Circulating RNAs in Acute Congestive Heart Failure

NCT03345446 | Active Not Recruiting

• 3 other identifiers: 2016P00125016SFRN294900001K23HL127099-01A1
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Acute Congestive Heart Failure; Heart Failure With Reduced Ejection Fraction; Heart Failure With Normal Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Plasma RNAs levels (rpm by RNAseq) in patients with acute CHF

  Identification of plasma RNAs (absolute reads per million) by RNA sequencing in 1 ml of plasma that are greater than 2 fold increased with p value \< 0.05.

  admission vs. decongestion (up to 2 weeks)

Secondary Outcomes (1)

• Correlation of plasma RNA levels (rpm by RNAseq) with CMR measurements of ventricular function and in vitro fibroblast proliferation assay.

  6 months

Other Outcomes (1)

• Correlation of candidate plasma RNA levels (measured by qRT-PCR in fold change compared to endogenous control RNA) with short-term and long-term combined cardiovascular outcome

  4 years

Study Arms (2)

Patients with HF-rEF

These patients have Heart Failure with Reduced Ejection Fraction (EF \< 55% per the protocol).

Diagnostic Test: Cardiac MRI

Patients with HF-pEF

These patients have Heart Failure with Preserved Ejection Fraction (EF \> 55% per the protocol).

Diagnostic Test: Cardiac MRI

Interventions

Cardiac MRI DIAGNOSTIC_TEST

Cardiac MRI is a test that allows us to look at how the heart muscle works and the amount of scar tissue in your heart. Screening questions will be asked to make sure that patients are not pregnant, and that they have kidney function tests to confirm that IV contrast used (gadolinium) during the MRI is safe for them.

Patients with HF-pEF; Patients with HF-rEF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Acute Congestive Heart Failure, either with preserved ejection fraction (HF-pEF) or reduced ejection fraction (HF-rEF). The subjects will be enrolled in the acute CHF setting from two sites: * Beth Israel Deaconess Medical Center (BIDMC; under direction of Dr. Pablo Pinzon-Quintero, Heart Failure/Transplant Attending Physician) * Massachusetts General Hospital (MGH; under direction of Dr. Ravi Shah, Heart Failure/Transplant Attending Physician) Subjects will be drawn from the inpatient population at both hospitals, admitted with a diagnosis of heart failure.

You may qualify if:

• Age \>/= 18 years of age
• Assessment of LV function within the last year or planned during hospital admission
• Acute CHF diagnosis, requiring clinical signs and/or symptoms (including exertional or rest dyspnea, orthopnea or PND) AND
• N-terminal pro-BNP level \> 1000 pg/ml or BNP \> 400 pg/ml, OR
• 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)
• Clinical response to IV diuretic therapy (as judged by a physician)

You may not qualify if:

• Hematocrit at time of consent \< 30%
• End-stage non-cardiovascular diseases
• Known HIV/AIDS
• Cirrhosis
• Hemodialysis-dependent renal failure
• Pregnancy (as adjudicated by patient history)
• Ventricular assist device support
• Acute mechanical support on admission
• Post-heart transplant
• Malignancy within the last 1 year or clinically active rheumatologic or autoimmune illnesses

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator
• Brigham and Women's Hospital: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• American Heart Association: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Chatterjee E, Rodosthenous RS, Kujala V, Gokulnath P, Spanos M, Lehmann HI, de Oliveira GP, Shi M, Miller-Fleming TW, Li G, Ghiran IC, Karalis K, Lindenfeld J, Mosley JD, Lau ES, Ho JE, Sheng Q, Shah R, Das S. Circulating extracellular vesicles in human cardiorenal syndrome promote renal injury in a kidney-on-chip system. JCI Insight. 2023 Nov 22;8(22):e165172. doi: 10.1172/jci.insight.165172.

  PMID: 37707956 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Venous blood draws collected at the following times and processed for ex-RNAs: 1. After consent 2. Prior to discharge 3. Follow-up within 60 days of leaving the hospital

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Director of Resynchronization and Advanced Cardiac Therapeutics Program

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: November 17, 2017
• Study Start: August 17, 2016
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)