Clinical trial NCT02700425: His Bundle Pacing Versus Coronary Sinus Pacing for Cardiac Resynchronization Therapy
Official title: His Bundle Pacing Versus Coronary Sinus Pacing for Cardiac Resynchronization Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Congestive Heart Failure
Keywords: Wide QRS
Ventricular Dyssynchrony
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: Northwestern University
name: Rush University Medical Center
name: Geisinger Clinic
name: Indiana University
name: Edward Hospital
name: Baptist Health, Louisville
First posted: 2016-03-07
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to compare the effectiveness of pacing from a physiologic His bundle (HB) lead position versus with the standard coronary sinus (CS) lead position in subjects with heart failure undergoing cardiac resynchronization therapy (CRT). While placement of left ventricular leads via the coronary sinus has anatomic limitations, we hypothesis that the achievement of QRS narrowing with His bundle capture will be superior for improving systolic function by echocardiographic indices (ejection fraction and strain) and quality of life and decreased rehospitalization and mortality.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Left Ventricular Ejection Fraction (LVEF)
timeFrame: baseline and 6 months
measure: Change in QRS Duration
timeFrame: baseline and 12 months
measure: Time to First Cardiovascular Hospitalization or Death
timeFrame: Through study completion, an average of 12 months.
Secondary outcomes:
measure: New York Heart Association (NYHA) Functional Class Change
timeFrame: baseline, 6 months, and 12 months
measure: Quality of Life Change by Kansas City Questionnaire (KCCQ)
timeFrame: baseline and 12 months
measure: Time to First Cardiovascular Rehospitalization
timeFrame: Through study completion, an average of 12 months
measure: Time to First Treated Ventricular Arrhythmia/Ventricular Tachycardia (VT/VF)
timeFrame: Through study completion, an average of 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The University of California, Los Angeles
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Louisville
country: United States
facility: Baptist Health Louisville
state: Kentucky
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Chicago
name: Roderick Tung, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago
name: Gaurav A. Upadhyay, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS, Saleem M, Mandrola J, Genovese D, Tung R; His-SYNC Investigators. His Corrective Pacing or Biventricular Pacing for Cardiac Resynchronization in Heart Failure. J Am Coll Cardiol. 2019 Jul 9;74(1):157-159. doi: 10.1016/j.jacc.2019.04.026. Epub 2019 May 9. No abstract available.
citation: Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS, Saleem M, Mandrola J, Genovese D, Oren JW, Subzposh FA, Aziz Z, Beaser A, Shatz D, Besser S, Lang RM, Trohman RG, Knight BP, Tung R; His-SYNC Investigators. On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial. Heart Rhythm. 2019 Dec;16(12):1797-1807. doi: 10.1016/j.hrthm.2019.05.009. Epub 2019 May 13.