Effects of CRT Optimization as Assessed by Cardiac MR

• ClinicalTrials.gov Identifier: NCT04763460
• Recruitment Status: Recruiting
• First Posted: February 21, 2021
• Last Update Posted: September 27, 2021
• Sponsor: Allina Health System
• Collaborator: Minneapolis Heart Institute Foundation
• Information provided by (Responsible Party): Alan J. Bank, MD, Allina Health System

Study Description

Brief Summary:

Cardiac resynchronization therapy (CRT), or atrial-synchronized biventricular (BiV) pacing, is an FDA-approved device therapy option for heart failure (HF) patients with reduced left ventricular ejection fraction and electrical dyssynchrony. A traditional CRT device has pacing leads implanted within the right atrium (RA), the right ventricle (RV), and within a coronary vein overlying the lateral or posterior left ventricle (LV). Within the past decade, various multi-center randomized controlled trials have reported improved quality of life, aerobic exercise capacity, LV systolic function and structure, as well as decreased hospitalization rates and mortality among patients with HF. Despite improvements in CRT technology with multipoint pacing, quadripolar leads, and adaptive pacing algorithms, approximately 30% of patients do not clinically benefit and are considered non-responders. This study looks to optimize CRT device programming in patients considered non-responders to CRTusing information obtained from standard ECG machines, and to assess acute and chronic effects of CRT optimization using cardiac magnetic resonance imaging (CMR).

Condition or disease	Intervention/treatment	Phase
Heart Failure, Systolic	Device: Programming of CRT device settings	Not Applicable

Detailed Description:

This is a prospective, randomized study designed to evaluate if CRT device optimization, guided by electrocardiography, improves cardiac function and clinical outcomes among patients considered non-responders to CRT. All patients will have electrocardiographic assessment of electrical dyssynchrony at a range of device settings using standard ECG machines. All patients will then have a baseline CMR study at baseline CRT programming, underlying rhythm, and optimal settings derived from the electrocardiographic assessment to assess acute effects of CRT optimization on mechanical synchrony, LV regional wall motion, and LV structure/ function. To assess chronic effects of CRT optimization, patients will be randomized in a 1:1 ratio after baseline CMR to either the active comparator arm (baseline CRT programming), or the experimental arm (CRT device programmed to optimal settings derived from the electrocardiographic assessment). Patients will be blinded to randomization. After 6 month, all patients will return for follow up CMR study to assess chronic effects. After follow up CMR imaging, the active comparator group will crossover to the experimental group. After 12 months, all patients will return for follow up echocardiogram to further evaluate the chronic effects of CRT optimization.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel (with 6 month crossover) 1:1 randomization - active comparator and experimental arm (note: at 6 month, the active comparator arm will crossover to the experimental arm)
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Patients blinded to which group they are randomized and how their CRT device is programmed during the study. Individuals (readers) who perform cardiac magnetic resonance and echocardiographic imaging measurements blinded to patient randomization and CRT programming.
• Primary Purpose: Treatment
• Official Title: Effects of CRT Optimization on LV Mechanical Synchrony, Structure, and Function in CRT Patients as Assessed by Cardiac MR
• Actual Study Start Date: July 1, 2021
• Estimated Primary Completion Date: April 1, 2024
• Estimated Study Completion Date: April 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Baseline CRT programming; The comparator arm patients will remain at baseline CRT programming for the first 6 months, and then will crossover to the experimental arm and CRT device will be programmed to optimal settings derived from the electrocardiographic assessment for the following 6 months.	Device: Programming of CRT device settings; Reprogramming of CRT device to maximize the benefit derived from the electrocardiographic assessment.
Experimental: Electrocardiography-guided optimal CRT programming; The experimental arm patients will have CRT device programmed based on the electrocardiographic assessment for 12 months.	Device: Programming of CRT device settings; Reprogramming of CRT device to maximize the benefit derived from the electrocardiographic assessment.

Outcome Measures

Primary Outcome Measures :

1. Acute changes in left ventricular mechanical synchrony in study population [ Time Frame: During Baseline Assessment ]
   Acute changes, measured by cardiac magnetic resonance imaging, in left ventricular mechanical synchrony at underlying rhythm, baseline CRT programming, and optimal programming derived from electrocardiographic assessment in all patients.
2. Acute changes in left ventricular regional wall motion in study population [ Time Frame: During Baseline Assessment ]
   Acute changes, measured by cardiac magnetic resonance imaging, in left ventricular wall motion at underlying rhythm, baseline CRT programming, and optimal programming derived from electrocardiographic assessment in all patients.
3. Acute changes in left ventricular end-diastolic volume in study population [ Time Frame: During Baseline Assessment ]
   Acute changes, measured by cardiac magnetic resonance imaging, in left ventricular end-diastolic volume at underlying rhythm, baseline CRT programming, and optimal programming derived from electrocardiographic assessment in all patients.
4. Acute changes in left ventricular end-systolic volume in study population [ Time Frame: During Baseline Assessment ]
   Acute changes, measured by cardiac magnetic resonance imaging, in left ventricular end-systolic volume at underlying rhythm, baseline CRT programming, and optimal programming derived from electrocardiographic assessment in all patients.
5. Chronic changes in left ventricular mechanical synchrony [ Time Frame: Baseline to 12 months ]
   Chronic changes, measured by cardiac magnetic resonance imaging and echocardiography, in left ventricular mechanical synchrony between the experimental and active comparator group.
6. Chronic changes in left ventricular regional wall motion [ Time Frame: Baseline to 12 months ]
   Chronic changes, measured by cardiac magnetic resonance imaging and echocardiography, in left ventricular regional wall motion between the experimental and active comparator group.
7. Chronic changes in left ventricular end-diastolic volume [ Time Frame: Baseline to 12 months ]
   Chronic changes, measured by cardiac magnetic resonance imaging and echocardiography, in left ventricular end-diastolic volume between the experimental and active comparator group.
8. Chronic changes in left ventricular end-systolic volume [ Time Frame: Baseline to 12 months ]
   Chronic changes, measured by cardiac magnetic resonance and echocardiographic imaging, in left ventricular end-systolic volume between the experimental and active comparator group.

Secondary Outcome Measures :

1. Change in 6 Minute Hall Walk (6MHW) [ Time Frame: Baseline to 12 months ]
   Comparison between experimental arm and active comparator arm in 6MHW
2. Change in Kansis City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: Baseline to 12 months ]
   Comparison between experimental arm and active comparator arm in KCCQ. Scores are scaled 0-100. Higher scores indicate better outcomes.

Other Outcome Measures:

1. Correlation in electrical dyssynchrony and left ventricular function in study population [ Time Frame: Baseline to 12 months ]
   Changes in electrical dyssynchrony, measured by electrocardiography, and correlation to change in left ventricular function, measured by cardiac magnetic resonance and echocardiographic imaging, in all patients.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Currently on standard medical therapy
2. CRT device in place for > 4 months
3. Non-responder (ejection fraction improvement with CRT < 5%) or incomplete responder (ejection fraction < 40%)
4. Suboptimal electrical wavefront fusion at current CRT programming as observed on 12-lead ECG
5. Left bundle branch block, interventricular conduction delay or right ventricular paced underlying QRS complex
6. Age > 18 years

Exclusion Criteria:

1. Decompensated heart failure
2. Right bundle branch block
3. Pregnancy or lactation
4. History of severe allergic reactions to ECG gels, electrode adhesives, and/or cardiac magnetic resonance contrast (e.g. gadolinium)
5. Implantation of pacing lead in the his bundle or left bundle branch
6. Frequent ventricular ectopy as defined as >10% premature ventricular contraction burden by either device interrogation or Holter monitor, or sustained ventricular tachycardia/ventricular fibrillation
7. Uncontrolled atrial fibrillation (HR > 100 bpm)
8. Patient is enrolled in concurrent research study that would potentially confound the results of this study (noting: co-enrollment acceptable if patient is enrolled in registry study)

Contacts and Locations

Contacts

Contact: Christopher D Brown; 651-241-2806; christopher.brown2@allina.com

Locations

United States, Minnesota

Minneapolis Heart Institute - Abbott Northwestern Hospital (MHI West); Recruiting

Minneapolis, Minnesota, United States, 55407

Contact: Christopher D Brown 651-241-2806 christopher.brown2@allina.com

Sub-Investigator: João L Cavalcante, MD

Sub-Investigator: Jay D Sengupta, MD

United Heart & Vascular Clinic - Nasseff Specialty Center (MHI East); Recruiting

Saint Paul, Minnesota, United States, 55102

Contact: Christopher D Brown 651-241-2806 christopher.brown2@allina.com

Principal Investigator: Alan J Bank, MD

Sponsors and Collaborators

Allina Health System

Minneapolis Heart Institute Foundation

Investigators

• Principal Investigator: Alan J Bank, MD; Allina Heath System

More Information

• Responsible Party: Alan J. Bank, MD, Medical Director of Research - United Heart & Vascular Clinic (MHI East), Allina Health System
• ClinicalTrials.gov Identifier: NCT04763460
• Other Study ID Numbers: IRBnet#: 1706252
• First Posted: February 21, 2021
• Last Update Posted: September 27, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: We do not plan to share IPD with other external researchers.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Alan J. Bank, MD, Allina Health System:

Cardiac Resynchronization Therapy; Pacing; Electrocardiography; Cardiac Magnetic Resonance Imaging; Echocardiography; Optimization of Cardiac Devices; Heart Failure

Additional relevant MeSH terms:

Heart Failure; Heart Failure, Systolic; Heart Diseases; Cardiovascular Diseases