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The molecular autopsy: an indispensable step following sudden cardiac death in the young?

Molekulare Autopsie: unverzichtbarer Schritt nach plötzlichem Herztod bei jungen Menschen?

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Abstract

Annually thousands of sudden deaths involving young individuals (< 35 years of age) remain unexplained following a complete medicolegal investigation that includes an autopsy. In fact, epidemiological studies have estimated that over half of sudden deaths involving previously healthy young individuals have no morphological abnormalities identifiable at autopsy. Cardiac channelopathies associated with structurally normal hearts such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS), leave no evidence to be found at autopsy, leaving investigators to only speculate that a lethal arrhythmia might lie at the heart of a sudden unexplained death (SUD). In cases of autopsy-negative SUD, continued investigation, through the use of a cardiological and genetic evaluation of first- or second-degree relatives and/or a molecular autopsy, may pinpoint the underlying mechanism attributing to the sudden death and allow for the identification of living family members with the pathogenic substrate that renders them vulnerable to an increased risk for cardiac events, including sudden death.

Zusammenfassung

Jährlich bleiben Tausende von Fällen plötzlichen Herztods bei jungen Menschen (< 35 Jahre) auch nach einer vollständigen rechtsmedizinischen Untersuchung einschließlich Autopsie ungeklärt. So finden sich bei mehr als der Hälfte der Fälle plötzlichen Herztods bei zuvor gesunden jungen Menschen nach Schätzungen epidemiologischer Studien keine bei der Autopsie erkennbaren morphologischen Veränderungen. Kardiale Ionenkanalerkrankungen wie das Long-QT-Syndrom (LQTS), die katecholaminerge polymorphe ventrikuläre Tachykardie (CPVT) und das Brugada-Syndrom (BrS), die mit einem strukturell normalen Herzen einhergehen, hinterlassen keine Spuren, die bei einer Autopsie feststellbar wären. So bleibt den Untersuchern nur zu vermuten, dass dem ungeklärten plötzlichen Herztod („sudden unexplained death“, SUD) eine letale Arrhythmie zugrunde liegen könnte. In Fällen von autopsienegativem SUD kann eine weiterführende Untersuchung unter Einsatz kardiologischer und genetischer Diagnostik bei Verwandten ersten oder zweiten Grades und/oder eine molekulare Autopsie zur Erkennung des dem plötzlichen Herztod zugrunde liegenden Mechanismus führen und die Identifizierung lebender Familienmitglieder ermöglichen, die das pathogene Substrat tragen, welches sie für ein erhöhtes Risiko kardialer Ereignisse einschließlich des plötzlichen Herztods anfällig macht.

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Conflict of interest

On behalf of all authors, the corresponding author states the following: M.J.A. is a consultant for Biotronik, Boston Scientific, Medtronic, St. Jude Medical, Inc., and Transgenomic. Intellectual property derived from M.J.A.’s research program resulted in license agreements in 2004 between Mayo Clinic Health Solutions (formerly Mayo Medical Ventures) and PGxHealth (formerly Genaissance Pharmaceuticals, now recently acquired by Transgenomic). N.J.B. and D.J.T. have no conflicts to disclose.

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Authors and Affiliations

  1. Mayo Graduate School, Mayo Clinic, Rochester, MN, USA

    Nicole J. Boczek BA

  2. Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN, USA

    Nicole J. Boczek BA, David J. Tester BS & Michael J. Ackerman MD, PhD

  3. Department of Medicine (Division of Cardiovascular Diseases), Mayo Clinic, Rochester, MN, USA

    David J. Tester BS

  4. Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA

    Michael J. Ackerman MD, PhD

  5. Department of Pediatrics (Division of Pediatric Cardiology), Mayo Clinic, Rochester, MN, USA

    Michael J. Ackerman MD, PhD

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  1. Nicole J. Boczek BA
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  2. David J. Tester BS
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  3. Michael J. Ackerman MD, PhD
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Corresponding author

Correspondence to Michael J. Ackerman MD, PhD.

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Boczek, N., Tester, D. & Ackerman, M. The molecular autopsy: an indispensable step following sudden cardiac death in the young?. Herzschr Elektrophys 23, 167–173 (2012). https://doi.org/10.1007/s00399-012-0222-x

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  • DOI: https://doi.org/10.1007/s00399-012-0222-x

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