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Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)

Conditions
Heart Failure
Registration Number
NCT06280820
Lead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Brief Summary

Background:

More than 6.5 million people in the United States live with heart failure (HF), and more than a million new cases are diagnosed each year. Treatments have improved in recent years, but researchers want to understand more about how HF develops. To do this, they need to compare blood and other samples from many people with HF.

Objective:

To collect blood and other samples from people with HF. These samples will be used to identify and study proteins and other factors that may lead to decreased heart function over time.

Eligibility:

People aged 18 years and older with heart failure.

Design:

Participants will be asked to join the study based on a review of their medical records.

They will have 1 study visit. They will provide a blood sample: About 3 tablespoons will be collected from a needle inserted into a vein.

Other tests are optional: Participants may provide urine and stool samples. They may have a cotton swab rubbed on the inside of the mouth to collect DNA.

Participants may also take 3 questionnaires. They will answer questions about dietary, social, and other factors that affect their health. Participants will receive compensation.

Researchers will follow the participants health by monitoring their medical records for up to 5 years.

Detailed Description

Study Description:

Our general hypothesis is that clinical and molecular data will generate new mechanistic knowledge and transform our understanding of the heterogeneous forms of heart failure (HF) syndrome. To do so, we will create a data-rich ecosystem by building a diverse population-based registry. By grounding our work in the community within the District of Columbia / Maryland/Virginia metropolitan region (DMV) with deliberate intent on recruiting diverse participants from diverse populations, we will optimize inference and facilitate community translation. We will prospectively recruit a diverse community cohort of 2000 participants with clinical HF from the DMV area and collect biospecimens (blood, urine, stool, and buccal specimens) to measure multi-omics (specifically proteomics, metabolomics)signatures. We will integrate the results of the multi-omics assays to electronic medical records (EMR)-driven phenotypic representation (e.g. symptoms at clinical presentation, comorbid conditions, frailty, imaging data, ejection fraction, and laboratory values) collected during clinical care. Patients records will be followed for up to 5 years after recruitment to monitor key characteristics and events including death.

Objectives:

Primary Objective:

-To study the association between multi-omics signatures with all-cause mortality

Secondary Objectives:

* To study the association between multi-omics signatures with cardiovascular mortality

* To study the cross-sectional association between multi-omics signatures with clinical sub-phenotypes of heart failure

Exploratory Objectives:

* To study the association between multi-omics signatures with HFrelated hospitalizations.

* To study the cross-sectional association between multi-omics signatures and HF sub-phenotypes based on clinical biomarkers across the spectrum of heart failure.

* To investigate the relationship between multi-omics signatures and findings (may include clinical or research data), and advanced imaging data used in clinical characterization and phenotyping of heart failure and its various underlying etiologies

* To explore both germline (i.e., inherited) and somatic (i.e., de novo or acquired) genetic variants contributing to HF sub phenotypes.

* To explore epigenetic and gene expression alterations contributing to HF sub phenotypes.

Endpoints:

Primary Endpoint will be all-cause mortality.

Secondary Endpoints will be:

* Cardiovascular mortality

* Clinical sub-phenotypes of heart failure are defined by the following:

* Ejection Fraction, by echocardiogram (\>=50% vs. \< 50%)

* Severity measured by New York Heart Association class (3-4 vs. 1-2)

* HF duration (\>=18 months vs. \< 18 months)

* Etiology (Ischemic vs. Non-Ischemic)

* Comorbidity - diabetes, hypertension, chronic obstructive pulmonary disease, atrial fibrillation, cerebrovascular disease, body mass index (\>=30 vs. \< 30), age (median cut)

Exploratory Endpoints will be:

* HF-related hospitalization

* Biomarkers related to HF including N-terminal pro-brain natriuretic peptide (NT-proBNP), Cystatin C, Neutrophil gelatinase-associated lipocalin (NGAL), Galectin-3, soluble interleukin 1 1 (ST2), Troponin T, I, or C, Vascular cell adhesion protein 1 (VCAM-one), ICAM, E-selectin, CRP, TNF- alpha, interleukins, cortisol, and/or adiponectin

* Genomic analyses including whole exome or whole genome sequencing (WGS) to determine pathways, genes, genetic variants, and structural changes to DNA that may be related to HF syndrome.

* Epigenetic analyses including DNA methylation measurements to characterize differentially methylated sites that may be related to HF syndrome.

* Transcriptomic analyses to characterize alterations to gene expression that may be related to HF syndrome.

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
2000
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To study the association between multi-omics signatures with all-cause mortality10 years

The heterogeneous HF syndrome encompasses different and poorly defined entities. Multi-omics can improve its characterization and the prediction of mortality, which remains high. All-cause mortality will be analyzed as the time from enrollment to all-cause death.

Secondary Outcome Measures
NameTimeMethod
Clinical phenotypes defined by:Ejection Fraction (>=50 vs. < 50)NYHA (3-4 vs. 1-2)>=18 months vs. < 18 months

Cardiovascular mortality is an important part of all-cause mortality and will be evaluated as a secondary outcome. Cardiovascular mortality will be analyzed as the time from enrollment to cardiovascular death

To study the cross-sectional association between multi-omics signatures with clinical sub-phenotypes of heart failure5 years

Clinical phenotypes defined by:Ejection Fraction (\>=50 vs. \< 50) NYHA (3-4 vs. 1-2)Duration of HF (\>=18 months vs. \< 18 months) Etiology (Ischemic vs. Non- Ischemic) Comorbidity - diabetes, hypertension, chronic

Trial Locations

Locations (1)

INOVA Fairfax Hospital

🇺🇸

Falls Church, Virginia, United States

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