Comparing Three Types of Specialist Pacemakers to Improve Heart Function and Reduce Rhythm Problems in Heart Failure

Daily ordinal scale with mobile application based assessment of quality of life (using visual analogue scale), with clinical over-rides as detailed below:

• Death
• Intractable symptoms leading to trial exit/unblinding
• Heart failure hospitalisation
• Non-heart failure hospitalisation
• Appropriate implantable cardioverter defibrillator therapy (anti-tachycardia pacing or shock, deemed appropriate as per clinical care team interrogating device)
• Symptom score (1-600, with 1 representing minimum limitation from patient ascribed heart failure symptom and 600 representing maximum limitation)

Ordinal arrhythmia scale using clinical endpoints as detailed below:

• Death
• Appropriate implantable cardioverter defibrillator therapy (anti-tachycardia pacing or shock, deemed appropriate as per clinical care team interrogating device)
• Sustained ventricular arrhythmia (VA) (>30s of rhythm determined to be ventricular in origin by clinical team on device interrogation)
• Sustained atrial arrhythmia
• Non-sustained VA
• >10% ventricular ectopy on 24h ECG

Ordinal contractility scale using clinical endpoints as detailed below:

• Death
• Intractable symptoms leading to trial exclusion/unblinding
• Heart failure hospitalisation
• Non-heart failure hospitalisation
• Left ventricular ejection fraction (measured on transthoracic echocardiogram)

Death, any cause

Intractable symptoms leading to exit of trial considered to be a single event. Symptoms will be assessed routinely at a single remote consultation with a blinded research team member 1-4 months after device implant. If at this visit or after a patient directed consultation, symptoms are felt to have deteriorated after the device implant likely due to the device, the case will be discussed with the blinded principal-investigator to adjudicate. If the conclusion is that the deterioration is device mediated, the patient will be unblinded, exit from the trial and the device will be programmed to whatever is felt to be optimal by the clinical team.

Adjudicated unplanned heart failure acute care (hospital admissions or ambulatory diuretic therapy i.e. diuretic lounge visit)

Adjudicated unplanned non-heart failure acute care (hospital admissions or ambulatory service i.e. ambulatory emergency clinic).

Anti-tachycardia pacing or shock delivered by device adjudicated to be appropriate for ventricular arrhythmia

Bespoke mobile phone application based daily ordinal symptom score. Patients asked to identify their most associated heart failure symptom at the beginning of the study, they then grade that symptom on a 0-600 (non-labelled) continuum rating this symptom's severity for the previous day (0 being not limited at all, 600 being extremely limited).

Adjudicated sustained arrhythmia suspected to be ventricular in origin of >30s on device interrogation

Adjudicated sustained arrhythmia suspected to be atrial in origin of >30s on device interrogation

Adjudicated non-sustained arrhythmia suspected to be ventricular in origin of <30s on device interrogation

LVEF within group differences

Non-invasive epicardial electrical mapping (ECGi) derived left ventricular repolarisation time and left ventricular repolarisation gradient

Non-invasive epicardial electrical mapping (ECGi) derived left ventricular activation time and left ventricular activation recovery interval

Measured from 24h ECG monitors patients are fitted with 12 weeks after device implant

LVEDV within group differences

LVESV within group differences

Within group comparison

Within group comparison

14 point questionnaire consisting of Likert scale answers to determine quality of life affected by heart disease. Score between 0-42 with a lower score indicating worse quality of life.

12 point questionnaire consisting of Likert scale answers to determine quality of life affected by heart failure. Scores between 12-70 with the lower score suggesting a greater reduction in quality of life and worse symptoms.

21 point questionnaire consisting of Likert scale answers to determine quality of life affected by heart disease. Scores between 0-125 with a lower score representing a better quality of life.

Activity levels as measured by the implanted pacemaker generator.

Proportion of time rhythm is atrial fibrillation as determined by implanted pacemaker detetection.

Taken from device checks at 3 and 6 months. Manufacturer specific defined alerts and intrathoracic normal ranges used, to allow to inter-manufacturer comparisons.

Assessed using Bang Blinding Index (BBI), with patients asked regarding allocated treatment arm at the point of discharge following device implant and again before unblinding at 6 months. Scores will be allocated -1 for stating the incorrect treatment arm, 0 for the patient stating they do not know he treatment arm and +1 for a correctly stating the treatment arm.

Treatment related adverse events include; device infections (requiring device extraction or hospital admission), need for lead revision or reimplantation, premature generator change within study period, haematoma, pericardial effusion requiring intervention and pneumothorax. Other treatment related adverse events non included in this list, but adjudicated by trial steering committee may also be included.