Transcript Stable angina pectoris

Coronary Heart Disease
冠心病
张力
[email protected]
on behalf of
Zhu Jianhua M.D.
朱建华
The First Affiliated Hospital,
School of Medicine, Zhejiang University
CVD—1st Cause of Death
6%
3%
7%
43%
14%
27%
CVD
心脑血管疾病
Cancer
恶性肿瘤
Respiratory dis.
呼吸系统疾病
Accident
意外伤害
Digestive dis.
消化系统疾病
其他Others
Number around us
In this country，one person
died from CVD per 10 seconds
中国冠心病死亡率位列世界第二
俄罗斯：674，881
中国：702，925
印度：1531，543
单位；人
印度、中国和俄罗斯是世界上冠心病死亡人口最多的3个国家
其中，中国的冠心病死亡人口总数列世界第二
急性心肌梗死
——他们离我们而去的缘由
Coronary arteries--anatomy
Lipids
• LDL = primary target of therapy
• Risk categories
- > 20% risk of major coronary event in 10 years = high risk
• Known CAD
• Diabetes
• Known atherosclerotic disease (PVD, carotid disease and abdominal aortic
aneurysm)
• > 2 risk factors
• Consider causes of secondary hyperlipidemia
- Diabetes
- Hypothyroidism
- Obstructive liver disease
- Chronic renal failure
- Drugs such as progestins, anabolic steroids, corticosteroids
Major Risk Factors
• Smoking
• Hypertension (>=140/90 or on
antihypertensive treatment)
• HDL < 40*
• Family History premature CAD (<55
males, <65 females)
• Age (men >=45; women >=55)
* HDL >60 is a negative risk factor, its presence removes one risk factor from total count
Coronary heart disease
atherosclerosis
Coronary stenosis
coronary spasm
Myocardial ischemia, anoxaemia
Coronary heart disease, CHD
Ischemic heart disease
•Atherosclerosis
•Stable angina pectoris(SAP)
•Acute coronary syndrome
Unstable angina(UAP) and non-STEMI
(UA/NSTEMI)
ST elevation myocardial infarction(STEMI)
Atherosclerosis
Atherosclerosis
•leading cause of death and disability
•Common location:
Coronary circulation: Proximal left anterior
descending coronary artery(LAD)
Proximal portion of renal arteries
Extracranial circulation to the brain
Carotid bifurcation
Three fundamental biological
processes of atherosclerosis
1. Accumulation of intimal cells:
• smooth muscle cells
• Macrophages
• T-lymphocytes
2. Proliferated connective tissue matrix
• Collagen
• elastic fibers
• proteoglycans
3. Accumulation of lipid:
• cholesteryl esters
• free cholesterol
Evolution of the atherosclerotic plaque
Pathophysiology of coronary artery
atherosclerosis
1. Fatty streak
2. Fibroatheroma
3. Complicated lesions
Atherosclerosis related not only to lipids
Less smooth
muscle cells
Much
inflammatory
cells
Much smooth
muscle cells
Less
inflammatory
Thick cells
fibrous cap
Thin fibrous
cap
Eroded
endothelium
Active
macrophage
Integrated
endothelium
Unstable plaque
Adapted from Libby. Circulation. 1995;91:2844-2850
Foam cells
Stable plaque
Clinical events related to rupture of
unstable plaque
Repaired
Smooth muscle cell
Inflammation
Macrophage/T-cell
Plaque
stable
Adapted from Weissberg. Atherosclerosis. 1999;147:S3–S10
Plaque
unstable
O2 supply
O2 demand
Normal ECG
Normal coronary flow
in balance
O2 supply
Significant stenosis reduce
coronary flow
Low Demand is in balance with a
diminished coronary flow（ Under
resting condition ）
O2 supply
Significant stenosis reduce
coronary flow
O2
demand
Normal ECG
（CAD Under
resting condition）
O2
demand
（exertion or emotional stress）
Ischemia ECG
（Angina pectoris）
Prevention and Treatment of
Athrosclerosis
1.Lifestyle modification
2.Lipid disorders (Dyslipidemia):
cholesterol screening in all >20yrs
Elevated: cholesterol (Tc and LDL-c), TG, ApoB/ApoA,Lp(a),
Low: HDL-c
LDL lowering by HMG-CoA reductase(statins):
cardiovascular events 30%，risk of MI 62%
3.Hypertension：
4.DM,Metabolic syndrome or insulin resistance syndrome:
BP, BMI ,TG, serum insulin
HDL-c, OGTT
Prevention and Treatment of
Athrosclerosis
5. Cigarette smoking：more thrombogenic
6. Family history：
7. Aging：>40yrs adults ，4/5 fatal myocardial
infarction occured in patiens > 65 yrs
8. Male gender/ postmenopausal state：
male:female = 2：1, man develop CHD 10-15 yrs
earlier than woman
9. alcohol
10. Others: diet,homocysteine, hemostatic factors
inflammation/infection
Prevention and Treatment of
Athrosclerosis
•Drug therapy：
anti-platelet：
aspirin, clopidogrel, GPIIb/IIIa
inhitibor,
Dipyridamole, cilostazol
Lipid-lowering
Prevention and Treatment of
Athrosclerosis Lipid-lowering drugs
1. HMG-CoA reductase inhibitors（statins）
Atorvastatin,Fluvastatin,Lovastatin,Pravastatin,Sim
vastatin,Cerivastatin, Rosuvastatin：
*elevation of aminopherase, rhabdomyolysis
2. Bile acid-binding Resins
cholestyramine，colestipol
3. Nicotinic Acid：
4. Fibric acid derivatives（fibrates）
Gemifibrozil, clofibrate, Fenofibrate
5. Cholesterol absorption inhibitors: ezetimibe
6. Probucol
Prevention and Treatment of
Athrosclerosis
Surgery
1 Surgery : CABG。
2 PCI:
Coronary heart disease
(CHD)
CHD - Overview
• Stable CHD
• Unstable CHD
- Angina
- MI
• Pathophysiology
• Clinical Features
- History/PE
• Differential Diagnosis
• Diagnostic Testing
• Treatment
How Does CHD Present?
• Chest pain is primary symptom
- However, pain not always prominent in patients with CAD; Patients can present
with “anginal equivalents”
• Dyspnea, faintness, fatigue, exercise intolerance
- “Painless” CAD can also present as:
• Silent ischemia; CHF; Arrhythmias; Sudden death
• Obstruction of coronary artery by athreomatuous
plague is most common cause
- Other causes of nonatherosclerotic obstruction include
• Congenital abnormalities, arteritis, “bridging”
• Myocardial Ischemia can occur in absence of
obstructive CHD
- Aortic stenosis and hypertrophic cardiomyopathy
What about physical
examination items in CHD?
• Physical Examination
- Xanthelasma –intracellular lipid
deposits near lower lids
- Blood pressure
- Arterial – decrease peripheral pulses
- Cardiac examination
The Pathophysiology of Stable CHD
• Imbalance between myocardial O2
requirements and supply
- Increased requirements in tachycardia, increase wall
stress, increased contractility
• Physical exertion; heavy meat; fever; thyrotoxicosis;
emotional stress (increased catecholamines)
- Supply determined by coronary blood flow and coronary
arterial O2 content
• “Fixed” CHD
• Transient vasoconstriction- Coronary “tone” affected
by a variety of stimuli
What else should we consider in
the differential diagnosis?
More likely to be confused:
• Esophageal problems – reflux; motility
disorders; spasm;
- Chest pain with normal coronaries commonly due to esophageal
abnormalities
- Key elements like CHD = characteristics of pain; relieved with
nitro
- Key elements unlike CHD = pain changes with posture or meals;
relieved with antacids (GI cocktail);
• Pericarditis
- Chest pain not relieved with rest or nitro; pericardia fiction
rub and diffuse ST elevations on ECG
- Key elements like CHD = retrosternal location, abnormal ECG
- Key elements unlike CHD = pain is positional
What else should we consider in
the differential diagnosis?
Less likely to be confused:
• Aortic dissection
- Severe, sharp, radiates to back, with or without aneurysm
- Diagnosis with chest CT or TEE
• Severe pulmonary hypertension
- From right ventricular ischemia
• Pulmonary emboli
- From Dyspnea is cardianl symptom; pleuritic chest pain with infarction;
pleural friction rub
CHD categories ：
1、 Absence of symptoms
2、Angina pectoris (AP)
3. Myocardial infarction (MI)
4. Ischemia heart disease
5. sudden death
Stable angina pectoris
definition:
acute and transient myocardial ischemia and
anoxaemia
usually caused by coronary insufficiency during
exertion
Characteristics:
paroxysmal precordial squeezing-like chest pain,
behind the mid sternum，
radiated to left shoulder and upper arm
precipitated by stress or exertion
relieved rapidly by rest or nitrates
Stable angina pectoris
Pathology
in angiography
Significant coronary lesion with
diameter stenosis > 70% in 75% pts
No significant stenosis in about 510% pts, Ischemia may be related to
coronary spasm or microvascular
dysfunction.
Stable angina pectoris
Clinical manifestation
symptom：chest pain or
oppression
•location
behind
or slightly to the left of
the mid sternum
no definite borderline
radiated to the left shoulder and
upper arm
Atypical location: lower jaw, the
back of neck
Stable angina pectoris
Clinical manifestation
chest pain
•characteristics：
tightness, squeezing, burning, pressing, choking,
bursting,rarely sharp, not spasmodic
 force the patient stop the activity till the symptom
relieved
•precipitation
exertion or emotional agitation。
•duration：
3－5 mins
•pain relief: within several mins after rest or using
nitroglycerin
What about non-invasive test?
• Metabolic abnormalities
-
Lipids
• LDL< 100 mg/dl is optimal
- Esp for patients with multiple risk factors,
DM and established CAD
• HDL<40 mg/dl is an independent risk factor
• TG’s > 200 mg/dl should be treated (lifestyle)
-
Glucose
• Impaired fasting glucose= 110-126 mg/dl
• DM = FBS > 126 mg/dl
- Others – presence increase the risk of future
CV events – no consensus on routine measurement
• C-reactive protein; homocysteine; lipoprotein
Lp(a)
What about non-invasive test?
• ECG
- Resting ECG is normal in 50%
patients with stable angina
- Most common abnormality with
chronic CAD is non-specific ST-T
wave changes
Non specific changes also seen in
electrolyte abnormalities, LVH,
antiarrhythmic drugs
Stable CHD: Non invasive tests
• Exercise ECG ( treadmill test )
- Looking for ST segment depression and
symptoms
• 1mm (+) typical symptoms = 90% positive predictive
value
•
•
•
•
2mm (+) typical symptoms= diagnostic
1mm (-) typical symptoms= 70% predictive value
2mm (-) typical symptoms = 90% predictive value
Overall sensitivity = 70%; Specificity = 80%
- Patients need to get to >85% predicted maximal
• Predicted max HR = (220 – age)
Stable CHD :Non invasive tests
• Radionuclide Perfusion
imaging (“Cardiolyte”)
- Exercise ECG with images of myocardial
blood flow
• Compare images at maximal exercise
with images at rest
- “Defects” with exercise and not
with rest = ischemia
- “Defects” with both exercise and
rest = MI
• Sensitivity = 90%; Specificity = 80%
• 64 slice MSCT
CHD----Diagnosis
ECG
Treadmill
Cardiac Echo
ECT
Chest X ray
Angiograph
Coronary
stenosis
Myocardial
ischemia
ST segment depression
Normal coronary
flow
Normal
Normal ST segment
Myocardial
infarction
Coronary
occlusions
ST segment elevation
Treadmill test
Cardiac Echo
Cardiac ECT（201TI 或99mTc-MIBI）:
CHD-- Radionuclide
Perfusion imaging
201TI
perfusion
defects
Chest X-ray
Soft or
‘Vulnerable’
Plaque
Imaging by
64 slice MSCT
Stable CHD invasive tests
Coronary angiography
- golden standard
Coronary angiography
Left Coronary Angiogram （ LCA）
Arterial Anatomy & Projections
Left Coronary Artery
Right Anterior Oblique RAO 30
Coronary Angiography
Stable angina pectoris
Prevention and treatment
1. General consideration：
 rest，avoid provocative factors , risk factors
control
2. Drug therapy:
 prevent MI and death
 symptom relief and quality of life improvment
3. Coronary revascularization:
 percutaneous coronary intervention (PCI)
 Coronary artery bypass surgery (CABG)
SVG, LIMA
Stable angina pectoris
Drug therapy
antianginal and anti-ischemic therapy
Oxygen
supply
Oxygen
demand
a.nitrates
b.beta-adrenergic blockers
c.Calcium antagonists
d.Drugs improving metabolism
Stable angina pectoris
Drug therapy
a.nitrates
lower oxygen demand: decrease arteriolar and
venous tone, reduce preload and afterload
increase coronary supply: Coronary dilatation
•Nitroglycerin
•Isosorbide dinitrate
•isosorbide 5-mononitrate (long-acting nitrates)
Stable angina pectoris
Drug therapy
b. ß－blockers:
reduce myocardial oxygen: reduce HR,
myocardial contractility, BP,the LV wall stress
Abslute contraindications：
sever bradycardia: high-degree A-V block, SSS,
severe unstable LV failure
Relative contraindications:
asthma and bronchospastic disease
peripheral vascular disease
ß1-selective：metoprolol, atenolol, bisoprolol
Stable angina pectoris
Drug therapy
c.Calcium antagonists：
Increase oxygen supply: dilate conduit and
resistance vessels, release spasm, improve
microvascular function
Decrease oxygen demand: negative inotropic
effect, decrease BP
Antiplatelet effect
d. Drugs improving metabolism：
trimethazine（vasorel），selectively inhibit 3-KAT
（3-酮酰辅酶A硫解酶），partly inhibit FA
Stable angina pectoris
Drug therapy
prevent MI and death therapy
a.antiplatelet angents：
ASA，75-325mg/d
clopidogrel; ticlopidine: ADP receptor- antagonists:
Cilostazol: phosphodiesterase inhititor,50-100mg bid
b. Lipid-lowering angents: statins
c. Angiotesin-converting enzyme inhibitor (ACEI)
Stable angina pectoris
stenting
Coronary Artery Bypass Graft
--CABG
Acute Coronary Syndromes
• ST segment elevation MI (STEMI)
• Unstable angina (UA)
• Non ST segment elevation MI
(NSTEMI)
- Non Q wave MI
Plaque rupture/erosion → thrombosis→
coronary completed/incomplete occlusion
Acute Coronary Syndromes
• Patients presenting to ER with acute
chest pain
- 15% will be found to have an MI
- 30% found to have unstable angina
• 50% of deaths from AMI occur within one
hour of symptoms onset usually due to
arrhythmia (V. fib)
• MI’s due to coronary atherosclerosis with
superimposed coronary thrombosis – brought
on by plaque rupture
- This is the cause of almost all acute coronary
syndromes leading to either complete occlusion of
coronaries leading to Q wave infarction or partial
occlusion leading to acute coronary syndrome of
unstable angina or non-Q MI
ACS—the top of iceberg
Coronary Heart Disease
Stable plaque
Unstable plaque
Disrupted plaque
From Eugene Braunwald, Heart Disease, A Textbook of Cardiovascular Medicine
CHD –Sudden death (arrhythmia)
Ventriclar Tachycardia
Ventricular flutter
Ventricular fibrillation
Unstable Angina and Non-ST segment
elevation myocardial infarction
(NSTEMI)
• Caused by non occlusive thrombus
• Risk of death and non-fatal cardiac ischemic events can
be determined
• “High risk” history:
• Nature of Symptoms
- Accelerating ischemic in past 48 hours and
prolonged ongoing (>20 minutes) rest pain
• Prior Hx MI
• Age
• Sex
• number of traditional risk factors present
Circulation 2000; 102:1193
Unstable Angina and Non-ST segment
elevation myocardial infarction (NSTEMI)
• “High Risk” PE Findings
- Pulmonary edema
- S3 gallop
- New or worse MR murmur
- Hypotension, bradycardia, tachycardia
• ECG findings
- ST-segment changes of >= 1mm
- Sustained V. Tachy
- New or presumed new BBB
Chest Pain Assessment
• ECG most important single source of
data in the evaluation of patients with
chest pain
• ECG findings in patients with acute
chest pain
- New ST-segment elevation of >=1 mm
• Probability of MI = 80%
- ST-segment depression or T-wave inversion no know to be old
• Sensitivity = 90%; Specificity = 80%
Myocardial Infarction
• >75% of patients with MI have > 1
coronary artery diseased;
- However about 6% of patients with AMI will have
angiographically normal coronary arteries
• Biochemical markers of necrosis are
CK-MB or troponin
MI ECG
Culprit lesion
MI area
Total
occlu
sion
Cardiac Biomarkers “enzymes”
• Enzymes (cardiac biomarkers) diffuse into
the cardiac interstitium after MI and
become detectable in the blood within
hours.
• CK-MB detectable 4 hours after MI and up
to about 2 days
- Some CK-MB detectable in healthy patients
• Troponin I detectable 4 hours after an MI
and up to a week afterwards
- Therefore, difficult to use to diagnose re-infarction
- Troponin I not detectable in healthy patients
- “Microinfarctions” can increase troponin I and not increase CK-MB (30%
of patients with UA)
Time Course of Cardiac Biomarkers after
MI
Aspects of Diagnosis of Myocardial
Infaction by Different Techniques
Therapeutics--patients with ACS
Anti-ischemic therapy
• Nitrates
- relieve pain and ischemia, given sublingually or IV acutely
• Morphine sulfate
- Relieve pain, decreases agitation and decreases preload
(decreased venous congestion)
• B- Blockers
- Decreases myocardial oxygen demand, decreases heart
rate, stabilizes membranes thereby decreasing
arrhythmia risk
Do not use short acting Calcium channel
blockers (nifedipine)
Therapeutics--patients with ACS
Antiplatelet and anticoagulant therapy
• Antiplatelets
- ASA
• Give promptly
- Clopridogel
• Give promptly
• Anticoagulants
- Heparin – LMWH or unfractionated
RE-vascularization (thrombolytics or PTCA
with stent) in patients with STEMI
Treatment : myocardial reperfusion
PCI: The first choice
经皮冠脉介入治疗（PCI）
无论是否经溶栓治疗，冠状动脉闭
塞或再通后又再堵塞，或虽再通但仍有重
度狭窄者，如禁忌可紧急施行PCI并安置支
架。
目前认为有条件时应首选PCI
CAD—Intervention therapy
• Percutanouse transluminal coronary
angioplasty
(PTCA)
• Stent
• Rotational atherectomy
（RA）
Acute Myocardial
Infarction
ischemia
ischemic necrosis
Reopen the vessels
Reduce the area of
infarction
Rescue the dying
myocardium
Time = Myocardium!
Best time
Mild impairment
Slightly injury
Mild injured
Severe injured
Moderate
impairment
Time = Life !
severe
impairment
Management: onset of STEMI
Treatment : myocardial reperfusion
Fibrinolysis
原理：起病3～6小时内，使闭塞的冠状动脉再通，心肌得到再灌注，
濒临坏死的心肌可能得以存活，或使坏死范围缩小。
溶栓疗法
常用药物
尿激酶、链激酶、重组组织型纤溶酶原激活
剂(rt-PA)
溶栓成功的判断
间接判断
ST段2小时内回降>50％；胸痛2小时内基本消
失；再灌注性心律失常；CK-MB峰值提前
直接判断
冠状动脉造影
Reperfusion therapy： PCI vs. Fibrinolysis
Reperfusion therapy： PCI vs. Fibrinolysis
PCI : Time and outcome
PCI of STEMI
PCI of STEMI
Technique revolution → New time
手术要求高
费用昂贵
病人创伤大
并发症多
恢复时间长
创伤小
操作简单
并发症多
病人恢复迅速
创伤小
操作简单
并发症少
病人恢复迅速
Restenosis <5%
DES！
Restenosis 20%~30% (2002- )
Restenosis ≧50%
CABG
POBA
(1977-1994)
BMS
(1994- )
One year follow up after PCI
before
after
4m
1y
Therapeutics
Acute Coronary Syndromes-Post discharge
• A: Antiplatelets / ACE-I
• B: β- blockers / Bp control
• C: Cholesterol lowering (Statins) /
Cigarette quitting
• D: Diabetes control / Diet
• E: Exercise / Education
Potential clinical benefits of Statins in ACS
Statins
LDL-C↓
VLDL↓, IDL↓,
LDL-C↓
•
•
•
•
Macrophages
lumen
Lipid core
SMC
Endothelium function
SMC function
Anti-inflammation
Thrombosis↓
Take Home Messages
Atherosclerosis is the leading cause of death and
disability, also the main cause of CHD
Risk factors and prevention of atherosclerosis
CHD is due to the imbalance between myocardial oxygen
supply and demand
Two large groups of CHD: chronic(stable angina pectoris)
and ACS
ACS composed of UAP/NSTEMI and STEMI, resulting
from the plaque rupture or erosion, with differing degree
of thrombosis and distal embolization, with different
obstruction of the coronary artery.
 reperfusion either by fibrinolysis or primary PCI is the
mainstay of therapy of STEMI
Thanks!