Background-Left ventricular (LV) pacing through the coronary sinus is the standard approach for cardiac resynchronization therapy. When this route is unavailable, the alternatives have major limitations. LV endocardial pacing through the interventriuclar septum may offer a simpler solution. We describe an initial case series to demonstrate technical feasibility and to describe our refinement of the puncture technique. Methods and Results-Ten patients with previous failed coronary sinus lead implant or with nonresponse to cardiac resynchronization therapy and a suboptimal LV lead position were selected. All patients were anticoagulated. Left ventriculography and coronary angiography were performed to identify LV borders and septal vessels. Subclavian vein access was used for a superior approach ventricular transseptal puncture under fluoroscopic guidance, using a steerable sheath and a standard transseptal needle, radiofrequency needle, or radiofrequency energy delivered through a guidewire. An active-fixation pacing lead was successfully delivered to the endocardial wall of the lateral LV in all patients (9 men; age, 62±10 years). LV lead implant procedure time shortened with experience. The use of radiofrequency energy delivered through a guidewire was the most effective technique. Mean threshold and R wave at implant were 0.8±0.3 V and 10.8±3.9 mV. At follow-up (mean, 8.7 months; minimum, 0; and maximum 19), thresholds were stable, and there were no thromboembolic events. Of 9 patients, 8 were classed as clinical responders (1 had inadequate follow-up to assess response). Conclusions-LV endocardial pacing through a ventricular septal puncture is a feasible approach for cardiac resynchronization therapy. (Circ Arrhythm Electrophysiol. 2014;7:17-22.)Key Words: cardiac resynchronization therapy ◼ endocardium ◼ heart ventricles ◼ septal Received September 11, 2013; accepted December 16, 2013. From the Oxford Heart Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom (T.R.B., J.H.P.G., R.K., Y.B., K.R.); and Department of Cardiology, Milton Keynes Hospital NHS Foundation Trust, Milton Keynes, United Kingdom (R.K. Figure 1). Once a LV pressure trace was seen, a hand injection of contrast media was used to confirm that the needle was in the LV cavity. The dilator and sheath were then advanced 10 to 20 mm into the chamber over the needle. The needle was withdrawn and a 0.032-inch stiff 260-cm J guidewire was advanced through the sheath and dilator and curled in the LV cavity. The sheath and dilator were then advanced through the septum until the sheath tip was 1 to 2 cm inside the LV. The sheath and dilator were withdrawn and exchanged over the stiff guidewire for a slit-able, deflectable lead delivery catheter and dilator (Medtronic Attain or Select Secure; Medtronic, Minneapolis, MN). 2. Radiofrequency needle (cases 2 and 3): the procedure was performed using a stiff 98-cm radiofrequency transseptal needle (NRG; Bayliss Medical, Montreal, Canada). When opposed against the s...