risk groups:

- <3% low risk- >3% high risk

- Followed for at least 2 years, charts reviewed for 2 outcomes:

- Primary: combined SCD, VT/VF- Secondary: SCD alone

Results:- 58 patients in high risk group (median 3 risk factors)- 8 patients met primary end point (4 in high risk group). Table 2↑

Sens = 0.5Spec = 0.93HR 12.4

Sens = 0.5Spec = 0.92HR 12.5

Primary outcome

Secondary outcome

- PACES/HRS Guideline ICD indication in 19 (11 with ICDS. Primary outcome in 2, no SCD:- sens = 0.25, spec = 0.98Conclusions:- PREVENTION-ACHD risk score with cut off of 3% annual risk improved prediction of sudden death, although sensitivity at this cutoff remained modest- Limitations: Not all CHD dx in score, and not all dx met endpoint (ie Mustard/Senning, despite representing 16% of high risk group)

Vehmeijer JT, Koyak Z, Leerink J, et al. Heart Rhythm 2021 (Link to article)

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Role of amiodarone in the management of atrial arrhythmias in adult Fontan patientsKawada S, Chakraborty P, Roche L, et al. Heart 2020 (Link to article)Background:- The Fontan operation is associated with a high long-term

incidence of atrial arrhythmias- Rhythm control in these patients is important, but

challenging- Amiodarone is effective for atrial arrhythmias, but there is

little data regarding its longer term use specifically in Fontan patients

Study Objective:- Describe efficacy, safety, and adverse effects of amiodarone

in a cohort of Fontan patientsMethods:- Single center retrospective cohort of all Fontan patients who

received Amiodarone for atrial arrhythmias at a single center from 1995-2018

- Reviewed chart for documented arrhythmia recurrence, and amiodarone toxicities

Results:- Identified 61 patients, mean age 31.6±11.3 yrs, dx in Table 1- Median follow up 50.5 (IQR 25.4–80.1) months - 43/61 (70.5%) had recurrence of arrhythmia - 34/61 (55.7%) had side effects, leading to d/c in 20/34 (59%

with symptoms; or 33% of all patients on Amio) - Thyrotoxicosis most common AE, & most common DC reason- Patients with thyrotoxicosis more likely to need admission for

heart failure- Younger age, and lower body weight were univariate

predictors of side effects leading to discontinuation

Conclusions/Discussion:- Amiodarone had reasonable early effect,

comparable to published non-CHD series (~3/4 arrhythmia free at 1 year), but effect appeared to wane

- Lack of control group limits conclusions of efficacy

- High proportion of atriopulmonary Fontan (perhaps an era or center effect), which may make recurrence more likely. No stratification by Fontan type was performed

- Cumulative incidence of side effects was high, with thyrotoxicosis being most common, and a risk for heart failure admit

1 year:Free from arrhythmia: 76.2%

5 years:Side effects: 52%Free from arrhythmia: 30.6%

1 year:Side effects: 12%

Section # 2: AblationTom Carberry, MD

Lurie Children’s Hospital

Risk Factors for Early Recurrence Following Ablation for Accessory Pathways - The Role of Consolidation LesionsDionne A, Gauvreau K, O’Leary E, et al. Circ A&E 2020. (Link to article)

Background:

• Recurrence after successful accessory pathway (AP) ablation is reported in up to 12% of patients.

• Modifiable risk factors associated with recurrence have not been identified.

Objective:

• Describe the outcome after ablation of APs and identify risk factors associated with recurrence.

Results:

Methods:• Single-center retrospective study of children and

young adults who underwent EPS and ablation of accessory pathways over 2013-2018.

• PJRT and atriofascicular pathways were excluded.

• For patients with multiple procedures, each procedure was evaluated individually.

• Recurrence of AP conduction after acutely successful ablation was defined as:

1. SVT documented with ECG tracings

2. Ventricular preexcitation on 12-lead ECG3. Evidence of antegrade or retrograde AP

conduction on repeat electrophysiology study.

Significance:• This study provided evidence for the utility of consolidation

lesions (>90 seconds) for accessory pathway ablation.

• There is an 8% incidence of early recurrence after accessory pathway ablation in this cohort, which is consistent with prior studies

Results:• Of 558 AP ablation procedures, 542 (97%) were acutely successful.

• Media follow up of 0.4 years (0.1-1.4), 42 (8%) patients had recurrence.

• Multiple associations with recurrence on univariate analysis (see tables).

Limitations:• Retrospective, single-center study• Placement of consolidation lesions was not standardized during

the study period and varied based on multiple factors, including operator and procedural era.

• Reasons for applying consolidation lesions were not documented

Risk Factors for Early Recurrence Following Ablation for Accessory Pathways - The Role of Consolidation LesionsDionne A, Gauvreau K, O’Leary E, et al. Circ A&E 2020. (Link to article)

• Only multiple APs and RF consolidation time <90 seconds were associated with early recurrence on multivariate analysis.

Intracardiac echocardiography-guided transseptal puncture for fluoroless catheter ablation of left-sided tachycardiasŽižek D, Antolič B, Prolič Kalinšek T, et al. J Interv Card Electrophysiol 2020. (Link to article)

Background:

• Intracardiac echocardiography (ICE) and 3D electroanatomic mapping system allows transseptal punctures (TSP) without the use of fluoroscopy.

Objective:

• Evaluate efficacy and safety of entirely ICE-guided TSP in patients who underwent fluoroless catheter ablation of left-sided tachycardias.

ResultsMethods:• Single-center retrospective review of 524

adult and pediatric patients from 2014 to 2019 who underwent ICE-guided TSP for left-sided ablation.

• Adverse events following TSP and within 30 days of the procedure were analyzed,

Figure 1. Intracardiac echocardiography-guided workflow for achieving transseptal access.

Significance:

• Transseptal puncture under ICE guidance is a feasible option for left-sided ablation in pediatric patients

• More data is needed to compare the safety of ICE compared to fluoroscopy for TSP, especially in pediatric patients

Results:• Overall procedural complication rate was 1.9% (11/586 procedures)

• Adverse event rate attributed to the transseptal access was only 0.3% (3/949)

• 1 CIED lead dislocation• 1 patient with pericardial tamponade (counted as 2 events

because there were two attempts at TSP)

• 46 (7.8%) procedures with TSP were performed in pediatric patients. • 41 AP-mediated tachycardia, 4 focal AT, and 1 fascicular VT. • 7/46 (15%) were performed in patients weighing less than 30 kg. • Mean age and weight of pediatric patients were 12.5 ± 4 years

and 51.8 ± 19.5 kg, respectively.• No TSP complications in the pediatric group

Limitations:

• Retrospective, single-center study

• Primarily adult data

• No direct comparison of TSP under fluoroscopic guidance to TSP under ICE guidance

Intracardiac echocardiography-guided transseptal puncture for fluoroless catheter ablation of left-sided tachycardiasŽižek D, Antolič B, Prolič Kalinšek T, et al. J Interv Card Electrophysiol 2020. (Link to article)

Section # 3:Inherited Arrhythmias

Muhammad Mohsin, MDStollery Children’s Hospital

Echocardiography-Guided Risk Stratification for Long QT SyndromeSugrue et al. JACC 2020 Volume 76, 2834-2843 (Link to article)

Figure 5. ROC Curves of EMW and QTc forSymptomatic Status in LQTS

Figure 1. Calculation of EMW Using Continuous-Wave Doppler From the Apical Window

Figure 2. Variation in EMW Between Asymptomatic and Symptomatic Patients With LQTS

BACKGROUND• The identification of patients with highest phenotypic risk for long QT syndrome

(LQTS)–associated life-threatening cardiac events remains imperfect. • Risk prediction relies on many factors, including phenotype and genotype

characteristics combined with the surface electrocardiogram (ECG), to guide risk stratification and management approaches.

• This study investigated the association between electromechanical window (EMW) negativity and the symptomatic status of patients with genotype-positive LQTS.

METHODS• Retrospective review of electro and echocardiographic data to determine the

EMW of 651 genotype-positive LQTS patients as compared to 50 age- and sex-matched control patients.

• EMW was calculated as the difference between the interval from QRS onset to aortic valve closure (QAoC interval) and the QTc interval from the ECG for the same beat (Fig. 1).

• The primary outcome evaluated in this study was the presence of symptomatic LQTS, defined as arrhythmogenic syncope, generalized seizure, aborted cardiac arrest, appropriate implantable cardioverter-defibrillator shock, or sudden cardiac death.

RESULTS• A negative EMW was found among nearly all patients with LQTS compared to

controls, with more profound EMW negativity in patients with symptomatic LQTS as compared to those with asymptomatic LQTS (−52 ± 38 ms vs. −18 ± 29 ms; p < 0.0001) (Fig. 2).

• EMW, heart rate–corrected QT interval (QTc), female sex, and LQTS genotype were identified as univariate predictors of symptomatic status after logistic regression.

• EMW remained an independent predictor of symptomatic status after multivariate analysis.

• EMW outperformed QTc in predicting symptomatic patients (AUCEMW 0.78 compared to AUCBazettQTc 0.70; p=0.01) (Fig. 6).

Figure 6. Difference in EMW Between LQTS Genotypes

DISCUSSION• In healthy individuals, the end of electrical systole occurs slightly before

the end of mechanical systole (closure of aortic valve), resulting in a positive EMW.

• However, a negative EMW occurs when there is a mismatch between the end of electrical and mechanical systole as a result of shortening of mechanical systole, prolongation of electrical systole, or both.

• Association of a negative EMW has previously been demonstrated with increased mortality in patients with coronary artery disease and mitral valve prolapse. More relevant, a negative EMW is associated with increased torsades de pointes susceptibility in animal models of LQTS.

• The link behind the increased risk of symptoms/arrhythmogenesis associated with a negative EMW remains unclear. However, the predominant theory is that electrical–mechanical mismatch results from abnormalities in cell calcium handling, with sustained or increased calcium concentration.

• Due to prolongation of the action potential duration, ongoing calcium release may promote afterdepolarizations, which can trigger arrhythmias.

CONCLUSIONS• In this validation study, patients with a history of LQTS-associated life-

threatening cardiac events had a more profoundly negative EMW.

• EMW outperformed heart rate–corrected QT interval (QTc) as a predictor of symptomatic status.

LIMITATIONS• This was a retrospective research study from 1 center which may cause referral bias

and retrospective data abstraction.

• Circadian variation in QT interval and potentially beat-to-beat variation were notaccounted for in this study.

• The best marker for quantifying electromechanical dysfunction (e.g. EMW, strain,tissue Doppler) is not clear, as none have been compared against each other.

IMPLICATIONS• With validation of these marker in future prospective studies, it seems that

integration of echocardiography-guided risk stratification can be a useful tool inclinical practice for LQTS patients.

Figure 2. Difference in EMW Between LQTS and Healthy Controls

Left Cardiac Sympathetic Denervation Monotherapy in Patients With Congenital Long QT Syndrome

Talha Niaz et al. Circ Arrhythm Electrophysiol. 2020 (Link to article)BACKGROUND• Left cardiac sympathetic denervation (LCSD) is an effective antifibrillatory, minimally

invasive therapy for patients with long QT syndrome and is recommended (class I recommendation) as a mode of treatment intensification in patients with LQTS experiencing breakthrough cardiac events while on an effective (beta blocker) pharmacotherapy.

• This study adds early experience with LCSD monotherapy for carefully selected patients with LQTS and to describe the clinical features of those potentially eligible for this approach.

METHODS• Single center retrospective study of patients with LQTS who underwent LCSD from

2005 to 2020 as monotherapy (Table 2).• Clinical data on symptomatic status before diagnosis, clinical, and genetic diagnosis,

and breakthrough cardiac events after diagnosis were analyzed to determine efficacy of LCSD monotherapy.

• Follow-up data post-LCSD was obtained for complications (short- and long-term) and occurrence of any break through cardiac events. Cumulative event-free survival was calculated using Kaplan–Meier curves and tested in subgroups by log-rank for trend.

RESULTS• A total of 204 patients underwent LSCD out of which 64 patients were treated

with LCSD alone. • Mean QTc 466±30 ms. 16 patients (25%) were symptomatic before diagnosis

while 5 [8%] had ≥1 breakthrough cardiac event after diagnosis. Mean age at LCSD was 21.1±11.4 years.

• In the complete cohort of 204 patients with LQTS and LCSD, 42 (21%) patients experienced ≥1 BCE over a follow-up of 3±3 years. In the LCSD monotherapy group, only 3/64 (5%) patients experienced a nonlethal, post-LCSD cardiac event with a BCE-free survival of 93%.

• The primary motivation for LCSD monotherapy was an unacceptable quality of life stemming from beta-blocker related side effects in 56/64 patients (88%). The main underlying LQTS genotypes were LQT1 in 36 (56%) and LQT2 in 20 (31%).

• There were no significant LCSD-related surgical complications. With a mean follow-up of 2.7±2.4 years, only 3 patients experienced a nonlethal, post-LCSD breakthrough cardiac event in 180 patient-years (Figure 1).

Figure 1. Event-free survival in patients with long QT syndrome before and after left cardiac sympathetic denervation.

DISCUSSION• While beta blockers are an effective therapy, some patients experience quality of

life-limiting side effects including fatigue, depression, mood changes, and a decrease in exercise capacity leading to nonadherence and medication adherence issues.

• This current study shows that LCSD can be used as a safe and effective monotherapy in a carefully selected group of patients with low risk LQTS, who suffer debilitating side effects from beta blocker pharmacotherapy.

• However, selection of patients who can be offered LCSD as monotherapy is crucial and should entail a careful risk assessment on all domains.

• Although LCSD is a relatively safe procedure, there are multiple possible short- and long-term potential complications including unilateral hand dryness, color or temperature variance between sides of face, abnormal sweating, transient left eyelid ptosis, and typical postoperative pain.

CONCLUSIONS• LCSD may be a safe and effective stand-alone therapy for select patients with LQTS

who do not tolerate beta-blockers. However, LCSD is not curative and patient selection will be critical when potentially considering LCSD as monotherapy.

LIMITATIONS• One of the inherent limitations of study is the retrospective design.

• The patients who were offered LCSD as monotherapy in this cohort were older at the time of diagnosis at the time of LCSD and had a lower median QTc. Only 28% patients had a symptomatic presentation before diagnosis of LQTS that could be reason of sampling bias, as patients who chose to pursue LCSD monotherapy were generally low risk.

Figure 2. Pie chart demonstrating procedural complications related to LCSD.

Section # 4: DevicesEllis Rochelson, MD

Texas Children’s Hospital

Impact of Cardiac Resynchronization Therapy onHeart Transplant–Free Survival in Pediatric and

Congenital Heart Disease PatientsHenry Chubb, MBBS, PhD; David N. Rosenthal, MD; Christopher S. Almond, MD, MPH; Scott R. Ceresnak, MD;

Kara S. Motonaga, MD; Alisa A. Arunamata, MD; Jin Long, PhD; Anthony V. Trela, NP; Debra Hanisch, NP; Doff B. McElhinney, MD; Anne M. Dubin, MD. Circ Arrhythm Electrophysiol. 2020. (Link to article)

Background

Is CRT associated with transplant-free survival

in pediatric/CHD patients with electrical

dyssynchrony and heart failure?

MethodsResearch Question

CRT is an established treatment for adults with LBBB and low ejection fraction.

The survival benefit of CRT in select children and CHD patients is not known.

Single-center retrospective 1:1 comparison of 84 CRT patients with

propensity-score matched controls.

Inclusion criteria:EF ≤45%, symptomatic heart failure, and QRSd Z score ≥3

(or V-pace burden ≥40%)

Outcomes measured: Time to transplant/death • Survival • Transplant listing• Time to HF-related hospitalization

Cardiac resynchronization therapy (CRT): Multisite pacing, including the systemic ventricle.

Impact of Cardiac Resynchronization Therapy on Heart Transplant–Free Survival in Pediatric

and Congenital Heart Disease Patients

Henry Chubb, MBBS, PhD, et al. Circ Arrhythm Electrophysiol. 2020.Pediatric Cardiology, Lucile Packard Children's Hospital, Stanford

ResultsCRT patients vs. propensity-score matched controls

When compared to propensity-score matched controls, pediatric/CHD patients who received cardiac

resynchronization therapy had reduced risk of heart transplant or death.

LimitationsSelection bias of patients who received

CRT vs. those who did not.(Bias mitigated by propensity score matching)

Conclusions

Slides by: Ellis Rochelson, M.D.Propensity-score matched across 21 indices, such as

EF, QRS duration, CHD, and HF class

Improved outcome was seen in both CHD and non-CHD patients, as well as those with and without an

independent bradycardia device indication.

CRT should be considered in pediatric/CHD patients with EF <45%, symptomatic heart failure, and

significant electrical dyssynchrony (wide QRS).

Subcutaneous Implantable Cardioverter-Defibrillators in Pediatrics and Congenital Heart Disease: A Pediatric and Congenital Electrophysiology Society Multicenter Review

Johannes C. von Alvensleben, MD; Brynn Dechert, CPNP; David J. Bradley, MD; Frank A. Fish, MD; Jeremy P. Moore, MD, MS; Thomas A. Pilcher, MD; Carolina Escudero, MD, MSC; Scott R. Ceresnak, MD; Sit Yee Kwok, MBCHB; Seshadri Balaji, MBBS,

MRCP, PHD; Peter F. Aziz, MD; John Papagiannis, MD; Daniel Cortez, MD; Jason Garnreiter, MD; Adam Kean, MD, MPH; Michal Schäfer, PHD; Kathryn K. Collins, MD. JACC Clin Electrophysiol. 2020. (Link to article)

Background

What are the short and midterm

outcomes of S-ICD placement in pediatric

and CHD patients?

MethodsResearch QuestionMulticenter, retrospective study conducted

through the Pediatric & Congenital Electrophysiology Society (PACES)

Inclusion criteria:S-ICD implanted (2010-18) at age <21yo, or with CHD (total

n = 115)

Outcomes measured: Shock efficacy • Inappropriate shock • Defibrillation testing • Infection

The subcutaneous implantable

cardioverter-defibrillator (S-ICD) may be a valuable

option for pediatric and CHD patients by avoiding

lead-related complications and intravascular access.

Subcutaneous Implantable Cardioverter-Defibrillators in Pediatrics and Congenital Heart Disease: A

Pediatric and Congenital Electrophysiology Society Multicenter Review

Johannes C. von Alvensleben, MD, et al JACC Clin Electrophysiol. 2020.

Results of S-ICD in pediatrics and congenital heart disease

In the largest report of S-ICD use in pediatrics and CHD (115 patients), the S-ICD was effective at terminating

malignant ventricular arrhythmias(92.5% first shock success)

Limitations• Heterogeneous patient population• Retrospective• Relatively small cohort size

Conclusions

Slides by: Ellis Rochelson, M.D.

Incidence of inappropriate shock was similar to that seen in studies of transvenous ICD systems.

The S-ICD may be an attractive option, particularly in complex congenital heart disease and patients with

limited vascular access.

DFT success rate:97.9% successful first shock conversion

Causes of inappropriate shocksOversensing 9.5%

Atrial arrhythmia rate > shock zone 6%

Median follow-up: 32 months (19 to 52)

Other 0.8%