Genotype is associated with left ventricular reverse remodelling and early events in recent-onset dilated cardiomyopathy

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216224:14110/24:00136839 RIV/00216208:11110/24:10482768 RIV/61989592:15110/24:73628481 RIV/00098892:_____/24:10158923 a 2 dalších

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Genotype is associated with left ventricular reverse remodelling and early events in recent-onset dilated cardiomyopathy

Popis výsledku v původním jazyce

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 &lt;= 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 &gt;50% or &gt;= 10% absolute increase, with a left ventricular end-diastolic diameter &lt;= 33 mm/m(2) or &gt;= 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.

Název v anglickém jazyce

Genotype is associated with left ventricular reverse remodelling and early events in recent-onset dilated cardiomyopathy

Popis výsledku anglicky

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 &lt;= 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 &gt;50% or &gt;= 10% absolute increase, with a left ventricular end-diastolic diameter &lt;= 33 mm/m(2) or &gt;= 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ESC heart failure [online]

ISSN

2055-5822

e-ISSN

2055-5822

Svazek periodika

2024

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

4127-4138

Kód UT WoS článku

001288249100001

EID výsledku v databázi Scopus

2-s2.0-85200972427