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Prolonged QRS duration (QRS) has been associated with left ventricular dyssynchrony and dysfunction and with the development of heart failure. However, whether persistence or development of increased QRS over time is associated with an increased incidence of heart failure in hypertensive patients, independent of blood pressure lowering and regression of electrocardiographic left ventricular hypertrophy (LVH) has not been examined.The relation of QRS over time to incident heart failure was examined in 8945 hypertensive patients without history of heart failure who were randomly assigned to losartan-based or atenolol-based treatment. During 4.7 ± 1.1 years follow-up, heart failure hospitalization occurred in 282 patients (3.2%): in 157 with in-treatment QRS less than 110 ms (4.6 per 1000 patient-years) and in 125 with persistence or development of QRS 110 ms or more (13.4 per 1000 patient-years). In univariate Cox analyses in which QRS during the study was entered as a time-varying covariate, in-treatment persistence or development of a QRS 110 ms or more was associated with a 153% increased risk of developing heart failure [hazard ratio 2.53, 95% confidence interval (CI) 2.00–3.20]. After adjusting for treatment, baseline risk factors for heart failure, incident myocardial infarction and for baseline and in-treatment electrocardiographic LVH and blood pressure, persistence or development of a QRS 110 ms or more remained associated with a 102% increased risk of new-onset heart failure (hazard ratio 2.02, 95% CI 1.49–2.74).Persistence or development of a prolonged QRS during antihypertensive therapy is associated with an increased likelihood of new-onset heart failure, independent of blood pressure lowering, treatment modality and regression of electrocardiographic LVH in patients with essential hypertension. These findings suggest that serial assessment of QRS over time can be used to track the risk of heart failure in hypertensive patients.