Catecholaminergic Polymorphic Ventricular Tachycardia in Children

Abstract

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon, potentially lethal, ion channelopathy. Standard therapies have high failure rates and little is known about treatment in children. Newer options such as flecainide and left cardiac sympathetic denervation (LCSD) are not well validated. We sought to define treatment outcomes in children with CPVT. Methods and Results This is a Pediatric and Congenital Electrophysiology Society (PACES) multicenter, retrospective cohort study of CPVT patients diagnosed before 19 years of age. The cohort included 226 patients, including 170 probands and 56 relatives. Symptomatic presentation was reported in 176 (78%). Symptom onset occurred at 10.8 (IQR 6.8–13.2) years with a delay to diagnosis of 0.5 (0–2.6) years. Syncope (p<0.001), cardiac arrest (p<0.001) and treatment failure (p=0.008) occurred more often in probands. Beta-blockers were prescribed in 205 of 211 patients (97%) on medication, and 25% experienced at least one treatment failure event. Implantable cardioverter defibrillators (ICDs) were placed in 121 (54%) and was associated with electrical storm in 22 (18%). Flecainide was used in 24% and LCSD in 8%. Six deaths (3%) occurred during a cumulative follow-up of 788 patient-years. Conclusions This study demonstrates a malignant phenotype and lengthy delay to diagnosis in CPVT. Probands were typically severely affected. Beta-blockers were almost universally initiated; however, treatment failure, non-compliance and sub-therapeutic dosing were often reported. ICDs were common despite numerous device-related complications. Treatment failure was rare in the quarter of patients on flecainide. LCSD was not uncommon although the indication was variable.

Left Cardiac Sympathetic Denervation

“…Several centers have reported their experience with LCSD for LQTS and CPVT. [11][12][13][14][15][16] The rate of side effects in these studies is not as high as the current authors report. However, prevention of arrhythmia is not the only indication for sympathetic denervation.…”

Catecholaminergic Polymorphic Ventricular Tachycardia

“…When dealing with a patient with CPVT, it is important to realize to which of the previously outlined subgroups this patient belongs. The PACES study nicely shows the efficacy and drawbacks of different treatment modalities and the prognosis of patients with classic CPVT, 4 whereas our Dutch cohort is more informative when one is confronted with a patient identified through cascade screening. 5 Our task for the future is to extend and unite all the local observations to study a large CPVT populations that represents all parts of the spectrum.…”

“…11 Third, most observations of arrhythmic event rates have been done in patients with classic CPVT treated with β-blockers 7 and, since the past few years, flecainide. 8,12 A significant proportion of these events, including those in the PACES study, 4 can be attributed to nonadherence. On the basis of intention-to-treat principle, these events associated with nonadherence are also counted as treatment-failures.…”

“…This issue contains the largest analysis on patients with classic CPVT to date. 4 In this Pediatric and Congenital Electrophysiology Society (PACES) multicenter, retrospective cohort study, 226 children with CPVT from 27 pediatric centers were included. The lead investigators are to be applauded for uniting this impressive amount of centers and sampling this number of patients.…”

“…The PACES series, for example, included 2 cases in which CPVT was diagnosed by identifying a pathological RYR2 mutation postmortem. 4 For that matter, this approach may be hazardous in terms of genetic testing, because if no further relatives are available to investigate (or being investigated), there is no way to proof a causal relationship between the identified genetic information and the outcome. Thirty-two patients had a family history suggestive of CPVT because of young relatives who had died suddenly.…”