Salivary Extracellular Vesicle Associated lncRNAs in Heart Failure (SEAL-HF) (SEAL-HF)

The purpose of this study is to determine the relationship between the levels of Ribonucleic acid (RNA) circulating molecules, including ones in extracellular vesicles from different organs in the blood and in the saliva of patients with Acute Decompensated Heart Failure (ADHF) and Chronic Heart Failure (CHF) to see if a new, non-invasive diagnostic test can be developed for heart failure exacerbation.

Study Overview

• Status: Recruiting
• Conditions: CHF; Control; ADHF

Detailed Description

The primary objective of this study is to investigate the expression of extracellular vesicle RNAs (evRNAs) during admission for and decongestion of ADHF patients and determine their diagnostic and prognostic potential. The main hypothesis is that these evRNAs are dynamically regulated in response to volume status changes. Thus, the aim is to delineate: i) the utility of salivary evRNA expression in discriminating ADHF from compensated chronic heart failure states in ADHF patients, chronic heart failure patients and controls (n=30 each); and ii) assess changes in expression in ADHF patients during decongestion. Plasma and salivary evRNA levels will be correlated to determine accuracy of salivary Extracellular Vesicles (EVs) to reflect changes in plasma.

This is a multi-cohort study that will make use of clinical saliva and plasma samples of 90 subjects across three groups. The first group will consist of 30 patients admitted to the hospital for ADHF (clinical samples will be collected during acute decompensation and after diuresis of ADHF patients). The second group will consist of 30 patients with chronic heart failure who are seen in the outpatient clinic. The control group will also include 30 patients undergoing electrophysiology procedures recruited through the Electrophysiology Lab (EP). For each group, blood plasma and saliva samples will be obtained.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Saumya Das, MD, PhD; Phone Number: 617-724-4500; Email: sdas@mgh.harvard.edu
• Study Contact Backup: Name: Priyanka Gokulnath, PhD; Email: PGOKULNATH@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Saumya Das, MD, PhD; Phone Number: 617-724-4500; Email: sdas@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will involve patients admitted to the hospital for ADHF, patients with chronic heart failure who are seen in the outpatient clinic, and control patients recruited through the EP lab.

Description

Inclusion Criteria CHF:

• At least 18 years of age
• Stable disease defined as CHF of any type, New York Heart Association (NYHA) functional class II/III/IV, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥600 pg/ml if Left Ventricular Ejection Fraction (LVEF) ≤30%; ≥1000 pg/mL if LVEF 31-35%; ≥2500 pg/mL if EF >35%

Inclusion Criteria ADHF:

• At least 18 years of age
• Clinical signs and/or symptoms (including exertional or rest dyspnea, orthopnea or Paroxysmal Nocturnal Dyspnea (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 Jugular Venous Pulse (JVP), lower extremity edema, or rales on pulmonary examination, right heart catheterization evidence of elevated filling pressures (Right Atrium (RA) pressure > 10 mmHg; Pulmonary Capillary Wedge Pressure (PCWP) > 18 mmHg) and clinical response to Intravenous (IV) diuretic therapy (as judged by a physician)

Inclusion Criteria control:

• At least 18 years of age
• Will/have undergone an EP procedure in the EP lab

Exclusion Criteria:

• Active pregnancy or lactation
• Cardiac amyloidosis
• Active malignancies

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
ADHF; Patients with ADHF (during admission and discharge).
CHF; Patients with CHF.
Control; Patients undergoing electrophysiology procedures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between weight change (kg), fluid balance (cumulative fluid intake and output, mL), clinical response to diuretic therapy (as judged by a physician), and salivary biomarker levels assessed by quantitative Polymerase Chain Reaction (qPCR)		Through study completion, an average of 1 year
Rehospitalization event prediction	Linear regression analysis for biomarker prediction of subsequent hospital admissions.	Through study completion, an average of 1 year
Association between known biomarkers (NT-proBNP), volume status (right heart catheterization data, echocardiographic data), and salivary biomarker level assessed by qPCR		Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Study Director: Michail Spanos, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Actual): December 13, 2023

Study Record Updates

• Last Update Posted (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: November 11, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 2022P003352

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No