Ischemic Heart DiseaseIschemic Heart Disease

Amish C. Sura, M.D. F.A.C.C.Amish C. Sura, M.D. F.A.C.C.Clinical CardiologistClinical Cardiologist

Mercy Medical CenterMercy Medical CenterSeptember 2008September 2008

DisclosuresDisclosures

I have no relevant financial I have no relevant financial relationships with any commercial relationships with any commercial interest with the manufacturer of any interest with the manufacturer of any commercial product and/or provider commercial product and/or provider of commercial services discussed in of commercial services discussed in this presentation.this presentation.

What is Ischemic Heart What is Ischemic Heart Disease?Disease?

Cardiac dysfunction due to a decrease in the blood Cardiac dysfunction due to a decrease in the blood

supply caused by constriction or obstruction of the supply caused by constriction or obstruction of the blood vessels.blood vessels.

Manifestations:Manifestations:1.1. ““Silent” Myocardial Ischemia.Silent” Myocardial Ischemia.

2.2. Acute Coronary Syndromes (STEMI, NSTEMI, USA).Acute Coronary Syndromes (STEMI, NSTEMI, USA).

3.3. Cardiomyopathies and Congestive Heart Failure.Cardiomyopathies and Congestive Heart Failure.

4.4. Sudden Cardiac Death (SCD) and other Sudden Cardiac Death (SCD) and other arrhythmias.arrhythmias.

Diagnostic Tests for IHDDiagnostic Tests for IHD

1.1. SymptomsSymptoms

2.2. EKGEKG

3.3. Stress TestingStress Testing

4.4. Bio-markersBio-markers

5.5. Imaging (CT, MRI, PET)Imaging (CT, MRI, PET)

6.6. Coronary AngiographyCoronary Angiography

Indications for Stress Indications for Stress TestingTesting

Evaluation of patients with known or suspected Evaluation of patients with known or suspected coronary heart disease (CHD). coronary heart disease (CHD). (etiology of chest pain, (etiology of chest pain, planned revascularization, myocardial viability etc.)planned revascularization, myocardial viability etc.)

Assessment of the therapeutic effects of cardiac Assessment of the therapeutic effects of cardiac drugs.drugs.

Assessment of functional capacity.Assessment of functional capacity.

Try to predict risk of future coronary events among Try to predict risk of future coronary events among patients with documented CHD, a prior myocardial patients with documented CHD, a prior myocardial infarction, or a history of unstable angina. infarction, or a history of unstable angina.

Types of Stress TestsTypes of Stress TestsStress:Stress:

Physical vs. pharmacologicPhysical vs. pharmacologic Treadmill, bicycle, isometric hand grip.Treadmill, bicycle, isometric hand grip. Adenosine, Dipyridamole, Dobutamine.Adenosine, Dipyridamole, Dobutamine.

Imaging Modalities:Imaging Modalities: EKG.EKG. Echocardiogaphy.Echocardiogaphy. Perfusion imaging (SPECT MPI).Perfusion imaging (SPECT MPI). CT.CT. PET.PET. MRI.MRI.

Who should get perfusion Who should get perfusion imaging?imaging?

Patients with un-interpretable baseline Patients with un-interpretable baseline EKGs. EKGs. (significant baseline ST or T wave (significant baseline ST or T wave abnormalities, LBBB, paced rhythm, pre-excitation abnormalities, LBBB, paced rhythm, pre-excitation (WPW), Digoxin).(WPW), Digoxin).

Women-Women-lower accuracy and greater incidence of lower accuracy and greater incidence of false-positive EKG changes with standard tests; false-positive EKG changes with standard tests; perfusion imaging increases diagnostic accuracy.perfusion imaging increases diagnostic accuracy.

Patients who receive pharmacologic Patients who receive pharmacologic stress with adenosine/dipyridamole.stress with adenosine/dipyridamole.

Estimated positive predictive Estimated positive predictive value of Exercise EKG Stress testvalue of Exercise EKG Stress test

Depends on the pretest probability of coronary heart Depends on the pretest probability of coronary heart disease (CHD), ie, the prevalence of CHD in the disease (CHD), ie, the prevalence of CHD in the population studied. population studied.

Clinical IndicationClinical Indication Treadmill EKGTreadmill EKG Nuclear Perfusion Nuclear Perfusion ImagingImaging

Detect CAD (Sensitivity)Detect CAD (Sensitivity) Good (65%)Good (65%) Very Good(85%)Very Good(85%)

Exclude CAD (specificity)Exclude CAD (specificity) Good(65%)Good(65%) Very Good(90%)Very Good(90%)

Accuracy in presence of Accuracy in presence of marked ST/T abnormalitiesmarked ST/T abnormalities

PoorPoor Very GoodVery Good

Localize Myocardial Localize Myocardial IschemiaIschemia

PoorPoor Very GoodVery Good

Assess Myocardial Assess Myocardial ViabilityViability

PoorPoor GoodGood

Prognosis for IHD or Prognosis for IHD or Post –MIPost –MI

GoodGood Very GoodVery Good

CostCost Relatively Cheap ($900)Relatively Cheap ($900) Expensive ($1600)Expensive ($1600)

How Good are the Tests?Depends on the Question

Functional Capacity during Functional Capacity during stress testing is related to stress testing is related to

MortalityMortality

Snader CE, Marwick TH et al. JACC 1997;30:641-8

N=3400N=3400

Good

Poor

Duke treadmill score predicts Duke treadmill score predicts survivalsurvival

n=2,578 (70% men).n=2,578 (70% men). Duke prognostic treadmill score = Duke prognostic treadmill score = Exercise time (minutes based on the Bruce protocol) Exercise time (minutes based on the Bruce protocol)

- (5  x  max ST segment deviation in mm) - (4  x  exercise angina - (5  x  max ST segment deviation in mm) - (4  x  exercise angina [0=none, 1=non-limiting, and 2=exercise [0=none, 1=non-limiting, and 2=exercise

limiting]limiting]))

Effective for risk-stratifying men but Effective for risk-stratifying men but not womennot women..

65%

90%

>97%

Data from Shaw, LJ, Peterson, ED, Shaw, LK, et al. Circulation 1998; 98:1622.

Low-risk — score ≥+5 Moderate-risk — score from -10 to +4 High-risk — score ≤-11

Maisel AS et al. (2006) Cardiac biomarkers: a contemporary status reportNat Clin Pract Cardiovasc Med 3: 24–34 doi:10.1038/ncpcardio0405

Cardiac markers classified according to the different pathologic processes they indicate

What makes a biomarker clinically What makes a biomarker clinically useful?useful?

Morrow, DA, de Lemos, JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circ.2007;115:949-52.

Widely used biomarkersWidely used biomarkers

All meet criteria of Morrow & de All meet criteria of Morrow & de Lemos.Lemos.

1.1. Brain Natriuretic peptide (BNP).Brain Natriuretic peptide (BNP).

2.2. C-reactive protein (CRP).C-reactive protein (CRP).

3.3. Cardiac specific Troponins (TN-I, TN-T).Cardiac specific Troponins (TN-I, TN-T).

BNPBNP

Has been studied in many Has been studied in many manifestations of ischemic heart manifestations of ischemic heart disease.disease.

Adds prognostic significance beyond Adds prognostic significance beyond other measures.other measures.

Trends in individual levels maybe more Trends in individual levels maybe more important than discrete measurements.important than discrete measurements.

Protein secreted by the heart in response to excessive stretching of heart muscle cells.Causes excretion of sodium (water) and increases cardiac output.

BNP levels correlate with NYHA BNP levels correlate with NYHA ClassClass

NYHA Classes:NYHA Classes:I: No symptoms and no limitation in ordinary physical activity. I: No symptoms and no limitation in ordinary physical activity. II. Mild symptoms and slight limitation during ordinary activity.II. Mild symptoms and slight limitation during ordinary activity.III.Marked limitation in activity due to symptoms, even during III.Marked limitation in activity due to symptoms, even during

less-than-ordinary activity. Comfortable only at rest.less-than-ordinary activity. Comfortable only at rest.IV.Severe limitations. Experiences symptoms even while at IV.Severe limitations. Experiences symptoms even while at

rest, mostly bed-bound patientsrest, mostly bed-bound patients

Tokunaga, A.Onda, M et al. Biochemical Assessment of Cardiac Function in patients undergoing surgery for gastric cancer. J Nippon Med Sch.2001.

BNP and mortality in CHFBNP and mortality in CHFFrom VAL-HeFT: n=4300 NYHA Class II-III patients.Followed for 35 months.

Mortality rates at two years after randomization were significantly higher in higher quartiles of plasma BNP .

Anand IS et al. Changes in Brain Natriuretic Peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (VAL-HeFT).Circ. 2003; 107:1278-83.

BNP predicts mortality in Acute Coronary BNP predicts mortality in Acute Coronary SyndromesSyndromes

5-43.6 pg/ml43.7-81.2 pg/ml81.3-137.8 pg/ml137.9-1456.6 pg/ml

de Lemos JA; Morrow DA; Bentley JH et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001 Oct 4;345(14):1014-21.

C-reactive Protein (CRP)C-reactive Protein (CRP)

Non-specific acute Non-specific acute phase marker of phase marker of inflammation that is inflammation that is produced produced predominantly by predominantly by hepatocytes under the hepatocytes under the influence of cytokines influence of cytokines such as IL-6 and TNF-such as IL-6 and TNF-αα..

Confers prognostic Confers prognostic information in information in asymptomatic patients asymptomatic patients and patients with and patients with known ischemic heart known ischemic heart disease.disease.

Rader, DJ. Inflammatory Markers of Coronary Risk.N Engl J Med 343:1179

Actual 8-Year Cardiovascular Events Actual 8-Year Cardiovascular Events Compared with Framingham Estimate Compared with Framingham Estimate

& & hs-CRP in the WHShs-CRP in the WHS

0%

5%

10%

15%

20%

25%

0-1% 2-4% 5-9% >10%

<1.0

1.0-3.0

>3.0

Car

dio

vasc

ula

r E

ven

ts

Framingham Estimate of 10-Year Risk

hs-CRP

Ridker PM et al, N Engl J Med 2002;347:1557Ridker PM et al, N Engl J Med 2002;347:1557

CRP Predicts outcome in ACSCRP Predicts outcome in ACS

Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of Myocardial Damage and Inflammation in Relation to Long-Term Mortality in Unstable Coronary Artery Disease . N Engl J Med 343:1139

CRP is an independent predictor in CRP is an independent predictor in CHFCHF

Ishikawa C, Tsutamoto T et al. Prediction of mortality by high-sensitivity C-reactive protein and brain natriuretic peptide in patients with dilated cardiomyopathy. Circ J. 2006 Jul;70(7):857-63.

CRP is prognostic, but clinically CRP is prognostic, but clinically useful?useful?

From CDC and AHA:From CDC and AHA:

hs-CRP may be useful as an independent marker of hs-CRP may be useful as an independent marker of prognosis in patients with stable CHD or an ACS. prognosis in patients with stable CHD or an ACS.

At present there is insufficient evidence to At present there is insufficient evidence to recommend that CRP determine the application of recommend that CRP determine the application of specific therapies for acute management of ACS or specific therapies for acute management of ACS or for secondary prevention. for secondary prevention.

Though CRP may be an independent risk factor for Though CRP may be an independent risk factor for IHD, there is no direct evidence that lowering CRP IHD, there is no direct evidence that lowering CRP alone will result in a reduction in cardiovascular alone will result in a reduction in cardiovascular risk. risk.

Pearson, TA, Mensah, GA, Alexander, RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003; 107:499.

Cardiac TroponinCardiac Troponin Part of cardiac muscle.Part of cardiac muscle. Damage causes release of these Damage causes release of these

proteins into the blood.proteins into the blood. Confer independent prognostic Confer independent prognostic

information.information.

Troponin in ACS predicts Troponin in ACS predicts mortalitymortality

Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of Myocardial Damage and Inflammation in Relation to Long-Term Mortality in Unstable Coronary Artery Disease . N Engl J Med 343:1139

Troponin I independently predicts Troponin I independently predicts mortality in CHFmortality in CHF

N=251 advanced heart failure patients referred for cardiac transplantation.

Horwich TB; Patel J; MacLellan WR; Fonarow GC. Cardiac troponin I is associated with impaired hemodynamics, progressiveleft ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 2003 Aug 19;108(7):833-8

Coronary Calcium ScoringCoronary Calcium Scoring Based on relationship of vascular calcification Based on relationship of vascular calcification

and vascular disease.and vascular disease.

Detected initially using electron beam CT Detected initially using electron beam CT (EBCT), now usually detected using Multi-(EBCT), now usually detected using Multi-detector (MDCT) or Multi-slice CT.(MSCT)detector (MDCT) or Multi-slice CT.(MSCT)

Studies are based on EBCT and applied to Studies are based on EBCT and applied to MDCT/MSCT.MDCT/MSCT.

Most utilized scoring system is Agatston scoreMost utilized scoring system is Agatston score. . (derived by multiplying the calcified plaque area by a coefficient (derived by multiplying the calcified plaque area by a coefficient based on plaque attenuation values) based on plaque attenuation values)

CAC predicts coronary CAC predicts coronary stenosisstenosis

Men Women

Haberl R, Becker A, et al. Correlation of coronary calcification and angiographically documented stenoses in patients

with suspected coronary artery disease: results of 1,764 patients. J Am Coll Cardiol. 2001 Feb;37(2):451-7

•N=1764 patients with chest pain.•Significant stenosis defined as >50%.•There are gender, age and ethnic differences affecting sensitivity and specificity of calcium scoring.

Dx Uncertain

CAC independently predicts CAC independently predicts outcomeoutcome

•N=1461 asymptomatic patients (90% men) with risk factors for CAD.•7 year follow-up.•Demonstrates that CAC adds prognostic value to Framingham Model.

Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC. Coronary Artery Calcium Score Combined With Framingham Score for Risk Prediction in Asymptomatic Individuals. JAMA. 2004 Jan 14;291(2):210-5.

Significant Limitations preclude Significant Limitations preclude routine use of CAC routine use of CAC

No clear evidence that preventive measures based upon the CAC score No clear evidence that preventive measures based upon the CAC score leads to an improvement in outcomes.leads to an improvement in outcomes.

The potential harm associated with false-positive tests and radiation The potential harm associated with false-positive tests and radiation exposure (especially with repeated testing) is not known. exposure (especially with repeated testing) is not known.

Though the presence of CAC is highly sensitive for the presence of ≥50% Though the presence of CAC is highly sensitive for the presence of ≥50% angiographic stenosis, it is only moderately specific, especially in older angiographic stenosis, it is only moderately specific, especially in older patients (unclear to what extent data can be extrapolated to patients other patients (unclear to what extent data can be extrapolated to patients other than Caucasian men). than Caucasian men).

Providing patients with the results of CAC testing has not been shown to motivate patients to make lifestyle changes for managing their cardiovascular risk factors.

ACC/AHA Recommendations ACC/AHA Recommendations 20072007

Coronary artery calcium scoring has been less well studied in women Coronary artery calcium scoring has been less well studied in women and ethnic minorities than in Caucasian, non-Hispanic men. As a and ethnic minorities than in Caucasian, non-Hispanic men. As a result, the recommendations are less clearly applicable to these result, the recommendations are less clearly applicable to these groups.groups.

CAC NOT recommended for asymptomatic patients with low or high CAC NOT recommended for asymptomatic patients with low or high ten-year CHD risk as established by the Framingham and modified ten-year CHD risk as established by the Framingham and modified Framingham/ATP risk scores. Framingham/ATP risk scores.

For asymptomatic patients with an intermediate CHD ten year risk For asymptomatic patients with an intermediate CHD ten year risk (10-20%), CAC suggested when the result might lead to a change in (10-20%), CAC suggested when the result might lead to a change in management based upon reclassification to a lower or higher risk management based upon reclassification to a lower or higher risk group. group.

In patients who have undergone screening coronary CT scanning, In patients who have undergone screening coronary CT scanning, additional noninvasive or invasive testing is not recommended when additional noninvasive or invasive testing is not recommended when the CAC score is high (eg, greater than 400). the CAC score is high (eg, greater than 400).

In patients categorized as high risk by the Framingham risk score, In patients categorized as high risk by the Framingham risk score, there is no evidence that additional testing will lead to any change in there is no evidence that additional testing will lead to any change in management plan. management plan.

In patients assessed to be a low risk, a negative exercise test would In patients assessed to be a low risk, a negative exercise test would confirm the low likelihood of disease. confirm the low likelihood of disease.

Greenland, P, Bonow, RO, Brundage, BH, et al.ACCF/AHA 2007 Clinical Expert Consensus Document on Coronary Artery Calcium Scoring By Computed Tomography in Global Cardiovascular Risk Assessment and in Evaluation of Patients With Chest Pain: A Report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) Developed in Collaboration With the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular

Computed Tomography. J Am Coll Cardiol 2007; 49:378.

Gender DifferencesGender Differences Under-estimation of coronary risk in Under-estimation of coronary risk in

women.women. Delayed and underuse of testing in Delayed and underuse of testing in

women.women. Limited diagnostic accuracy of some tests Limited diagnostic accuracy of some tests

in women.in women. Women may have more co-morbidities Women may have more co-morbidities

than men at time of presentation.than men at time of presentation. These probably contribute to the increased These probably contribute to the increased

mortality in women after MI or CABG.mortality in women after MI or CABG.