His Bundle Pacing Versus Coronary Sinus Pacing for Cardiac Resynchronization Therapy

This is a randomized, single-blinded study of 40 patients to a strategy of HB pacing versus
CS pacing, and remain blinded to their treatment allocation. Both treatment options use
standard-of-care, FDA-approved devices. The distinction is only in the allocation toward HB
pacing and CS pacing. Treating physicians will be aware of assignment in order to facilitate
routine device follow-up. Echocardiographic and electrocardiographic evaluation will also be
performed in a blinded manner.

Cross-over is permitted between treatment group allocation if:

- CS lead cannot be placed due to difficult cannulation of the CS, limited branches at the
posterolateral or lateral wall, or phrenic nerve capture. These subjects may then
cross-over to HB pacing.

- HB pacing subjects may cross-over if HB lead cannot be positioned with adequate
stability and reasonable pacing output, or if QRS width does not narrow by at least 20%
or to a QRS width of ≤ 130 msec.

Implant procedure will be per routine percutaneous access, as is standard for pacemaker and
ICDs. All subjects will receive an FDA-approved cardiac resynchronization therapy pacemaker
or defibrillator device, as per standard of care outlined for the subject. In order to
facilitate optimal lead placement, arterial access for levo-phase CS angiography and/or LV
septal mapping to characterize site of bundle-branch block may also be performed, at the
discretion of the implanting physician per his/her standard practice.

Follow-up will be performed at 2 weeks post-implant for incision check and device
interrogation as is standard of care. In addition, routine device and clinical follow-up will
be scheduled at 1, 3, 6, and 12 months. Electrocardiography (ECG) will be performed
pre-implant, prior to hospital discharge, at 3 months, 6 months, and 12 months.
Echocardiography will be performed pre-implant and 6 months to evaluate for change in LVEF,
chamber dimension, and wall motion with strain imaging as is standard of care in the
treatment of patients with advanced heart failure. NYHA functional class and quality of life
(utilizing the Kansas City Cardiomyopathy Questionnaire) will be assessed pre-implant and at
6 months.

Inclusion Criteria:

- Patients at least 18 years of age

- LV systolic dysfunction with LVEF ≤ 35%

- Evidence of intraventricular conduction delay with QRS duration > 120 msec

- NYHA Class II, III, and ambulatory Class IV heart failure with either ischemic or
nonischemic cardiomyopathy and patients with NYHA Class I symptoms and ischemic
cardiomyopathy

- Left ventricular ejection fraction (LVEF) ≤ 35%, sinus rhythm (SR), left bundle-branch
block (LBBB) morphology, and QRS duration ≥ 150 msec, and NYHA Class II, III, or
ambulatory Class IV patients on goal-directed medical therapy (GDMT) [Class I]

- LVEF ≤ 35%, SR with LBBB with QRS 120-149 msec on GDMT [Class IIa]

- LVEF ≤ 35%, SR with non-LBBB with QRS ≥ 150 msec on GDMT [Class IIa]

- LVEF ≤ 35%, in AF if medication or AV nodal ablation will allow near 100% pacing
[Class IIa]

- LVEF ≤ 35% undergoing new or replacement device with anticipated >40% ventricular
pacing on GDMT [Class IIa]

- LVEF ≤ 30%, ischemic etiology of HF, SR with LBBB ≥ 150 msec and NYHA Class I symptoms
on GDMT [Class IIb]

- LVEF ≤ 35%, SR with non-LBBB with QRS 120-149 msec, NYHA Class III/ambulatory Class IV
HF on GDMT [Class IIb] LVEF ≤ 35%, SR with non-LBBB with QRS ≥ 150 msec, NYHA Class II
HF on GDMT [Class IIb]

Exclusion Criteria:

- Existing CRT device

- Inability of patient capacity to provide consent for themselves either due to medical
or psychiatric comorbidity

- Pregnancy

- Participation in other trials

- Difficulty with follow-up