Cardiovascular and Neurohormonal Effects of Faster Atrial Pacing Rate

• ClinicalTrials.gov Identifier: NCT00698139
• Recruitment Status: Terminated
• First Posted: June 17, 2008
• Results First Posted: July 14, 2014
• Last Update Posted: April 27, 2018
• Sponsor: Columbia University
• Collaborator: Medtronic
• Information provided by (Responsible Party): Paolo Colombo, Columbia University

Tracking Information

• First Submitted Date: June 11, 2008
• First Posted Date: June 17, 2008
• Results First Submitted Date: January 28, 2014
• Results First Posted Date: July 14, 2014
• Last Update Posted Date: April 27, 2018
• Study Start Date: April 2011
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 11, 2014)

Change in Cardiac Output (CO) [ Time Frame: baseline and 6 hours ]

The difference between post and pre CO

• Original Primary Outcome Measures (submitted: June 16, 2008): Cardiac output [ Time Frame: 8 hours ]

Current Secondary Outcome Measures (submitted: March 30, 2018)

• Changes in Thoracic Impedence [ Time Frame: 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) [ Time Frame: baseline and 6 hours ]
  B-type natriuretic peptide (BNP) was measured for all subjects to determint the difference between pre- and post-procedure.

Original Secondary Outcome Measures (submitted: June 16, 2008)

• Changes in transthoracic impedence [ Time Frame: 8 hours ]
• Changes in BNP [ Time Frame: 8 hours ]
• Changes in Norepinephrine [ Time Frame: 8 hours ]
• Changes in Renin [ Time Frame: 8 hours ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cardiovascular and Neurohormonal Effects of Faster Atrial Pacing Rate
• Official Title: Cardiovascular and Neurohormonal Effects of Faster Atrial Pacing Rate for Six Hours in Patients With Congestive Heart Failure, Heart Rate <70 Beats Per Minute and Fluid Overload.

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).

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

Device: Medtronic 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.

Other Names:

• Medtronic Cardiac Resynchronization Therapy (CRT)
• Dual Chamber Pacemaker

Study Arms

• Active Comparator: 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.

  Intervention: Device: Medtronic Pacemaker
• Active Comparator: 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.

  Intervention: Device: Medtronic Pacemaker
• Active Comparator: 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.

  Intervention: Device: Medtronic Pacemaker

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 18, 2012): 3
• Original Estimated Enrollment (submitted: June 16, 2008): 40
• Actual Study Completion Date: September 2012
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00698139
• Other Study ID Numbers: AAAC6786
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Paolo Colombo, Columbia University
• Study Sponsor: Columbia University
• Collaborators: Medtronic

Investigators

• Principal Investigator: Paolo Colombo, MD; Columbia University

• PRS Account: Columbia University
• Verification Date: July 2014