Genetic testing postmortem can give families answers and determine whether life-long follow up is needed.
All sudden cardiac death victims with inconclusive autopsy findings should be genetically tested for concealed cardiomyopathy, Australian researchers say.
The results would allow families with a genetic vulnerability to take preventative action, possibly saving lives. It would also provide much-needed reassurance to those not at risk.
A study by researchers at the Centenary Institute in Sydney has found that in young people who died from sudden cardiac death, but had inconclusive autopsies, 22% had a genetic variant that would account for their death. And 70% of these variants were in genes implicated in cardiomyopathy.
Speaking at the annual scientific meeting of the Cardiac Society of Australia and New Zealand in the Gold Coast last month, cardiologist Dr Julia Isbister said that current guidelines only recommended genetic testing for cardiomyopathy if the autopsy found signs of cardiomyopathy.
But there was growing evidence that life-threatening arrhythmia could occur before any structural changes in the hearts of people with inherited cardiomyopathy, known as concealed cardiomyopathy, Dr Isbister said.
Dr Isbister told TMR that genes implicated in cardiomyopathies should be included in routine testing of anyone who died of a sudden cardiac event, as well as genes implicated in arrhythmia syndromes which are already tested where no cause of death is found at autopsy.
“Based on this work, we believe that concealed cardiomyopathy should be considered in all autopsy-indeterminate sudden cardiac death cases,” she told TMR.
The study, led by Dr Isbister and Professor Chris Semsarian, included 91 people who died from sudden cardiac death.
All cases had comprehensive autopsies which showed no structural changes or definitive cause of death.
The researchers divided those individuals into one group with completely normal hearts and another group of people who had very subtle sub-diagnostic changes.
After genetic testing, they found that 20 people carried genetic variants that would account for their death. Fourteen of the variants were in cardiomyopathy-associated genes, that would not routinely be tested according to current guidelines.
“Identifying concealed cardiomyopathy meant that we found the cause of the young person’s death in 14 more families than we would have in this cohort if we hadn’t looked at cardiomyopathy genes,” Dr Isbister said.
Identifying the genetic cause of disease in the sudden death victim meant that relatives could be tested for the genetic change to see if they are at risk of the same condition that killed their loved one.
“Family members who carry the genetic variant can be screened and closely followed, while those who do not can be released from follow-up.
“Identifying cases of concealed cardiomyopathy in this study allowed for targeted care of 20 relatives who carry the variant and importantly, release of 47 relatives who do not carry the genetic cause of disease from follow-up.
“If they don’t carry the variant, then that’s one of the best results we can give people because we can reassure them that they are not at risk and don’t need lifelong cardiology follow-up. And that has a big impact on families.”
They also found that almost half of the relatives who carried the variant in cardiomyopathy genes had clinical signs of cardiomyopathy when they were assessed.
Finding a genetic cause of sudden cardiac death had a huge impact on families, she said.
“When a family comes in because their child has died suddenly either overnight in bed or on the sports field, they almost universally ask two questions: why did it happen, and how can we stop this happening to others in my family?
“If we can find a cause in the deceased person, it gives the family a degree of closure and psychological relief, and it guides how we then care for the surviving relatives.”
One study found that 8% of people who died from sudden cardiac death had previously seen a doctor for fainting or seizure.
Dr Isbister said GPs played a key role in referring young people to cardiologists if they had concerns.
“GPs are the lynchpin, and they know families. If they have a gut feeling about a child who is blacking out, they have the best chance of flagging a family they’re worried about.”
Any family who lost a loved one to sudden cardiac death should be referred to a specialist sudden cardiac death unit, Dr Isbister said.
“Families where an autopsy-inconclusive sudden cardiac death has occurred should be assessed and cared for by a specialised multidisciplinary genetic heart disease team to undertake combined clinical and genetic evaluation.”
A 2016 NEJM study led by Chris Semsarian found that in 40% of young people who died suddenly from non-traumatic deaths, no cause was found at autopsy. Adding genetic testing to autopsy investigation substantially increased the identification of a possible cause of sudden cardiac death.
Dr Isbister said there had historically been an assumption that if a patient died from conditions such as like hypertrophic cardiomyopathy or arrhythmogenic cardiomyopathy, there would be evidence at autopsy.
But that approach risked missing concealed cardiomyopathy in family members of the deceased, she said.
Genetic testing usually only included those genes implicated in inherited arrhythmia syndromes, such as long QT syndrome.
Dr Isbister said genetic testing and autopsies were both useful tests, but that these results suggest that autopsy findings should not dictate genetic testing.
“Autopsies reports aren’t black and white, and attributing causality to a finding at autopsy can be difficult.”
Abnormalities on autopsies such as fibrosis or fatty infiltration of the myocardium lay on a spectrum from normal to pathological, with a huge grey zone in between, Dr Isbister said.
