Mechanisms and Innovations in Cardiac Resynchronisation Therapy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Evaluation of Mechanisms and Innovations in Cardiac Resynchronization Therapy

Conditions
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Heart Failure, Left Ventricular Systolic Dysfunction, Left Bundle-Branch Block, Right Bundle-Branch Block, Non-Specific Intraventricular Conduction Defect

Intervention / Treatment
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* Device: His-bundle pacing.


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 60 patients with heart failure, severe left ventricular systolic dysfunction and cardiac conduction abnormality (QRS > 120ms) will be recruited and undergo an attempt at His bundle, left bundle pacing and biventricular pacing. Patients will have acute haemodynamic and electrical measurements.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heart failure and abnormal cardiac conduction<br>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.<br>* 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.<br>* Other names: Combined His-bundle and left ventricular epicardial pacing (HOT-CRT);|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac resynchronization therapy, His bundle pacing, Haemodynamics, ECGI