In cardiac resynchronization therapy (CRT), biventricular pacing is performed by pacing the right ventricle (RV) and epicardium of the left ventricular (LV) postero-lateral wall. A significant proportion of apparently suitable patients fail to benefit from CRT. One of the problems of CRT is proper positioning and fixation of the LV pacing lead in the coronary vein. LV septal pacing may be a good alternative for BiV pacing in patients with an indication for CRT.

Cardiac pump function depends on physiological electrical activation of the ventricles. This normal activation is disturbed during artificial electrical stimulation (pacing) of the right ventricle (RV), the common therapy to treat symptomatic slow heart rate ("rate control"), as well as during electrical dyssynchrony such as left bundle branch block (LBBB). As a consequence, RV pacing and LBBB reduce cardiac pump function and increase cardiac morbidity and mortality. During the last two decades cardiac resynchronization therapy (CRT) has emerged as treatment to "resynchronize" ventricular electrical activation by pacing the RV apical septum and left ventricular (LV) postero-lateral wall simultaneously ("biventricular" (BiV) pacing).

Since initial approval of the therapy over 10 years ago, there have been hundreds of thousands of implants performed worldwide. In the Netherlands currently more than 2000 CRT devices are implanted each year. Large clinical trials have shown that CRT improves LV systolic pump function, reverses structural remodelling, improves quality of life and exercise tolerance, and decrease mortality. However, a significant proportion of apparently suitable patients fail to benefit. Depending on the definition used, the response to CRT is positive in 50-70% of treated patients, leaving 30-50% without significant effect. One of the problems of CRT is proper positioning and fixation of the LV pacing lead in the coronary vein.

Research in the laboratory of the the investigators revealed that in dogs with AV-block and in patients with sinus node disease, pacing at the LV endocardial side of the interventricular septum (LV septal pacing) provides near physiological ventricular activation, near uniform distribution of workload, and near normal pump function. Furthermore, pump function during LV septal pacing was at least as good as during BiV pacing. A recent study, with acute hemodynamic data in dogs with LBBB and in a small group of patients with LBBB, further indicates that LV septal pacing may be used for CRT. A weakness of the patient data is that these patients were either non-responders to conventional CRT or patients where no access to the coronary sinus was obtained. Therefore, this group may not be representative for the entire CRT candidate population.

Two factors appear to determine the positive effect of LV septal pacing: the slow impulse conduction across the interventricular septum and the fast impulse conduction along the inner layers of the LV wall through superficial, non-Purkinje fibers. Following this reasoning, the investigators expect that the exact pacing site at the septum is not critical. This would be of great advantage for future applications in patients, since proper implantation of an LV lead in the coronary sinus requires attention in order to position the lead in the latest activated region.

The aim of the present study is to compare the electrophysiological and hemodynamic effects of several modes and sites of LV septal pacing with those of BiV pacing in patients undergoing CRT device implantation. The results may have a large impact on future pacing therapy. The LV septum may become an alternative for BiV pacing, but easier to apply, less invasive, and more cost-effective.

Inclusion Criteria:

• Chronic heart failure with NYHA functional class II-IV
• Left ventricular ejection fraction (LVEF) < 35%
• LBBB and QRS duration ≥ 130 ms or non-LBBB and QRS duration ≥ 150 ms
• In sinus rhythm
• Optimal pharmacological therapy

Exclusion Criteria:

• Persistent atrial fibrillation
• ≥ 2 premature ventricular complexes on standard 12-lead electrocardiogram (ECG)
• Age < 18 years
• Incapable of giving informed consent
• Moderate to severe aortic valve stenosis
• Peripheral vascular disease