Left bundle branch block in dilated and non-dilated left ventricular cardiomyopathy: relation to genetics, imaging and endomyocardial biopsy

Background

Dilated cardiomyopathy (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC) present structural and functional abnormalities of the left ventricle. The detrimental effect of left bundle brunch block (LBBB) on left ventricular ejection fraction (LVEF) and clinical outcomes is well established, as is the benefit of cardiac resynchronization therapy (CRT). How LBBB or response to CRT relates to genetic features, CMR findings, and EMB data remains largely unknown.

Aim

To compare clinical/imaging characteristics in patients with DCM or NDLVC with or without LBBB, and to evaluate the predictive value of genetic, CMR, and EMB for response to CRT in LBBB.

Methods

1.102 patients with DCM or NDLVC from the Maastricht Cardiomyopathy Registry were included. Patients were stratified according to the presence of LBBB.

Data on genetic testing, CMR, EMB, medical and device-based therapies were collected.

Response to CRT at 6 months follow-up, defined as an improvement in left ventricular end-systolic volume (LVESV) of at least 15%, assessed by echocardiography, was evaluated in patients with available echo before and after CRT.

Results

The study population consisted of 233 patients with LBBB and 869 without LBBB. Patients with LBBB were older (59.6 ± 10.7 vs 55.0 ± 12.6 years) and had lower rate of atrial fibrillation and chronic kidney disease compared to those without LBBB. LBBB patients had a significantly lower LVEF (32.9 ± 13.3% vs 35.2 ± 13.4%), lower prevalence of pathogenic (P) or likely pathogenic (LP) variants (12% vs 25.6%), and were more frequently treated with CRT (66.5% vs 6.9%).

On CMR, LBBB was related to a significantly higher left ventricular mass

(143.8 ± 44.1 vs 125.9 ± 40.2 g), and worse global circumferential strain (GCS, -13.4 ± 6.1 vs -18.1 ± 13.9).

The LBBB group had a lower number of CD3+ T lymphocytes.

In a subgroup of LBBB patients who underwent CRT (n = 109 out of 233 LBBB patients), 73 (67%) responded to therapy, while 36 did not. Responders showed a reduction in LVESV (-41.4% vs +4.6%) and an improvement in LVEF (+14.5 vs -0.8%) compared with non-responders.

A better CRT response was associated with wider QRS (163 ± 19 vs 155 ± 16.7), higher GCS (-10.6 ± 3.5 vs -14.1 ± 4.9), and absence of subepicardial LGE, while genetics negative showed a trend of benefit. In multivariable analysis, impaired GCS and genetics negative resulted independent predictors of a favourable CRT response.

Conclusions

LBBB patients represent a distinct DCM/NDLVC phenotype characterized by older age, fewer comorbidities and higher left ventricular mass. Impaired GCS at CMR and genetics negative identify those patients most likely to benefit from CRT.

These findings support integrating electrocardiographic, imaging parameters and genetic tests to guide patient selection for CRT.Baseline characteristics DCM/NDLVCFor image description, please refer to the figure legend and surrounding text.LBBB response to CRT: Sankey plotFor image description, please refer to the figure legend and surrounding text.