The primary objective is to measure the association between extracellular RNA (ex-RNA) levels in plasma in patients receiving aggressive outpatient therapy for CHF with (1) cardiac remodeling and (2) cardiovascular events. The investigators will follow patients during standard medical therapy for CHF to assess changes in ex-RNA levels in the plasma, and how these are associated with cardiac remodeling (by cardiac imaging) and outcomes.

Nearly 5 million people in the United States have congestive heart failure (CHF). Although medical therapy such as beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs) and aldosterone antagonists has improved prognosis, the overall rate of hospital admissions has continued to rise in the last decade and the mortality for patients with symptomatic heart failure remains worse than the majority of cancers in this country. Accordingly, significant opportunities exist for the improvement in outcomes of patients with CHF, both from a morbidity and mortality standpoint. Such opportunities may lie in the outpatient medical management of patients with CHF.

In this study, the primary objective is to measure the association between extracellular RNA (ex-RNA) levels in plasma in patients receiving aggressive outpatient therapy for CHF with (1) cardiac remodeling and (2) cardiovascular events. The investigators will follow patients during standard medical therapy for CHF to assess changes in ex-RNA levels in the plasma, and how these are associated with cardiac remodeling (by cardiac imaging) and outcomes.

Inclusion Criteria:

1. Age > 21 years of age
2. Left ventricular ejection fraction ≤ 50% (at any time in the past)
3. Symptomatic (NYHA class II-IV) heart failure (as diagnosed by clinician, radiographic images, or abnormal natriuretic peptide level)
4. 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:

1. Severe renal insufficiency defined as serum creatinine > 2.5 mg/dl
2. United Organ Network Sharing status 1B for heart transplantation (outpatient inotrope use, LV assist device)
3. Inoperable aortic valvular heart disease
4. Life expectancy <1 year due to causes other than HF such as advanced cancer
5. Cardiac transplantation or revascularization indicated or expected within 6 months
6. Severe obstructive or restrictive pulmonary disease, defined as a forced expiratory volume in 1 sec <1 L (when diagnosed as standard of care)
7. Subject unable or unwilling to provide written informed consent
8. Coronary revascularization (percutaneous coronary intervention or bypass surgery) within the previous 3 months

The study population will consist of 200 eligible subjects. These subjects will be enrolled from the Massachusetts General Heart Failure Center population, from the Yawkey Center for Outpatient Care, upon discharge from the inpatient services at Massachusetts General Hospital.