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Objective: Left bundle branch block (LBBB), which is associated with underlying cardiac disease, is believed to play a role in the pathogenesis of cardiomyopathy through delays in interventricular conduction, leading to dyssynchrony. However, this has not been established in previous studies. It is unclear whether LBBB indicates clinically advanced cardiac disease or is an independent factor responsible for increased mortality and the development of heart failure. We investigated the natural history of isolated LBBB without any associated structural heart disease in order to determine its clinical significance. Methods: We performed a retrospective chart review on consecutive patients who fulfilled the 12-lead electrocardiographic (ECG) criteria for complete LBBB and had a normal echocardiogram with no evidence of structural heart disease and left or right ventricular systolic dysfunction within three months of the initial ECG between January 1, 2000 and December 31, 2009. We excluded patients with documented coronary artery disease (CAD) at any time, any structural heart disease, or cardiac devices. We evaluated the primary endpoints of mortality and incidence of cardiomyopathy, as well as any heart failure hospitalizations over a 1- and 10-year period. Results: We identified 2522 eligible patients. The mean follow-up duration was 8.4±3.2 years. The one-year mortality rate was 7.8%, with a 10-year mortality rate of 22.0%. The incidence of cardiomyopathy over one year was 3.2% and over 10 years was 9.1%. There was no significant difference in QRS duration between patients who were alive and those that were deceased at 10 years (141+/-18 vs. 141+/-17 ms; p=0.951) and patients with and without cardiomyopathy at 10 years (142±17 vs. 141±17 ms; p=0.532). Conclusion: Isolated LBBB occurring without structural heart disease, ventricular dysfunction, or CAD is associated with a low mortality rate and incidence of cardiomyopathy. [ABSTRACT FROM AUTHOR]