Cardiomyopathies, Heart Failure，Congestive, Left Ventricular Dysfunction
Conditions
Keywords
Heart Failure, Cardiac Resynchronization Therapy
Brief summary
This is a randomized, prospective, single-blinded trial to determine the overall rate of successful His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy (HOT-CRT) versus biventricular pacing using coronary sinus lead (BVP) to compare acute and mid-term outcomes. Acute outcomes include change in QRS duration pre-and post-pacing (degree of QRS narrowing) and incidence of major periprocedural complications (pericardial tamponade, need for lead revision, etc.). Mid-term outcomes include echocardiographic response at 6 months along with a composite clinical outcome of heart failure hospitalization, ventricular arrhythmias, crossover, and all-cause mortality.
Detailed description
This is a single-blinded study of 100 patients randomized to a strategy of His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy (HOT-CRT) versus biventricular pacing using coronary sinus (CS) lead (BVP). Both treatment options use standard-of-care, FDA-approved devices. The distinction is only in the allocation toward HOT-CRT and BVP. Treating physicians will be aware of assignment in order to facilitate routine device follow-up. Echocardiographic and electrocardiographic evaluation will also be performed in a blinded manner. Cross-over is permitted between treatment group allocation if: CS lead cannot be placed due to difficult cannulation of the CS, limited branches at the posterolateral or lateral wall, or phrenic nerve capture. These subjects may then cross-over to HOT-CRT. HOT-CRT subjects may cross-over if His or left bundle pacing lead cannot be positioned with adequate stability and reasonable pacing output, or if optimal QRS narrowing cannot be achieved. Implant procedure will be per routine percutaneous access, as is standard for pacemaker and Implantable Cardioverter Defibrillators (ICDs). . All subjects will receive an FDA-approved cardiac resynchronization therapy pacemaker or defibrillator device, as per standard of care outlined for the subject. Follow-up will be performed at 2 weeks post-implant for incision check and device interrogation as is standard of care. In addition, routine device and clinical follow-up will be scheduled at 3 and 6 months. Electrocardiography (ECG) will be performed pre-implant, prior to hospital discharge, at 3 months, and 6 months. Echocardiography will be performed pre-implant and 6 months to evaluate for change in Left Ventricular Ejection Fraction (LVEF), chamber dimensions, volumes, and change in Left Ventricular (LV) end systolic volume index as is standard of care in the treatment of patients with advanced heart failure. New York Heart Association (NYHA) functional class and quality of life (utilizing the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EQ 5D) will be assessed pre-implant and at 6 months.
Interventions
DEVICEHOT-CRT
Subjects enrolled in the study will receive a permanent cardiac implantable electronic device (CIED) (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to HOT-CRT will have His bundle pacing lead placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and left ventricular timing may be optimized to achieve maximal resynchronization.
DEVICEBiventricular Pacing
Subjects enrolled in the study will receive a permanent CIED (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to Biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.
Sponsors
Pugazhendhi Vijayaraman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Subjects will be blinded to treatment arm. Echocardiographic evaluation will be performed by study physician blinded to lead placement
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients at least 18 years of age * Diagnosis is NYHA Class II, III, and ambulatory Class IV heart failure with either ischemic or nonischemic cardiomyopathy and patients with NYHA Class I symptoms and ischemic cardiomyopathy, with at least one of the following: * LV systolic dysfunction with LVEF ≤ 35% and Evidence of bundle branch block with QRS duration \> 120 msec * LV systolic dysfunction with LVEF ≤ 50% and with need for \>40% Right Ventricular (RV) pacing
Exclusion criteria
* Existing CRT device * Inability of patient capacity to provide consent for themselves either due to medical or psychiatric comorbidity * Pregnancy * Participation in other device trials * Inability to complete study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Endpoint | 6 months | Improvement in left ventricular ejection fraction (LVEF) - change in LVEF% measured by 2D echo at 6 months compared to baseline |
| Primary Safety | 6 months | Freedom from major complications or need for CRT lead revision - complication such as lead dislodgment, pericardial tamponade, pneumothorax, systemic embolism, phrenic nerve stimulation not correctable by programming |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Composite | 6 months | Crossover, ventricular tachycardia (VT)/ventricular fibrillation (VF), Heart failure hospitalization (HFH) or death |
| Echocardiographic Response | 6 months | change in LVEF \>5% |
Countries
United States
Participant flow
Recruitment details
Subjects will be recruited from Geisinger Wyoming Valley, Geisinger Medical Center, and Geisinger Community Medical Center. Investigators will identify eligible subjects, describe the study procedures and invite them to participate in the study. Informed Consent (ICF) will be provided to the subject and they will have ample time and opportunity to review and consider participation. Prior to performing any study procedures, the subject will sign the ICF and be considered enrolled at that point.
Pre-assignment details
Subjects were screened to meet inclusion/exclusion criteria pre consent and post consent, pre implant. In some cases, a repeat echo was scheduled to obtain ejection fraction (EF) measurement as part of inclusion/exclusion criteria, and result was pending at time of consent, therefore when resulted and patient no longer met inclusion criteria, they were screen failed.
Participants by arm
| Arm | Count |
|---|---|
| HOT-CRT Subjects randomized to HOT-CRT will undergo CRT as described below. His bundle pacing lead will be placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and LV timing may be optimized to achieve maximal resynchronization. This will be at the discretion of the implanting physician. Only FDA approved leads and devices will be used.
HOT-CRT: Subjects enrolled in the study will receive a permanent cardiac implantable electronic device (CIED) (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to HOT-CRT will have His bundle pacing lead placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and left ventricular timing may be optimized to achieve maximal resynchronization. | 50 |
| Biventricular Pacing Subjects randomized to biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.Only FDA approved leads and devices will be used.
Biventricular Pacing: Subjects enrolled in the study will receive a permanent CIED (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to Biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches. | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | HOT-CRT | Biventricular Pacing | Total |
|---|---|---|---|
| Age, Continuous All patients | 71 years STANDARD_DEVIATION 13.4 | 68.9 years STANDARD_DEVIATION 11.5 | 70 years STANDARD_DEVIATION 12.5 |
| Atrial fibrillation | 12 Participants | 22 Participants | 34 Participants |
| Chronic kidney disease | 17 Participants | 18 Participants | 35 Participants |
| Coronary Artery Disease | 23 Participants | 22 Participants | 45 Participants |
| Diabetes | 26 Participants | 23 Participants | 49 Participants |
| Hypertension | 42 Participants | 38 Participants | 80 Participants |
| Left bundle branch block | 31 Participants | 31 Participants | 62 Participants |
| Left ventricular ejection fraction | 30.1 percent ejection fraction STANDARD_DEVIATION 9.1 | 30.7 percent ejection fraction STANDARD_DEVIATION 9.3 | 30.4 percent ejection fraction STANDARD_DEVIATION 9.1 |
| Medications ACE | 22 Participants | 13 Participants | 35 Participants |
| Medications Aldosterone antagonist | 14 Participants | 15 Participants | 29 Participants |
| Medications Amiodarone | 9 Participants | 8 Participants | 17 Participants |
| Medications ARB | 10 Participants | 5 Participants | 15 Participants |
| Medications ARNI | 11 Participants | 14 Participants | 25 Participants |
| Medications Beta blocker | 45 Participants | 47 Participants | 92 Participants |
| New York Heart Association (NYHA) functional class | 2.5 units on a scale STANDARD_DEVIATION 0.7 | 2.5 units on a scale STANDARD_DEVIATION 0.7 | 2.5 units on a scale STANDARD_DEVIATION 0.7 |
| Nonischemic cardiomyopathy | 30 Participants | 31 Participants | 61 Participants |
| QRS | 164 ms STANDARD_DEVIATION 26 | 166 ms STANDARD_DEVIATION 28 | 165.0 ms STANDARD_DEVIATION 26.5 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male All patients Female | 11 Participants | 20 Participants | 31 Participants |
| Sex: Female, Male All patients Male | 39 Participants | 30 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 57 | 2 / 43 |
| other Total, other adverse events | 0 / 57 | 0 / 43 |
| serious Total, serious adverse events | 17 / 57 | 32 / 43 |
Outcome results
Primary
Primary Endpoint
Improvement in left ventricular ejection fraction (LVEF) - change in LVEF% measured by 2D echo at 6 months compared to baseline
Time frame: 6 months
Population: 50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HOT-CRT | Primary Endpoint | 12.4 percent ejection fraction | Standard Deviation 7.3 |
| Biventricular Pacing | Primary Endpoint | 8.0 percent ejection fraction | Standard Deviation 10.1 |
Primary
Primary Safety
Freedom from major complications or need for CRT lead revision - complication such as lead dislodgment, pericardial tamponade, pneumothorax, systemic embolism, phrenic nerve stimulation not correctable by programming
Time frame: 6 months
Population: 50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HOT-CRT | Primary Safety | 49 Participants |
| Biventricular Pacing | Primary Safety | 48 Participants |
Secondary
Echocardiographic Response
change in LVEF \>5%
Time frame: 6 months
Population: 50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HOT-CRT | Echocardiographic Response | 35 Participants |
| Biventricular Pacing | Echocardiographic Response | 27 Participants |
Secondary
Secondary Composite
Crossover, ventricular tachycardia (VT)/ventricular fibrillation (VF), Heart failure hospitalization (HFH) or death
Time frame: 6 months
Population: 50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HOT-CRT | Secondary Composite | 9 Participants |
| Biventricular Pacing | Secondary Composite | 14 Participants |