Key result
Pathogenic/likely pathogenic variants in dilated cardiomyopathy with LBBB were associated with worse clinical outcomes and attenuated reverse remodeling after CRT (ΔLVEF 1% vs. 14%; P<0.001).
Why the study?
The prevalence and clinical implications of pathogenic or likely pathogenic variants in patients with DCM and LBBB remain unclear despite routine genetic testing recommendations.
Does the presence of pathogenic/likely pathogenic genetic variants predict CRT response and clinical outcomes in patients with dilated cardiomyopathy and left bundle branch block?
Cohort (n=347)
Yes
Does the presence of pathogenic/likely pathogenic genetic variants predict CRT response and clinical outcomes in patients with dilated cardiomyopathy and left bundle branch block?
p-value: p=<0.001
In patients with dilated cardiomyopathy and left bundle branch block, pathogenic genetic variants are rare (6%) but are associated with atypical LBBB, less mechanical dyssynchrony, poor CRT response, and worse clinical outcomes.
AIMS: Genetic testing is routinely recommended in dilated cardiomyopathy (DCM), yet the prevalence and implications of pathogenic/likely pathogenic (P/LP) variants in patients with DCM and left bundle branch block (LBBB) remain unclear. We therefore investigated the electromechanical profile of genotyped patients with DCM and LBBB, and its relationship with cardiac resynchronization therapy (CRT) response and clinical outcomes. METHODS: Patients with LBBB were selected from a multicenter cohort of 1206 consecutive DCM patients undergoing genetic testing. All underwent sequencing of 20 clinically validated DCM-related genes (ClinGen) and comprehensive electro- and echocardiographic phenotyping, including speckle-tracking strain analysis, categorizing septal strain curves into five stages (LBBB-0 to LBBB-4). CRT response was assessed as end-systolic volume (ESV) reduction and left ventricular ejection fraction (LVEF) improvement. The clinical endpoints were a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, and heart failure hospitalization (HFH). RESULTS: Among 347 DCM patients with LBBB (median age 60[53-68], median LVEF 31%[23-39]), 22 (6%) exhibited P/LP variants. Genotype-positive patients less frequently fulfilled strict LBBB criteria (Strauss:P<0.001) and exhibited less mechanical dyssynchrony (predominantly LBBB-0/1;P<0.001). They showed attenuated reverse remodeling after CRT (ΔLVEF 1%[-6-6] vs. 14%[7-22];P<0.001) and worse clinical outcomes (both composite outcome and HFH;P<0.001). Conversely, advanced LBBB stages excluded an underlying rare genetic variant. P/LP variant status, LVEF, and LBBB stage independently predicted CRT response and composite outcome. CONCLUSIONS: Genetic testing has a low diagnostic yield in patients with DCM and LBBB. Genotype-positive variants exhibit a distinct electromechanical profile, characterised by atypical electrocardiographic features and markedly reduced mechanical dyssynchrony, poor CRT response, and worse long-term outcomes. Integrating genetic and electromechanical phenotyping may improve individualized risk stratification and management.
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Overmeiren et al. (2026) conducted a cohort in Dilated cardiomyopathy with left bundle branch block (n=347). Pathogenic/likely pathogenic (P/LP) genetic variants vs. Absence of P/LP variants (genotype-negative) was evaluated on Composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, and heart failure hospitalization (HFH) (p=<0.001). Pathogenic/likely pathogenic variants in dilated cardiomyopathy with LBBB were associated with worse clinical outcomes and attenuated reverse remodeling after CRT (ΔLVEF 1% vs. 14%; P<0.001).
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