Heart Failure
Conditions
Brief summary
The purpose of this study is to gather information on the safety and effectiveness of cardiac resynchronization therapy (CRT) in patients who have mild heart failure (HF) and left bundle branch block (LBBB).
Interventions
DEVICECardiac resynchronization therapy pacemaker (CRT-P)
A pacemaker is an implantable, battery-powered minicomputer that sends electrical pulses to the heart whenever it detects a slow heartbeat or no heartbeat at all. When it senses a slow heartbeat or lack of heartbeat, it sends electrical impulses to restore a normal rhythm. Cardiac resynchronization therapy pacemakers, or CRT-Ps, treat heart failure by resynchronizing electrical impulses in the heart's four chambers, improving the heart's ability to pump blood to the body effectively and efficiently.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Biotronik SE & Co. KG
Yong-Mei Cha
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants randomly assigned to have CRT-ON or OFF. At 6 months, participant CRT function will be crossed over.
Intervention model description
Single-center, randomized cross-over study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Left Ventricular Ejection Fraction (LVEF) 35%-50% * New York Heart Association (NYHA) class I-II * QRS duration of ≥120ms * Left bundle branch block (LBBB) * Patient is able to receive a transvenous pectoral CRT implant * Patient is able to sign informed consent * Two echocardiograms are required to confirm a stable reduced LVEF * Patient is on optimal and stable medical therapy (ACE inhibitor or angiotensin II type 1 (AT1 )blocker, beta blocker, etc. over the last 6 months)
Exclusion criteria
* Advanced comorbid conditions with life expectancy \<1 year * Patient is \<18 of years of age * Patient has a CRT device * Female patients who is pregnant or not on a reliable form of birth control. Women of childbearing potential are required to have negative pregnancy test within the 7 days prior to device implant * Unwilling or unable to return for required follow-up visits * Patient decides study participation is cost-prohibited
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Left Ventricle End-Systolic Volume Index (LVESVI) | baseline, 12 months | LVESVI is the volume of blood in the left ventricle at the end of contraction, or systole, adjusted for the individual's body surface area. |
| Number of Subjects Experiencing Any System-Related Complications | Approximately 12 months | This is a composite endpoint; system-related complications could include any of the following: device pocket hematoma, pneumothorax, myocardial perforation, lead dislodgement, lead revision and device-related infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Experience Sustained Ventricular Tachycardia or Fibrillation Greater Than 30 Seconds | Approximately 12 months | In ventricular tachycardia, abnormal electrical signals in the ventricles cause the heart to beat faster than normal, usually 100 or more beats a minute, out of sync with the upper chambers. Ventricular fibrillation is the most serious cardiac rhythm disturbance. The lower chambers quiver and the heart can't pump any blood, causing cardiac arrest. |
| Number of Subjects Admitted to the Hospital for Heart Failure | Approximately 12 months | The total number of subjects hospitalized for heart failure during the study. |
| Number of Subjects Who Die in One Year | Approximately 12 months | The total number of subjects to die for any reason during the study. |
| Change in Left Ventricular Ejection Fraction (LVEF) | Baseline, 12 months | LVEF refers to how well your left ventricle (or right ventricle) pumps blood with each heart beat. Most times, EF refers to the amount of blood being pumped out of the left ventricle each time it contracts. The left ventricle is the heart's main pumping chamber. |
| Change in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) by CRT Randomization From 6 Months to 12 Months | 6 months, 12 months | The NT-proBNP is a substance that is produced in the heart and released when the heart is stretched and working hard to pump blood, measured in pg/mL. The change was calculated as the value at 12 months minus the value at 6 months. |
Countries
United States
Participant flow
Pre-assignment details
82 participants were enrolled, 6 withdrew prior study randomization.
Participants by arm
| Arm | Count |
|---|---|
| CRT-On First, Then CRT-Off Subjects will be randomized to have the cardiac resynchronization therapy pacemaker (CRT-P) programmed on in the first intervention period, and after six months the CRT function will be turned off in the second intervention period.
Cardiac resynchronization therapy pacemaker (CRT-P): A pacemaker is an implantable, battery-powered minicomputer that sends electrical pulses to the heart whenever it detects a slow heartbeat or no heartbeat at all. When it senses a slow heartbeat or lack of heartbeat, it sends electrical impulses to restore a normal rhythm. Cardiac resynchronization therapy pacemakers, or CRT-Ps, treat heart failure by resynchronizing electrical impulses in the heart's four chambers, improving the heart's ability to pump blood to the body effectively and efficiently. | 38 |
| CRT-Off First, Then CRT-On Subjects will be randomized to have the cardiac resynchronization therapy pacemaker (CRT-P) programmed off in the first intervention period, and after six months the CRT function will be turned on in the second intervention period.
Cardiac resynchronization therapy pacemaker (CRT-P): A pacemaker is an implantable, battery-powered minicomputer that sends electrical pulses to the heart whenever it detects a slow heartbeat or no heartbeat at all. When it senses a slow heartbeat or lack of heartbeat, it sends electrical impulses to restore a normal rhythm. Cardiac resynchronization therapy pacemakers, or CRT-Ps, treat heart failure by resynchronizing electrical impulses in the heart's four chambers, improving the heart's ability to pump blood to the body effectively and efficiently. | 38 |
| Total | 76 |
Baseline characteristics
| Characteristic | CRT-On First, Then CRT-Off | Total | CRT-Off First, Then CRT-On |
|---|---|---|---|
| Age, Continuous | 68.5 years STANDARD_DEVIATION 9.8 | 68.4 years STANDARD_DEVIATION 9.8 | 68.3 years STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 76 Participants | 38 Participants |
| Region of Enrollment United States | 38 participants | 76 participants | 38 participants |
| Sex: Female, Male Female | 10 Participants | 22 Participants | 12 Participants |
| Sex: Female, Male Male | 28 Participants | 54 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 76 | 3 / 76 |
| other Total, other adverse events | 44 / 76 | 29 / 76 |
| serious Total, serious adverse events | 6 / 76 | 8 / 76 |
Outcome results
Primary
Change in Left Ventricle End-Systolic Volume Index (LVESVI)
LVESVI is the volume of blood in the left ventricle at the end of contraction, or systole, adjusted for the individual's body surface area.
Time frame: baseline, 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT-ON | Change in Left Ventricle End-Systolic Volume Index (LVESVI) | -11.6 mL/m^2 | Standard Deviation 12.8 |
| CRT-OFF | Change in Left Ventricle End-Systolic Volume Index (LVESVI) | -4.1 mL/m^2 | Standard Deviation 12.2 |
p-value: 0.0001t-test, 2 sided
p-value: 0.009t-test, 2 sided
Primary
Number of Subjects Experiencing Any System-Related Complications
This is a composite endpoint; system-related complications could include any of the following: device pocket hematoma, pneumothorax, myocardial perforation, lead dislodgement, lead revision and device-related infection.
Time frame: Approximately 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CRT-ON | Number of Subjects Experiencing Any System-Related Complications | 2 Participants |
| CRT-OFF | Number of Subjects Experiencing Any System-Related Complications | 2 Participants |
Secondary
Change in Left Ventricular Ejection Fraction (LVEF)
LVEF refers to how well your left ventricle (or right ventricle) pumps blood with each heart beat. Most times, EF refers to the amount of blood being pumped out of the left ventricle each time it contracts. The left ventricle is the heart's main pumping chamber.
Time frame: Baseline, 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT-ON | Change in Left Ventricular Ejection Fraction (LVEF) | 5.3 percent | Standard Deviation 8.2 |
| CRT-OFF | Change in Left Ventricular Ejection Fraction (LVEF) | 2.2 percent | Standard Deviation 7 |
p-value: 0.0001t-test, 2 sided
p-value: 0.011t-test, 2 sided
Secondary
Change in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) by CRT Randomization From 6 Months to 12 Months
The NT-proBNP is a substance that is produced in the heart and released when the heart is stretched and working hard to pump blood, measured in pg/mL. The change was calculated as the value at 12 months minus the value at 6 months.
Time frame: 6 months, 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT-ON | Change in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) by CRT Randomization From 6 Months to 12 Months | 0.1 pg/mL | Standard Deviation 0.6 |
| CRT-OFF | Change in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) by CRT Randomization From 6 Months to 12 Months | -0.3 pg/mL | Standard Deviation 0.6 |
p-value: 0.024t-test, 2 sided
Secondary
Number of Subjects Admitted to the Hospital for Heart Failure
The total number of subjects hospitalized for heart failure during the study.
Time frame: Approximately 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CRT-ON | Number of Subjects Admitted to the Hospital for Heart Failure | 0 Participants |
| CRT-OFF | Number of Subjects Admitted to the Hospital for Heart Failure | 0 Participants |
Secondary
Number of Subjects Who Die in One Year
The total number of subjects to die for any reason during the study.
Time frame: Approximately 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CRT-ON | Number of Subjects Who Die in One Year | 0 Participants |
| CRT-OFF | Number of Subjects Who Die in One Year | 3 Participants |
Secondary
Number of Subjects Who Experience Sustained Ventricular Tachycardia or Fibrillation Greater Than 30 Seconds
In ventricular tachycardia, abnormal electrical signals in the ventricles cause the heart to beat faster than normal, usually 100 or more beats a minute, out of sync with the upper chambers. Ventricular fibrillation is the most serious cardiac rhythm disturbance. The lower chambers quiver and the heart can't pump any blood, causing cardiac arrest.
Time frame: Approximately 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CRT-ON | Number of Subjects Who Experience Sustained Ventricular Tachycardia or Fibrillation Greater Than 30 Seconds | 1 Participants |
| CRT-OFF | Number of Subjects Who Experience Sustained Ventricular Tachycardia or Fibrillation Greater Than 30 Seconds | 0 Participants |