A novel RYR2 variant associated with catecholaminergic polymorphic ventricular tachycardia requiring extracorporeal cardiopulmonary resuscitation and complicated by cervical vascular injury: a case report

Technical Summary

Problem Statement
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome often triggered by adrenergic stress, which can lead to sudden cardiac arrest. A critical diagnostic challenge arises in the post-resuscitation setting, where serum troponin elevation and transient ventricular dysfunction frequently mimic fulminant myocarditis, potentially obscuring the underlying genetic etiology. Furthermore, the management of refractory cardiac arrest in pediatric CPVT patients often necessitates extracorporeal cardiopulmonary resuscitation (ECPR) via cervical cannulation. This approach carries significant risks, including vascular thrombosis and bleeding, yet pediatric experience with ECPR in CPVT remains limited to isolated case reports. There is a specific need to document cases involving novel genetic variants and complex post-decannulation vascular complications to inform clinical decision-making.

Methodology
This study presents a detailed case report of a 9-year-old boy who experienced a startle-triggered out-of-hospital cardiac arrest. The patient underwent continuous cardiopulmonary resuscitation (CPR) followed by the establishment of right cervical veno-arterial extracorporeal membrane oxygenation (VA-ECMO) after a resuscitation-to-flow interval of approximately 60 minutes. The clinical team conducted serial investigations, including echocardiography, continuous cardiac monitoring, and whole-exome sequencing (WES) of DNA from a buccal swab. Genetic variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria and cross-referenced with ClinVar and population databases (gnomAD). The management strategy involved standard ECMO support, treatment for suspected myocarditis (including immunoglobulin), and subsequent antiarrhythmic therapy once the diagnosis was clarified. The patient's course was monitored through decannulation, surgical intervention for vascular complications, and a 41-day hospitalization, with follow-up assessments at discharge and one month post-discharge.

Key Contributions and Results

• Clinical Presentation and Diagnosis: The patient presented with recurrent polymorphic ventricular tachycardia and cardiac arrest triggered by a sudden fright, preceded by two syncopal episodes. Despite initial findings suggestive of fulminant myocarditis (troponin I peak of 11.78 µg/L and LVEF dropping to 33%), WES identified a novel heterozygous RYR2 variant, c.11836G>A (p.Gly3946Ser). This variant was classified as pathogenic, absent from population databases, and concordant with the CPVT phenotype, confirming the diagnosis of RYR2-associated CPVT.
• ECPR and Recovery: The patient was supported on VA-ECMO for 6 days. Following decannulation, the left ventricular ejection fraction recovered significantly, improving from a nadir of 33% to 67% at discharge. The patient was discharged in sinus rhythm with no focal neurological deficits, despite brain MRI findings of hypoxic-ischemic injury in the basal ganglia.
• Vascular Complications: A rare and complex complication occurred post-decannulation involving the right internal jugular vein (RIJV). While anticoagulation was initiated for thrombosis, the patient developed an enlarging cervical hematoma with active extravasation and tracheal compression. This required urgent surgical evacuation, carotid repair, jugular thrombectomy, and venorrhaphy. The RIJV ultimately remained occluded, while the carotid artery remained patent.
• Therapeutic Management: Post-diagnosis management included non-selective beta-blockade (propranolol), titrated to 0.8 mg/kg/day due to bradycardia, and aspirin for carotid patency.

Significance and Claims
The authors assert that this case highlights the necessity of reconsidering CPVT in children presenting with adrenergic cardiac arrest, even when post-arrest biomarkers and imaging suggest myocarditis. The identification of the novel RYR2 variant, supported by ACMG/AMP criteria and clinical concordance, underscores the value of genetic testing in refining the diagnosis and guiding specific antiadrenergic therapy.

Regarding ECPR, the paper posits that while it can serve as a temporary rescue strategy for refractory arrest, the favorable neurological outcome in this specific case does not validate prolonged CPR-to-flow intervals or prove the efficacy of ECPR in CPVT generally, given the observational nature of the data.

Finally, the report emphasizes the competing risks of thrombosis and bleeding following cervical ECMO cannulation. The coexistence of progressive venous thrombosis and active arterial bleeding necessitates urgent vascular imaging and multidisciplinary intervention rather than anticoagulation alone. The authors conclude that early recognition of CPVT, appropriate genetic evaluation, and vigilant post-decannulation vascular surveillance are critical for managing these complex pediatric cases.