Nesiritide Therapy to Preserve Function of the Left Ventricle After Myocardial Infarction

Post acute myocardial infarction (AMI) left ventricular (LV) remodeling begins within hours
of the acute event with permanent consequences. Previous studies have demonstrated that LV
remodeling is one of the major determinants of long-term survival post AMI. Recent studies
have reported that the cardiac natriuretic peptides, ANP and BNP have direct anti-fibrotic
and anti-proliferative effects on the myocardium. More importantly, it has been reported
that in the acute phase of AMI, the secretion of the cardiac natriuretic peptides may be
insufficient relative to the chronic phase. Therefore, augmentation of the cardiac
natriuretic peptide system, such as by exogenous administration of exogenous peptide may
prevent post AMI LV remodeling because of the cardioprotective effects. The objective of
this study is to to determine the efficacy of IV human BNP (Nesiritide) as compared to
placebo to prevent adverse post AMI LV remodeling. This is a randomized double blinded
placebo controlled study to determine efficacy of 72 hours of IV BNP at 0.006µg/Kg/min as
compared to placebo in patients with anterior ST-elevation myocardial infarction and
successful revascularization. The study population will include 60 patients admitted to the
CCU with a first anterior AMI and successful reperfusion therapy (TIMI grade 3 flow) within
24 hours of onset of chest pain documented by coronary angiography.

Inclusion criteria:

- Patients with acute ST elevation myocardial infarction with > or = 2 mm ST elevation
in one or any combination of anterior leads, with successful revascularization (TIMI
grade 3 flow) of the lesion within 24 hours of symptoms and consented within 24 hours
of procedure.

Exclusion criteria:

- Cardiogenic shock or hypotension, Systolic BP< 90 mmHg or overt CHF

- Previous history of MI

- Previous ECG suggesting previous MI

- Known EF < 30%

- Atrial fibrillation

- Previously known significant valvular disease (Grade III, IV), cardiomyopathy and
congenital heart disease.

- Hemoglobin <10mg/dl.

- Pregnant women/nursing mothers

- Participants still menstruating and have not been surgically sterilized must have a
negative pregnancy test prior to participating in this study.

- Unable to undergo cardiac MRI. Contraindications to MRI include pacemaker or
defibrillator, pregnant women, atrial fibrillation or other arrhythmia, cerebral
aneurysm clips or severe claustrophobia.