Levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP) a hormone released from the heart in patients with heart failure (HF) are strongly prognostic of adverse events, such as hospitalization or death from HF. Therapies that are beneficial for HF (such as beta blockers or angiotensin converting enzyme inhibitors) tend to lower levels of NT-proBNP in parallel with improvements in outcomes of patients so treated. Importantly, Nt-proBNP levels may identify a patient at high risk for adverse outcome from their HF, even in periods of apparent stability.

It remains unclear, however, whether treating patients based on their NT-proBNP concentrations would be associated with better outcomes compared to standard HF therapy without measurement of NT-proBNP values.

The goal of the PROTECT study is to evaluate whether treatment of patients with advanced and recently destabilized HF would benefit from NT-proBNP guided HF treatment, compared to standard HF therapy without such 'hormone guided' treatment.

300 patients with class II-IV heart failure (HF) due to systolic dysfunction (left ventricular ejection fraction <40%) and recent (within 6 months) destabilized HF will be randomized 1:1 to either 'standard of care' therapy for their HF versus 'standard of care plus NT-proBNP guided' care.

At randomization, patients at MGH will undergo a 2-dimensional echocardiogram for cardiac structure and function.

Patients randomized to the 'standard of care' arm of the study will receive aggressive therapy for their HF, including evidence-based addition/titration of therapeutic agents in the trial, such as carvedilol or metoprolol XL, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, spironolactone inhibitors (for those in class III or IV), digoxin (when applicable), loop diuretics, as well as nitrates with or without hydralazine. Biventricular pacing with/without ICD capability will be performed at the discretion of the investigator. Any changes in therapy will be accompanied by a 2 week follow up for re-assessment and further titration of medications, based on clinical judgment.

At each interim visit, patients in the 'standard of care' arm will have a Minnesota Living with Heart Failure questionnaire taken. For all visits, including those triggered by med changes, laboratories will be checked including serum chemistries; a sample of blood for blinded NT-proBNP, troponin T, and high sensitivity CRP will be obtained for measurement after the trial is complete.

Patients randomized to the 'standard of care plus NT-proBNP guided' arm will receive the same aggressive medical care as above, but will also have an unblinded measurement of NT-proBNP provided to the study investigator within an hour of first patient contact. Therapeutic decision-making will be first based on clinical acumen/judgment, but if the NT-proBNP is elevated, per protocol, the investigator will adjust therapies accordingly, including escalation of existing therapies with known effects on NT-proBNP levels, as well as possible addition of similar therapies not yet in use (such as spironolactone).

Patients will be followed for events including destabilized HF (in or outpatient), cardiovascular events (including ischemic complications, ICD discharge, or development of non-fatal arrhythmia such as atrial fibrillation), or death.

At the end of one year, event rates will be assessed and the outcomes in the two arms will be compared. As well, echocardiography will be performed on subjects at one year and differences from baseline in both groups will be assessed.

Inclusion Criteria:

• Age > 21 years of age
• Left ventricular ejection fraction ≤ 40%
• NYHA class II-IV heart failure
• Hospital admission, Emergency Department visit, or outpatient diuretic escalation of therapy for destabilized HF at least once in the 6 months prior to enrollment

Exclusion Criteria:

• Severe renal insufficiency defined as serum creatinine > 2.5 mg/dl
• Inoperable aortic valvular heart disease
• Life expectancy <1 year due to causes other than HF such as advanced cancer
• Cardiac transplantation or revascularization indicated or expected within 6 months
• Severe obstructive or restrictive pulmonary disease, defined as a forced expiratory volume in 1S <1 L when diagnosed as standard of care.
• Subject unable or unwilling to provide written informed consent
• Coronary revascularization (PCI or CABG) within the previous 3 months