BOAT: Beta Blocker Uptitration With OptiVol After Cardiac Resynchronization Therapy (CRT)

Study Overview
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Brief Summary
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Many heart failure patients are unable to reach target beta blocker doses. This study will address whether cardiac resynchronization therapy (CRT) will enable uptitration of beta-blockers to target doses and whether it will favorably affect remodeling by reducing left ventricular end systolic volume (LVESV), with measurable clinical benefit, beyond CRT alone (without changes in beta-blocker dose).

Detailed Description
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Beta blockers have been proven to have benefit in heart failure (HF) patients with regard to morbidity and mortality. However, initiation and uptitration remains a challenge in many patients. Worsening of heart failure, symptomatic hypotension and symptomatic bradycardia all limit up-titration to the target doses that have been shown to have mortality benefits (carvedilol [Coreg] 25 mg bid, metoprolol succinate [Toprol-XL] 200 mg qd) in the large clinical trials (COPERNICUS, MERIT-HF). It is debated whether the benefit of beta-blockade is solely due to heart rate reduction or more broadly from the cardiac, central and peripheral effects of blocking sympathetic activity. Clearly, there is a remodeling effect on the dilated ventricle. Furthermore, patients with heart rates of 64 bpm or less are rarely begun on beta-blocker therapy. It is not known whether these patients should be given a pacemaker in order to then safely initiate beta-blocker therapy. It is also clear that isolated right ventricular pacing can have deleterious effects on ventricular dyssynchrony and symptomatic heart failure despite medical therapy. Biventricular pacing (BIVPM), also known as cardiac resynchronization therapy (CRT), is the pacing mode of choice for patients with wide QRS complexes and symptomatic HF. It is hypothesized that CRT therapy allows for increased Beta -blocker dose (or initiation of beta-blocker in patients previously intolerant) with improved NYHA, ejection fraction, and remodeling effects. The synergy between two established heart failure therapies requires further evaluation in a prospective randomized trial.

Official Title
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Beta-blocker Uptitration in Heart Failure Patients Receiving Cardiac Resynchronization Therapy With Optivol Fluid Status Monitoring System

Conditions
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Congestive Heart Failure

Intervention / Treatment
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* Drug: Beta blocker (carvedilol or metoprolol succinate)
* Procedure: CRT (cardiac resynchronization therapy)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NYHA III-IV QRS > 120 msec On medical therapy, but beta blocker dose not @ target (carvedilol 25 bid, metoprolol succinate 200 qd) Exclusion Criteria: QRS < 120 msec On target beta blocker dose

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>CRT and b-blocker uptitration to target dose | Drug: Beta blocker (carvedilol or metoprolol succinate)<br>* Both groups get CRT. Group 1 is uptitrated to target dose beta blocker after CRT. Group 2 maintains their b-blocker dose from study entry.<br>Procedure: CRT (cardiac resynchronization therapy)<br>* Both arms<br>|
| Active Comparator: 2<br>CRT and continuation of entry b-blocker dose to 6 month evaluation | Drug: Beta blocker (carvedilol or metoprolol succinate)<br>* Both groups get CRT. Group 1 is uptitrated to target dose beta blocker after CRT. Group 2 maintains their b-blocker dose from study entry.<br>Procedure: CRT (cardiac resynchronization therapy)<br>* Both arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LVESVI change in patients with CRT/ increased dose of beta-blockers vs CRT and no change in beta-blocker dose. |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of Optivol fluid measurement increases (decreased impedance) with symptomatic worsening of heart failure during beta blocker uptitration |  | 6 months | 
| Optivol measurements (decreased impedance, increase volume index) correlated with the need for adjusting diuretic therapy when uptitrating beta blocker dose |  | 12 months | 
| Functional improvements |  | 6 months | 
| Exercise - 6 minute walk |  | 6 months | 
| QOL - NYHA, Minnesota LWHFQ, Symptom Assessment Questionnaire |  | 6 months | 
| Ejection fraction |  | 6 months | 
| LVEDVI |  | 6 months | 
| Remodeling |  | 6 months | 
| HF Hospitalizations/ Mortality |  | 6 months | 
| Evaluation of LVESVI in patients who actually achieve target dose |  | 6 months | 
| Comparison of LVESVI changes based on initial beta-blocker dose |  | 6 months | 
| Plasma Brain natriuretic peptide (BNP) change |  | 6 months | 
| 12 month comparison after Group 2 has been uptitrated. |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Beta blockers, Resynchronization, Congestive Heart Failure, NYHA III-IV, Candidate for BIVPM, Not on Target Dose (Coreg 25 Bid or Toprol XL 200 qd)