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Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection

Hypertrophic cardiomyopathy (HCM) and heterozygous familial hypercholesterolemia (HeFH), two of the most common genetic cardiovascular disorders, can lead to sudden cardiac death. These conditions could be complicated by concomitant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infect...

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Autores principales: Marziliano, Nicola, Medoro, Alessandro, Mignogna, Donatella, Saccon, Giovanni, Folzani, Stefano, Reverberi, Claudio, Russo, Claudio, Intrieri, Mariano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307649/
https://www.ncbi.nlm.nih.gov/pubmed/34359312
http://dx.doi.org/10.3390/diagnostics11071229
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author Marziliano, Nicola
Medoro, Alessandro
Mignogna, Donatella
Saccon, Giovanni
Folzani, Stefano
Reverberi, Claudio
Russo, Claudio
Intrieri, Mariano
author_facet Marziliano, Nicola
Medoro, Alessandro
Mignogna, Donatella
Saccon, Giovanni
Folzani, Stefano
Reverberi, Claudio
Russo, Claudio
Intrieri, Mariano
author_sort Marziliano, Nicola
collection PubMed
description Hypertrophic cardiomyopathy (HCM) and heterozygous familial hypercholesterolemia (HeFH), two of the most common genetic cardiovascular disorders, can lead to sudden cardiac death. These conditions could be complicated by concomitant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as in the case herein described. A young amateur soccer player died in late October 2020 after a fatal arrhythmia and the autopsy revealed the presence of HCM with diffuse non-obstructive coronary disease. The molecular autopsy revealed a compound condition with a first mutation in the MYH7 gene (p.Arg719Trp) and a second mutation in the LDLR gene (p.Gly343Cys): both have already been described as associated with HCM and HeFH, respectively. In addition, molecular analyses showed the presence of SARS-CoV-2 lineage B.1.1.7 (UK variant with high titer in the myocardium. Co-segregation analysis within the family (n = 19) showed that heterozygous LDLR mutation was maternally inherited, while the heterozygous MYH7 genetic lesion was de novo. All family member carriers of the LDLR mutation (n = 13) had systematic higher LDL plasma concentrations and positive records of cardiac and vascular ischemic events at young age. Considering that HCM mutations are in themselves involved in the predisposition to malignant arrhythmogenicity and HeFH could cause higher risk of cardiac complications in SARS-CoV-2 infection, this case could represent an example of a potential SARS-CoV-2 infection role in triggering or unmasking inherited cardiovascular disease, whose combination might represent the cause of fatal arrhythmia at such a young age. Additionally, it can provide clues in dating the presence of the SARS-CoV-2 lineage B.1.1.7 in Northern Italy in the early phases of the second pandemic wave.
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spelling pubmed-83076492021-07-25 Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection Marziliano, Nicola Medoro, Alessandro Mignogna, Donatella Saccon, Giovanni Folzani, Stefano Reverberi, Claudio Russo, Claudio Intrieri, Mariano Diagnostics (Basel) Case Report Hypertrophic cardiomyopathy (HCM) and heterozygous familial hypercholesterolemia (HeFH), two of the most common genetic cardiovascular disorders, can lead to sudden cardiac death. These conditions could be complicated by concomitant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as in the case herein described. A young amateur soccer player died in late October 2020 after a fatal arrhythmia and the autopsy revealed the presence of HCM with diffuse non-obstructive coronary disease. The molecular autopsy revealed a compound condition with a first mutation in the MYH7 gene (p.Arg719Trp) and a second mutation in the LDLR gene (p.Gly343Cys): both have already been described as associated with HCM and HeFH, respectively. In addition, molecular analyses showed the presence of SARS-CoV-2 lineage B.1.1.7 (UK variant with high titer in the myocardium. Co-segregation analysis within the family (n = 19) showed that heterozygous LDLR mutation was maternally inherited, while the heterozygous MYH7 genetic lesion was de novo. All family member carriers of the LDLR mutation (n = 13) had systematic higher LDL plasma concentrations and positive records of cardiac and vascular ischemic events at young age. Considering that HCM mutations are in themselves involved in the predisposition to malignant arrhythmogenicity and HeFH could cause higher risk of cardiac complications in SARS-CoV-2 infection, this case could represent an example of a potential SARS-CoV-2 infection role in triggering or unmasking inherited cardiovascular disease, whose combination might represent the cause of fatal arrhythmia at such a young age. Additionally, it can provide clues in dating the presence of the SARS-CoV-2 lineage B.1.1.7 in Northern Italy in the early phases of the second pandemic wave. MDPI 2021-07-07 /pmc/articles/PMC8307649/ /pubmed/34359312 http://dx.doi.org/10.3390/diagnostics11071229 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Marziliano, Nicola
Medoro, Alessandro
Mignogna, Donatella
Saccon, Giovanni
Folzani, Stefano
Reverberi, Claudio
Russo, Claudio
Intrieri, Mariano
Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection
title Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection
title_full Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection
title_fullStr Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection
title_full_unstemmed Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection
title_short Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection
title_sort sudden cardiac death caused by a fatal association of hypertrophic cardiomyopathy (myh7, p.arg719trp), heterozygous familial hypercholesterolemia (ldlr, p.gly343lys) and sars-cov-2 b.1.1.7 infection
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307649/
https://www.ncbi.nlm.nih.gov/pubmed/34359312
http://dx.doi.org/10.3390/diagnostics11071229
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