Circulating RNAs in Acute Congestive Heart Failure

The purpose of this American Heart Association-funded and NIH-funded study is to examine circulating RNAs in the acute CHF setting, how they change with decongestive therapy, and their function in vitro and in vivo.

The investigators are testing the hypothesis that ex-RNA levels change significantly during decongestion therapy and can be used as a marker of those individuals who respond to CHF therapy (in terms of cardiac structure or outcome). Additionally, the translational research design allows the investigators to assay the effects of these RNAs on tissue phenotypes in vitro.

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).

Eligibility Criteria:
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