Characterization of Patients With Uncommon Presentations and/or Uncommon Diseases Associated With the Cardiovascular System

Cardiovascular Disease Discovery Protocol

Background:

- Researchers are interested in studying individuals who have known or suspected metabolic, inflammatory or genetic diseases that may put them at a high risk for heart diseases or diseases of their blood vessels. Depending on the condition being studied, both affected and nonaffected individuals may be asked to provide blood and other samples and may undergo tests to evaluate the heart, blood vessels and lung function. The testing is tailored to the individual and/or condition being studied. Nonaffected individuals may include relatives of affected individuals and healthy nonrelated volunteers.

Objectives:

- To study individuals who have or are at risk for cardiovascular diseases, and in some cases their unaffected relatives and healthy volunteers.

Eligibility:

- Individuals between 1 and 100 years of age. Participants may be healthy volunteers, individuals with cardiovascular diseases, or unaffected relatives of individuals with cardiovascular diseases.

Design:

• Participants will have some or all of the following tests, as directed by the study researchers:
• Photography of the face and full body
• Body measurements
• Radiography, including chest or limb x-rays
• Metabolic stress testing to study heart and muscle function
• Echocardiography to study heart function
• Magnetic resonance imaging (MRI) studies, including cardiovascular MRI, angiography, and contrast MRI, to study heart function and performance
• Computed tomography (CT) angiogram to obtain images of the heart and lungs
• Positron emission tomography (PET) imaging to study possible fat infiltration of the heart
• Six-minute walk test to study heart, lung, and muscle function and performance
• Vascular ultrasound to study blood vessel walls
• Blood, tissue, and other specimens will be collected for research and testing, and will be taken either as part of the clinical study or during surgical procedures.
• Follow-up studies may be performed under separate research protocols.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Atherosclerosis; Cardiomyopathy; Metabolic Disease; Inflammatory Disease; Li-Fraumeni Syndrome
• Intervention / Treatment: Device: NSR IDE-MRI: Research pulse sequences

Detailed Description

We propose to characterize the etiology and natural history of rare and uncommon diseases, both known and unknown that present with symptoms and signs associated with the risk of overt or potential cardiovascular dysfunction. We will also study rare genetic modifiers and identify novel disease mechanisms contributing to common cardiovascular diseases. In so doing, we will expand our knowledge about these disorders and provide access to subjects of interest for research, teaching, and clinical experience. Individual subjects seen under this protocol may initiate the establishment of specific disease-related protocols involving intensive natural history studies, disease discovery and potential innovative therapeutic studies. In addition to its role in investigating individuals who are of interest to the Cardiovascular Branch (CB) of the NHLBI, this protocol can provide a possible avenue for admitting subjects from other NIH programs such as the NIH Undiagnosed Diseases Program, the Center for Human Immunology Trans-institute program or other NIH protocols where subjects exhibit cardiovascular features.

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

• Study Contact: Name: Rebecca D Huffstutler, C.R.N.P.; Phone Number: (301) 594-1281; Email: rebecca.huffstutler@nih.gov

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20006
      • Recruiting
      • Hope Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov
    • Bethesda, Maryland, United States, 20814
      • Completed
      • Suburban Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

1. Adult index cases and relatives 2. Child index case and child relatives 3. Healthy adult volunteers 4. Illiterate, Blind, or Non-English-Speaking Subjects

Description

• INCLUSION CRITERIA:

Eligible subjects may include anyone over 1 year of age who is affected with diseases/disorders (index cases), or who is a relative of a person who is affected with diseases/disorders. Relatives may include genetic carriers and non-carriers.

• Healthy adult volunteers must be 18 years of age or older, and must agree to have blood or tissue samples studied, and potentially stored for future research.
• Index cases enrolled in this protocol will have been referred with a known or suspected pathology that may be associated with cardiovascular dysfunction or risk with a suspected atypical presentation, heritable disorder, or genetic predisposition. The investigator with expertise in the presentation of the subject, along with consulting specialists, will review the medical history and may review any medical records that are available of prospective subjects and offer admission based upon the potential to help the individual, to learn from the subject, or to initiate clinical or basic research suggested by the subject s workup.

EXCLUSION CRITERIA:

• Persons of less than 1 year of age or greater than 100 years of age
• Healthy volunteers unable to give informed consent or who decline to have blood and/or tissue studies, or who do not consent to have samples stored for future research may be excluded from this study.
• Pregnant women
• Persons who are not fluent in the English language will be excluded from Patient Reported Outcome Questionnaires. Such persons would be unable to properly complete questionnaires that are only valid in the English language.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1. Adult index cases and relatives; Enrolled with a known or suspected pathology that may be associated w/cardiovascular dysfunction or risk w/suspected atypical presentation, heritable disorder, or genetic predisposition.	Device: NSR IDE-MRI: Research pulse sequences; NSR IDE-MRI: Research pulse sequences, Device Manufacturer NIH. Research pulse sequences are customized pulse sequences and analysis software developed by NIH scientists.
2. Child index case and child relatives; Children over 1 year of age who is affected with diseases/disorders (index cases), or who is a relative of a person who is affected with diseases/disorders.	Device: NSR IDE-MRI: Research pulse sequences; NSR IDE-MRI: Research pulse sequences, Device Manufacturer NIH. Research pulse sequences are customized pulse sequences and analysis software developed by NIH scientists.
3. Healthy adult volunteers; Healthy adult volunteers must be 18 years of age or older, and must agree to have blood or tissue samples studied, and potentially stored for future research.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Diagnosis	This protocol will allow condition-specific evaluation and sample collection to subjects with conditions associated with cardiovascular features and risk that may have long eluded diagnosis and to advance medical knowledge about rare and uncommon human diseases.	Ongoing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Potential genetic counseling	Determining molecular etiology of diseases encountered on this protocol	Ongoing
Understanding disease pathophysiolgy	Assist in the understanding of disease pathophysiology and in the generation of diagnoses in subjects with uncommon presentations of diseases with cardiovascular consequences.	Ongoing

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Paul M Hwang, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Han K, Singh K, Rodman MJ, Hassanzadeh S, Wu K, Nguyen A, Huffstutler RD, Seifuddin F, Dagur PK, Saxena A, McCoy JP, Chen J, Biancotto A, Stagliano KER, Teague HL, Mehta NN, Pirooznia M, Sack MN. Fasting-induced FOXO4 blunts human CD4+ T helper cell responsiveness. Nat Metab. 2021 Mar;3(3):318-326. doi: 10.1038/s42255-021-00356-0. Epub 2021 Mar 15.
• Han K, Singh K, Meadows AM, Sharma R, Hassanzadeh S, Wu J, Goss-Holmes H, Huffstutler RD, Teague HL, Mehta NN, Griffin JL, Tian R, Traba J, Sack MN. Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects. Cell Rep Med. 2023 Sep 19;4(9):101157. doi: 10.1016/j.xcrm.2023.101157. Epub 2023 Aug 15.
• Han K, Klein RJ, Recupero TC, Russo AC, Sharma R, Gupta AK, Hassanzadeh S, Huffstutler RD, Dagur PK, Fisk B, Redekar NR, Sack MN. NAD+ augmentation by nicotinamide riboside engages SLIT2/ROBO1 signaling to attenuate Th17 inflammation in psoriasis. JCI Insight. 2026 Apr 28;11(12):e203826. doi: 10.1172/jci.insight.203826. eCollection 2026 Jun 22.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2010

Study Registration Dates

• First Submitted: June 11, 2010
• First Submitted That Met QC Criteria: June 11, 2010
• First Posted (Estimated): June 14, 2010

Study Record Updates

• Last Update Posted (Actual): September 1, 2026
• Last Update Submitted That Met QC Criteria: August 29, 2026
• Last Verified: June 29, 2026

More Information

Terms related to this study

• Keywords: Natural History; Heart Disease; Cardiac Disease; iPS Cells; Cardiac Risk Factors; Cardiac Disease Discovery; Heart Disease Risk
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Nutrition Disorders; Neoplasms; Genetic Diseases, Inborn; Overnutrition; Body Weight; Overweight; Neoplastic Syndromes, Hereditary; Arteriosclerosis; Arterial Occlusive Diseases; DNA Repair-Deficiency Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Heart Diseases; Cardiomyopathies; Metabolic Diseases; Atherosclerosis; Li-Fraumeni Syndrome
• Other Study ID Numbers: 100126; 10-H-0126

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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