Congenital Heart And Pediatric Electrophysiology

Preventing Arrhythmic Death in Patients With Tetralogy of Fallot: JACC Review Topic of the Week

Preventing Arrhythmic Death in Patients With Tetralogy of Fallot: JACC Review Topic of the Week. Cohen MI, Khairy P, Zeppenfeld K, Van Hare GF, Lakkireddy DR, Triedman JK. J Am Coll Cardiol. 2021 Feb 16;77(6):761-771. doi: 10.1016/j.jacc.2020.12.021. PMID: 33573746 Review.   Take Home Points: Despite improvement in the overall survival of patients with tetralogy of Fallot (TOF), the long-term risk of arrhythmias and sudden cardiac death (SCD) persists. Risk stratification should be based on non-invasive markers and judicious use of programmed ventricular stimulation in selected patients. PVR timing strategies are needed to identify the ideal time for the RV to best remodel and reduce late VT and SCD. Most ventricular arrhythmias after TOF repair involve monomorphic re-entrant ventricular tachycardia, although some involve slow-conducting pathways in the right ventricle amenable to catheter-based ablation. LV dysfunction is a powerful predictor of outcomes after TOF repair with or without pulmonary valve replacement. Ablation failure is likely due to a combination of hypertrophied myocardium and overlying prosthetic material after PVR, preventing effective radiofrequency energy delivery. Inappropriate ICD shocks, most often related to SVT, have been observed in 20% to 42% of adult TOF ICD recipients     Comment from Dr. Khyati Pandya (Augusta, GA), section editor of Congenital Electrophysiology Journal Watch: TOF remains one of the main adult congenital heart diseases carrying the risk of late SCD. Ventricular tachycardia and sudden cardiac death in patients with Tetralogy of Fallot can occur decades following surgical repair. The pathogenesis of VT and SCD is multifactorial.     A risk score distinguished between low risk, intermediate, and high-risk patients with ICDs with an annualized rate of appropriate ICD shocks of 0%, 3.8%, and 17.5%, respectively.     The electrical and mechanical factors from the left and right ventricle, contributing to sudden cardiac death are well illustrated in the picture above.   In contemporary TOF, isthmus 3 - between the pulmonary annulus and the upper margin of the VSD patch - may be the most important isthmus. However, ablation at this isthmus is often unsuccessful, likely due to a combination of hypertrophied myocardium and overlying prosthetic material after PVR, preventing effective radiofrequency energy delivery and achievement of complete conduction block.   As pointed out by the authors, although ICDs have proven to be quite reliable in sensing and terminating VT, inappropriate ICD shocks, most often related to SVT, have been observed in 20% to 42% of adult TOF ICD recipients.   While the complications associated with an endocardial lead can be overcome by implanting a subcutaneous ICD, not all patients qualify for the same in the presence of a wide QRS related to right bundle branch block. Besides, a subcutaneous ICD is not an option for patients who require antibradycardia or anti-tachycardia pacing.     A larger study with long term follow up is required to determine if an EP study comprising mapping and preventive ablation before or during PVR decreases the incidence of ventricular tachycardia.   As pointed out by the authors, patients with TOF constitute the largest subgroup of ICD recipients in adults with CHD. Although the decision for secondary prevention ICD implant is often clear cut in survivors of cardiac arrest or spontaneous sustained VT, current guidelines and consensus statements recommend primary prevention ICD implantation in adults with TOF and multiple risk factors for SCD including LV dysfunction, nonsustained VT, QRS duration >180 ms, inducible sustained VT on programmed stimulation, extensive RV scarring, or diastolic dysfunction. ICD implantation should also be considered in patients with syncope of unknown etiology with inducible ventricular arrhythmia at EPS or in those in whom there is a high clinical suspicion of VT. Other studies using a similar score adjusted model have been able to distinguish between low and intermediate/high-risk, but not between intermediate and high-risk subgroups. Monomorphic VT, depicted in the image below, comprises nearly 80% of all appropriate ICD therapies in patients with TOF with only 18% having polymorphic VT or ventricular fibrillation. Although ICDs have proven to be quite reliable in sensing and terminating VT they are not without complications. Inappropriate ICD shocks, most often related to SVT, have been observed in 20% to 42% of adult TOF ICD recipients.     Electrocardiogram demonstrating monomorphic ventricular tachycardia with left bundle branch block and inferior axis; the qR pattern in V1 is consistent with a right ventricular outflow tract focus.   Acute procedural complication rates for ICD implantation in patients with repaired CHD approximate 2% and are predominantly lead related. Given the high incidence of adverse events associated with endocardial ICD lead systems, the subcutaneous ICD has emerged as an alternative option for selected patients who do not require antibradycardia or antitachycardia pacing.   As depicted elsewhere in literature, the authors have reiterated the cause of SCD to be VT for the majority of patients with tetralogy of Fallot, and that the anatomical and physiological myocardial substrates are variable and evolve over time. RV adaptation and remodeling in response to chronic volume overload from PR remains poorly understood. Although much has been learned regarding RV–LV interaction and the important deleterious effect on LV function, its arrhythmogenic potential remains unknown. LV dysfunction has repeatedly been validated to be a strong predictor of SCD. However, a limited understanding of RV adaptation has challenged our ability to select candidates and appropriate timing for PVR. Also, whether PVR may curtail further maladaptive RV and LV behaviors that could potentially impact late VT remains to be discerned.   Electrocardiogram demonstrating sinus rhythm with right bundle branch block. QRS fragmentation in V4 with multiple notched R waves (arrow).   FIGURE 2 Repaired Tetralogy of Fallot With Right Bundle Branch Block and QRS Fragmentation   The authors have highlighted the importance of following certain unconventional markers of sudden cardiac death in this patient subgroup such as QRS fragmentation (fig 2). They have also referenced a study depicting that an RV mass/volume ratio > 0.45 g/ml is a more important long-term risk predictor for death or VT than right ventricular end-diastolic indexed volume (RVEDVi).   Advances in knowledge related to the risk factors for VT and their interaction in TOF patients, as well as an understanding of the anatomical basis for macroreentrant VT have led to sophisticated models of risk to guide decision making. However, long term studies are needed to determine if these strategies will also lead to reduction of morbidity and mortality. Future studies should rely on multicenter collaboration to generate an aggregate risk score with the greatest discriminative ability for sudden cardiac death in patients with tetralogy of Fallot. Until then, risk stratification with the aforementioned EP and imaging criteria, combined with a diligent record of progression of patient symptomatology, maybe used to guide surgical and antiarrhythmic therapy with appropriate utilization of invasive EP and ICD implantation.   

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Identification of patients at risk of sudden cardiac death in congenital heart disease. The prospective study on implantable cardIoverter defibrillator therapy and sudden cardiac death in adults with congenital heart disease: Prevention-ACHD

Identification of patients at risk of sudden cardiac death in congenital heart disease. The prospective study on implantable cardIoverter defibrillator therapy and sudden cardiac death in adults with congenital heart disease: Prevention-ACHD. Vehmeijer JT, Koyak Z, Leerink JM, Zwinderman AH, Harris L, Peinado R, Oechslin EN, Robbers-Visser D, Groenink M, Boekholdt SM, de Winter RJ, Oliver JM, Bouma BJ, Budts W, Van Gelder IC, Mulder BJM, de Groot JR. Heart Rhythm. 2021 Jan 16:S1547-5271(21)00029-1. doi: 10.1016/j.hrthm.2021.01.009. Online ahead of print. PMID: 33465514   Take Home Points: The PREVENTION-ACHD risk model appears useful for identification of VT/VF or SCD risk among a heterogenous group of adults with congenital heart disease. Prospective validation suggests a sensitivity of 0.5 and specificity of 0.93 for prediction of VT/VF or SCD The proposed risk model outperforms existing classification schemes and may be useful for clinical practice and future guideline-based ICD indications.   Commentary by Dr. Jeremy Moore (Los Angeles) Congenital and Pediatric Cardiac EP section editor: This recent manuscript out of Amsterdam serves as prospective validation work to a previously proposed risk-stratification model from 2019 that is applicable to a broad group of adults with congenital heart disease (ACHD). The investigators had originally conducted a case-control study across several institutions involving the CONCOR (11,535 patients) registry, the Toronto Congenital Cardiac Centre for Adults, and the University Hospital Leuven (refer to Koyak et al. Circulation 2012) in order to identify predictors of sudden cardiac death (SCD) across multiple forms of ACHD. The proposed risk factors were subsequently externally validated in a retrospective group of 3,197 patients followed at the La Paz University Hospital in Spain that was published later that year (Gallego et al. Am J Cardiol 2012). Using the baseline hazards derived from the large CONCOR registry, the authors were able to calculate annual rates of SCD using the results of the original multicenter case-control study. The predictors were modified slightly, as QRS duration and QT dispersion were dichotomized (QRSd>120 ms and QTd>70 ms) thus allowing for the inclusion of two additional risk factors in the model, specifically a history of coronary artery disease and clinical heart failure (refer to Vehmeijer et al. Neth Heart J 2019). The proposed risk model that was first described in 2019 is shown below.     The present manuscript examines the performance of the previously proposed model in a prospective validation cohort derived from 783 consecutive ACHD followed for 2 years at the Amsterdam University beginning in 2019. Patients were grouped as high (>3%) or low (<3%) annual risk for SCD based on the risk model. The primary outcome of this study was the combined endpoint of SCD or VT/VF, including appropriate ICD therapy. The secondary outcome was SCD alone. The authors found that actual KM estimates for a primary outcome after 2 years was 7% for high risk patients vs 0.6% for low risk patients (HR 12.5, 95%CI 3.1-50.9; p<0.001). Similarly for the secondary outcome of SCD alone, KM estimates were 3.5% vs 0.3% (HR 12.4, 95%CI 1.8-88.1; p=0.01).   More importantly, the PREVENTION-ACHD risk score showed an overall sensitivity of 0.5 and specificity of 0.93 for SCD or VT/VF at 2 years and a sensitivity of 0.5 and specificity of 0.92 for SCD alone. This compared favorably with the PACES/HRS Expert Consensus Statement using the patient population, which showed a sensitivity of 0.25 and specificity of 0.98 for SCD or VT/VF at 2 years and a sensitivity of 0.0 and specificity of 0.98 for SCD alone.   Conclusions This present work attempts to improve risk stratification for ACHD and as such, improves upon the existing classification schemes. Although patients considered to be high risk (i.e. annual risk of SCD or VT/VF >3%) were only identified with a sensitivity of 50% in the present cohort, this represents a significant improvement over the PACES/HRS Expert Consensus Statement. Meanwhile, this still equates to “missing” 50% of high-risk cases. Further work is still needed in order to accurately identify patients in whom primary prevention ICD placement is needed.    

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