Coronary Artery Disease

• 1.1 million MIs in U.S. annually

• 500,000 deaths due to acute MI

• Major cause of sudden death not associated with acute MI ( chronic coronary artery disease ).

• Major cause of CHF

• Acute and chronic anginal syndromes

Coronary athero progression

Stable vs unstable angina

• Unstable plaque, Large lipid core,thin fibrous cap and lg amount of inflammatory cells.

• Stable plaque, Small lipid core,thick fibrous cap and sparse inflammatory cells.

CCTA: Right Coronary Artery

Symptomatic CAD: Influence of CT Calcium Score(JACC 2007; 50: 1469)

N = 254 (symptomatic)

CAD: >50% stenosis in 1 vessel by cath

Probability (%) Low Intermediate High(0-30) (31-70) (>71)

Pretest 13 53 87

CT Calcium positive 68 * 88 * 96

• CT calcium is useful in symptomatic patients with low/ intermediate pretest probability

•CT calcium is not useful in symptomatic high risk patients

CAD: Inflammatory Plaque (NEJM 2000; 342: 101)

•Large, eccentric lipid-rich pool > 40% volume

•Foam cell infiltration

•Thin fibrous cap < 1 m

•Local inflammatory environment

macrophages, T cells, neutrophils

smooth muscle cells

enzymes, cytokines metalloproteinases

•Neovascularization → intra-plaque hemorrhage

Indications for cardiac catheterization

• Selected cases of acute ST elevation MIs• Post MI ischemia• Unstable angina• Selected cases of non ST elev. MI• Chronic angina with strong pos stress test• Patients undergoing valve surgery who have

coronary risk factors• ? All MI patients ( open vessel theory )• Cardiogenic shock.

Coronary arteries

• Left main coronary artery

• Left anterior descending

• Circumflex

• Right coronary artery

Branched of coronary arteries

• L main : LAD and Circumflex

• LAD : septal perforators and diagonals branches

• Circumflex : obtuse marginals,posterolateral and atrioventricular

• RCA : SA nodal, AV nodal, conus, RV, posterolateral and posterior descending

RX L Main Coronary artery

• Degree of stenosis may be difficult to grade• Occlusion causes massive MI• Stenosis-markedly positive stress test• Usual RX is CABG• In special circumstances may be stented.

RX LAD

• Major stenosis of LAD usually gives strong positive stress test.

• Occlusion of LAD causes a large MI with major decrease in EF

• Stenting of high grade proximal stenosis of LAD usually yields excellent results

• Stenting of LAD with a large diagonal branch off the lesion may be problematic.

RX Circumflex

• CX stenosis often with few ECG findings although classically should show in AVL and V6.

• When CX is non dominent MI causes only minor decrease in EF

• CX marginal branches are targets for CABG

RX RCA disease

• Usually dominant ( main supply to inferior and posterior LV ). PDA usually is a branch of RCA

• Occlusion of proximal RCA usually results in a lessor decrease in EF and lower mortality than LAD block

• Brady arrhythmias and temporary heart block is common.

• RV infarction is uncommon but has a high morbidity and mortality

Presentations of CAD

• Sudden death

• ST elevation MI

• Non ST elevation MI

• Unstable angina

• Stable angina

• Variant ( vasospastic angina )

Cardiac Sudden Death

• Ventricular fibrillation

• Electro-mechanical dissociation

• Asystole

• Etiologies : Acute MI, Old MI with EF less than 30 %, Cardiac myopathies from various diseases and various etiolgies with NL LV function ( Brugada,Long QT,idiopathic,IHSS etc.).

Courage Trial

• Randomized 2287 pts with chronic stable angina to optimal medical RX vs optimal medical RX plus bare metal stenting.

• Patients excluded were UA, strong pos stress test,50% or greater L Main disease,class 4 angina or EF less than 30%.

Courage Trial

• No change in outcomes ( death or MI ) but less angina in stent gp at 1 and 3 years but not at 5 years.

• 33% of pts in Med RX alone limb eventually needed intervention.

Recommendations based on Courage trial

• Pts with symptomatic or asymptomatic stable CAD should undergo assessment of LV fx and risk stratification with ischemia testing.

• Stable pts with good LV fx and low risk stress test can be managed medically without cath.

Recommendations from Courage trial

• Pts with impaired LV Fx or high risk features on ischemia testing should be cathed.

• If angina not well controlled, cath.• 1 or 2 vessel disease with good LV fx

should be stented• L main, 3 vessel disease or 2 vessel

disease (with LAD): CABG or in selected cases stents.

Outcomes after thrombolytic RX

• LAD occlusion: 4-5 lives saved/ 100 pts treated

• New LBBB: 6-7 lived saved/ 100 pts treated

• RCA or Circumflex occlusion ( Inferior MI,uncomplicated: 1 life saved/ 100 pts treated

• Best outcomes occur when pts treated within 4 hours of symptom onset

RX Stable angina

• Aspirin

• Statin

• Beta blocker

• All patients after stent or those with ASA intolerance - Clopidogrel

• ACE ( Ramipril preferred ) for high risk patients ie diabetes,prior MI,HTN etc. )

RX Unstable angina

• Nitrates• Low molecular heparin• Beta blockers to HR about 60• ASA,preferably non coated• Clopidogrel • 2b3a platelet inhibitor• Statin• ACE for BP control• Cardiology consult quickly to consider cath

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Routine Stress testing in Asymptomatic Diabetics(DIAD trial: Diabetes Care 2004; 27: 1954)

N = 1123 (asymptomatic DM, age 50-75 years)MPI + Rx vs Usual Rx for 5 years

•Positive MPI: 22%

•Moderate- large perfusion defects: 40%

•Other risk factors / inflammation biomarkers not predictive of positive MPI except autonomic dysfunction

•Using ADA guidelines would have failed to predict 41% of patients with silent ischemia

• Chest pain where tests are equivocal

Post MI Care ( ST elevation )

• Ischemia testing when pt stable ( usually 3-5 days

• Pos stress– cardiac cath

• Neg stress usually not cathed

• All patients instructed about life style changes ( cigs,diet,exercise etc. )

• Meds usually asa,beta blocker,ace and a statin.

Ischemia Tests

• Treadmill stress test

• Treadmill stress test with Echocardiogram

• Treadmill stress test with Thallium

• Adenosine or Persantine nucleotide test without exercise ( Sestamibi )

• Dobutamine Echo test without exercise

Contraindications to Stress Testing

• MI in past 48 hours

• Unstable angina, ongoing

• Poorly controlled CHF or arrhythmias

• Acute Aortic dissection or PE

• Myocarditis

• Major associated conditions ie pneumonia,severe anemia,acute renal failure

Relative contraindications to Stress Testing

• Severe Aortic Stenosis

• SBP >200 or diastolic > 110

• Known L main CAD

• Significant arrhythmias

• HOCM

• Major electrolyte imbalance

Stress Echocardiography

• Higher specificity

• Versatility: more extensive evaluation of cardiac anatomy and function

• Greater convenience, efficacy and availability

• Lower cost

Stress Perfusion imaging

• Higher technical success rate

• Higher sensativity, particularly with 1 vessel disease

• Better accuracy when multiple rest-LV wall motion abnormalities are present

• Better when good technical Echo can not be obtained

• More extensive published data available

Dobutamine Echo

• Causes ischemia by increasing O2 demand

• Must have a good technical Echo

• Used in pts who can not exercise

• A positive test is a new regional wall motion abnormality

• Usually not helpful with myopathic LV

• Don’t use in UA or recent V tach.

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Setup for intervention or CABG

• Severe ( > 75-80% ) proximal stenosis with the distal vessel being 2.5 mm or larger and free of major disease.

• If the distal vessel is very small or has major diffuse disease an intervention or CABG will usually not be successful

Etiologies of ischemia other than Atherosclerosis

• Congenital coronary artery anomalies• Cocaine• Prinzmetal’s varient angina• Aortic stenosis or HOCM• Coronary arteritis• Coronary artery ectasia• Bridging coronary arteries ?• Syndrome X• Coronary thrombus

CAD: Screening Asymptomatic Patients

(Ann Int Med 2004; 141: 57)

“ACP/AHA recommends against screening asymptomatic outpatients for CAD”

CAD: Lifetime Risk

(Framingham Heart Study. Circulation 2006; 113: 791; Lancet 1999; 353: 89)

Asymptomatic population between 40-90 years

•At age 40 years, lifetime risk is:

Male: 49%

Female: 32%

Aggressive identification and management of asymptomatic patients at risk recommended

Classification of CAD in all Patients

•Established CAD

MI, cath-proven CAD, PCI, CABG

•CAD equivalent

DM, Cr Cl < 60 ml/min, CVA/carotid IMT > 1.1 mm, PVD, Atherosclerotic aortic aneurysm

•Chronic coronary syndrome (CCS)

Chronic stable angina, silent ischemia, Syndrome X

•Acute coronary syndrome (ACS)

NSTE-ACS, STE-ACS

•Risk for CAD

RX LAD

Vulnerable Patient: Risk Effects (Circulation 2004; 109: 2613)

•Cigarette smoking and DM are strongest risk factors

•Most common dyslipidemia: (↑TG + ↓HDL-C)

•Strongest lipid factor: T-C/HDL-C ratio (JAMA 2001;285: 2481)

At age 40 years (Framingham Heart Study):

Reduced life expectancy (years) MenWomen

Obesity 5.8 7.1

Smoking 8.66 7.59

HTN 5.1 4.9

Sedentary lifestyle 1.3-3.7 1.5-3.5

Vulnerable Plaque : hs CRP (Circulation 2002; 105: 1135)

•hs CRP: most sensitive independent marker of CV risk, including sudden death (Circulation 2002; 105: 2595; Arch Int Med 2002; 162: 867; TIMI 11A substudy: JACC 1998; 31: 1460)

•Asymptomatic persons with hsCRP coronary atherosclerosis / calcification (Framingham Heart Study: Circulation 2002; 106: 1189).

•hsCRP is an independent and stronger predictor of CV events than LDL-C; best prediction is hsCRP + T-C/HDL-C ratio (WHS study: NEJM 2002; 347: 1557)

•hsCRP is predictor of CV events even when LDL-C levels are below target values (WHS group: NEJM 2000; 342: 836; CARE study: Circulation 1999; 100: 230)

•Statins hsCRP (PRINCE study: JAMA 2001; 286: 64; CARE study: Circulation

1999; 100: 230) CV events (AFCAPS/TEXCAPS study: NEJM 2001; 344: 1959)

Vulnerable Plaque: MDCT Coronary Calcium Score

Coronary calcium: > 130 Hounsfield units

•Calcium is 100% specific for atherosclerosis

•Calcium shows weak correlation with luminal narrowing

•Area of calcium correlated (r = 0.9) with area of plaque

•Calcium area approximately 20% of associated plaque area

•“Soft plaque” → no detectable calcium

Symptomatic CAD: Influence of CT Calcium Score(JACC 2007; 50: 1469)

N = 254 (symptomatic)

CAD: >50% stenosis in 1 vessel by cath

Probability (%) Low Intermediate High

Pretest 13 53 87

CT Calcium positive 68 * 88 * 96

• CT calcium is useful in symptomatic patients with low/ intermediate pretest probability

•CT calcium is not useful in symptomatic high risk patients

Vulnerable Myocardium: No Structural Disease (JACC 2004; 43: 1137)

Long QT syndromes (LQTS)(QTc > 440 msecs in males, > 460 msecs in

females)

Brugada syndrome

Pre-excitation (WPW syndrome)------------------------------------------------------------

Short-coupled torsades

Drug-induced torsades

Idiopathic VT

Commotio cordis

Selection of Stress Test

Patient can Exercise:

•Low incidence of false positive:

Exercise EKG

•↑ False positives with exercise EKG:

Exercise Echo; Exercise thallium-sestamibi

Patient cannot Exercise / Uninterpretable exercise EKG:

Pharmacologic stress test:

Dobutamine echo

Adenosine thallium-sestamibi

CAD: Risk Assessment (Prognosis)

Virtually all patient management decisions must driven by the clinician's assessment of the patient's prognosis.

It is risk assessment that should indicate the need for testing and/or therapy

Failure to assess risk leads to inappropriate and expensive testing in low risk patients, and less aggressive management in those at very high risk.