Genomic Investigation of Cardiovascular Diseases

The completion of the human genome project within the final months of the previous
millennium, is a landmark of scientific accomplishment. This achievement heralds the
importance human and molecular genetics will play in the coming century in medicine. In
short, one expects that dissecting the phenotypic aspects of disease to a culprit
mutation/variation of a gene or collection of genes, will modify and or augment our present
diagnostic ability leading on to new therapeutic interventions that are targeted based on
these discoveries.

The broad application of human genetics will progress from the study of rare mendelian traits
with complete penetrance compiled over the last 3-4 decades to a large number of "common"
diseases that have multi-gene etiology with variable penetrance such as non-insulin dependent
diabetes mellitus and hypertension. Cardiology will probably stay at a forefront of this
transformation, as cardiovascular diseases (CVD) remain the major source of morbidity and
mortality in developing countries, and is fast reaching the same status in the underdeveloped
countries. Furthermore, the track record of rapid adaptation of new technology and research
in the field of cardiology, would give further impetus to this transition. In the midst of
these dynamic currents, this proposal puts forward a research plan to initiate a genetic
databank, henceforth referred to as The Genebank at Scripps Clinic Registry. This database
will usher in genomic research at Scripps as we strive to stay at the forefront of
cardiovascular research in the new century.

The objective of this study is, to obtain blood samples in order to define genes for various
cardiovascular conditions. The blood samples will go through DNA analysis and noted for 1
million SNP's per individual.

Inclusion Criteria:

Candidates for this study must meet ALL of the following criteria:

- Age 18 years or older

- Be reliable, cooperative and willing to comply with all protocol-specified procedures
and sub-study if consented.

- Able to understand and grant informed consent

- Have at least one of the following (a-g):

1. Coronary Artery Disease (defined as):

- Coronary artery bypass surgery or

- Lesion >70% on cardiac or CT angiogram or

- Percutaneous Coronary Intervention

2. Myocardial infarction (defined as):

- Diagnosed by elevated troponin level or

- Diagnosed by ST segment elevations on EKG or

- Diagnosed by pathologic Q waves on EKG or

- Documented in the medical record or by self report

3. Atrial Fibrillation (defined as):

- Lone Atrial fibrillation (paroxysmal, persistent or permanent); OR

- Lone Atrial Flutter (paroxysmal, persistent or permanent)

4. Automatic Internal Cardiac Defibrillator

5. Aortic Stenosis (defined by):

- Calculated Aortic Valve Area ≤ 1.0 cm² or

- Mean Pressure Gradient ≥ 40 mmHg or

- Peak Pressure Gradient ≥ 64 mmHg or

- Dimensionless Index < .25 or

- Prior or planned Aortic Valve Replacement for Aortic Stenosis

6. Mitral Regurgitation (insufficiency) (defined as)

- Moderate to Severe (equivalent to +3 to +4) mitral regurgitation
(insufficiency) on transthoracic echocardiogram as determined by the reading
physician and structurally abnormal valve (i.e. myxomatous) and/or thickened
or redundant leaflets; OR

- Prior or planned Mitral Valve repair or replacement for mitral regurgitation

7. Idiopathic (non-ischemic) Cardiomyopathy (defined as):

- Diagnosed < age 40; OR

- Non-ischemic etiology confirmed by cardiac angiography or CT angiography
(may have non-obstructive or stable coronary artery disease if diagnosis of
non-ischemic etiology of CM is established by cardiologist).

Exclusion Criteria:

Patients will be excluded if ANY of the following conditions apply:

- Previously enrolled in The Genebank at Scripps Clinic Registry

- Any active bleeding (i.e. GI bleed).

- Has a significant medical condition which in the investigator's opinion may interfere
with the patient's optimal participation in the study

- Treatment with any investigational agents or devices within 30 days preceding
enrollment in the study.

- Been administered or taken any CNS sedatives or depressants in the past 12 hours.

- Been administered or taken any CNS sedatives or depressants in the past 12 hours.

- Subject's qualifying diagnosis is Atrial fibrillation and they are known to have any
one of the following:

1. Prior myocardial infarction, coronary artery bypass surgery, or percutaneous
coronary intervention

2. EF < 45% at time of diagnosis (excluding tachycardia induced cardiomyopathy
diagnosed by a cardiologist)

3. Elevated left atrial pressures (> 20 mmHg)

4. Dilated left atrium (> 4.0 cm or >2.0 cm/m2 body surface)

5. Mitral valve disease with significant valve pathology

- Mitral regurgitation/insufficiency greater than trace to mild on echo as
determined by reading physician

- Rheumatic mitral valve disease

6. Congestive heart failure prior to diagnosis

7. Hypertrophic cardiomyopathy

8. Diagnosis following coronary artery bypass or valve replacement surgery

9. Post heart transplant

10. Congenital heart disease

11. Diagnosed in setting of hyperthyroid

12. COPD

13. Obstructive sleep apnea

- Subject's qualifying diagnosis is Aortic Stenosis and they are known to have any one
of the following:

1. Bicuspid valve or other congenital abnormality of the aorta or aortic valve

2. Evidence of Rheumatic involvement of the Aortic Valve

- Subject's qualifying diagnosis is Mitral regurgitation (insufficiency) and they are
known to have any one of the following:

1. Ejection fraction <50%

2. Evidence of significant ischemic disease with regions of akinetic myocardium

3. Rheumatic changes on echocardiogram (as determined by the reading physi4ian)

5. Significant Mitral stenosis (greater than "mild" on echocardiogram as determined by
the reading physician) 6. Evidence of valve perforation 7. Evidence of congenital
abnormality (i.e. cleft valve)

- Subject's qualifying diagnosis is Idiopathic (non-ischemic) cardiomyopathy and they
are known to have any one of the following:

1. Ischemic cardiomyopathy

2. Hypertrophic cardiomyopathy

3. Viral cardiomyopathy

4. Alcohol/drug induced cardiomyopathy