Yield of molecular autopsy in sudden cardiac death in athletes : data from a large registry in the UK
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology..
AIMS: Sudden cardiac death (SCD) may occur in apparently healthy individuals, including athletes. The aim was to investigate the diagnostic role of post-mortem genetic testing, molecular autopsy (MA), in elucidating the cause of SCD in athletes.
METHODS AND RESULTS: We reviewed a database of 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre. All cases underwent detailed cardiac autopsy, and 748 were deemed to be athletes. Of these, 42 (6%) were investigated with MA (28 using a targeted sequencing, 14 exome sequencing). Variants were classified as pathogenic, likely pathogenic, or variant of unknown significance using international guidelines. Clinical information was obtained from referring coroners who completed a detailed health questionnaire. Out of the 42 decedents (average age 35 years old, 98% males) who were investigated with MA, the autopsy was in keeping with a structurally normal heart [sudden arrhythmic death syndrome (SADS)] in n = 33 (78%) cases, followed by arrhythmogenic cardiomyopathy (ACM) in eight (19%) individuals and idiopathic left ventricular fibrosis in one (2%). Death occurred during exercise and at rest in 26 (62%) and 16 (38%) individuals, respectively. Variants that were adjudicated clinically actionable were present in seven cases (17%). There was concordance between the genetic and phenotypic findings in two cases of ACM (in FLNC and TMEM43 genes). None of the variants identified in SADS cases were previously linked to channelopathies. Clinically actionable variants in cardiomyopathy-associated genes were found in five cases of SADS.
CONCLUSION: The yield of MA in athletes who died suddenly is 17%. In SADS cases, clinically actionable variants were found in cardiomyopathy-associated genes and not in channelopathy-associated genes. Arrhythmogenic cardiomyopathy is a common cause of SCD in athletes, and one in four decedents with this condition had a clinically actionable variant in FLNC and TMEM43 genes.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
|---|---|
| Enthalten in: |
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology - 26(2024), 2 vom: 01. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Finocchiaro, Gherardo [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 14.02.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/europace/euae029 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367800543 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367800543 | ||
| 003 | DE-627 | ||
| 005 | 20240214233204.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240131s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/europace/euae029 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1293.xml |
| 035 | |a (DE-627)NLM367800543 | ||
| 035 | |a (NLM)38289717 | ||
| 035 | |a (PII)euae029 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Finocchiaro, Gherardo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Yield of molecular autopsy in sudden cardiac death in athletes |b data from a large registry in the UK |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.02.2024 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. | ||
| 520 | |a AIMS: Sudden cardiac death (SCD) may occur in apparently healthy individuals, including athletes. The aim was to investigate the diagnostic role of post-mortem genetic testing, molecular autopsy (MA), in elucidating the cause of SCD in athletes | ||
| 520 | |a METHODS AND RESULTS: We reviewed a database of 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre. All cases underwent detailed cardiac autopsy, and 748 were deemed to be athletes. Of these, 42 (6%) were investigated with MA (28 using a targeted sequencing, 14 exome sequencing). Variants were classified as pathogenic, likely pathogenic, or variant of unknown significance using international guidelines. Clinical information was obtained from referring coroners who completed a detailed health questionnaire. Out of the 42 decedents (average age 35 years old, 98% males) who were investigated with MA, the autopsy was in keeping with a structurally normal heart [sudden arrhythmic death syndrome (SADS)] in n = 33 (78%) cases, followed by arrhythmogenic cardiomyopathy (ACM) in eight (19%) individuals and idiopathic left ventricular fibrosis in one (2%). Death occurred during exercise and at rest in 26 (62%) and 16 (38%) individuals, respectively. Variants that were adjudicated clinically actionable were present in seven cases (17%). There was concordance between the genetic and phenotypic findings in two cases of ACM (in FLNC and TMEM43 genes). None of the variants identified in SADS cases were previously linked to channelopathies. Clinically actionable variants in cardiomyopathy-associated genes were found in five cases of SADS | ||
| 520 | |a CONCLUSION: The yield of MA in athletes who died suddenly is 17%. In SADS cases, clinically actionable variants were found in cardiomyopathy-associated genes and not in channelopathy-associated genes. Arrhythmogenic cardiomyopathy is a common cause of SCD in athletes, and one in four decedents with this condition had a clinically actionable variant in FLNC and TMEM43 genes | ||
| 650 | 4 | |a Review | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Molecular autopsy | |
| 650 | 4 | |a Sudden cardiac death | |
| 700 | 1 | |a Radaelli, Davide |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, David |e verfasserin |4 aut | |
| 700 | 1 | |a Bhatia, Raghav T |e verfasserin |4 aut | |
| 700 | 1 | |a Westaby, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a D'Errico, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Papadakis, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Sanjay |e verfasserin |4 aut | |
| 700 | 1 | |a Sheppard, Mary N |e verfasserin |4 aut | |
| 700 | 1 | |a Behr, Elijah R |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology |d 1999 |g 26(2024), 2 vom: 01. Feb. |w (DE-627)NLM111066492 |x 1532-2092 |7 nnns |
| 773 | 1 | 8 | |g volume:26 |g year:2024 |g number:2 |g day:01 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/europace/euae029 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 26 |j 2024 |e 2 |b 01 |c 02 | ||