Optimal Cardiac Resynchronization Therapy Pacing Rate

Study Overview
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Brief Summary
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The optimal pacing rate during cardiac resynchronization therapy (CRT) is not known. Investigators investigate the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL).

Detailed Description
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This is a double-blinded randomized crossover pilot study testing two basal pacing rates: DDD-60 versus DDD-80. Each patient is paced for 2 periods of 90 days with DDD-60 and DDD-80 in a randomly sequence. Blood samples NT-proBNP plasma levels are analysed at baseline and at the end of each phase using electrochemiluminescence-immunoassay. Patients rest for 15 minutes before the samples are taken. These result are monitored by supervisory group to ensure that increase of more than 15% than baseline values result in termination of study. Investigators conduct two distinct questionnaires (Minnesota Living with Heart Failure (LIfHE) questionnaire and Medical Outcome Survey Short Form (SF-36)) A symptom limiting bicycle (Ergoline, Baden-Württemberg, Germany) exercise test is performed to measure maximum work capacity and oxygen consumption at each phase. Recordings of resting muscle sympathetic nerve activity (MSNA) are sought in all patients at both rates of pacing. All patients are studied on the same set-up in the semi-recumbent position after 30 minutes of rest. Tungsten microelectrodes (Iowa Bioengineering) are inserted into the common peroneal nerve just below the knee.

Official Title
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Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-ischemic Heart Failure Patients: a Randomized Crossover Pilot Trial.

Conditions
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Cardiac Resynchronization Therapy, Heart Failure, Bi-ventricular Pacing, Sympathetic Activity, Quality of Life

Intervention / Treatment
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* Procedure: DDD-80
* Procedure: DDD-60


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis with idiopathic dilated cardiomyopathy CRT device implanted (with initial indication in accordance with European guidelines) at least 6 months prior to inclusion. New York Heart Association functional (NYHA) class II-IV Sinus rhythm, Hemodynamically stable Biventricular pacing > 90% of the time On optimal medical treatment for heart failure with no changes in medications during the past 3 months. Exclusion Criteria: NYHA I unable to perform exercise test (e.g. chronic obstructive pulmonary disease, severe arthritis) cancer plasma creatinine > 200 micromole per litre an admission for decompensated HF or acute coronary syndrome in the preceding 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DDD-80 pacing<br>To investigate the impact of basal pacing rates of 80-bpm (DDD-80) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) and (iii) self-perceived quality of life (QoL). | Procedure: DDD-80<br>* Basal pacing rate set to 80-bpm. Note:Patients have already pacemaker implanted before this study.<br>|
| Sham Comparator: DDD-60 pacing<br>To investigate the impact of basal pacing rates of 60-bpm (DDD-60) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) self-perceived quality of life (QoL). | Procedure: DDD-60<br>* Basal pacing rate set to 60-bpm. Note:Patients have already pacemaker implanted before this study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| N-terminal pro-brain natriuretic peptide | Observing the change in N-terminal pro-brain natriuretic peptide in 15 patients | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Autonomic nerve function | Autonomic nerve function by micro-neurography measured in bursts/min and bursts/cardiac cycle in 15 patients | 3 months | 
| Peak oxygen consumption (pVO2) | pVO2 measured by a symptom limiting bicycle exercise test in 15 patients | 3 months | 
| Self-perceived quality of life | Measured with the LIfHE and SF-36 questionnaires in 15 patients | 3 months |