Atrial Fibrillation (Permanent), Systolic Heart Failure
Conditions
Keywords
Atrial Fibrillation, CRT, AV Junction Ablation, LVESV
Brief summary
Cardiac resynchronization therapy (CRT) is a demonstrably effective device intervention for patients with heart failure with reduced ejection fraction and specific indication. However, many patients with heart failure (HF) are unable to maintain sinus rhythm and approximately 30-36% of CRT patients are in atrial fibrillation (AF).
Detailed description
This study is designed to evaluate if patients with AF indicated for CRT will have significant reduction in left ventricular end-systolic volume when randomized to atrioventricular junction (AVJ) ablation. In this study, subjects will be randomized to receive CRT-D or CRT-D with AVJ ablation. Randomization will be stratified by enrolling center (1:1 ratio).
Interventions
PROCEDUREAtrioventricular junctional (AVJ) ablation
RF energy delivery to AV node to create complete AV block
DEVICECardiac resynchronization therapy - defibrillator
Insertion of device capable of providing biventricular pacing and cardiac defibrillation
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Optimal pharmacologic therapy is defined by published guidelines from the American Heart Association and the American College of Cardiology * Initial implantation of CRT-D or prior implantation of CRT-D within one year * Ischemic or nonischemic cardiomyopathy * LVEF ≤ 35% * NYHA class II-IV (ambulatory) * QRS ≥ 120 ms for LBBB and ≥ 150 ms for non-LBBB patients * Continuous AF \> 3 months when no further efforts to restore sinus rhythm are feasible or pursued
Exclusion criteria
* Ventricular rate \> 110 bpm at rest despite maximal medical therapy * Ventricular rate \< 50 bpm at rest * Heart block/symptomatic bradycardia that necessitates permanent pacing * Acute coronary syndrome or coronary artery bypass surgery within 12 weeks * Severe aortic or mitral valvular heart disease * Prior AVJ ablation * Any medical condition likely to limit survival to \< 1 year * Patients with ACC/AHA Stage D refractory Class IV symptoms listed for transplant or requiring inotropic support * Contraindication to systematic anticoagulation * Renal failure requiring dialysis * AF due to reversible cause e.g. hyperthyroid state * Pregnancy * Participation in other clinical trials that will affect the objectives of this study * History of non-compliance to medical therapy * Inability or unwillingness to provide informed consent * Patients with short-lived AF or those in sinus rhythm are ineligible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Reduction ≥ 15% in Left Ventricular End-systolic Volume (LVESV) | Baseline to 6 months | Number of patients with reduction ≥ 15% in left ventricular end-systolic volume (LVESV) in each arm of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Left Ventricular Ejection Fraction (EF) | Baseline to 6 months | Change in left ventricular ejection fraction from baseline to 6 months. Units are expressed in percent and change may vary from -20% to 20%. More negative numbers are desired representing improvement from baseline to 6 months. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Implantable Cardioverter-defibrillator Delivered Inappropriate Therapy | Baseline to 6 months | Number of patients with implantable cardioverter-defibrillator delivered inappropriate therapy in each arm of the study |
| Number of Patients With Implantable Cardioverter-defibrillator Delivered Appropriate Therapy for VT or VF | Baseline to 6 months | Number of patients with implantable cardioverter-defibrillator delivered appropriate therapy treatment by ICD for VT/VF in each arm of the study. |
| Percent Change in Left Ventricular End-diastolic Volume (LVEDV) | Baseline to 6 months | Percent change in left ventricular end-diastolic volume (LVEDV) by study arm. |
| Kansas City Cardiomyopathy Questionnaire | Baseline and 6 months | Scoring scale from 0 to 100. Higher scores represent better quality of life. |
| Number of Participants With Episodes of Ventricular Fibrillation Following AV Junctional Ablation as Detected on ICD | Baseline to one month | Episodes of ventricular fibrillation following AV junctional ablation as detected on ICD in each arm of the study. |
| Percentage of Biventricular Pacing | At 6 months | Amount of time that CRT is delivered |
| Number of Patients With Heart Failure Hospitalizations | Baseline to 6 months | Number of patients with heart failure hospitalizations in each arm of the study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CRT-D Patients will be randomized at enrollment. Patients in this arm of the study will receive cardiac resynchronization therapy with defibrillator (CRT-D).
Cardiac resynchronization therapy - defibrillator: Insertion of device capable of providing biventricular pacing and cardiac defibrillation | 13 |
| CRT-D and AVJ Ablation Patients in this arm of the study will receive CRT-D and undergo atrioventricular junctional (AVJ) ablation.
Atrioventricular junctional (AVJ) ablation: RF energy delivery to AV node to create complete AV block
Cardiac resynchronization therapy - defibrillator: Insertion of device capable of providing biventricular pacing and cardiac defibrillation | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | CRT-D | CRT-D and AVJ Ablation | Total |
|---|---|---|---|
| Age, Continuous | 72 years | 73 years | 73 years |
| LV End Systolic Volume | 115 cc STANDARD_DEVIATION 29 | 121 cc STANDARD_DEVIATION 39 | 118 cc STANDARD_DEVIATION 30 |
| Race/Ethnicity, Customized Caucasian | 11 Participants | 13 Participants | 24 Participants |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 13 | 0 / 13 |
| other Total, other adverse events | 0 / 13 | 0 / 13 |
| serious Total, serious adverse events | 1 / 13 | 1 / 13 |
Outcome results
Primary
Number of Patients With Reduction ≥ 15% in Left Ventricular End-systolic Volume (LVESV)
Number of patients with reduction ≥ 15% in left ventricular end-systolic volume (LVESV) in each arm of the study.
Time frame: Baseline to 6 months
Population: Some patients did not undergo outcome measures due to inability to come for follow-up due to COVID-19.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CRT-D | Number of Patients With Reduction ≥ 15% in Left Ventricular End-systolic Volume (LVESV) | 5 Participants |
| CRT-D and AVJ Ablation | Number of Patients With Reduction ≥ 15% in Left Ventricular End-systolic Volume (LVESV) | 6 Participants |
p-value: 195% CI: [0.14, 7.21]Regression, Logistic
Secondary
Change in Left Ventricular Ejection Fraction (EF)
Change in left ventricular ejection fraction from baseline to 6 months. Units are expressed in percent and change may vary from -20% to 20%. More negative numbers are desired representing improvement from baseline to 6 months.
Time frame: Baseline to 6 months
Population: A small number patients were unable to return for follow-up due the the outbreak of COVID-19 and some outcome measures were not completed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT-D | Change in Left Ventricular Ejection Fraction (EF) | -7.0 percentage | Standard Deviation 11.8 |
| CRT-D and AVJ Ablation | Change in Left Ventricular Ejection Fraction (EF) | -8.6 percentage | Standard Deviation 9.1 |
p-value: 0.974Wilcoxon (Mann-Whitney)
Other Pre-specified
Kansas City Cardiomyopathy Questionnaire
Scoring scale from 0 to 100. Higher scores represent better quality of life.
Time frame: Baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CRT-D | Kansas City Cardiomyopathy Questionnaire | 6 months | 69.1 score on a scale | Standard Deviation 20.3 |
| CRT-D | Kansas City Cardiomyopathy Questionnaire | Baseline | 56.6 score on a scale | Standard Deviation 17.6 |
| CRT-D and AVJ Ablation | Kansas City Cardiomyopathy Questionnaire | 6 months | 81.3 score on a scale | Standard Deviation 18.2 |
| CRT-D and AVJ Ablation | Kansas City Cardiomyopathy Questionnaire | Baseline | 61.9 score on a scale | Standard Deviation 26.9 |
p-value: 0.565Wilcoxon (Mann-Whitney)
Other Pre-specified
Number of Participants With Episodes of Ventricular Fibrillation Following AV Junctional Ablation as Detected on ICD
Episodes of ventricular fibrillation following AV junctional ablation as detected on ICD in each arm of the study.
Time frame: Baseline to one month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CRT-D | Number of Participants With Episodes of Ventricular Fibrillation Following AV Junctional Ablation as Detected on ICD | 1 participants |
| CRT-D and AVJ Ablation | Number of Participants With Episodes of Ventricular Fibrillation Following AV Junctional Ablation as Detected on ICD | 0 participants |
p-value: 195% CI: [0, 42]Fisher Exact
Other Pre-specified
Number of Patients With Heart Failure Hospitalizations
Number of patients with heart failure hospitalizations in each arm of the study.
Time frame: Baseline to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CRT-D | Number of Patients With Heart Failure Hospitalizations | 1 participants |
| CRT-D and AVJ Ablation | Number of Patients With Heart Failure Hospitalizations | 1 participants |
p-value: 195% CI: [0.1, 84.4]Fisher Exact
Other Pre-specified
Number of Patients With Implantable Cardioverter-defibrillator Delivered Appropriate Therapy for VT or VF
Number of patients with implantable cardioverter-defibrillator delivered appropriate therapy treatment by ICD for VT/VF in each arm of the study.
Time frame: Baseline to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CRT-D | Number of Patients With Implantable Cardioverter-defibrillator Delivered Appropriate Therapy for VT or VF | 1 Participants |
| CRT-D and AVJ Ablation | Number of Patients With Implantable Cardioverter-defibrillator Delivered Appropriate Therapy for VT or VF | 0 Participants |
p-value: 195% CI: [0, 42]Fisher Exact
Other Pre-specified
Number of Patients With Implantable Cardioverter-defibrillator Delivered Inappropriate Therapy
Number of patients with implantable cardioverter-defibrillator delivered inappropriate therapy in each arm of the study
Time frame: Baseline to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CRT-D | Number of Patients With Implantable Cardioverter-defibrillator Delivered Inappropriate Therapy | 0 participants |
| CRT-D and AVJ Ablation | Number of Patients With Implantable Cardioverter-defibrillator Delivered Inappropriate Therapy | 0 participants |
p-value: 1Fisher Exact
Other Pre-specified
Percentage of Biventricular Pacing
Amount of time that CRT is delivered
Time frame: At 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT-D | Percentage of Biventricular Pacing | 77.1 % BiV pacing | Standard Deviation 26.3 |
| CRT-D and AVJ Ablation | Percentage of Biventricular Pacing | 97.7 % BiV pacing | Standard Deviation 3.6 |
p-value: 0.005Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change in Left Ventricular End-diastolic Volume (LVEDV)
Percent change in left ventricular end-diastolic volume (LVEDV) by study arm.
Time frame: Baseline to 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT-D | Percent Change in Left Ventricular End-diastolic Volume (LVEDV) | -1.1 % change in volume | Standard Deviation 23.7 |
| CRT-D and AVJ Ablation | Percent Change in Left Ventricular End-diastolic Volume (LVEDV) | -3.5 % change in volume | Standard Deviation 13.2 |
Comparison: Some patients did not undergo 6 month echocardiogram due to restrictions related to COVID-19.p-value: 1Wilcoxon (Mann-Whitney)