Medical research

SADS HK medical research

SADS HK medical research report was published in "Hong Kong Medical Journal" in January 2019
Sudden Arrhythmia Death Syndromes (SADS) in Young Victims of Sudden Cardiac Death in Hong Kong Identified by Clinical or Molecular Autopsy of Victims and Clinical Evaluation of Their First Degree Relatives

Brief Reult of SADS-HK Study (Oct 2017)

Under the two-year research project, young cardiac death victims with uncertain causes of death or inheritable cardiomyopathy examined at public mortuaries were chosen for molecular autopsies, while their first-degree relatives were referred for clinical assessment and/or genetic screening. Findings revealed that nearly 30% of the 21 sudden cardiac death victims carried SADS-related genetic variants. Approximately a quarter of sudden cardiac cases saw their victims died in sleep and three of them had a family history of sudden deaths. Around 30% of SADS victims experienced fainting for uncertain reasons when alive but failed to seek medical treatment or actively followed up on their conditions. Dr. Mok Ngai-shing, Specialist in Cardiology and Consultant of Princess Margaret Hospital, who oversees this project, said: “A family history of sudden deaths and fainting for uncertain reasons are vital clues to SADS and those with the conditions should seek early medical intervention to avoid missing the golden hour for diagnosis and treatment.”

According to the study, more than 50% of first-degree relatives subjected to genetic screening were found to carry SADS-related genetic variants , requiring follow-up medical care and preventive therapies. Dr. Chloe Mak, Specialist in Chemical Pathology and Consultant of Princess Margaret Hospital, who is responsible for the genetic screening administered in this project, said: “In this study, there are families with a strong family history of two to three sudden death victims with unknown causes. This causes the surviving family members great distress. This study not only partially confirms the causes of death among the sudden death victims but also facilitates their relatives with the dormant SADS disease to receive early preventive treatment based on their conditions, in order to reduce their risk exposure to sudden death.” Next-generation sequencing (NGS) was applied in the investigation into the victims’ causes of death, which yielded important genetic data and valuable experiences for the first time in local SADS research. The study is considered a major leap forward in genetic studies conducted in Hong Kong and also has established the foundation of a feasibility model on incorporating molecular autopsy in forensic investigation, next-generation sequencing analysis in hereditary cardiac disorders, genetic counseling, clinical assessment and referral.
Written by Dr. Ngai-Shing MOK,
Coordinating Principal Investigator,
Princess Margaret Hospital,Hong Kong


Sudden Cardiac Death (SCD) is one of the most common causes of death and a major and tragic complication of a number of cardiovascular diseases. The death is most often unexpected and has major implications for the surviving family and the community. SCD is defined as a death occurring usually within an hour of the onset of symptoms, due to an underlying cardiac disease. Whereas SCD in the older populations is most frequently due to underlying coronary artery disease and heart failure, SCD in young people (aged < 40 years) is commonly caused by genetic diseases such as inherited arrhythmogenic cardiomyopathies including hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC), and cardiac ion channel diseases including Brugada syndrome (BrS), congenital long QT syndrome (LQTS), short QT syndrome (SQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). They are collectively known as Sudden Arrhythmia Death Syndromes (SADS). While autopsy may reveal the underlying cardiac diseases in young SCD victims, up to 30% of the autopsy fails to identify a cause of death and those SCD victims are referred to as suffering from Sudden Unexplained Death (SUD). Recently we conducted a retrosepective 5-year review of autopsies done in local young SCD vicitms aged 5-40 years and found 25% of them suffered from SUD. It is believed that a significant proportion of SUD is caused by SADS.

As SADS are genetic diseases, two different approaches to identify SADS among young SUD victims have been used. The first approach involves detailed clinical and targeted genetic examination of the surviving relatives of SUD victims. Studies using this approach suggested that SADS may account for approximately 40% of autopsy-negative SUD in young people. However, this approach may not be able to identify subjects with concealed form of SADS due to incomplete penetrance and variable expressivity of the pathological mutations. The second approach is to perform molecular autopsy on SUD victims which involves post-mortem genetic testing for SADS. The landmark study on molecular autopsy by Mayo Clinic showed over one-third of SUD cases hosted a presumably pathogenic mutations of cardiac ion channel diseases. Thus a combined approach using both cardiac evaluation of surviving relatives and molecular autopsy on SUD victims should theoretically give a higher yield on elucidating the underlying causes of SUD. Identification of the underlying cause of SCD has at least two major clinical implications. First, the identification of a cause of death has a major influence in families in coming to terms as to why their child or spouse died suddenly. The diagnosis brings some level of closure in this respect. Second, the identification of a genetic cause of SCD provides the family with a diagnostic test for screening other at-risk family members, in conjunction with clinical screening approach and allows for an early initiation of therapeutic and preventive strategies in affected family members with the ultimate goal to reduce sudden death.

To date, there is scarce local data on the prevalence and types of SADS underlying SCD or SUD in young people. There is little local experience of performing molecular autopsy for SUD victims in Hong Kong. Molecular autopsy is not included as part of medico-legal investigation of underlying cause of SUD by forensic pathologists or within HA hospitals. We recently identified Brugada syndrome in a young SUD victim in Princess Margaret Hospital through molecular autopsy and clinical and genetic evaluation of his first-degree relatives. The present study is first of its kind in Hong Kong and it will provide important data on the prevalence and types of SADS among young SCD victims in local population.

Protocol Synopics

Protocol Title: Sudden Arrhythmia Death Syndromes in Young Victims of Sudden Cardiac Death in Hong Kong Identified by Clinical or Molecular Autopsy of Victims and Clinical Evaluation of Their First Degree Relatives

Study Location: Hong Kong

No. of Study Sites: 1

Study Design:
This is a prospective study. Young sudden cardiac death (SCD) victims (age 5-40 years old) will be identified and recruited into study by forensic pathologists after finding of either an inheritable arrhythmogenic cardiomyopathy or no structural heart disease on autopsy and a negative toxicology screening. Their first-degree relatives will be referred by forensic pathologists to study centre for genetic counseling and recruitment into the study

Primary Objective: To determine the prevalence and types of Sudden Arrhythmia Death Syndromes (SADS) as the underlying causes of SCD among local young victims through clinical and molecular autopsy of SCD victims and clinical and genetic evaluation of their first degree relatives

Secondary Objectives:
  1. To study the genetic basis of SADS among young SCD victims in Hong Kong
  2. To study the diagnostic yields of various approaches in identifying SADS in sudden unexplained death (SUD) families using (A) molecular autopsy in young SUD victims using the next generation sequencing techniques; (B) clinical evaluation of the first-degree relatives of young SUD victims, and (C) combining molecular autopsy in young SUD victims and clinical and targeted genetic evaluation of their first-degree relatives
No. of Subjects: 40 SCD victims and approximately 160 first degree relatives

Recruitment Period: 2 years

Follow-up Period: up to 6 months

Follow-up: Follow-up clinic visits at 3 months and if indicated at 6 months

Primary Endpoint:
Prevalence and types of SADS among the young SCD families in the study population identified by clinical and molecular autopsy of SCD victims and/ clinical and targeted genetic evaluation of their first-degree relatives

Secondary Endpoints:
  1. Genotypes of SADS victims in the study population
  2. Number of young SUD families identified with SADS by molecular autopsy
  3. Number of young SUD families identified with SADS by clinical evaluation of first-degree relatives
  4. Number of young SUD families identified with SADS by a combined approach
  5. Pattern of inheritance of SADS and their clinical and genetic characteristics among young SUD families

International Medical Research

Other International Medical Research and Articles on SADS/ Sudden Cardiac Death: