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

Study Overview
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Brief Summary
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Background: - Researchers are interested in studying individuals who have known or suspected metabolic or genetic diseases that put them at a high risk for heart diseases or diseases of their blood vessels. To improve the results of the study, both affected and nonaffected individuals will be asked to provide blood and other samples and will undergo tests to evaluate heart and lung function. Nonaffected individuals will include relatives of affected individuals and healthy nonrelated volunteers. Objectives: - To study individuals who have or are at risk for cardiovascular diseases, as well as 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.

Detailed Description
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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.

Official Title
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Cardiovascular Disease Discovery Protocol

Conditions
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Cardiomyopathy, Li-Fraumeni Syndrome, Parkinson's Disease, Atherosclerosis, Cardiovascular Capacity

Intervention / Treatment
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* Drug: 11C-Acetate
* Drug: 13N-Amonia


Participation Criteria
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Eligibility Criteria
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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 case subjects 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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1. Adult index cases and relatives<br>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. | Drug: 11C-Acetate<br> <br> Drug: 13N-Amonia<br> <br> |
| 2. Child index case and child relatives<br>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. | Drug: 11C-Acetate<br> <br> Drug: 13N-Amonia<br> <br> |
| 3. Healthy adult volunteers<br>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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Diagnosis | This protocol will complement the aims of the Undiagnosed Diseases Program (UDP), which may admit some of its subjects through this protocol, to provide answers to subjects with conditions associated with cardiovascular features 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 |
| --- | --- | --- |
| Understanding disease pathophysiolgy | to assist in the understanding of disease pathophysiology and in the generation of diagnoses in subjects with uncommon presentations of diseases with cardiovascular consequences. | Ongoing | 
| Potential genetic counseling | Determining molecular etiology of diseases encountered on this protocol | Ongoing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Disease, iPS Cells, Cardiac Risk Factors, Cardiac Disease Discovery, Natural History, Heart Disease, Heart Disease Risk