Transcript Ischemic Heart Disease

Ischemic Heart Disease
Amish C. Sura, M.D. F.A.C.C.
Clinical Cardiologist
Mercy Medical Center
September 2008
Disclosures
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I have no relevant financial relationships
with any commercial interest with the
manufacturer of any commercial product
and/or provider of commercial services
discussed in this presentation.
What is Ischemic Heart Disease?
Cardiac dysfunction due to a decrease in the blood supply
caused by constriction or obstruction of the blood
vessels.
Manifestations:
1.
2.
3.
4.
“Silent” Myocardial Ischemia.
Acute Coronary Syndromes (STEMI, NSTEMI, USA).
Cardiomyopathies and Congestive Heart Failure.
Sudden Cardiac Death (SCD) and other arrhythmias.
Diagnostic Tests for IHD
1.
2.
3.
4.
5.
6.
Symptoms
EKG
Stress Testing
Bio-markers
Imaging (CT, MRI, PET)
Coronary Angiography
Indications for Stress Testing
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Evaluation of patients with known or suspected
coronary heart disease (CHD). (etiology of chest pain, planned
revascularization, myocardial viability etc.)
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Assessment of the therapeutic effects of cardiac drugs.
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Assessment of functional capacity.
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Try to predict risk of future coronary events among
patients with documented CHD, a prior myocardial
infarction, or a history of unstable angina.
Types of Stress Tests
Stress:
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Physical vs. pharmacologic
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Treadmill, bicycle, isometric hand grip.
Adenosine, Dipyridamole, Dobutamine.
Imaging Modalities:
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EKG.
Echocardiogaphy.
Perfusion imaging (SPECT MPI).
CT.
PET.
MRI.
Who should get perfusion imaging?
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Patients with un-interpretable baseline EKGs.
(significant baseline ST or T wave abnormalities, LBBB,
paced rhythm, pre-excitation (WPW), Digoxin).
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Women-lower accuracy and greater incidence of false-
positive EKG changes with standard tests; perfusion imaging
increases diagnostic accuracy.
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Patients who receive pharmacologic stress
with adenosine/dipyridamole.
Estimated positive predictive value of
Exercise EKG Stress test
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Depends on the pretest probability of coronary heart disease
(CHD), ie, the prevalence of CHD in the population studied.
How Good are the Tests?
Depends on the Question
Clinical Indication
Treadmill EKG
Nuclear Perfusion
Imaging
Detect CAD (Sensitivity)
Good (65%)
Very Good(85%)
Exclude CAD (specificity)
Good(65%)
Very Good(90%)
Accuracy in presence of
marked ST/T abnormalities
Poor
Very Good
Localize Myocardial
Ischemia
Poor
Very Good
Assess Myocardial
Viability
Poor
Good
Prognosis for IHD or
Post –MI
Good
Very Good
Cost
Relatively Cheap ($900)
Expensive ($1600)
Functional Capacity during stress
testing is related to Mortality
N=3400
N=3400
Poor
Good
Snader CE, Marwick TH et al. JACC 1997;30:641-8
Duke treadmill score predicts survival
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n=2,578 (70% men).
Duke prognostic treadmill score =
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Effective for risk-stratifying men but not women.
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Exercise time (minutes based on the Bruce protocol) - (5 x max
ST segment deviation in mm) - (4 x exercise angina [0=none, 1=non-limiting, and 2=exercise limiting])
>97%
90%
65%
Low-risk — score ≥+5
Moderate-risk — score from -10 to +4
High-risk — score ≤-11
Data from Shaw, LJ, Peterson, ED, Shaw, LK, et al. Circulation 1998; 98:1622.
Cardiac markers classified according to the different
pathologic processes they indicate
Maisel AS et al. (2006) Cardiac biomarkers: a contemporary status report
Nat Clin Pract Cardiovasc Med 3: 24–34 doi:10.1038/ncpcardio0405
What makes a biomarker clinically useful?
Morrow, DA, de Lemos, JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circ.2007;115:949-52.
Widely used biomarkers
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All meet criteria of Morrow & de Lemos.
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2.
3.
Brain Natriuretic peptide (BNP).
C-reactive protein (CRP).
Cardiac specific Troponins (TN-I, TN-T).
BNP
Protein secreted by the heart in response to excessive
stretching of heart muscle cells.
Causes excretion of sodium (water) and increases cardiac output.
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Has been studied in many manifestations
of ischemic heart disease.
Adds prognostic significance beyond other
measures.
Trends in individual levels maybe more
important than discrete measurements.
BNP levels correlate with NYHA Class
NYHA Classes:
I: No symptoms and no limitation in ordinary physical activity.
II. Mild symptoms and slight limitation during ordinary activity.
III.Marked limitation in activity due to symptoms, even during lessthan-ordinary activity. Comfortable only at rest.
IV.Severe limitations. Experiences symptoms even while at rest, 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 CHF
From 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 Syndromes
5-43.6 pg/ml
43.7-81.2 pg/ml
81.3-137.8 pg/ml
137.9-1456.6 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)
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Non-specific acute phase
marker of inflammation
that is produced
predominantly by
hepatocytes under the
influence of cytokines
such as IL-6 and TNF-α.
Confers prognostic
information in
asymptomatic patients
and patients with known
ischemic heart disease.
Rader, DJ. Inflammatory Markers of Coronary Risk.N Engl J Med 343:1179
Actual 8-Year Cardiovascular Events
Compared with Framingham Estimate &
hs-CRP in the WHS
Cardiovascular Events
25%
20%
hs-CRP
15%
<1.0
1.0-3.0
>3.0
10%
5%
0%
0-1%
2-4%
5-9%
>10%
Framingham Estimate of 10-Year Risk
Ridker PM et al, N Engl J Med 2002;347:1557
CRP 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 CHF
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 useful?
From CDC and AHA:
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hs-CRP may be useful as an independent marker of
prognosis in patients with stable CHD or an ACS.
At present there is insufficient evidence to recommend
that CRP determine the application of specific
therapies for acute management of ACS or for
secondary prevention.
Though CRP may be an independent risk factor for
IHD, there is no direct evidence that lowering CRP
alone will result in a reduction in cardiovascular 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 Troponin
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Part of cardiac muscle.
Damage causes release of these proteins
into the blood.
Confer independent prognostic
information.
Troponin in ACS predicts mortality
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
mortality 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, progressive
left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 2003 Aug 19;108(7):833-8
Coronary Calcium Scoring
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Based on relationship of vascular calcification and
vascular disease.
Detected initially using electron beam CT (EBCT),
now usually detected using Multi-detector (MDCT)
or Multi-slice CT.(MSCT)
Studies are based on EBCT and applied to
MDCT/MSCT.
Most utilized scoring system is Agatston score. (derived
by multiplying the calcified plaque area by a coefficient based on plaque
attenuation values)
CAC predicts coronary stenosis
Women
Men
Dx Uncertain
•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.
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
CAC independently predicts outcome
•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 routine
use of CAC
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No clear evidence that preventive measures based upon the CAC score
leads to an improvement in outcomes.
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The potential harm associated with false-positive tests and radiation
exposure (especially with repeated testing) is not known.
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Though the presence of CAC is highly sensitive for the presence of ≥50%
angiographic stenosis, it is only moderately specific, especially in older
patients (unclear to what extent data can be extrapolated to patients other
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 2007
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Coronary artery calcium scoring has been less well studied in women and
ethnic minorities than in Caucasian, non-Hispanic men. As a result, the
recommendations are less clearly applicable to these groups.
CAC NOT recommended for asymptomatic patients with low or high ten-year
CHD risk as established by the Framingham and modified Framingham/ATP
risk scores.
For asymptomatic patients with an intermediate CHD ten year risk (1020%), CAC suggested when the result might lead to a change in
management based upon reclassification to a lower or higher risk group.
In patients who have undergone screening coronary CT scanning, additional
noninvasive or invasive testing is not recommended when the CAC score is
high (eg, greater than 400).
In patients categorized as high risk by the Framingham risk score, there is
no evidence that additional testing will lead to any change in management
plan.
In patients assessed to be a low risk, a negative exercise test would 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 Differences
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Under-estimation of coronary risk in women.
Delayed and underuse of testing in women.
Limited diagnostic accuracy of some tests in
women.
Women may have more co-morbidities than men
at time of presentation.
These probably contribute to the increased
mortality in women after MI or CABG.