Heart Failure
Conditions
Keywords
heart failure, chronotropic incompetence
Brief summary
Many patients with heart failure are unable to increase their heart rate appropriately when their body needs increased blood flow. As a result, they may be unable to mobilize excess fluid that their body retains. We hypothesize that we can provide assistance to their body in mobilizing this fluid by artificially increasing their heart rate using a pacemaker. We plan to conduct a prospective clinical trial to evaluate this hypothesis. We will use a cross over design to study patients who already have biventricular pacemakers implanted or a narrow QRS and volume overload. We will screen them using a blood test that is a rough estimate of volume overload. Patients who meet the inclusion criteria will be randomly assigned to have their pacemakers adjusted or to have no intervention during the first of 2 visits. They will be unaware of which group they are in. Following adjustment, they will be monitored for six hours. Prior to the pacemaker adjustment, several tests will be performed to evaluate heart function and the levels of hormones related that are affected by heart failure. These tests will be repeated at the end of the six hour intervention period in each visit. At the end of the visit patients who had their pacemakers adjusted will have it reset to their original settings.
Detailed description
Many patients with heart failure suffer from chronotropic incompetence, an inability to raise their heart rate in response to metabolic demand. Previous studies have shown that brief increases in pacing rates in patients with biventricular pacemakers can improve cardiac contractility. We hypothesize that the benefits of an increased biventricular pacing rate could be sustained and would improve cardiovascular and neurohormonal parameters in patients suffering from volume overload. We intend to prospectively evaluate this hypothesis in a single blind randomized cross-over design trial. We will screen 40 patients who have previously implanted biventricular pacemakers (or a narrow QRS) and an elevated B-type Natriuretic Peptide (BNP) level. Following enrollment, patients will be randomly assigned to have their atrial pacing rate increased to 85 beats per minute or to be unchanged during the first of 2 visits. Patients will be unaware of their treatment assignment. They will be observed for six hours in a monitored setting. The primary outcome will be cardiac output, as measured noninvasively by NICOM (Cheetah Medical Inc., Israel) system before and after the observation period. Secondary outcomes will include changes in neurohormonal measures and thoracic impedance. If this proof-of-concept study demonstrates a positive effect, future research would evaluate the ability of increased pacing rates to prevent or abort decompensation of Congestive Heart Failure (CHF).
Interventions
DEVICEMedtronic Pacemaker
Patients will come to clinic in the morning for baseline measurements. Subsequently, the atrial pacing rate will be increased to 85bpm for 6 hours. The control group will be given the illusion that their pacer has been adjusted, but the settings will remain unchanged. Patients will eat a standard breakfast provided by the hospital prior to the treatment session, and then will fast for the six-hour observation period. Patients will remain in supine position and will be clinically monitored for 6 hours. All patients will be on continuous cardiac monitors. Vital signs and symptoms of congestion/ischemia will be recorded every hour.
Sponsors
Medtronic
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Age\>18 2. Congestive Heart Failure (CHF) (\>6 months duration) 3. Left Ventricular Ejection Fraction (LVEF) \<40% 4. Functional Class II-III 5. Stable oral treatment (\>1 month), 6. Implanted Medtronic pacemaker/defibrillator with a) an atrial pacing lead and biventricular leads, or b) an atrial pacing lead and a single ventricular lead in patients with a narrow (normal) QRS complex (\<120 msec) thus with no clinical indication for biventricular pacing. 7. Low heart rate (HR) (sinus rhythm (SR) or atrial pacing \<70 bpm) 8. Symptomatically stable (with no clinical requirement for adjustments in medical therapy, i.e. diuretics) 9. Increase in intrathoracic fluid as evidenced by rain natriuretic peptide (BNP) \>200.
Exclusion criteria
1. Atrial fibrillation 2. Stable or unstable angina 3. Myocardial infarction within 6 months before the study 4. Intravenous inotropic support 5. Pregnant or breast feeding women. Women of child bearing potential must have a negative serum pregnancy test prior to enrollment. 6. Severe renal failure (creatinine\> 2.5 mg/dl, hemodyalisis or peritoneal dialysis) 7. Known hepatic impairment (total bilirubin \>3 mg/dL, albumin \<2.8 mg/dL, or increased ammonia levels if performed) 8. Hemoglobin (hgb) \<8 mg %, or active bleeding requiring transfusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cardiac Output (CO) | baseline and 6 hours | The difference between post and pre CO |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Thoracic Impedence | baseline and 6 hours | Impedence will be measured using the pacemaker programmer to determine the difference in thoracic impedence pre- and post-procedure. |
| Changes in B-type Natriuretic Peptide (BNP) | baseline and 6 hours | B-type natriuretic peptide (BNP) was measured for all subjects to determint the difference between pre- and post-procedure. |
Countries
United States
Participant flow
Recruitment details
Overall 3 subjects completed the study. One subject underwent the intervention only (i.e., 6 hours of faster pacing). Subsequently the protocol was modified to a prospective, randomized single-blind, cross over design. Two subjects completed the protocol according to this modification and underwent both real and sham intervention.
Participants by arm
| Arm | Count |
|---|---|
| Intervention First, Then Control Ambulatory out-patients will be identified at Columbia-Presbyterian and New York University Medical Centers.
On the first encounter, patients will come to clinic in the morning for baseline measurements. Subsequently, the atrial pacing rate will be increased to 85bpm for 6 hours. Patients will eat a standard breakfast provided by the hospital prior to the treatment session, and then will fast for the six-hour observation period. Patients will remain in supine position and will be clinically monitored for 6 hours. All patients will be on continuous cardiac monitors. Vital signs and symptoms of congestion/ischemia will be recorded every hour.
On the second encounter, patients will come to clinic in the morning for baseline measurements.Subsequently, they will be given the illusion that their pacer has been adjusted, but the settings will remain unchanged. The rest of the protocol will be as described for the first encounter. | 1 |
| Control First, Then Intervention Ambulatory out-patients will be identified at Columbia-Presbyterian and New York University Medical Centers.
On the first encounter, patients will come to clinic in the morning for baseline measurements.Subsequently, the control group will be given the illusion that their pacer has been adjusted, but the settings will remain unchanged. Patients will eat a standard breakfast provided by the hospital prior to the treatment session, and then will fast for the six-hour observation period. Patients will remain in supine position and will be clinically monitored for 6 hours. All patients will be on continuous cardiac monitors. Vital signs and symptoms of congestion/ischemia will be recorded every hour.
On the second encounter, patients will come to clinic in the morning for baseline measurements. Subsequently, the atrial pacing rate will be increased to 85bpm for 6 hours. The rest of the protocol will be as described for the first encounter. | 1 |
| Intervention Only Ambulatory out-patients will be identified at Columbia-Presbyterian and New York University Medical Centers.
Patients will come to clinic in the morning for baseline measurements. Subsequently, the atrial pacing rate will be increased to 85bpm for 6 hours. Patients will eat a standard breakfast provided by the hospital prior to the treatment session, and then will fast for the six-hour observation period. Patients will remain in supine position and will be clinically monitored for 6 hours. All patients will be on continuous cardiac monitors. Vital signs and symptoms of congestion/ischemia will be recorded every hour. | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Intervention First, Then Control | Control First, Then Intervention | Intervention Only | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 0 | 85 years STANDARD_DEVIATION 0 | 84 years STANDARD_DEVIATION 0 | 69 years STANDARD_DEVIATION 27 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Change in Cardiac Output (CO)
The difference between post and pre CO
Time frame: baseline and 6 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention First, Then Control | Change in Cardiac Output (CO) | 1st Visit | -0.14 L/min | Standard Deviation 0 |
| Intervention First, Then Control | Change in Cardiac Output (CO) | 2nd Visit | 0.95 L/min | Standard Deviation 0 |
| Control First, Then Intervention | Change in Cardiac Output (CO) | 1st Visit | -0.05 L/min | Standard Deviation 0 |
| Control First, Then Intervention | Change in Cardiac Output (CO) | 2nd Visit | 2.15 L/min | Standard Deviation 0 |
| Intervention Only | Change in Cardiac Output (CO) | 1st Visit | 1.36 L/min | Standard Deviation 0 |
| Intervention Only | Change in Cardiac Output (CO) | 2nd Visit | NA L/min | — |
Secondary
Changes in B-type Natriuretic Peptide (BNP)
B-type natriuretic peptide (BNP) was measured for all subjects to determint the difference between pre- and post-procedure.
Time frame: baseline and 6 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention First, Then Control | Changes in B-type Natriuretic Peptide (BNP) | 1st Visit | 265 ng/L | Standard Deviation 0 |
| Intervention First, Then Control | Changes in B-type Natriuretic Peptide (BNP) | 2nd Visit | 261 ng/L | Standard Deviation 0 |
| Control First, Then Intervention | Changes in B-type Natriuretic Peptide (BNP) | 1st Visit | 19 ng/L | Standard Deviation 0 |
| Control First, Then Intervention | Changes in B-type Natriuretic Peptide (BNP) | 2nd Visit | 92 ng/L | Standard Deviation 0 |
| Intervention Only | Changes in B-type Natriuretic Peptide (BNP) | 1st Visit | 110 ng/L | Standard Deviation 0 |
| Intervention Only | Changes in B-type Natriuretic Peptide (BNP) | 2nd Visit | NA ng/L | — |
Secondary
Changes in Thoracic Impedence
Impedence will be measured using the pacemaker programmer to determine the difference in thoracic impedence pre- and post-procedure.
Time frame: baseline and 6 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention First, Then Control | Changes in Thoracic Impedence | 1st Visit | 3.8 ohm | Standard Deviation 0 |
| Intervention First, Then Control | Changes in Thoracic Impedence | 2nd Visit | 2.6 ohm | Standard Deviation 0 |
| Control First, Then Intervention | Changes in Thoracic Impedence | 1st Visit | 0 ohm | Standard Deviation 0 |
| Control First, Then Intervention | Changes in Thoracic Impedence | 2nd Visit | -1.4 ohm | Standard Deviation 0 |
| Intervention Only | Changes in Thoracic Impedence | 1st Visit | 1.2 ohm | Standard Deviation 0 |
| Intervention Only | Changes in Thoracic Impedence | 2nd Visit | NA ohm | — |