Mechanisms and Innovations in Cardiac Resynchronisation Therapy (MIC)

Evaluation of Mechanisms and Innovations in Cardiac Resynchronization Therapy

The aim of this study is to compare the effectiveness of multiple modalities of cardiac resynchronisation therapy using high precision acute electrical and haemodynamic measurements.These modalities include biventricular pacing and conduction system pacing utilising His bundle and left bundle pacing. Conduction system pacing is a more physiological form of pacing. The study hypothesises that this will produce more effective cardiac resynchronisation.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Left Bundle-Branch Block; Left Ventricular Systolic Dysfunction; Right Bundle-Branch Block; Non-Specific Intraventricular Conduction Defect
• Intervention / Treatment: Device: His-bundle pacing.

Detailed Description

This is a single centre acute electrical/haemodynamic and observational study of a subgroup of patients with heart failure. A total of 60 will be recruited. The acute study involves within patient comparison of biventricular and conduction system pacing using detailed electrical mapping and high precision haemodynamic measurement protocol.

Participants will have permanent conduction system pacing if;

• Baseline left bundle branch block and QRS > 140ms or QRS >150ms and any QRS morphology AND
• Conduction system pacing is successful at reducing QRS duration by 20ms or more with satisfactory pacing parameters.

Participants who receive permanent conduction system pacing will have follow up at 6 weeks, 3 months, 6 months and 12 months. Non-invasive markers including mechanical activation pattern (echocardiography and cardiac MRI) and electrical activation pattern (ultra-high frequency electrocardiography) will be used to identify the characteristics of patients who benefit from conduction system pacing.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital Imperial College NHS trust

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients referred for conventional CRT
• Severe heart failure (LVEF, a measure of heart pumping, < 35% - severe)
• Prolonged QRS duration (>120ms)
• Adults willing to take part (age > 18 years)
• Able to give consent

Exclusion Criteria:

• Unable to give consent
• Children (age < 18 years)
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Heart failure and abnormal cardiac conduction; Subjects will have an attempt at His-bundle pacing, left bundle pacing and biventricular pacing. Pacing at the His bundle and the left bundle will be attempted using a Medtronic SelectSecure™, Model 3830 lead. Delivery of the lead utilizes a deflectable sheath, the Medtronic SelectSite™, Model C304. Biventricular pacing will utilise a left ventricular lead placed in the coronary sinus using any of the 5 manufactures of CS leads Biotronik, Boston Scientific, Medtronic, Sorin, and St. Jude Medical or in participants receiving permanent conduction system pacing left ventricular pacing will be achieved using a Cordis ATW™ wire placed in the coronary sinus.

Device: His-bundle pacing.; Cardiac resynchronisation therapy can be achieved using biventricular pacing involving placement of three leads into the right atrium, right ventricle and coronary sinus (epicardial left ventricle). Alternatively the third lead may be placed at the bundle of His or left ventricular septum to pace the left bundle directly.; Other Names: Left bundle pacing; Biventricular pacing; Combined His-bundle and left ventricular epicardial pacing (HOT-CRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute change is systolic blood pressure	Mean change in systolic blood pressure (mmHg) from atrial pacing to AV sequential CRT pacing (HBP, LBP, epiBVP and combined HPB with epiLVP) at optimal AV delay measured in mmHg.	20 minutes
Acute electrical measurements	Mean change in left ventricular activation time (Milliseconds) (measured using ECGI) during AV sequential CRT pacing (HBP, LBP, epiBVP and combined HPB with epiLVP) at optimal AV delay measured in Milliseconds.	20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conduction system battery longevity	The measurements include battery longevity measured in months.	6 weeks, 3 months, 6 months, 12 months.
Conduction system lead threshold	The measurements include lead threshold to achieved QRS narrowing measured in Volts at 0.5ms and 1ms.	6 weeks, 3 months, 6 months, 12 months.
Heart failure symptoms	Heart failure symptoms of patients with permanent conduction system leads will be assessed at follow up at 3 month, 6 months and 12 months. The symptoms will be assessed using the Minnesota living with heart failure questionnaire score.	6 months
Left ventricular ejection fraction	Patients with permanent conduction system leads will undergo a repeat echocardiography and measure their left ventricular ejection fraction.	12 months
Cardiopulmonary exercise testing	Patients with permanent conduction system leads will undergo symptom assessment with a repeat cardio-pulmonary exercise test to measure MVO2 in litres/minute.	6 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Study Chair: Zachary Whinnett, BM BS B, Imperial College London

Publications and helpful links

General Publications

• Cleland JG, Abraham WT, Linde C, Gold MR, Young JB, Claude Daubert J, Sherfesee L, Wells GA, Tang AS. An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart J. 2013 Dec;34(46):3547-56. doi: 10.1093/eurheartj/eht290. Epub 2013 Jul 29.
• Vijayaraman P, Herweg B, Ellenbogen KA, Gajek J. His-Optimized Cardiac Resynchronization Therapy to Maximize Electrical Resynchronization: A Feasibility Study. Circ Arrhythm Electrophysiol. 2019 Feb;12(2):e006934. doi: 10.1161/CIRCEP.118.006934.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2019
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: January 6, 2020
• First Posted (Actual): January 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Cardiac resynchronization therapy; His bundle pacing; Haemodynamics; ECGI
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Bundle-Branch Block; Heart Block; Cardiac Conduction System Disease
• Other Study ID Numbers: 18HH4801; FS/19/4/34013 (Other Grant/Funding Number: British Heart Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to share the electrical data obtained from non-invasive electrical mapping with Medtronic (industry company)
• IPD Sharing Time Frame: 3 years
• IPD Sharing Access Criteria: Medtronic will only have access to anonymised data in the form of non-invasive electrical maps (ECGi, CardioInsight)
• IPD Sharing Supporting Information Type: ANALYTIC_CODE

Drug and device information, study documents

• 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.: Yes