Cardiovascular and Neurohormonal Effects of Faster Atrial Pacing Rate

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.

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.

Study Overview

• Status: Terminated
• Conditions: Heart Failure
• Intervention / Treatment: Device: Medtronic Pacemaker

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
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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
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.	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
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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cardiac Output (CO)	The difference between post and pre CO	baseline and 6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Thoracic Impedence	Impedence will be measured using the pacemaker programmer to determine the difference in thoracic impedence pre- and post-procedure.	baseline and 6 hours
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.	baseline and 6 hours

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Medtronic
• Investigators: Principal Investigator: Paolo Colombo, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 11, 2008
• First Submitted That Met QC Criteria: June 16, 2008
• First Posted (Estimate): June 17, 2008

Study Record Updates

• Last Update Posted (Actual): April 27, 2018
• Last Update Submitted That Met QC Criteria: March 30, 2018
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: heart failure; chronotropic incompetence
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: AAAC6786

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No