Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy
Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multi...
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| Veröffentlicht in: | JACC. Clinical electrophysiology 2024-06, Vol.10 (6), p.1178-1190 |
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| creator | Bermudez-Jimenez, Francisco J. Protonotarios, Alexandros García-Hernández, Soledad Pérez Asensio, Ana Rampazzo, Alessandra Zorio, Esther Brodehl, Andreas Arias, Miguel A. Macías-Ruiz, Rosa Fernández-Armenta, Juan Remior Perez, Paloma Muñoz-Esparza, Carmen Pilichou, Kalliopi Bauce, Barbara Merino, Jose L. Moliner-Abós, Carlos Ochoa, Juan P. Barriales-Villa, Roberto Garcia-Pavia, Pablo Lopes, Luis R. Syrris, Petros Corrado, Domenico Elliott, Perry M. McKenna, William J. Jimenez-Jaimez, Juan |
| description | Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce.
This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort.
We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM.
Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants.
DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.
[Display omitted] |
| doi_str_mv | 10.1016/j.jacep.2024.02.031 |
| format | Article |
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This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort.
We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM.
Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants.
DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.
[Display omitted]</description><identifier>ISSN: 2405-500X</identifier><identifier>ISSN: 2405-5018</identifier><identifier>EISSN: 2405-5018</identifier><identifier>DOI: 10.1016/j.jacep.2024.02.031</identifier><identifier>PMID: 38727660</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; arrhythmogenic cardiomyopathy ; Arrhythmogenic Right Ventricular Dysplasia - genetics ; Arrhythmogenic Right Ventricular Dysplasia - physiopathology ; Death, Sudden, Cardiac - etiology ; Defibrillators, Implantable ; desmin ; Desmin - genetics ; desminopathy ; Female ; genetics ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Phenotype ; Young Adult</subject><ispartof>JACC. Clinical electrophysiology, 2024-06, Vol.10 (6), p.1178-1190</ispartof><rights>2024 American College of Cardiology Foundation</rights><rights>Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-9a45b01ea60a0d3786297301f9e313ac77435ce59aefc0800d926812d1ab7e2f3</citedby><cites>FETCH-LOGICAL-c359t-9a45b01ea60a0d3786297301f9e313ac77435ce59aefc0800d926812d1ab7e2f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38727660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bermudez-Jimenez, Francisco J.</creatorcontrib><creatorcontrib>Protonotarios, Alexandros</creatorcontrib><creatorcontrib>García-Hernández, Soledad</creatorcontrib><creatorcontrib>Pérez Asensio, Ana</creatorcontrib><creatorcontrib>Rampazzo, Alessandra</creatorcontrib><creatorcontrib>Zorio, Esther</creatorcontrib><creatorcontrib>Brodehl, Andreas</creatorcontrib><creatorcontrib>Arias, Miguel A.</creatorcontrib><creatorcontrib>Macías-Ruiz, Rosa</creatorcontrib><creatorcontrib>Fernández-Armenta, Juan</creatorcontrib><creatorcontrib>Remior Perez, Paloma</creatorcontrib><creatorcontrib>Muñoz-Esparza, Carmen</creatorcontrib><creatorcontrib>Pilichou, Kalliopi</creatorcontrib><creatorcontrib>Bauce, Barbara</creatorcontrib><creatorcontrib>Merino, Jose L.</creatorcontrib><creatorcontrib>Moliner-Abós, Carlos</creatorcontrib><creatorcontrib>Ochoa, Juan P.</creatorcontrib><creatorcontrib>Barriales-Villa, Roberto</creatorcontrib><creatorcontrib>Garcia-Pavia, Pablo</creatorcontrib><creatorcontrib>Lopes, Luis R.</creatorcontrib><creatorcontrib>Syrris, Petros</creatorcontrib><creatorcontrib>Corrado, Domenico</creatorcontrib><creatorcontrib>Elliott, Perry M.</creatorcontrib><creatorcontrib>McKenna, William J.</creatorcontrib><creatorcontrib>Jimenez-Jaimez, Juan</creatorcontrib><title>Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy</title><title>JACC. Clinical electrophysiology</title><addtitle>JACC Clin Electrophysiol</addtitle><description>Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce.
This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort.
We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM.
Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants.
DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.
[Display omitted]</description><subject>Adolescent</subject><subject>Adult</subject><subject>arrhythmogenic cardiomyopathy</subject><subject>Arrhythmogenic Right Ventricular Dysplasia - genetics</subject><subject>Arrhythmogenic Right Ventricular Dysplasia - physiopathology</subject><subject>Death, Sudden, Cardiac - etiology</subject><subject>Defibrillators, Implantable</subject><subject>desmin</subject><subject>Desmin - genetics</subject><subject>desminopathy</subject><subject>Female</subject><subject>genetics</subject><subject>Heart Transplantation</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Phenotype</subject><subject>Young Adult</subject><issn>2405-500X</issn><issn>2405-5018</issn><issn>2405-5018</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKxDAUhoMoKjpPIEiXblpPkqaXhQsZryB4QcFdyCSnToa2qUlH6NvMs8yTWR116eqcxfefn_MRckQhoUCz00WyUBq7hAFLE2AJcLpF9lkKIhZAi-2_HV73yCSEBQBQwQpG012yx4uc5VkG--TxYY6t64cOI9WaaFrb1mpVR_fLXrsGw3pl2_XqAkNj2_gJa9Wjic69nw_9vHFvONLRVHljXTO4TvXz4ZDsVKoOOPmZB-Tl6vJ5ehPf3V_fTs_vYs1F2celSsUMKKoMFBieFxkrcw60KpFTrnSep1xoFKXCSkMBYEqWFZQZqmY5soofkJPN3c679yWGXjY2aKxr1aJbBslB8DIXJeMjyjeo9i4Ej5XsvG2UHyQF-aVTLuS3TvmlUwKTo84xdfxTsJw1aP4yv_JG4GwD4Pjmh0Uvg7bYajTWo-6lcfbfgk9d34h3</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Bermudez-Jimenez, Francisco J.</creator><creator>Protonotarios, Alexandros</creator><creator>García-Hernández, Soledad</creator><creator>Pérez Asensio, Ana</creator><creator>Rampazzo, Alessandra</creator><creator>Zorio, Esther</creator><creator>Brodehl, Andreas</creator><creator>Arias, Miguel A.</creator><creator>Macías-Ruiz, Rosa</creator><creator>Fernández-Armenta, Juan</creator><creator>Remior Perez, Paloma</creator><creator>Muñoz-Esparza, Carmen</creator><creator>Pilichou, Kalliopi</creator><creator>Bauce, Barbara</creator><creator>Merino, Jose L.</creator><creator>Moliner-Abós, Carlos</creator><creator>Ochoa, Juan P.</creator><creator>Barriales-Villa, Roberto</creator><creator>Garcia-Pavia, Pablo</creator><creator>Lopes, Luis R.</creator><creator>Syrris, Petros</creator><creator>Corrado, Domenico</creator><creator>Elliott, Perry M.</creator><creator>McKenna, William J.</creator><creator>Jimenez-Jaimez, Juan</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20240601</creationdate><title>Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy</title><author>Bermudez-Jimenez, Francisco J. ; Protonotarios, Alexandros ; García-Hernández, Soledad ; Pérez Asensio, Ana ; Rampazzo, Alessandra ; Zorio, Esther ; Brodehl, Andreas ; Arias, Miguel A. ; Macías-Ruiz, Rosa ; Fernández-Armenta, Juan ; Remior Perez, Paloma ; Muñoz-Esparza, Carmen ; Pilichou, Kalliopi ; Bauce, Barbara ; Merino, Jose L. ; Moliner-Abós, Carlos ; Ochoa, Juan P. ; Barriales-Villa, Roberto ; Garcia-Pavia, Pablo ; Lopes, Luis R. ; Syrris, Petros ; Corrado, Domenico ; Elliott, Perry M. ; McKenna, William J. ; Jimenez-Jaimez, Juan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-9a45b01ea60a0d3786297301f9e313ac77435ce59aefc0800d926812d1ab7e2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>arrhythmogenic cardiomyopathy</topic><topic>Arrhythmogenic Right Ventricular Dysplasia - genetics</topic><topic>Arrhythmogenic Right Ventricular Dysplasia - physiopathology</topic><topic>Death, Sudden, Cardiac - etiology</topic><topic>Defibrillators, Implantable</topic><topic>desmin</topic><topic>Desmin - genetics</topic><topic>desminopathy</topic><topic>Female</topic><topic>genetics</topic><topic>Heart Transplantation</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Phenotype</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bermudez-Jimenez, Francisco J.</creatorcontrib><creatorcontrib>Protonotarios, Alexandros</creatorcontrib><creatorcontrib>García-Hernández, Soledad</creatorcontrib><creatorcontrib>Pérez Asensio, Ana</creatorcontrib><creatorcontrib>Rampazzo, Alessandra</creatorcontrib><creatorcontrib>Zorio, Esther</creatorcontrib><creatorcontrib>Brodehl, Andreas</creatorcontrib><creatorcontrib>Arias, Miguel A.</creatorcontrib><creatorcontrib>Macías-Ruiz, Rosa</creatorcontrib><creatorcontrib>Fernández-Armenta, Juan</creatorcontrib><creatorcontrib>Remior Perez, Paloma</creatorcontrib><creatorcontrib>Muñoz-Esparza, Carmen</creatorcontrib><creatorcontrib>Pilichou, Kalliopi</creatorcontrib><creatorcontrib>Bauce, Barbara</creatorcontrib><creatorcontrib>Merino, Jose L.</creatorcontrib><creatorcontrib>Moliner-Abós, Carlos</creatorcontrib><creatorcontrib>Ochoa, Juan P.</creatorcontrib><creatorcontrib>Barriales-Villa, Roberto</creatorcontrib><creatorcontrib>Garcia-Pavia, Pablo</creatorcontrib><creatorcontrib>Lopes, Luis R.</creatorcontrib><creatorcontrib>Syrris, Petros</creatorcontrib><creatorcontrib>Corrado, Domenico</creatorcontrib><creatorcontrib>Elliott, Perry M.</creatorcontrib><creatorcontrib>McKenna, William J.</creatorcontrib><creatorcontrib>Jimenez-Jaimez, Juan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>JACC. Clinical electrophysiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bermudez-Jimenez, Francisco J.</au><au>Protonotarios, Alexandros</au><au>García-Hernández, Soledad</au><au>Pérez Asensio, Ana</au><au>Rampazzo, Alessandra</au><au>Zorio, Esther</au><au>Brodehl, Andreas</au><au>Arias, Miguel A.</au><au>Macías-Ruiz, Rosa</au><au>Fernández-Armenta, Juan</au><au>Remior Perez, Paloma</au><au>Muñoz-Esparza, Carmen</au><au>Pilichou, Kalliopi</au><au>Bauce, Barbara</au><au>Merino, Jose L.</au><au>Moliner-Abós, Carlos</au><au>Ochoa, Juan P.</au><au>Barriales-Villa, Roberto</au><au>Garcia-Pavia, Pablo</au><au>Lopes, Luis R.</au><au>Syrris, Petros</au><au>Corrado, Domenico</au><au>Elliott, Perry M.</au><au>McKenna, William J.</au><au>Jimenez-Jaimez, Juan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy</atitle><jtitle>JACC. Clinical electrophysiology</jtitle><addtitle>JACC Clin Electrophysiol</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>10</volume><issue>6</issue><spage>1178</spage><epage>1190</epage><pages>1178-1190</pages><issn>2405-500X</issn><issn>2405-5018</issn><eissn>2405-5018</eissn><abstract>Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce.
This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort.
We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM.
Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants.
DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38727660</pmid><doi>10.1016/j.jacep.2024.02.031</doi><tpages>13</tpages></addata></record> |
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| ispartof | JACC. Clinical electrophysiology, 2024-06, Vol.10 (6), p.1178-1190 |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adolescent Adult arrhythmogenic cardiomyopathy Arrhythmogenic Right Ventricular Dysplasia - genetics Arrhythmogenic Right Ventricular Dysplasia - physiopathology Death, Sudden, Cardiac - etiology Defibrillators, Implantable desmin Desmin - genetics desminopathy Female genetics Heart Transplantation Humans Male Middle Aged Phenotype Young Adult |
| title | Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy |
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