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):

• Coronary Artery Disease (defined as):

• Coronary artery bypass surgery or
• Lesion >70% on cardiac or CT angiogram or
• Percutaneous Coronary Intervention
• 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
• Atrial Fibrillation (defined as):

• Lone Atrial fibrillation (paroxysmal, persistent or permanent); OR
• Lone Atrial Flutter (paroxysmal, persistent or permanent)
• Automatic Internal Cardiac Defibrillator
• 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
• 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
• 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:

• Prior myocardial infarction, coronary artery bypass surgery, or percutaneous coronary intervention
• EF < 45% at time of diagnosis (excluding tachycardia induced cardiomyopathy diagnosed by a cardiologist)
• Elevated left atrial pressures (> 20 mmHg)
• Dilated left atrium (> 4.0 cm or >2.0 cm/m2 body surface)
• 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
• Congestive heart failure prior to diagnosis
• Hypertrophic cardiomyopathy
• Diagnosis following coronary artery bypass or valve replacement surgery
• Post heart transplant
• Congenital heart disease
• Diagnosed in setting of hyperthyroid
• COPD
• Obstructive sleep apnea
• Subject's qualifying diagnosis is Aortic Stenosis and they are known to have any one of the following:

• Bicuspid valve or other congenital abnormality of the aorta or aortic valve
• 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:

• Ejection fraction <50%
• Evidence of significant ischemic disease with regions of akinetic myocardium
• Rheumatic changes on echocardiogram (as determined by the reading physi4ian)

• 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:

• Ischemic cardiomyopathy
• Hypertrophic cardiomyopathy
• Viral cardiomyopathy
• Alcohol/drug induced cardiomyopathy