BACKGROUND: Direct His-bundle pacing (DHBP) produces synchronous ventricular depolarization and improved cardiac function relative to apical pacing. Although it has been performed transiently in the electrophysiology laboratory and persistently in open-chested canines, permanent DHBP in humans has not been achieved. METHODS AND RESULTS: A total of 18 patients aged 69+/-10 years who had a history of chronic atrial fibrillation, dilated cardiomyopathy, and normal activation (ie, QRS< or =120 ms) were screened for permanent DHBP using an electrophysiology catheter. In 14 patients, the His bundle could be reliably stimulated. Of these 14, permanent DHBP using a fixed screw-in lead was successful in 12 patients. Radiofrequency atrioventricular node ablation was performed in patients exhibiting a fast ventricular response. All patients received single-chamber rate-responsive pacemakers. Acute pacing thresholds were 2.4+/-1.0 V at a pulse duration of 0.5 ms. Lead complications included exit block requiring reoperative adjustment and gross lead dislodgment. Echocardiographic improvement in heart function was shown by reductions in the left ventricular end-diastolic dimension from 59+/-8 to 52+/-6 mm (P</=0.01) and in the end-systolic dimension from 51+/-10 to 43+/-8 mm (P<0.01), with an accompanying increase in fractional shortening from 14+/-7% to 20+/-10% (P=0.05). The left ventricular ejection fraction improved from 20+/-9% to 31+/-11% (P<0. 01), and the cardiothoracic ratio decreased from 0.61+/-0.06 to 0. 57+/-0.07 (P<0.01). Despite DHBP, 2 patients died at 8 and 36 months. Conclusions-Permanent DHBP is feasible in select patients who have chronic atrial fibrillation and dilated cardiomyopathy. Long-term, DHBP results in a reduction of left ventricular dimensions and improved cardiac function.