Circulating RNAs in Acute Congestive Heart Failure

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. Specifically
acute CHF represents a particularly underserved area of CHF care.

In this regard, the investigative group and others have demonstrated the utility of
extracellular RNAs (short, 20-22 nucleotide RNA molecules stable in circulation in humans) to
predict cardiac structural changes and fibrosis in patients post-myocardial infarction with
significant changes in cardiac structure. However, little has been done looking at the acute
CHF setting. Specific questions include:

1. What RNAs change in the acute CHF setting, and how do these change over time with
diuretic therapy?

2. Are these changes in RNA functional? That is, do they cause characteristic changes in
the heart in vitro and on heart phenotypes in patients?

3. Do these RNAs predict outcomes in long-term follow-up?

To answer these questions, the investigators will enroll patients who are currently admitted
at MGH or BIDMC with acute CHF. The study protocol involves:

1. Venous blood draw, 40 ml anytime within their hospitalization

2. Venous blood draw, 40 ml within 48 hours of planned hospital discharge

3. Venous blood draw, 40 ml at follow-up (within one year of discharge)

Eligible patients (e.g., absence of standard MRI contraindications, GFR > 40ml/min/1.73m2)
will be asked pre-discharge or by telephone contact after discharge about coming in for a
cardiac MRI study at any point within one year of discharge to examine cardiac
structure/function and fibrosis. MRI imaging will be performed by Partners investigators (Dr.
Ravi Shah, Dr. Michael Steigner, Dr. Michael Jerosch-Herold) at the 221 Longwood BRIC Imaging
Facility (at the Brigham and Women's Hospital, BWH).

Inclusion Criteria:

1. Age >/= 18 years of age

2. Assessment of LV function within the last year or planned during hospital admission

3. Acute CHF diagnosis, requiring clinical signs and/or symptoms (including exertional or
rest dyspnea, orthopnea or PND) AND

1. N-terminal pro-BNP level > 1000 pg/ml or BNP > 400 pg/ml, OR

2. Clinical evidence of congestion:

- X-ray evidence of pulmonary edema or pleural effusions

- Elevated JVP, lower extremity edema, or rales on pulmonary examination

- Right heart catheterization evidence of elevated filling pressures (RA
pressure > 10 mmHg; PCWP > 18 mmHg)

4. Clinical response to IV diuretic therapy (as judged by a physician)

Exclusion Criteria:

1. Hematocrit at time of consent < 30%

2. End-stage non-cardiovascular diseases

1. Known HIV/AIDS

2. Cirrhosis

3. Hemodialysis-dependent renal failure

3. Pregnancy (as adjudicated by patient history)

4. Ventricular assist device support

5. Acute mechanical support on admission

6. Post-heart transplant

7. Malignancy within the last 1 year or clinically active rheumatologic or autoimmune
illnesses