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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Congestive Heart Failure
• Intervention / Treatment: Other: Monitoring on heart failure therapy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with congestive heart failure; 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; This is a prospective observational study where participants will have serial blood collection on medical therapy for heart failure.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimated): December 17, 2015

Study Record Updates

• Last Update Posted (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 2015P001658