Plasma ExtrAcellular RNAs and Biomarkers of Heart FaiLure During Decongestion: PEARL-HF Study

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