Mechanism and Impact of Left Atrial Dyssynchrony on Long-Term Clinical Outcome During Cardiac Resynchronization Therapy

Background: Left bundle branch block (LBBB) causes left atrial (LA) dyssynchrony. It is unknown if LA dyssynchrony impacts long-term prognosis.

Objectives: The purpose of this study was to determine mechanisms of LA dyssynchrony in LBBB and if LA dyssynchrony impacts long-term prognosis.

Methods: In a prospective multicenter study of 168 heart failure patients with LBBB, echocardiographic strain imaging was done before and after 6 months with cardiac resynchronization therapy (CRT). Outcome was assessed after 6 years. Dyssynchrony was measured relative to septum as delay in left ventricular (LV) lateral wall shortening and LA lateral wall stretch. Response to CRT was defined as at least 15% reduction in LV end-systolic volume.

Results: Before CRT, there was marked LA dyssynchrony of 105 ± 76 ms, which decreased to 37 ± 68 ms in CRT-responders (P < 0.001), whereas nonresponders showed only a modest reduction in LA dyssynchrony (P < 0.05). There was strong association between LA and LV dyssynchrony (r = 0.70), consistent with direct LV-LA mechanical interaction. CRT caused modest increase in LA reservoir strain (P < 0.01) and marked increase of LV filling time (P < 0.001) in responders. Mortality after 6 years was 21% (35 deaths). LA dyssynchrony did not independently predict mortality. However, the combination of preserved LA reservoir strain (≥18%) and resolved LA dyssynchrony (≤53 ms) after 6 months with CRT was associated with excellent long term-prognosis: HR: 0.11 (95% CI: 0.03-0.42) vs preserved reservoir strain and persistent LA dyssynchrony.

Conclusions: LA dyssynchrony in LBBB was attributed to direct LV-LA mechanical interactions. CRT improved diastolic function by increasing LV filling time. Patients with preserved LA reservoir strain and resolution of LA dyssynchrony by CRT had excellent long-term prognosis. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185).