به نام خدا. management of stable angina pectoris
TRANSCRIPT
Angina Pectoris
• Classic angina is characterized by substernal squeezing chest pain, occurring with stress and relieved with rest or nitroglycerin.
• May radiate down the left arm
• May be associated with nausea, vomiting, or diaphoresis.
Stable AnginaClassification
• Exertional
• Variant
• Anginal Equivalent Syndrome
• Prinzmetal’s Angina
• Syndrome-X
• Silent Ischemia
Angina: Exertional
• Coronary artery obstructions are not sufficient to result in resting myocardial ischemia. However, when myocardial demand increases, ischemia results.
Angina: Variant Angina
• Transient impairment of coronary blood supply by vasospasm or platelet aggregation
• Majority of patients have an atherosclerotic plaque
• Generalized arterial hypersensitivity
• Long term prognosis very good
Angina: Anginal Equivalent Syndrome
• Patient’s with exertional dyspnea rather than exertional chest pain
• Caused by exercise induced left ventricular dysfunction
Angina: Prinzmetal’s Angina
• Spasm of a large coronary artery
• Transmural ischemia
• ST-Segment elevation at rest or with exercise
• Not very common
Angina: Syndrome X
• Typical, exertional angina with positive exercise stress test
• Anatomically normal coronary arteries• Reduced capacity of vasodilation in
microvasculature• Long term prognosis very good• Calcium channel blockers and beta blockers
effective
Angina: Silent Ischemia
• Very common
• More episodes of silent than painful ischemia in the same patient
• Difficult to diagnose
• Holter monitor
• Exercise testing
Angina: Prognosis
• Left ventricular function
• Number of coronary arteries with significant stenosis
• Extent of jeoporized myocardium
In patient with SIHD or suspected CAD metabolic abnormalities that are risk factors for the development of CAD are frequently detected.
Total cholesterolLDLHDLTGSerum creatinineFBS
• Lipoprotein (a)
• Apoprotein B
• Small dense LDLs
• Lipoprotein-associated phospholipase A2
(Lp-PLA2)
Risk Factors for Future Cardiovascular Events: WHS
0 1.0 2.0 4.0 6.0
Lipoprotein(a)
Homocysteine
IL-6
TC
LDLC
sICAM-1
SAA
Apo B
TC: HDLC
hs-CRP
hs-CRP + TC: HDLC
Relative Risk of Future Cardiovascular Events
Ridker et al, N Engl J Med. 2000;342:836-43
Homocysteine
• Intermediary amino acid formed by the conversion of methionine to cysteine
• Moderate hyperhomocysteinemia occurs in 5-7% of the population
• Recognized as an independent risk factor for the development of atherosclerotic vascular disease and venous thrombosis
• Can result from genetic defects, drugs, vitamin deficiencies, or smoking
Homocysteine
• Homocysteine implicated directly in vascular injury including:• Intimal thickening• Disruption of elastic lamina• Smooth muscle hypertrophy• Platelet aggregation
• Vascular injury induced by leukocyte recruitment, foam cell formation, and inhibition of NO synthesis
Homocysteine
• Elevated levels appear to be an independent risk factor, though less important than the classic CV risk factors
• A modest increase in risk associated with elevated homocysteine levels.
• General screening for elevated homocysteine levels not recommended.
• Screening recommended in patients with premature CV disease (or unexplained DVT) and absence of other risk factors
• Treatment includes supplementation with folate, B6 and B12
CRP vs hs-CRP
• CRP is an acute-phase protein produced by the liver in response to cytokine production (IL-6, IL-1, tumor necrosis factor) during tissue injury, inflammation, or infection.
• Standard CRP tests determine levels which are increased up to 1,000-fold in response to infection or tissue destruction, but cannot adequately assess the normal range
• High-sensitivity CRP (hs-CRP) assays (i.e. Dade Behring) detect levels of CRP within the normal range, levels proven to predict future cardiovascular events.
C-Reactive Protein:Risk Factor or Risk Marker?
• CRP previously known to be a marker of high risk in cardiovascular disease
• More recent data may implicate CRP as an actual mediator of atherogenesis
• Multiple hypotheses for the mechanism of CRP-mediated atherogenesis:• Endothelial dysfunction via ↑ NO synthesis• ↑LDL deposition in plaque by CRP-stimulated
macrophages
1 mg/L 3 mg/L 10 mg/L
LowRisk
ModerateRisk
HighRisk
Acute Phase ResponseIgnore Value, Repeat Test in 3
weeks
>100 mg/L
Ridker PM. Circulation 2003;107:363-9
Clinical Application of hs-CRP forCardiovascular Risk Prediction
• Measurement of hsCRP in patients judged at intermediate risk
1. May help direct further evaluation and therapy in the primary prevention of CHD
2. May be useful as an independent marker of prognosis in patient with established CAD.
Current Biomarkers for ACS• Biomarker assessment of high risk patients may include:
• Inflammatory cytokines
• Cellular adhesion molecules
• Acute-phase reactants
• Plaque destabilization and rupture biomarkers
• Biomarkers of ischemia
• Biomarkers of myocardial stretch (BNP)
• Biomarkers of myocardial necrosis (Troponin, CK-MB, Myoglobin)
Apple Clinical Chemistry March 2005
Progression of Biomarkers in ACS
ACS, acute coronary syndrome; UA, unstable angina; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction
Adapted from: Apple Clinical Chemistry March 2005
STEMIUA/NSTEMISTABLE CAD PLAQUE RUPTURE
MPOCRPIL-6
MPO ICAMsCD40LPAPP-A
MPOD-dimerIMAFABP
TnITnTMyoglobinCKMB
Inflammation has been linked to the development of vulnerable plaque and to plaque rupture
Stefan Blankenberg, MD; Renate Schnabel, MD; Edith Lubos, MD, et al., Myeloperoxidase Early Indicator of Acute Coronary Syndrome and Predictor of Future Cardiovascular Events 2005
History: Troponin
• Troponin I first described as a biomarker specific for AMI in 19871; Troponin T in 19892
• Now the biochemical “gold standard” for the diagnosis of acute myocardial infarction via consensus of ESC/ACC
1 Am Heart J 113: 1333-442 J Mol Cell Cardiol 21: 1349-53
Troponins
• Circulating biomarkers of myocyte injury have now detected in patients with clinically SIHD and shown to have a graded relationship with the subsequent risk of cardiovascular mortality and HF.
• Clinical use in this population not recommended.
BNP
• BNP is associated with the risk of future cardiovascular events in those at risk for and with established CAD.
RESTING ECG
• Normal >50
even patients with severe CAD
Suggest normal resting LV function
Favorable long term prognostic sign
RESTING ECG
• Normal >50
even patients with severe CAD
Suggest normal resting LV function
Favorable long term prognostic sign
• The most ECG abnormality are nonspecific ST-T wave changes+/- Q waves
DD of ST-T change: LVH Electrolyte abnormality Neurogenic effect antiarrhytmic drugsThe occurrence ST-T change in resting ECG can correlate with
the severity of CAD.
Interval ECGs may reveal the development of Q wave MIs that have gone unrecognized .
Conduction disturbances
• Most frequently LBBB and LAHB
Impairment LV function
Multivessel CAD
Previous myocardial damage
Such conduction disturbances are an indicator of a relatively poor prognosis
LVH
• An indicator of worse prognosis in SIHD
• This finding suggests the presence of underlying HTN, AS, HCM, old MI
• during of episode of CP, the ECG becomes abnormal in >50% or more of patient with normal resting ECG
• Most common finding ST-T depression • Ambulatory ECG monitory has shown that
many patient with symptomatic myocardial ischemia also have episodes of silent ischemia
Stable AnginaExercise Testing
• The goal of exercise testing is to induce a controlled, temporary ischemic state during clinical and ECG observation
Exercise Electrocardiography
• Diagnosis of CAD
helpful for patient whit CP syndrome & moderate probability of CAD & normal resting ECG
• The test provide additional useful information about the degree of functional limitation
• Severity of ischemia and prognosis in patient with a high pretest probability
• Antianginal therapy reduces the sensitivity of ET as a screening tools
2 or 3 days of interruption for long acting BB
1day for long acting nitrats, CCB, short acting BB
Angina: Exercise TestingHigh Risk Patients
• Significant ST-segment depression at low levels of exercise and/or heart rate<130
• Fall in systolic blood pressure
• Diminished exercise capacity
• Complex ventricular ectopy at low level of exercise
ECG Treadmill EST in Women
• Higher false-positive rate
• Reduces procedures without loss of diagnostic accuracy
• Only 30% of women need be referred for further testing
Exercise TestingContraindications
• MI—impending or acute• Unstable angina• Acute myocarditis/pericarditis• Acute systemic illness• Severe aortic stenosis• Congestive heart failure• Severe hypertension• Uncontrolled cardiac arrhythmias
Nuclear cardiology techniques
• Stress myocardial perfusion imaging
• Pharmacologic nuclear stress testing
Stress myocardial perfusion imaging
• It is superior to ET in detecting CAD, multivessel CAD, localizing diseased vessel, magnitude of ischemia and infarct myocardium
• Sensitivity 88%, specificity 72%
• It is valuable for detecting myocardial viability in patient with LV dysfunction
• Important information about prognosis in all patients
Stable AnginaGuidelines for Nuclear EST
Diagnosis/prognosis for CAD
• Non-diagnostic EST
• Abnormal resting ECG( LBBB, receiving digitals, LVH)
• Negative EST with continued chest pain
• Intermediate probability of disease
Stable AnginaGuidelines for Nuclear EST
Defined CAD
• Post infarct risk stratification
• Risk stratification to determine need for
revascularization ( viability study )
Stable AnginaDipyridamole or Adenosine Nuclear EST
• Near equivalent sensitivity/specificity with symptom-limited nuclear EST
• Most useful in patients who cannot exercise
• Major contraindication is severe bronchospastic lung disease ( consider Dobutamine study )
Stable AnginaStress Echo
• Ischemia may cause wall motion abnormalities, no rise of fall in LVEF
• Sensitivity/specificity same as nuclear testing
Stress Cardiac magnetic resonance imaging
• SCMR particularly for individuals who present limitation for the use of other imaging modalities.
Clinical application of noninvasive testing
• Once men and women are stratified appropriately according to the pretest prevalence of disease the results of stress testing are similar, although the specify is slightly less in women.
• Exercise imaging modalities have greater accuracy diagnostic than ET in M&F
Asymptomatic persons
• ET in asymptomatic individuals without CAD is not recommended.
• Indication of ET for asymptomatic individual: 1.with DM who plan to begin vigorous exercise
2.evidence of ischemia in ambulatory ECGM
3.severe coronary calcification on CT
Stable AnginaNon-Invasive Evaluation
C oron ary A rte riog rap h y
L V D ys fu n c tion
C oron ary A rte riog rap h y
H ig h R isk
M ed ica l Th erap y
S tab le
C oron ary A rte riog rap h y
R ecu rren t A n g in a
M ed ica l Th erap y
L ow R isk
S tress Tes tin g
N orm a l L V F u n c tion
R es tin g L V F u n c tion(C lin ica l A ssessm en t)
N on d isab lin g A n g in a
CT
• A noninvasive approach to imaging atherosclerosis
• Detecting coronary calcium
calcium score good marker of the total coronary atherosclerotic burden
• Provide angiogram of coronary arterial tree
Clinical Indications for MSCT
• Calcium Scoring (CS) - risk stratification in the intermediate risk patient
• Non-invasive coronary angiography (CTA) in the symptomatic patient intermediate-risk patient
*A negative test (normal CTA) has a 98% chance of revealing normal coronary arteries on invasive angiography*
CT Angiogram Interpretation
• Calcium Volume Score: ZERO
• CT angiography:
• Left Main, Circumflex, and Right coronary arteries: normal
• LAD: eccentric, soft plaque adjacent to origin of first diagonal (~60% stenosis)
• Correlation recommended
Myocardial Viability
• Differentiation between viable and non-viable myocardium is important
• Transmural extent
• Viable myocardium may benefit from revascularization and resume normal cardiac function
• Function cannot be restored to nonviable tissue
Stress Cardiac MRI Exam.
• Physical stress may not be feasible within the MRI environment
• Pharmacological stress will be more easily to implement using vasodilator e.g. adenosine
• Myocardial blood flow will increase fourfold to fivefold downstream of normal coronary arteries, but does not increase downstream of stenosed arteries because the related arteriolar beds have already vasodilated maximally
Stress Cardiac MRI Exam.
• Myocardium receiving blood supply from an significantly stenosed coronary artery will show hypoperfusion compared with normal myocardium
• Normally perfused myocardium shows greater enhancement at a faster rate than hypoperfused myocardium
LV
Normalmyocardium
Infarcted orIschaemic
myocardium
CMR coronary angiography
• It is established as a modality to characterize congenital coronary anomalies
• Method to detect stenoses in the proximal and middle segments of major epicedial vessels or surgical bypass grafts.
• MRI has a definite role in the assessment and management of patients with IHD
• It is an ideal imaging technique for serial follow-up and screening due to being non-invasive and involves no irradiation
• An single examination can assess cardiac function, structure, blood flow, regional wall motion, regional perfusion, and the extent of infarction
IVUS, Angioscopy, thermography
• Advanced invasive technique (IVUS) provide cross sectional view of the coronary artery and have enhanced detection and quantification of coronary atherosclerosis
• The potential characterize the vulnerability of coronary atheroma
Coronary angiography finding
• Differ between MI and SIHD
• Patient with MI :
1.fewer diseased vessels
2.fewer stenoses& chronic occlusion
3.Less diffuse disease
4.Differ pathophysiology and substrate and probancity for thrombosis
Coronary artery ectasia and aneurysm
• 1-3% of patient with obstructive CAD
• This angiographic not affect symptoms, survival or incidence of MI
• >50% caused by atheroschelerosis
the rest by congenital anomaly and inflammatory diseases.
• Despite of overt obstruction, 70% of patient with multivessels fusiform CA ectasia or aneurysm have ischemia
Coronary collateral vessels
• Protect against MI when total occlusion occurs
• Small myocardial infarct size and no LV dysfunction
• Normal baseline blood flow but severely limited reserveains
(protect against resting ischemia but not against exercise –induced angina)
Myocardial bridging
• <5% in normal coronary angiography• Occasionally, compression of portion of a
coronary artery by a myocardial bridge associated with clinical manifestations of myocardial ischemia during strenuous physical activity or MI, VT.
• Increased risk of MI : increased bridge thickness&length proximal vessel location
LV function
• Assessed by biplane contrast ventriculography
• Abnormality of regional wall motion are more characteristic of CAD
Coronary blood flow and myocardial metabolism
• Abnormal myocardiasl metabolism in SIHD• Catheter in coronary sinus, arterial and coronary
venous, the measurement lactate at rest and stress (reliable sign of ischemia)
• Coronary flow reserve and endothelial function are abnormal in SIHD
(determining the functional significance of stenosis or detecting microvascular dysfunction)
Cardiac CatheterizationIndications
• Suspicion of multi-vessel CAD
• Determine if CABG/PTCA feasible
• Rule out CAD in patients with persistent/disabling chest pain and equivocal/normal noninvasive testing
Natural history and risk stratification
• 29% patient with SIHD angina 1or more times per week, with associated greater physical limitation and worse quality of life.
• Incidence M=F • Higher risk of mortality • Annual rate of mortality 1-3%• Annual rate of major ischemic events 1-2%
Clinical, noninvasive, invasive tools are useful for refining the estimate of risk for the patient with SIHD
Clinical criteriaPredictive of the presence of CAD• Age • Male • DM• Previous MI• Symptoms typical of anginaAdverse prognostic implication• HF• Severity of angina especially the tempo of intensification • dyspnea
ET
• The most important predictors is exercise capacity
• The peak exercise capacity (METs) is the strongest predictors of mortality in M with CAD
Radionuclide Imaging
• Prognostic value
• Ability to identify patients at low, intermediate or high risk for future events
(for management)• Prognostic data> ET &clinical
Echocardiography
• LV function should be measured by ECHO:
1.Previous MI
2.ST-T change, Q wave.
3.conduction defect
• Stress echocardiography either by exercise or by pharmacological to provide incremental prognostic information
Angiographic criteria in prognosis
• Multivessel& LV dysfunction
• number of stenosis vessels
• Severity of obstruction& location
Limitation of angiography
• CAG is not a reliable indicator of the functional significance of stenosis
• Under estimation of severity and extent of atherosclerosis.
• Its inability to identify which coronary lesions to be vulnerable for future events