Sudden Cardiac Death and SADS

The most useful figures come from a prospective, population-based study of everyone aged 1 to 35 years who died suddenly in Australia and New Zealand between 2010 and 2012 (490 deaths).^[1]

Incidence: 1.3 per 100,000 per year across ages 1 to 35. Incidence rose with age and was highest at 31 to 35 years (3.2 per 100,000 per year), but unexplained death peaked earlier, at 16 to 20 years (0.8 per 100,000 per year). 72% of all cases were male.^[1]

Findings at autopsy in that cohort:

Finding at autopsy	Proportion
Unexplained (structurally normal heart)	40%
Coronary artery disease	24%
Inherited cardiomyopathies	16%
All other causes combined	Remainder

Unexplained death was the single commonest finding in every age band except 31 to 35 years, where coronary disease overtook it.^[1] Age matters when interpreting these proportions: above 35 the balance shifts further towards coronary disease, so this table should not be read as the distribution for sudden death at all ages.

The terms overlap in everyday use and are worth separating.

Term	What it means
Sudden cardiac death (SCD)	Sudden death presumed to be of cardiac cause, whether or not a structural abnormality is found.
Sudden arrhythmic death syndrome (SADS)	Sudden death with a structurally normal heart at expert autopsy, and negative histology and toxicology.[4]
Sudden unexplained death (SUD)	Used broadly for a sudden death with no cause found; often used interchangeably with SADS, though some reserve SUD for cases where the autopsy was not specialist.
Sudden infant death syndrome (SIDS)	Sudden unexplained death under 1 year of age. A minority carry cardiac ion channel variants, so the family history still matters.

The label is one of exclusion, and its reliability tracks the quality of the autopsy. A negative report from a general autopsy is weaker evidence than a negative report from a cardiac pathologist working to a structured protocol.^[4]

This section describes the route in England and Wales. Scotland (Procurator Fiscal) and Northern Ireland differ.

1. Notification. Under the Notification of Deaths Regulations 2019, a registered medical practitioner must notify the senior coroner in defined circumstances, including where the cause of death is unknown after reasonable efforts, or where the death is suspected to be unnatural.^[6] A sudden death in a young person with no known cardiac disease falls squarely within this.

2. Post-mortem examination. An examination directed by the coroner proceeds under the coroner's authority as part of the investigation, rather than by family consent. This is a different route from a hospital post-mortem, which is a consented examination. Families often do not know this, and it is worth explaining early.

3. Expert cardiac pathology. Where the heart looks structurally normal, or where a cardiomyopathy is suspected, the coroner can refer the heart to a specialist cardiac pathology centre. In the UK the CRY Centre for Cardiac Pathology at St George's, London, is a national referral centre and most UK coroners use it. Referral is arranged through the coroner, not by the family or the treating team.

4. Inquest. An inquest is usually opened and adjourned pending the pathology result, then resumed. The conclusion is recorded and the family receives the report.

The Association for European Cardiovascular Pathology publishes a structured protocol for autopsy in sudden cardiac death, updated in 2017. It sets out how the heart should be examined, what should be sampled histologically, and what should be retained.^[4]

A complete study includes:

• Full autopsy, not a cardiac-only examination
• Toxicology, which can reclassify a death entirely
• Systematic histological sampling of the myocardium and conduction system
• Retention of material suitable for DNA extraction^[4]

Sampling for DNA is the step most often missed. Formalin fixation fragments DNA and degrades the yield of later genetic testing, so EDTA blood or fresh frozen tissue (typically spleen or liver) should be taken at the time of the autopsy rather than requested afterwards.^[4]

Where the initial examination is not specialist, a normal-looking heart does not close the question. Referral for expert cardiac pathology can identify arrhythmogenic cardiomyopathy, subtle hypertrophic changes or myocarditis that a general autopsy may not detect.^[4]

Molecular autopsy is genetic testing performed on material retained from the deceased. In the prospective population study above, a clinically relevant variant was identified in 31 of 113 (27%) unexplained cases in which genetic testing was carried out, using a panel of at least 59 cardiac genes.^[1]

Adding genetic testing to the autopsy substantially increased the proportion of deaths with a possible cause identified.^[1] It does not replace family evaluation: in the same cohort, a clinical diagnosis of inherited cardiovascular disease emerged in 13% of families during follow-up.^[1]

Evaluating first-degree relatives is the single highest-yield action after a SADS death, because the conditions that cause it are heritable and treatable.

What the yield actually is:

• In 57 consecutively referred SADS families, 53% were diagnosed with an inheritable cardiac condition. Long QT syndrome was commonest, followed by Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy.^[2]
• In a larger UK series of 303 SADS families (911 relatives), an inherited cardiac disease was diagnosed in 42% of families and 22% of relatives. Brugada syndrome was the commonest single diagnosis, in 28% of families.^[3]

Provocation testing changes the yield substantially. In that series, ajmaline testing was required to unmask Brugada syndrome in 97% of those diagnosed with it, and recording from high right precordial leads diagnosed a further 49 families, a 16% incremental yield.^[3] This is a large part of why evaluation belongs in a centre that offers the full protocol.

The finding is not academic. On follow-up, 17% of relatives with concealed Brugada syndrome developed a spontaneous type 1 pattern or clinically significant arrhythmic events.^[3]

Who to evaluate: first-degree relatives, meaning parents, siblings and children. Where the pedigree suggests a wider pattern, or a first-degree relative has died, evaluation extends outwards.^[5]

Baseline evaluation:

• Detailed personal and family history, including circumstances of the index death (rest, sleep, exertion, emotion, fever)
• 12-lead ECG, with high right precordial leads considered^[3]
• Echocardiogram
• Exercise ECG
• Ambulatory ECG monitoring^[2]

Selected further testing, guided by the above and by how the person died: ajmaline provocation, cardiac MRI, and signal-averaged ECG.^[2][3]

For a clinician meeting this situation for the first time:

• Act early on tissue. The window to retain unfixed blood or tissue for DNA is at the autopsy. Once material is fixed, the genetic yield falls.^[4]
• A normal autopsy is a finding, not the end. It moves the question from the deceased to the living relatives, where the diagnostic yield is 40 to 50%.^[2][3]
• A resting ECG alone is not a screen. Most Brugada diagnoses in this setting were concealed and needed provocation to reveal.^[3]
• Refer, do not screen piecemeal. First-degree relatives are best assessed together in a service that can offer the whole protocol and the counselling that goes with it.^[3]
• Say what is not yet known. Families are often told the heart was normal and hear that nothing is wrong. Explaining that a normal structural examination is compatible with an inherited electrical condition avoids a false reassurance that stops them attending screening.
• The bereavement is part of the clinical problem. Relatives are being asked to undergo testing while grieving, and attendance suffers if that is not acknowledged.