Ventricular Pacing Lead Location Alters Systemic Hemodynamics and Left Ventricular Function in Patients With and Without Reduced Ejection Fraction Randy Lieberman, Luigi Padeletti, Jan Schreuder, Kenneth Jackson, Antonio Michelucci, Andrea Colella, William Eastman, Sergio Valsecchi, Douglas A. Hettrick Left ventricular (LV) pressure and volume data were determined in 31 patients with normal QRS duration in groups with ejection fraction (EF) ≥40% or EF <40% during pacing from the right ventricular (RV) apex, RV free wall, RV septum, LV free wall, and biventricular (BiV). In patients with EF ≥40%, RV pacing significantly impaired cardiac output, stroke work, EF, and LV relaxation compared to atrial pacing. Left ventricular and BiV pacing increased cardiac output, stroke work, EF, and LV +dP/dt in patients with LV EF <40%. Left ventricular and BiV pacing preserve LV function in patients with EF >40% and improve function in patients with EF <40% despite no indication for BiV pacing. We compared left ventricular (LV) systolic and diastolic function during right ventricular (RV), LV, and biventricular (BiV) pacing in patients with narrow QRS duration with and without LV dysfunction. The optimal RV pacing lead location for patients with a standard indication for ventricular pacing remains controversial. Left ventricular pressure and volume data were determined via conductance catheter during electrophysiology study in 31 patients divided into groups with ejection fraction (EF) ≥40% (n = 17) or EF <40% (n = 14). QRS duration was 91 ± 18 versus 106 ± 25 ms, respectively (p = NS). Hemodynamic data were recorded during atrial and dual chamber pacing from the RV apex, RV free wall, RV septum, LV free wall, and BiV. In patients with EF ≥40%, RV pacing at 1 or more sites, but not LV free wall or BiV pacing, significantly (p < 0.05) impaired cardiac output (CO), stroke work (SW), EF, and LV relaxation compared with atrial overdrive pacing. Right ventricular pacing also impaired hemodynamics and LV function in patients with EF <40%. However, LV and BiV pacing increased CO, SW, EF, and LV +dP/dt MAX in patients with LV dysfunction. Left ventricular and BiV pacing enhanced an index of global LV cycle efficiency in patients with depressed EF. The detrimental hemodynamic effects of RV pacing were attenuated by selecting the optimal RV pacing site. Right ventricular pacing worsens LV function in patients with and without LV dysfunction unless the RV pacing site is optimized. Left ventricular and BiV pacing preserve LV function in patients with EF >40% and improve function in patients with EF <40% despite no clinical indication for BiV pacing.