Clinical trial NCT00698139: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Heart Failure
Keywords: heart failure
chronotropic incompetence
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2008-06-17
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Change in Cardiac Output (CO)
timeFrame: baseline and 6 hours
Secondary outcomes:
measure: Changes in Thoracic Impedence
timeFrame: baseline and 6 hours
measure: Changes in B-type Natriuretic Peptide (BNP)
timeFrame: baseline and 6 hours
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University
state: New York
Study officials:
affiliation: Columbia University
name: Paolo Colombo, MD
role: PRINCIPAL_INVESTIGATOR
References: