His Bundle Pacing Versus Coronary Sinus Pacing for Cardiac Resynchronization Therapy (His-SYNC)

• ClinicalTrials.gov Identifier: NCT02700425
• Recruitment Status: Completed
• First Posted: March 7, 2016
• Results First Posted: August 10, 2021
• Last Update Posted: September 5, 2021
• Sponsor: University of Chicago
• Collaborators: University of California, Los Angeles; Northwestern University; Rush University Medical Center; Geisinger Clinic; Indiana University; Edward Hospital; Baptist Health, Louisville
• Information provided by (Responsible Party): University of Chicago

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Congestive Heart Failure	Device: CRT Pacemaker	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: His Bundle Pacing Versus Coronary Sinus Pacing for Cardiac Resynchronization Therapy
• Actual Study Start Date: May 17, 2016
• Actual Primary Completion Date: July 31, 2020
• Actual Study Completion Date: July 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: His Bundle Pacing; Subjects will be randomized to the HB lead position with their cardiac resynchronization therapy (CRT) pacemaker. HB lead pacing will be performed with the Medtronic SelectSecure™, Model 3830 lead. Delivery of the lead utilizes a deflectable sheath, the Medtronic SelectSite™, Model C304. Both devices are FDA approved for the purpose of HB pacing. It is the only device available which is presently FDA approved for selective HB pacing.	Device: CRT Pacemaker; Cardiac Resynchronization Therapy (CRT) is the use of a pacemaker with two endocardial leads placed in the right atrium (RA) and right ventricle (RV). The third lead is traditionally placed in a tributary of the coronary sinus (CS) overlying the epicardial surface of the left ventricle (LV). Alternatively, the third lead may be positioned based on mapping of the common His bundle and actively fixed to achieve QRS normalization via direct His bundle capture.
Active Comparator: Coronary Sinus Pacing; Subjects will be randomized to the CS lead position with their cardiac resynchronization therapy (CRT) pacemaker. CS lead and CRT device generator selected for implant will be left to the discretion of the operator. Only FDA approved CS leads and CRT generators will be utilized in the study. There are five present manufacturers of CS leads and CRT generators: Biotronik, Boston Scientific, Medtronic, Sorin, and St. Jude Medical.	Device: CRT Pacemaker; Cardiac Resynchronization Therapy (CRT) is the use of a pacemaker with two endocardial leads placed in the right atrium (RA) and right ventricle (RV). The third lead is traditionally placed in a tributary of the coronary sinus (CS) overlying the epicardial surface of the left ventricle (LV). Alternatively, the third lead may be positioned based on mapping of the common His bundle and actively fixed to achieve QRS normalization via direct His bundle capture.

Outcome Measures

Primary Outcome Measures :

1. Change in Left Ventricular Ejection Fraction (LVEF) [ Time Frame: baseline and 6 months ]
   Change in left ventricular ejection fraction (LVEF) as measured by echocardiography in a blinded core lab.
2. Change in QRS Duration [ Time Frame: baseline and 12 months ]
   Change in QRS duration as measured by electrocardiography
3. Time to First Cardiovascular Hospitalization or Death [ Time Frame: Through study completion, an average of 12 months. ]
   Time to first cardiovascular hospitalization or death in months

Secondary Outcome Measures :

1. New York Heart Association (NYHA) Functional Class Change [ Time Frame: baseline, 6 months, and 12 months ]
   New York Heart Association (NYHA) functional class change for baseline, 6 months, and 12 months. NYHA class determines the functional status of the patient. There are classes I-IV. Class I is no symptoms or limitation of physical activity, II is slight limitation of physical activity but comfortable at rest, III marked limitation of physical activity, and IV is unable to carry any physical activity without discomfort, heart failure symptoms at rest, and discomfort increases with any physical activity as described the American Heart Association (AHA).
2. Quality of Life Change by Kansas City Questionnaire (KCCQ) [ Time Frame: baseline and 12 months ]
   Quality of life change as measured by Kansas City Questionnaire (KCCQ) is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from minimum of 0-100 (maximum); higher scores show better health status. Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
3. Time to First Cardiovascular Rehospitalization [ Time Frame: Through study completion, an average of 12 months ]
   Time to first cardiovascular rehospitalization in 12 months
4. Time to First Treated Ventricular Arrhythmia/Ventricular Tachycardia (VT/VF) [ Time Frame: Through study completion, an average of 12 months ]
   Time to first treated ventricular arrhythmia/ventricular tachycardia (VT/VF) in 12 months

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

The University of California, Los Angeles

Los Angeles, California, United States, 90095

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

Rush University Medical Center

Chicago, Illinois, United States, 60612

The University of Chicago

Chicago, Illinois, United States, 60637

Edward Hospital

Naperville, Illinois, United States, 60540

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Kentucky

Baptist Health Louisville

Louisville, Kentucky, United States, 40207

United States, Pennsylvania

Geisinger Wyoming Valley Medical Center

Wilkes-Barre, Pennsylvania, United States, 18711

Sponsors and Collaborators

University of Chicago

University of California, Los Angeles

Northwestern University

Rush University Medical Center

Geisinger Clinic

Indiana University

Edward Hospital

Baptist Health, Louisville

Investigators

• Principal Investigator: Roderick Tung, MD; University of Chicago
• Principal Investigator: Gaurav A. Upadhyay, MD; University of Chicago

  Study Documents (Full-Text)

Documents provided by University of Chicago:

Study Protocol and Statistical Analysis Plan  [PDF] December 9, 2019

More Information

Publications of Results:

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.

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.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT02700425
• Other Study ID Numbers: IRB15-1728
• First Posted: March 7, 2016
• Results First Posted: August 10, 2021
• Last Update Posted: September 5, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by University of Chicago:

Wide QRS; Ventricular Dyssynchrony

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases