به نام خدا. Management of Stable Angina Pectoris.

خدا نام به

Management of

Stable Angina Pectoris

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: Treatment Goals

• Feel better

• Live longer

Angina: Prognosis

• Left ventricular function

• Number of coronary arteries with significant stenosis

• Extent of jeoporized myocardium

Stable Angina

Risk stratification

• Noninvasive testing

• Invasive testing

In patient with SIHD or suspected CAD metabolic abnormalities that are risk factors for the development of CAD are frequently detected.

Total cholesterolLDLHDLTGSerum creatinineFBS

NOVEL BIOMARKERS and CARDIOVASCULAR DISEASE

NOVEL BIOMARKERS and CARDIOVASCULAR DISEASE

• 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

Non Invasive Stress Testing

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

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

Identification of patient at high risk

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

CXR

Multi-Slice CT for Coronary Calcium Scoring and Coronary Angiography

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

CARDIAC MRI

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

Catheterization and coronary arterioghraphy

Definite diagnosis of CAD

Anatomic severity

CAG+ SIHD

• Approximately 25% each have 1V, 2V, 3V

• 5-10% LMD

• 15% no flow-limiting obstruction

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

Noninvasive tests

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