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Sudden cardiac death in the young

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Cardiovascular Presentations/Arrhythmias and SCD

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A sudden cardiac arrest or sudden unexplained death in a person under 40, or a first-degree relative of someone with that history. The patient in front of you may be the survivor of a resuscitated event, a sibling of a decedent being screened, or a parent of a child found unresponsive. The diagnostic question is whether the substrate is electrical (channelopathy), structural (cardiomyopathy), vascular (aortopathy with dissection), preexcitation (WPW with degeneration to VF), or metabolic / FAO with cardiac involvement. Each lane has its own work-up.

The most useful first split is was the resting heart structurally normal? If the autopsy or echo shows a structurally normal heart, the diagnosis lives in the channelopathy category. If structural disease is present, the cardiomyopathies and aortopathies dominate. Two facts always influence the work-up:

  • Trigger context: exertion (LQT1, CPVT, HCM, ACM), swimming specifically (LQT1), auditory startle or postpartum (LQT2), sleep or rest (LQT3, Brugada), fever (Brugada), or none (any).
  • Family history: a careful three-generation pedigree including all unexplained deaths under 50, single-vehicle accidents, drownings, and "SIDS" cases. The proband's death is often not the first event in the family, just the first recognized one.

Channelopathies (structurally normal heart)

  • Long QT syndrome:
    • LQT1 (KCNQ1): exertion-triggered, classically swimming. AD; ~30% of LQTS.
    • LQT2 (KCNH2): auditory startle, alarm clock, emotional stress; postpartum is a known high-risk window.
    • LQT3 (SCN5A): events during sleep or rest. Smaller fraction but high lethality.
    • Jervell-Lange-Nielsen (KCNQ1 or KCNE1, biallelic): JLN syndrome is the autosomal-recessive form combining severe LQT with congenital sensorineural deafness. Test any deaf child with syncope.
  • Brugada syndrome (SCN5A, AD): characteristic coved ST elevation in V1-V2 (type 1 pattern), often unmasked by fever or sodium-channel blockers (procainamide, ajmaline). SCD typically during sleep or at rest, more common in Southeast Asian males.
  • Catecholaminergic polymorphic VT (CPVT) (RYR2, AD; CASQ2, AR): resting ECG is normal. Exercise stress test reproduces bidirectional or polymorphic VT. Beta-blockers and avoidance of competitive sport are the standard.
  • Short QT syndrome: rare; QTc < 340 ms with tall peaked T waves; AD, several genes (KCNH2, KCNQ1, KCNJ2, CACNA1C).
  • Idiopathic ventricular fibrillation: diagnosis of exclusion after the panels are negative.

Cardiomyopathies with SCD as the presenting event

  • Hypertrophic cardiomyopathy: the classic cause of SCD in a young athlete. MYH7, MYBPC3, others. Echo + ECG diagnostic. Risk stratify for ICD.
  • Arrhythmogenic right ventricular cardiomyopathy (ARVC / ACM): PKP2 is the most common gene; DSP, DSG2, DSC2, JUP. Fibrofatty replacement of RV (and LV in some forms). Epsilon waves, RV dilatation, and exertion-triggered VT. Exercise restriction is the central intervention.
  • DCM with conduction disease (LMNA): atrial arrhythmias and high-grade AV block in young adults; SCD often precedes the heart failure phase. Lower ICD threshold than non-LMNA DCM.

Vascular / aortopathy with dissection

  • Marfan syndrome (FBN1): tall thin habitus, ectopia lentis, aortic root dilatation, dissection.
  • Vascular Ehlers-Danlos (COL3A1): thin translucent skin, easy bruising, arterial / intestinal / uterine rupture without warning dilation.
  • Loeys-Dietz syndrome (TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3): hypertelorism, bifid uvula, cleft palate, aortic and peripheral arterial aneurysms. Dissect at smaller diameters than Marfan.
  • Turner syndrome: bicuspid aortic valve, coarctation, aortic dilatation with dissection risk especially during pregnancy.
  • Familial thoracic aortic aneurysm and dissection (TAAD): ACTA2, MYH11, MYLK, PRKG1.

Preexcitation

  • Wolff-Parkinson-White (WPW): accessory pathway. Can degenerate to VF in atrial fibrillation. Most isolated; in syndromic context think Danon disease (LAMP2), Pompe disease, and PRKAG2 cardiomyopathy.

Metabolic / FAO defects

  • VLCAD, LCHAD / TFP: cardiomyopathy + arrhythmia during illness or fasting, hypoketotic hypoglycemia.
  • Drowning death in a strong swimmer → LQT1 until proven otherwise.
  • SCD triggered by an alarm or phone ringing, or in the postpartum period → LQT2.
  • SCD during sleep in a young Southeast Asian man, fever recent → Brugada syndrome.
  • Bidirectional VT on exercise stress, normal resting ECG → CPVT.
  • Young athlete who collapses during sport, hypertrophied septum on echo → HCM.
  • VT with LBBB morphology + RV dilatation + epsilon waves in a young adult endurance athlete → ARVC / ACM. Stop competitive sport.
  • Aortic dissection at low diameter + hypertelorism + bifid uvula → Loeys-Dietz.
  • Sudden infant death + congenital deafness in a sibling → Jervell-Lange-Nielsen.

For the surviving proband:

  1. 12-lead ECG with careful QTc (Bazett and Fridericia; tall T waves; epsilon waves; type 1 Brugada pattern); high lead ECG (V1-V2 one and two intercostal spaces up) if Brugada suspected.
  2. Echocardiogram: HCM, DCM, ARVC features, aortic root.
  3. Exercise stress test (CPVT, LQT1 prolongation with exercise).
  4. Cardiac MRI: ARVC features, fibrosis, LVNC, infiltrative disease.
  5. Provocation testing where indicated: procainamide / ajmaline for Brugada; epinephrine for borderline LQT.
  6. Comprehensive arrhythmia + cardiomyopathy + aortopathy gene panel (or pan-cardiac panel).

For the SADS (sudden arrhythmic death syndrome) work-up after a relative's death:

  1. Review the autopsy for structurally normal heart and toxicology.
  2. DNA banking from the decedent if available (molecular autopsy).
  3. ECG, echo, exercise stress, cardiac MRI for all first-degree relatives.
  4. Cascade testing if a pathogenic variant is identified in the decedent or proband.
  5. Refer to a specialized inherited cardiac conditions clinic with cardiology, genetics, and counseling.
  • A "normal autopsy" in sudden death of the young is the channelopathy work-up's strongest indication. Structurally normal heart + sudden death = LQT, Brugada, CPVT, or SQT until proven otherwise.
  • Always ask about the trigger. Swimming, sleep, startle, postpartum, exertion, and fever each map to a specific channel.
  • The first event is often not the first family event. A careful pedigree turns up "drownings" and "single-vehicle accidents" that were misattributed.
  • Identifying the at-risk asymptomatic relative is the point. Cascade testing and lifestyle modification (sport restriction, beta-blockers, ICD) prevent the next event.
  • Bifid uvula in a tall patient with aortic disease is Loeys-Dietz until proven otherwise. Dissect at smaller diameters than Marfan; surgical thresholds differ.