High Intensity His Bundle Pacing in Heart Failure Patients With Narrow QRS Outcome Study

Study Overview
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Brief Summary
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Cardiac Resynchronization Therapy (CRT) decreases heart failure hospitalizations and mortality and increases left ventricular Ejection Fraction (EF) in patients with dilated cardiomyopathy, left bundle branch block and QRS duration >130msec. His bundle pacing has a similar effect in this category of patients. However, CRT is not beneficial in heart failure (HF) patients with narrow QRS. His-bundle pacing delivers physiological ventricular activation and has been shown to improve acute hemodynamic function in patients with heart failure, a prolonged PR interval, and either a narrow QRS or RBBB through AV delay optimization. We observed an acute hemodynamic effect during application of higher pacing output (3.5 Volts/1 msec) in HF patients with dilated or ischemic cardiomyopathy and narrow QRS independently of the paced QRS duration or AV delay shortening. This is a single-center, prospective randomized single-blinded study, recruiting a sub-population of patients with heart failure (dilated or ischemic cardiomyopathy, EF<50%, narrow QRS (<110 msec), in optimal medical treatment who have an indication for ICD.

Detailed Description
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Cardiac Resynchronization Therapy (CRT) decreases heart failure hospitalizations and mortality and increases left ventricular Ejection Fraction (EF) in patients with dilated cardiomyopathy, left bundle branch block and QRS duration >130msec. His bundle pacing has a similar effect in this category of patients. However, CRT is not beneficial in heart failure (HF) patients with narrow QRS. His-bundle pacing delivers physiological ventricular activation and has been shown to improve acute hemodynamic function in patients with heart failure, a prolonged PR interval, and either a narrow QRS or Right Bundle Branch Block (RBBB) through atrioventricular (AV) delay optimization. We observed an acute hemodynamic effect during application of higher pacing output (3.5 Volts/1 msec) in HF patients with dilated or ischemic cardiomyopathy and narrow QRS independently of the paced QRS duration or AV delay shortening. This is a single-center, prospective randomized single-blinded study, recruiting a sub-population of patients with heart failure (dilated or ischemic cardiomyopathy, EF<50%, narrow QRS (<110 msec), in optimal medical treatment who have an indication for ICD. All patients will be implanted with a CRT (Cardiac Resynchronization Therapy) defibrillator with one of the leads positioned on the His bundle to obtain direct His-bundle capture. (There will be a 1-month run-in period where the output voltage will be 3.5 Volts/1 or 2V/1msec according to the group so as to obtain stable threshold). A single-blinded design will then be employed to investigate the effect of His bundle pacing. Patients will be allocated in random order to six-month treatment periods in each of the following two states (1) 3.5 Volts/1 msec pacing output direct His-bundle pacing, AV delay will be programmed in order to obtain a PR interval of 120-140msec; (2)back up only pacing (pacemaker programmed to VVI 30 bpm or AAI(R-DDD(R) 60bpm). Endpoint measurements will be taken at baseline, 1 month run-in period of 3.5 Volts/1 msec or 2V/1msec pacing output and 6 months post randomization. Treating Physicians will be aware of assignment in order to facilitate routine device follow-up. Echocardiographic and electrocardiographic evaluation will be performed in a blinded manner. Treatment allocation will be blinded to the endpoint assessor and the patient. Patients entering the study will attend for implantation of a CRT pacemaker device with one lead positioned on the His bundle. This will be performed in Miulli General Hospital (and other participating centres) no later than 2 months after the patient's screening visit. Before the intervention patients will be randomized to either receive active pacing treatment with 3.5 V/1 msec or back up only pacing (pacemaker programmed to VVI 30 bpm or AAI(R)-DDD(R) 60) for 6 months. All patients will be implanted with an Implantable cardioverter defibrillator (ICD) and an ICD lead in the right ventricle (RV) (either RV apex or RV septum). In all patients a pacing lead will be positioned in the right atrium (typically the right atrial appendage). All patients will have a pacemaker lead positioned on the His bundle to obtain direct His-bundle capture. After implantation of the device there will be a 1-month run-in period that the device will be programmed to deliver His bundle pacing therapy during this period at 3.5 Volts/1msec or 2V/1msec according to the assignment group. One month after patients are implanted with their device, patients will either receive active pacing treatment with 3.5 V/1 msec or back up only pacing (pacemaker programmed to VVI 30 bpm or AAI(R)-DDD(R) 60bpm) for 6 months. Treatment allocation will be obtained using an Interactive Web Response System (IWRS) programmed with a randomization schedule provided by the trial statistician. Appropriate blocking will be used.

Official Title
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High Intensity His Bundle Pacing in Heart Failure Patients With Narrow QRS Outcome Study

Conditions
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Cardiac Conduction System, His Bundle Pacing, Heart Failure, Cardiomyopathies

Intervention / Treatment
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* Device: High Intensity His Bundle pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 or above Ventricular Ejection Fraction (EF) < 50%; BNP needs to be ≥250ng/L or N Terminal-pro BNP≥600ng/L for patients with EF 36-50% and they should have an ICD indication New York Heart Association (NYHA) class I-IV Narrow QRS duration (≤110ms) on 12 lead ECG Exclusion Criteria: Other serious medical condition with life expectancy of less than 1 year Lack of capacity to consent Pregnancy Previous aortic valve surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High intensity His bundle pacing<br>After implantation of the device there will be a 1-month run-in period that the device will be programmed to deliver His bundle pacing therapy during this period at 3.5V/1msec. After one month these patients will continue to receive active pacing treatment with 3.5V/1msec. | Device: High Intensity His Bundle pacing<br>* All patients will be implanted with an Implantable cardioverter defibrillator (ICD) and an ICD lead in the right ventricle (either RV apex or RV septum). In all patients a pacing lead will be positioned in the right atrium (typically the right atrial appendage). All patients will have a pacemaker lead positioned on the His bundle to obtain direct His-bundle capture.<br>|
| Sham Comparator: Back up only ventricular pacing<br>After implantation of the device there will be a 1-month run-in period that the device will be programmed to deliver His bundle pacing therapy during this period at 2V/1msec. After one month these patients will receive back up only pacing (pacemaker programmed to VVI 30 bpm or AAI(R)-DDD(R) 50bpm) for 6 months. | Device: High Intensity His Bundle pacing<br>* All patients will be implanted with an Implantable cardioverter defibrillator (ICD) and an ICD lead in the right ventricle (either RV apex or RV septum). In all patients a pacing lead will be positioned in the right atrium (typically the right atrial appendage). All patients will have a pacemaker lead positioned on the His bundle to obtain direct His-bundle capture.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular ejection fraction | change in left ventricular ejection fraction measured by 2D echo at 6 months compared to baseline | Baseline pre-intervention, randomisation and 6 months post randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in B-type Natriuretic Peptide (BNP) | Measured from blood samples | Baseline pre-intervention, randomisation and 6 months post randomisation | 
| Changes in Quality of Life (QOL) Scores | Change in QOL measured by the Kansas City Cardiomyopathy Questionnaire at 1 and 6 months compared to baseline. Scores are scaled 0-100, where 0 denotes the lowest reportable health status and 100 the highest | Baseline pre-intervention,1 and 6 months post randomisation | 
| Changes in arrhythmia burden | Measured during Pacemaker control | 1 month and 6 months post randomization. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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His bundle pacing, conduction system pacing, Heart failure, Cardiomyopathy, narrow QRS, Ejection Fraction