|Year : 2022 | Volume
| Issue : 1 | Page : 3-8
Clinical characteristics, outcomes, and genetic findings of patients with catecholaminergic polymorphic ventricular tachycardia in Hong Kong: A systematic review
Jeremy Man Ho Hui1, Yan Hiu Athena Lee1, Kyle Hui1, Jiandong Zhou2, Danish Iltaf Satti1, Cheuk To Chung1, Danny Radford3, Ishan Lakhani1, Amir Hossein Behnoush4, Leonardo Roever5, Khalid Bin Waleed6, Sharen Lee1, Gary Tse7
1 International Health Informatics Study Network, Cardiovascular Analytics Group, Hong Kong, China-UK Collaboration, China
2 Nuffield Department of Medicine, University of Oxford, Oxford, England, United Kingdom
3 International Health Informatics Study Network, Cardiovascular Analytics Group, Hong Kong, China-UK Collaboration; Kent and Medway Medical School, Canterbury, United Kingdom
4 International Health Informatics Study Network, Cardiovascular Analytics Group, Hong Kong, China-UK Collaboration; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
5 Department of Clinical Research, Federal University of Uberlândia, Uberlândia, Brazil
6 International Health Informatics Study Network, Cardiovascular Analytics Group, Hong Kong, China-UK Collaboration; Department of Cardiology, St George's Hospital University of London, London, United Kingdom
7 Kent and Medway Medical School, Canterbury, United Kingdom; Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
|Date of Submission||26-Jan-2022|
|Date of Decision||30-Mar-2022|
|Date of Acceptance||07-Apr-2022|
|Date of Web Publication||30-Jun-2022|
Dr. Sharen Lee
International Health Informatics Study Network, Cardiovascular Analytics Group, Hong Kong
Source of Support: None, Conflict of Interest: None
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare cardiac ion channelopathy. This was the first systematic review of published works on the clinical characteristics, outcomes, and genetic findings of patients with CPVT from Hong Kong. PubMed and Embase were searched electronically from their inception until February 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used to critically appraise included studies. Studies written in English describing at least one patient with CPVT were included. Studies describing overlapping CPVT patients from previous reports were excluded. Two studies describing 17 patients with CPVT were included. All included studies were rated of acceptable quality. The largest case series evaluated 16 CPVT patients with a mean presentation age of 11 ± 4 years. Of these, 15 patients (93.8%) were symptomatic at initial presentation. Ten patients presented with both premature ventricular complexes (PVCs) and ventricular tachycardia/ventricular fibrillation (VT/VF), whereas one had PVCs without VT/VF. Among the 14 patients (87.5%) who underwent genetic testing, eight (57.1%) tested positive for the ryanodine receptor 2 (RyR2) gene. Over a mean follow-up duration of 116 ± 36 months, six patients (37.5%) had incident VT/VF. In a 5-year review of autopsy data retrieved from public mortuaries for 289 sudden cardiac death patients, one CPVT patient (0.03%) was identified. All patients with CPVT in Hong Kong presented at or below 19 years old, of whom a majority were initially symptomatic or had incident VT/VF events. Novel genetic variants in the RyR2 gene not reported beyond our locality were identified.
Keywords: Catecholaminergic polymorphic ventricular tachycardia, ryanodine receptor 2, sudden cardiac death
|How to cite this article:|
Ho Hui JM, Athena Lee YH, Hui K, Zhou J, Satti DI, Chung CT, Radford D, Lakhani I, Behnoush AH, Roever L, Waleed KB, Lee S, Tse G. Clinical characteristics, outcomes, and genetic findings of patients with catecholaminergic polymorphic ventricular tachycardia in Hong Kong: A systematic review. Ann Clin Cardiol 2022;4:3-8
|How to cite this URL:|
Ho Hui JM, Athena Lee YH, Hui K, Zhou J, Satti DI, Chung CT, Radford D, Lakhani I, Behnoush AH, Roever L, Waleed KB, Lee S, Tse G. Clinical characteristics, outcomes, and genetic findings of patients with catecholaminergic polymorphic ventricular tachycardia in Hong Kong: A systematic review. Ann Clin Cardiol [serial online] 2022 [cited 2022 Sep 30];4:3-8. Available from: http://www.onlineacc.org/text.asp?2022/4/1/3/349336
| Introduction|| |
Cardiac ion channelopathies increase a patient's susceptibility to developing spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF) and sudden cardiac death (SCD).,,,,, When compared to Brugada syndrome (BrS) or long QT syndrome (LQTS), catecholaminergic polymorphic VT (CPVT) is less prevalent in Asia., For example, in Hong Kong, the most prevalent cardiac ion channelopathy is BrS,, followed by LQTS, and CPVT. No cases of short QT syndrome were identified.
CPVT is typically caused by mutations in either the ryanodine receptor 2 (RyR2) or the calsequestrin 2 genes.,, It is usually precipitated by exercise or distress, resulting in bidirectional VT in the first two decades of life. Globally, population-based data on CPVT have mainly come from Western countries. The largest registry reported the characteristics of 237 patients., In a multi-national study from France, outcomes in 101 patients were reported, complementing a smaller registry by the same group. By contrast, data from Asia have mainly come from Japan, including a multi-centre registry of 78 patients, national study of 50 probands, and another study of 29 patients. Two studies from China have reported on six patients and 12 patients. This is the first systematic review of published works on the clinical characteristics, outcomes, and genetic findings of patients with CPVT from Hong Kong.
| Methods|| |
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement.
PubMed and Embase were searched electronically to identify all studies describing patients with CPVT from all regions in Hong Kong without limitations. All databases were searched from their inception until February 2022. The search algorithm used was (“catecholaminergic polymorphic ventricular tachycardia” OR “CPVT”) AND “Hong Kong.” To maximize sensitivity, all search terms were combined with Boolean operators and searched as both keywords and MeSH terms. Reference lists of the included studies were manually searched to retrieve relevant studies.
At the title/abstract level, studies were first screened by at least two reviewers (JMHH, YHAL, GT). All identified studies were systematically assessed according to the inclusion and exclusion criteria. Any discrepancies were resolved by an independent reviewer (KH).
We included studies with data for at least one patient with CPVT. We considered only studies written in English. We excluded studies only describing overlapping CPVT patients from previous reports. Conference publications and studies without a description of the original patient with CPVT were excluded.
Data extraction – quality assessment
All the included studies were critically appraised by two independent reviewers (JMHH, YHAL) using The Joanna Briggs Institute Critical Appraisal Checklist. Predefined information about the included patients was extracted from the included studies by at least two independent reviewers (JMHH, YHAL, GT). Age, sex, family history of CPVT/SCD, symptoms, outcomes, and genetic findings were extracted.
| Results|| |
The systematic search identified eight non-duplicated studies. Full-texts of six studies were retrieved and assessed for inclusion eligibility, and two articles were included in this review [Figure 1]., All studies were assessed using The Joanna Briggs Institute Critical Appraisal Checklist. All included articles were deemed to be of acceptable quality for inclusion.
Clinical characteristics and outcomes of included patients
A total of 17 patients were included. The largest case series studied 16 patients (mean presentation age = 11 ± 4 years old; female = 50%) [Table 1]. Twelve patients fulfilled at least two criteria and four fulfilled one criterion of the 2013 Heart Rhythm Society (HRS)/European Heart Rhythm Association/Asia-Pacific HRS expert consensus statement [Table 2]. Fifteen patients (93.8%) were symptomatic at initial presentation to the hospitals. Ten patients had both premature ventricular complexes (PVCs) and VT/VF, whereas one had PVCs without VT/VF. The mean delay between initial presentation and diagnosis was 8 ± 10 months. All patients were prescribed beta-blockers (nadolol: n = 12, metoprolol: n = 5, atolol: n = 3, propranolol: n = 3, sotalol: n = 2), three received amiodarone, and two received verapamil. Eight patients had sympathectomy, three had implantable cardioverter defibrillators, and one had ablation. Over a mean follow-up duration of 116 ± 36 months, six patients (37.5%) had incident VT/VF.
|Table 2: Details on the diagnostic criteria met for individual catecholaminergic polymorphic ventricular tachycardia patients|
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In a 5-year review of autopsy data retrieved from public mortuaries for 289 SCD patients, one CPVT patient (0.03%) was identified. He had a history of syncope, with negative autopsy and toxicology screening results.
In the case series of 16 patients, genetic tests were performed in 14 (87.5%) [Table 3], of whom eight (57.1%) tested positive for gene mutations. All mutations involved the RyR2 gene [Table 4]. These included c.14848G>A, c.12475C>A, c.7420A>G, c.11836G>A, c.14159T>C (RCV000182842.2), c.10046C>T,, c.7202G>A and c.14861C>G. In the review of autopsy data, another RyR2 variant, c.1509C>A, was identified.
|Table 4: Genetic testing in individual catecholaminergic polymorphic ventricular tachycardia patients|
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| Discussion|| |
This is the first systematic review of published works on the clinical characteristics, outcomes, and genetic findings of patients with CPVT from Hong Kong. All patients presented at or below 19 years old, of whom a majority were initially symptomatic or had incident VT/VF events. Novel genetic variants in the RyR2 gene not reported beyond our locality were identified.
SCD is a problem of global importance, with congenital and acquired causes.,,, Of the congenital cardiac ion channelopathies, CPVT is characterized by exercise-induced bidirectional VT. When treatment is delayed, CPVT patients suffer from exceedingly high mortality rates. Several studies have examined the occurrence of adverse outcomes in CPVT cohorts such as syncope and SCD.,,, Patients who were initially symptomatic or younger at diagnosis, as seen in this study, have significantly higher risks of mortality and cardiac events. International registry studies on European and North American patients have reported a malignant arrhythmic phenotype of CPVT associated with significant delays between initial presentation and diagnosis of around six months., Similar findings were reported by our team in the largest CPVT study conducted in the region.
This study identified nine genetic variants. Of these, c.14848G>A, c.12475C>A, c.7420A>G, c.11836G>A, c.14159T>C (RCV000182842.2), c.10046C>T,, and c.7202G>A have been reported elsewhere. By contrast, c.14861C>G and c.1509C>A are novel RyR2 variants that give rise to changes in the A4954G and D503E amino acids, respectively. These mutations affect the cytoplasmic domain of the RyR2 gene and are expected to produce abnormalities in calcium handling, possible diastolic calcium leak, and triggered arrhythmogenesis. However, as RyR2 mutations can be associated with reduced conduction velocity in addition to disrupted calcium homeostasis,,, functional studies are needed to determine the precise mechanisms by which these structural changes can lead to the generation of electrophysiological substrate.
Several limitations should be noted for the present study. Firstly, as a systematic review, this study is inherently subjected to sampling bias. Nonetheless, included studies were assessed using standardized tools. Secondly, hospitals or clinics were not contacted for patients with CPVT. Finally, as some cases had no available data apart from the published descriptions, it was not possible to perform a meta-analysis.
| Conclusion|| |
All patients with CPVT in Hong Kong presented at or below 19 years old, of whom a majority were initially symptomatic or had incident VT/VF events. Novel genetic variants in the RyR2 gene not reported beyond our locality were identified. A national registry linking Hong Kong and mainland China as well as international cooperation are encouraged to improve risk stratification of this rare but devastating disease.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]