Genotype is associated with left ventricular reverse remodelling and early events in recent-onset dilated cardiomyopathy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F24%3A00085253" target="_blank" >RIV/00023001:_____/24:00085253 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/24:00136839 RIV/00216208:11110/24:10482768 RIV/61989592:15110/24:73628481 RIV/00098892:_____/24:10158923 and 2 more
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15009" target="_blank" >https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15009</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/ehf2.15009" target="_blank" >10.1002/ehf2.15009</a>
Alternative languages
Result language
angličtina
Original language name
Genotype is associated with left ventricular reverse remodelling and early events in recent-onset dilated cardiomyopathy
Original language description
Aims Recent-onset dilated cardiomyopathy (RODCM) is characterized by heterogeneous aetiology and diverse clinical outcomes, with scarce data on genotype-phenotype correlates. Our aim was to correlate individual RODCM genotypes with left ventricular reverse remodelling (LVRR) and clinical outcomes. Methods and results In this prospective study, a total of 386 Czech RODCM patients with symptom duration <= 6 months underwent genetic counselling and whole-exome sequencing (WES). The presence of pathogenic (class 5) or likely pathogenic (class 4) variants in a set of 72 cardiomyopathy-related genes was correlated with the occurrence of all-cause death, heart transplantation, or implantation of a ventricular assist device (primary outcome) and/or ventricular arrhythmia event (secondary outcome). LVRR was defined as an improvement of left ventricular ejection fraction to >50% or >= 10% absolute increase, with a left ventricular end-diastolic diameter <= 33 mm/m(2) or >= 10% relative decrease. Median follow-up was 41 months. RODCM was familial in 98 (25%) individuals. Class 4-5 variants of interest (VOIs) were identified in 125 (32%) cases, with 69 (18%) having a single titin-truncating variant (TTNtv) and 56 (14%) having non-titin (non-TTN) VOIs. The presence of class 4-5 non-TTN VOIs, but not of TTNtv, heralded a lower probability of 12-month LVRR and proved to be an independent baseline predictor both of the primary and the secondary outcome. The negative result of genetic testing was a strong protective baseline variable against occurrence of life-threatening ventricular arrhythmias. Detection of class 4-5 VOIs in genes coding nuclear envelope proteins was another independent predictor of both study outcomes at baseline and also of life-threatening ventricular arrhythmias after 12 months. Class 4-5 VOIs of genes coding cytoskeleton were associated with an increased risk of life-threatening ventricular arrhythmias after baseline assessment. A positive family history of dilated cardiomyopathy alone only related to a lower probability of LVRR at 12 months and at the final follow-up. ConclusionsRODCM patients harbouring class 4-5 non-TTN VOIs are at higher risk of progressive heart failure and life-threatening ventricular arrhythmias. Genotyping may improve their early risk stratification at baseline assessment.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ESC heart failure [online]
ISSN
2055-5822
e-ISSN
2055-5822
Volume of the periodical
2024
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
4127-4138
UT code for WoS article
001288249100001
EID of the result in the Scopus database
2-s2.0-85200972427