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

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.

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