Key result
Asymptomatic DCM genotype positivity links to lower LVGLS and LVEF versus genotype-negative relatives.
Why the study?
To investigate whether asymptomatic relatives carrying familial dilated cardiomyopathy (DCM) variants show early echocardiographic signs of myocardial disease.
Does carrying a pathogenic genetic variant for familial DCM cause early subclinical myocardial dysfunction in asymptomatic relatives?
Observational (n=176)
Blinded operators
Yes
Does carrying a pathogenic genetic variant for familial DCM cause early subclinical myocardial dysfunction in asymptomatic relatives?
Absolute Event Rate: -18.7% vs -20.1%
p-value: p=0.0029
Asymptomatic relatives carrying pathogenic variants for familial DCM show early signs of subclinical myocardial dysfunction, including lower LVGLS and LVEF, compared to non-carriers.
May support GLS monitoring for preclinical detection in asymptomatic variant carriers; leaves open whether screening alters outcomes in familial DCM.
Aim To investigate if asymptomatic relatives carrying genetic variants associated with familial dilated cardiomyopathy (DCM) show early signs of myocardial disease assessed by echocardiography. Methods and Results Asymptomatic relatives without a DCM-phenotype (n=176, 46% males, mean age 39 years ± 16) of 111 DCM index patients carrying likely pathogenic or pathogenetic variants in TTN, RBM20, and FLNC genes were recruited from two tertiary referral centers for inherited cardiac diseases. All participants underwent echocardiographic examinations focusing on left ventricular (LV) ejection fraction (LVEF), LV global longitudinal strain (LVGLS), and LV end-diastolic diameter (LVEDD), with operators blinded to genetic results. The participants were grouped into genotype positive ([G+], n=82) or genotype negative relatives ([G-], n=94) carrying or not carrying the disease-causing variant. The G+ group had significantly lower systolic LV parameters compared to G- individuals with a mean LVGLS of -18.7% ± 2.4 versus -20.1% ± 2.8, p: 0.0029; and a mean ejection fraction of 57.8% ± 3.7 versus 59.7% ± 2.4, p: <0.0001. The proportion of G+ individuals with an abnormal LVGLS (defined as less than -18%) was 46% compared to 18% in the G- group. 26 % of G+ individuals had an LVEF in the interval between 50 - 55% compared to of 5% G- individuals[MOU1] . Mean LVEDD did not differ significantly between G+ and G-groups (49.7 mm ± 4.9 versus 48.8 mm ± 4.7). However, LVEDD indexed to BSA were significantly increased in G+ individuals (26.7 mm/m2 ± 2.8 versus 25.4 mm/m2 ± 2.5, p-value 0.001). Conclusion Overall, the absolute mean values of LVGLS, LVEF, and LVEDD were within normal ranges in both G+ and G- groups of individuals. However, compared to non-carrier relatives, almost half of the asymptomatic G+ DCM relatives had signs of subclinical myocardial dysfunction with significantly lower values of LVGLS, LVEF, and larger left ventricular dimensions.
No takes yet. Share an insight, caveat, or question.
Tellefsen et al. (2024) conducted an observational in Familial dilated cardiomyopathy (n=176). Genotype positive (G+) for DCM variants vs. Genotype negative (G-) relatives was evaluated on Mean left ventricular global longitudinal strain (LVGLS) (p=0.0029). Asymptomatic genotype-positive relatives of DCM patients had significantly lower mean LVGLS (-18.7% vs -20.1%, p=0.0029) and LVEF (57.8% vs 59.7%, p<0.0001) compared to genotype-negative relatives.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: