AIMS:Pacing from multiple sites in the left ventricle (LV) may bring about further resynchronization of the diseased heart compared with biventricular (BiV) pacing. We compared acute haemodynamic response (LV dP/dtmax) of multisite and BiV pacing using a quadripolar LV lead. METHODS AND RESULTS:In 21 patients receiving cardiac resynchronization therapy, a quadripolar LV lead and conventional right atrial and ventricular leads were connected to an external pacing system. A guidewire pressure sensor was placed in the LV for continuous dP/dt measurement. Four multisite pacing configurations were tested three times each and compared with BiV pacing using the distal LV electrode. Nineteen patients had useable haemodynamic data. Median increase in LV dP/dtmax with BiV vs. atrial-only pacing was 8.2% (interquartile range 2.3%, 15.7%). With multisite pacing using distal and proximal LV electrodes, median increase in LV dP/dtmax was 10.2% compared with atrial-only pacing (interquartile range 6.1%, 25.6%). In 16 of 19 patients (84%), two or more of the four multisite pacing configurations increased LV dP/dtmax compared with BiV pacing. Overall, 72% of all tested configurations of multisite pacing produced greater LV dP/dtmax than obtained with BiV pacing. Pacing from most distal and proximal electrodes was the most common optimal configuration, superior to BiV pacing in 74% of patients. CONCLUSION:In the majority of patients, multisite pacing improved acute systolic function further compared with BiV pacing. Pacing with the most distal and proximal electrodes of the quadripolar LV lead most commonly yielded greatest LV dP/dtmax.