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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Congestive Heart Failure

Intervention / Treatment
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* Other: Monitoring on heart failure therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 21 years of age Left ventricular ejection fraction ≤ 50% (at any time in the past) Symptomatic (NYHA class II-IV) heart failure (as diagnosed by clinician, radiographic images, or abnormal natriuretic peptide level) 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 United Organ Network Sharing status 1B for heart transplantation (outpatient inotrope use, LV assist device) 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 1 sec <1 L (when diagnosed as standard of care) Subject unable or unwilling to provide written informed consent Coronary revascularization (percutaneous coronary intervention or bypass surgery) within the previous 3 months

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with congestive heart failure<br>Patients with congestive heart failure (CHF) who are followed in the hospital or clinic setting, with optimization of medical therapy | Other: Monitoring on heart failure therapy<br>* This is a prospective observational study where participants will have serial blood collection on medical therapy for heart failure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to death |  | 24 months | 
| Time to decompensated heart failure (HF) requiring in-patient admission or ER visit or IV diuretic therapy in the outpatient realm | • New onset of classic symptoms and signs of destabilized HF, including lower extremity edema, jugular venous distension, bibasilar crackles, orthopnea and paroxysmal nocturnal dyspnea | 24 months | 
| Time to acute coronary syndrome | Myocardial infarction | 24 months | 
| Time to stroke or transient ischemic attack |  | 24 hours | 
| Time to ventricular arrhythmia | Clinically significant ventricular arrhythmia, defined as ventricular arrhythmia plus one of the following: | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular (LV) end-systolic volume (in %) |  | 12 months | 
| Change in LV ejection fraction (%) |  | 12 months |