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Calcium Release Deficiency Syndrome: A New Inherited Arrhythmia Syndrome
Dania Kallas1, Jason D Roberts2, Shubhayan Sanatani3
1Department of Pediatrics, Division of Cardiology, BC Children's Hospital, Heart Center, 4480 Oak Street, Vancouver, British Columbia V6H 3V4, Canada. Electronic address: https://twitter.com/Daniakallas2.
Abstract:
Calcium release deficiency syndrome (CRDS) is a newly described form of inherited arrhythmia caused by damaging loss-of-function variants in the cardiac ryanodine receptor (RyR2). Unlike the prototypical RyR2 gain-of-function channelopathy, known as catecholaminergic polymorphic ventricular tachycardia, patients with CRDS are predisposed to sudden death usually in the absence of any electrical abnormalities at rest or during stress electrocardiography. This makes diagnosis incredibly challenging, however, an invasive electrophysiologic test appears to be effective in unmasking the phenotype, called the long-burst, long-pause, short-coupled ventricular extra-stimulus protocol. Optimal therapies for patients with CRDS remain unestablished, although flecainide appears to be a promising candidate drug.
Insights
Calcium release deficiency syndrome (CRDS) is a rare inherited arrhythmia linked to cardiac ryanodine receptor (RyR2) variants. Diagnosis is challenging due to normal resting ECGs, but an invasive electrophysiologic test may reveal the condition.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Calcium release deficiency syndrome (CRDS) is an inherited arrhythmia.
- It is caused by loss-of-function variants in the cardiac ryanodine receptor (RyR2).
- CRDS predisposes patients to sudden death, often without resting or stress ECG abnormalities.
Purpose of the Study:
- To describe Calcium release deficiency syndrome (CRDS).
- To highlight diagnostic challenges and potential diagnostic methods.
- To discuss potential therapeutic strategies for CRDS.
Main Methods:
- Review of existing literature on CRDS and RyR2 variants.
- Analysis of diagnostic utility of invasive electrophysiologic testing.
- Evaluation of potential pharmacological interventions.
Main Results:
- CRDS is a distinct entity from catecholaminergic polymorphic ventricular tachycardia.
- An invasive electrophysiologic test (long-burst, long-pause, short-coupled ventricular extra-stimulus protocol) can unmask the CRDS phenotype.
- Flecainide shows promise as a potential therapy for CRDS.
Conclusions:
- CRDS is a challenging diagnosis due to its often-normal baseline ECG.
- Invasive electrophysiology is crucial for diagnosing CRDS.
- Flecainide represents a promising therapeutic avenue for managing CRDS.
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