Dyssynchrony, Heart Failure and Reduced Ejection Fraction
Conditions
Keywords
Cardiac resynchronisation therapy, Conduction system pacing, optimised CRT, LOT-CRT, heart failure, dyssynchrony, left bundle branch pacing
Brief summary
The goal of this clinical trial is to find out which type of specialist pacemaker-known as cardiac resynchronisation therapy (CRT)-works best for people with heart failure and a delay in how the lower chambers of the heart beat together (called electrical dyssynchrony). The main aims of the study are: To compare the effects of conventional biventricular pacing (BVP), conduction system pacing (CSP) and left-bundle optimised CRT (LOT-CRT) on heart failure symptoms and heart rhythm problems over six months. To explore how these pacing methods affect heart muscle strength, electrical activity, and overall heart function. Participants will: Attend four hospital visits over a six-month period. At Visit 1, meet a member of the research team to discuss the study and have screening tests to check eligibility. Participants will also have a smartphone app installed and receive training on how to record their daily heart failure symptoms. At Visit 2, have a CRT pacemaker implanted. The type of pacemaker will be chosen at random, with a 1 in 3 chance of receiving: * Biventricular pacing (BVP); the current standard treatment * Conduction system pacing (CSP) * LOT-CRT (Left-bundle optimised CRT); a combination of both At Visit 3 (around 12 weeks after implantation) and Visit 4 (6 months after implantation), take part in routine follow-up assessments to check the pacemaker and heart function. At Visits 2 and 4, also undergo non-invasive electrical mapping tests, including wearing a specialised vest and having a low-dose CT scan of the chest. These tests help researchers understand how the heart's electrical system responds to different pacing methods.
Interventions
DEVICEBiventricular pacing
Cardiac resynchronisation therapy with one lead to right ventricular endocardium and one lead to left ventricular epicardium, accessed via the coronary sinus.
DEVICEConduction system pacing
Cardiac resynchronisation therapy with single lead targeting direct capture of the conduction system. Primary target should be left bundle area, with backup target of His bundle. If direct capture of the conduction system cannot be achieved by conventional clinical criteria, left septal pacing targeted at the left bundle branch area will be accepted.
DEVICELeft bundle optimised cardiac resynchronisation therapy
Cardiac resynchronisation therapy delivered by conduction system optimised hybrid configurations. Primary configuration should be conduction system pacing lead targeted at the left bundle area combined with left ventricular epicardial lead accessed via the coronary sinus (LOT-CRT). Backup configuration of conduction system pacing lead targeted at the His bundle combined with left ventricular epicardial lead accessed via the coronary sinus (HOT-CRT).
Sponsors
Imperial College London
Imperial College Healthcare NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
3-arm parallel (1:1:1) study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients referred/scheduled for a CRT procedure (new implant or upgrade) who have: * Symptomatic heart failure (NYHA II-IV) * Reduced ejection fraction (LVEF≤40%) * Prolonged QRS duration (≥130ms) and left bundle branch block ECG morphology or very prolonged QRS duration (\>150ms) and non-left bundle branch block ECG * Optimal medical therapy for HF
Exclusion criteria
* Unable to provide informed consent * \<18 years old * Pregnant patients (with female patients of childbearing age requiring a negative urine BHCG)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary outcome: Daily ordinal symptom score with clinical over-rides | From randomisation to 6-months post device implant | Daily ordinal scale with mobile application based assessment of quality of life (using visual analogue scale), with clinical over-rides as detailed below: 1. Death 2. Intractable symptoms leading to trial exit/unblinding 3. Heart failure hospitalisation 4. Non-heart failure hospitalisation 5. Appropriate implantable cardioverter defibrillator therapy (anti-tachycardia pacing or shock, deemed appropriate as per clinical care team interrogating device) 6. Symptom score (1-600, with 1 representing minimum limitation from patient ascribed heart failure symptom and 600 representing maximum limitation) |
| Primary arrhythmia outcome | From randomisation to 6-months post device implant | Ordinal arrhythmia scale using clinical endpoints as detailed below: 1. Death 2. Appropriate implantable cardioverter defibrillator therapy (anti-tachycardia pacing or shock, deemed appropriate as per clinical care team interrogating device) 3. Sustained ventricular arrhythmia (VA) (\>30s of rhythm determined to be ventricular in origin by clinical team on device interrogation) 4. Sustained atrial arrhythmia 5. Non-sustained VA 6. \>10% ventricular ectopy on 24h ECG |
| Primary contractility outcome | From randomisation to 6-months post device implant | Ordinal contractility scale using clinical endpoints as detailed below: 1. Death 2. Intractable symptoms leading to trial exclusion/unblinding 3. Heart failure hospitalisation 4. Non-heart failure hospitalisation 5. Left ventricular ejection fraction (measured on transthoracic echocardiogram) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of death | From randomisation up to 36 months, or death from any cause, whichever came first. | Death, any cause |
| Number of participants with intractable symptoms leading to trial exit/unblinding | From randomisation up to 36 months, or intractable symptoms leading to trial exit/unblinding, whichever came first. | 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. |
| Rate of heart failure hospitalisation | From randomisation up to 36 months | Adjudicated unplanned heart failure acute care (hospital admissions or ambulatory diuretic therapy i.e. diuretic lounge visit) |
| Rate of non-heart failure hospitalisation | From randomisation up to 36 months | Adjudicated unplanned non-heart failure acute care (hospital admissions or ambulatory service i.e. ambulatory emergency clinic). |
| Rate of appropriate implantable cardioverter defibrillator device therapy | From randomisation up to 36 months | Anti-tachycardia pacing or shock delivered by device adjudicated to be appropriate for ventricular arrhythmia |
| Daily heart failure symptom score | From randomisation up to 36 months | 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). |
| Rate of sustained ventricular arrhythmia | From randomisation up to 36 months | Adjudicated sustained arrhythmia suspected to be ventricular in origin of \>30s on device interrogation |
| Rate of sustained atrial arrhythmia | From randomisation up to 36 months | Adjudicated sustained arrhythmia suspected to be atrial in origin of \>30s on device interrogation |
| Rate of non-sustained ventricular arrhythmia | From randomisation up to 36 months | Adjudicated non-sustained arrhythmia suspected to be ventricular in origin of \<30s on device interrogation |
| Number of participants with >10% ventricular ectopy on 24h ECG | At 12-weeks post implant | — |
| Left ventricular ejection fraction (LVEF) | From baseline echocardiogram (pre device implant) to follow-up echocardiogram (at 6 months) | LVEF within group differences |
| Left ventricular repolarisation heterogeneity | From implant to 6-months | Non-invasive epicardial electrical mapping (ECGi) derived left ventricular repolarisation time and left ventricular repolarisation gradient |
| Left ventricular activation | From implant to 6-months | Non-invasive epicardial electrical mapping (ECGi) derived left ventricular activation time and left ventricular activation recovery interval |
| QT dispersion | From randomisation to 6 months post device implant | Measured from 24h ECG monitors patients are fitted with 12 weeks after device implant |
| Left ventricular end diastolic volume (LVEDV) | From baseline echocardiogram (pre device implant) to follow-up echocardiogram (at 6 months) | LVEDV within group differences |
| Left ventricular end systolic volume (LVESV) | From baseline echocardiogram (pre device implant) to follow-up echocardiogram (at 6 months) | LVESV within group differences |
| Six minute walk test | From baseline to 6 months post device implantation | Within group comparison |
| Serum B-type natriuretic peptide (BNP) | From baseline to 6 months post device implant | Within group comparison |
| Quality of life assessed via HeartQoL questionnaire | From baseline to 6 months post device implant | 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. |
| Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12) | From baseline to 6 months post device implant | 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. |
| Minnesota Living With Hearth Failure Questionnaire (MLWHFQ) | From baseline to 6 months post device implant | 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. |
| Heart failure status assessed by New York Heart Association classification | From baseline to 6 months post device implantation | — |
| Device derived patient activity level | At 6 months post device implant | Activity levels as measured by the implanted pacemaker generator. |
| Device determined atrial fibrillation burden | At 6 months post pacemaker implant | Proportion of time rhythm is atrial fibrillation as determined by implanted pacemaker detetection. |
| Percentage of days outside of the normal range device measured intrathoracic impedance or triggering device warning for fluid status | From implant to 6 months post pacemaker implant | Taken from device checks at 3 and 6 months. Manufacturer specific defined alerts and intrathoracic normal ranges used, to allow to inter-manufacturer comparisons. |
| Blinding index | From device implant, to 6 months post device implant | 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. |
| Number of patients with treatment related adverse events | From device implant to 36 months post device implant | 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. |
Countries
United Kingdom
Contacts
CONTACTJack W Samways, MBChB, MRes, MRCP
PRINCIPAL_INVESTIGATORZachary I Whinnett, MBBS, BMedSci, MRCP, PhD
Imperial College London
PRINCIPAL_INVESTIGATORAhran D Arnold, MBBS, BSc, MSc, MRCP, PhD
Imperial College London
Outcome results
None listed