Left bundle branch block in gene-elusive dilated cardiomyopathy is associated with better prognosis

Background

Genetic testing informs risk stratification in dilated cardiomyopathy (DCM), yet likely pathogenic/pathogenic (LP/P) variants are identified in only one-third of patients. Gene-elusive DCM may confer a lower risk of adverse clinical events than genotype-positive disease, but remains poorly characterised. Left bundle branch block (LBBB) is more common in gene-elusive DCM and its clinical significance is uncertain.1

Purpose

To characterise outcomes in gene-elusive DCM, identify predictors of adverse events and determine the significance of LBBB in this cohort.

Methods

Consecutive and unrelated DCM patients undergoing genetic testing and returning no LP/P variants were retrospectively recruited and compared to cohorts of DCM patients carrying LP/P variants in LMNA and TTN for a primary composite endpoint of end-stage heart failure (ESHF) or malignant ventricular arrhythmia (MVA). In the gene-elusive group, baseline predictors of the primary endpoint were evaluated, and outcomes stratified by the presence or absence of LBBB.

Results

Among patients without baseline MVA, the primary endpoint occurred in 36/423 (8.5%) of gene-elusive, 14/39 (35.9%) LMNA and 11/100 (11%) TTN cardiomyopathy patients (log-rank p < 0.001 for LMNA vs gene-elusive and LMNA vs TTN; p = 0.96 for TTN vs gene-elusive) during a median of 49 months of follow-up (Figure 1). For the gene-elusive group, lower left ventricular (LV) ejection fraction, larger LV end-diastolic diameter, ventricular ectopy on ECG and absence of LBBB were independently associated with the primary endpoint, including when accounting for cardiac resynchronisation therapy as a time-varying covariate.

Of 414 gene-elusive patients with baseline electrocardiograms, 35 (8.5%) experienced the primary endpoint during follow-up: 31/302 (10.3%) without LBBB and 4/112 (3.6%) with LBBB (log-rank p = 0.02; Figure 2).

Conclusions

Gene-elusive DCM patients have a risk of adverse events similar to TTN cardiomyopathy. Gene-elusive patients with LBBB are a particularly low-risk subgroup, which may reflect a distinct aetiology of LVSD independent of primary myocardial disease. Further research is needed to understand this phenotype and its response to prognostic heart failure therapies.