L6-Chest pain on exertion

							Chest Pain on Exertion

Prof. Chu-Pak Lau, Dept of Medicine Dr WH Chui, Department of Surgery
Queen Mary Hospital The University of Hong Kong
24 Oct 2008
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Angina Pections: General Approach
Trend:
1. Increasing use of intervention (stents) 2. More preventive (lifestyle modification and risk factor modification)

Strategy: 1. Goals: Prevent MI & death, improve QOL by symptom relief 2. Direct attack on CAD: anti-platelet and lipid lowering 3. Indirect management: myocardial supply and demand
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ABCDE of Prevention (ACC/AHA)
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A = Aspirin and ACE B= Beta blocker and blood pressure C= Cigarette smoking and cholesterol D= Diet and Diabetes E=Education and Exercise
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Atherothrombosis: a Generalized and Progressive Process
Normal Fatty streak Fibrous plaque Atherosclerotic plaque Plaque rupture/ fissure & thrombosis Unstable angina MI

}ACS

Ischemic stroke/TIA

Clinically silent Stable angina Intermittent claudication

Critical leg ischemia Cardiovascular death

Increasing age
ACS, acute coronary syndrome; TIA, transient ischemic attack
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Risk Factors for CAD
 Unavoidable: age, sex, family history  Treatable: hypertension, diabetes, hypercholesterolaemia  Avoidable: obesity (especially central), inactivity, stress, cigarette smoking  Newer tests: fibrinogen, ultrasensitive CRP, raised homocysteine
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Causes of Chest pain (1)
1. Myocardial ischaemia : Angina pectoris / MI 1.1 coronary atheroma, thrombus or vasospasm 1.2 aortic valve disease or HCM 1.3 Hypertension 1.4 severe anaemia/thyrotoxicosis Pericarditis Aortic aneurysm : Dissecting, Rupture Pulmonary embolism
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2. 3. 4.

Causes of Chest pain (2)
5. 6. 7. Pleurisy or pneumothorax Osesophageal pain (acid reflux, spasm, carcinoma) Chest wall lesions (I) rib fracture (ii) metastatic deposits in ribs (iii) fibrositis or myalgia (iv) herpes zoster Gastric or duodenal ulcer Gallbladder colic Pain referred from thoracic or cervical spine
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8 9. 10.

History & Physical Examination
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

Cornerstone for diagnosis & further investigations Try to make a diagnosis rather than exclusion Chest discomfort : Site, radiation, duration, provoking factors, relieving factor, frequency, and associated symptoms

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Aetiology of Chest Pain
GP
Musculoskeletal 43% Cardiac 20% Cardiac 45% Musculoskeletal 14%

A& E

Others 16% Pulmonary 4% Others 26%

Pulmonary 5% GI 6%

Psychiatry 11%

GI 5%

Psychiatry 8%
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Approach to Chest Pain Discomfort

New & acute onset Recurrent episodic Persistent

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New & Acute Onset Chest Discomfort
Principle : Exclude life-threatening CVS catastrophy Conditions : AMI Dissecting aortic aneurysm Pulmonary embolism Others : Pericarditis GI causes
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Persistent Chest Discomfort
Pain lasting for days are unlikely to be due to CVS causes Pericarditis : ECG (diffuse concave ST elevation), Echo, CXR Pulmonary conditions : CXR Gastrointestinal conditions
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Recurrent Episodic Chest Pain
Typical Angina Chest pain or discomfort brought on by exertion/emotional stresses, may radiate to arm or shoulder. Relieved with rest or sublingual nitrate within 5 minutes. Normally lasts 10-15 minutes (and <30 minutes) Atypical Chest pain
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Points to Remember
 Angina is diagnosed by history alone  It is unusual to have chest pain only precipitated by emotion without an exertion-related element  Inframammary pain : non cardiac  Beware of unstable angina :  Usually has a history of angina  Increasing frequency and severity  Rest pain
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Typical Angina : Prognostic factors
Prognostic factors : 1.
2.

Left ventricular function : Symptoms and signs of HF, pulmonary oedema, ECG old infarct
Severity of angina : Recent onset Unstable “Strongly” positive treadmill test

Thallium measured large or multiple defects and  EF on exercise 3. Extent of CAD 5 yr Mortality : 1 VD, 2 VD, 3 VD, LMS 2, 8, 11, 15%/yr Poor LV : worsen prognosis
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RCA

LMS

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Typical Angina : What to investigate
1. Exclude aortic stenosis, HCM, anaemia, thyrotoxicosis 2. Risk factors for CAD 3. Exercise test : indicated not for diagnosis, but to assess the severity of CAD. For patients with chronic stable angina, and those reluctant for invasive procedures to stratify risks 4. In pts with significant angina or unstable angina, direct proceed to cardiac catheterisation

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Non-invasive imaging modalities
• • • • • • • Exercise test Thallium / sestamibi scan Stress echocardiograpy MRI PET Coronary calcification score 64 slide CT coronary angiogram

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Strongly Positive Exercise Test
1. Bruce stage I (low workload) ST > 0.1 mV 2. ST > 0.2 mV at any stage 3. ST persisted for >5 minute on recovery 4. SBP > 10mmHg

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Coronary Calcification
 EBCT, 16 and 64-slide CT  Calcification proportional to Severity of disease  In asymptomatic individual with intermediate risk (10yrs 620%), coronary calcification improve risk predication (ESC / ACC)  Limitations : • Cannot determine the site or severity of lesions • Not a sign of plaque instability
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Contrast-Enhanced CT Coronary Angiography
Technology X Ray tube to scan coronaries at 180o slow HR Rapid contrast delivery Advantages
Highly sensitive (close to 94-100%) and high specificity (83-100%) Negative predictive accuracy is high
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Ropers D 28

CTA : Issues
 Long term prognostic impact of CTA uncertain  Useful to rule out CAD (e.g. women with atypical chest pain)  Assessment of severity of CAD depends on expertise  Considerations : Renal function, radiation (especially young women with breast cancer risk), calcification of arteries, insurance  New development : stents assessment, CABG, unstable plaque, 256 slice CT, dual source, LV function

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Angina Pectoris
A. Medical Treatment 1. Non-drug treatment 2. Drug treatment Beta-blocker Nitrate Calcium channel blocker Aspirin Platelet inhibitor Lipid lowering therapy Angiotensin consertingenzyme inhibitor (ACEI) Revascularisation PTCA CABG Angiogenesis (experimental)
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B.

Non-pharmacological Management
Stop smoking Alteration of life style Avoid competitive sport Treatment of precipitating factors : High output states,(e.g. anaemia, T4) Treatment of risk factors : DM, HT, lipids
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Relationship Between Cholesterol and CHD Risk: Epidemiologic Trials
Framingham Study (n=5209)
150
CHD indications per 1000 10-year CHD death rate
50 40
(Deaths/1000)

Multiple Risk Factor Intervention Trial (MRFIT) (n=361,662)

125 100 75 50 25 0
204 205-234 235-264 265-294 295

30 20 10

0

150

200

250

300

Serum cholesterol (mg/100 mL) Each 1% increase in total cholesterol level is associated with a 2% increase in CHD risk
Gotto AM Jr, et al. Circulation. 1990;81:1721-1733. Castelli WP. Am J Med. 1984;76:4-12.

Serum cholesterol (mg/dL) 1% reduction in total cholesterol resulted in a 2% decrease in CHD risk
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UPDATES : LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC) and Drug Therapy in Different Risk Categories
Risk Category LDL Goal (mmol/L) LDL Level at Which to Initiate Therapeutic Lifestyle Changes (TLC) (mmol/L) 2.59 LDL Level at Which to Consider Drug Therapy (mmol/L)

CHD or CHD Risk Equivalents (10-year risk >20%)

<2.59 (optional goal <1.81)

3.36 (2.59–3.35: drug optional) 10-year risk 10– 20%:>2.59-3.4
10-year risk <10%: 4.14

2+ Risk Factors (10-year risk 20%)

<3.36

3.36

0–1 Risk Factor

<4.14

4.14

4.91 (4.14–4.91: LDLlowering drug optional)

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Lipid control
 Statins  Fibrates  Ezetimide  Long acting nicotinic acid (raises HDL)

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Risk Factors Control
 Diabetes: tight glucose control improves microvascular complications (DM is a CAD equivalent). (Recent studies : ACCORD & ADVANCE) (New England Journal of Medicine 2008 :  Aggressive HgA1c < 7.5 improves microvascular but not macrovascular disease)  Lipid: reduce LDL cholesterol < 2.6 mmol/l with diet and statins  HT: aim at <140/85: angiotensin converting enzyme in high risk group  Aspirin: all CAD  Folic acid to manage hyperhomocysteinaemia- found to be ineffective   hs CRP

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CRP & Statins
Ridker PM et al N Engl J Med 2005; 352:20-28 (2)
Conclusions In pts with ACS :  CRP <2mg/l is associated with similar risk reduction as LDLC <70mg/dL (1.8mmol/l)  Pts with LDLC <1.8mmol/l and CRP <1mg/l had low event rate (1.9/100 person-yrs)  The benefits after achieving these targets are independent of the type of statins

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Aspirin and Thienoyridine Antagonist
1. Aspirin blocks cyclooxygenase dependent platelet activation 2. It is useful for both primary and secondary prevention of CAD 3. Thienopyridine antagonists (e.g. clopidogrel and ticlopidine) block ADP dependant aspirin aggregation, work synergistic with aspirin (esp. in coronary stenting and acute coronary syndrome)

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Coronary Artery Disease
Disease
Trials

Old MI
12

AMI
15

UA
12

CABG
25

PTCA
9

HF
2

Pt/C

9984/10022

9658/9644

2497/2534

3105/3126

1592/1620

66/68

% Reduction 0
-4

-10 -20 -30 -40
-41 -25 -30

-50 -60

-46 -53

~25% reduction

BMJ 2002

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Angiotensin Converting Enzyme Inhibitor (ACEI)
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ACEI is indicated in LV dysfunction In pts with CAD without LV dysfunction, ACEI is useful : • HOPE (Ranipril) in high risk CAD benefit • EUROPA (Perindopril) in CAD (MI or no MI)  CVS events by 20% in 13655pts • PEACE (trandelopril) in CAD pts NO change in CVS events  hospitalisation from HF and new onset DM ACEI is indicated in secondary prevention in stable CAD, especially with concomitant DM, HT, LV dysfunction or high risk features Angiotensin receptor antagonist (alternative if ACEI intolerant)
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Beta-blockers
Adrenoceptors :  : Vasoconstriction 1 : Heart muscle – contractility, rate 2 : Bronchial and vascular smooth muscle Beta stimulation acts through adenylate cyclase system (also acted on by glucagon, thyroid hormone and histamine) Actions : Reduces oxygen demand Rate pressure product (at rest and during exercise)  Contractility Improves blood supply  Diastole (Minor effect) Best for angina with hypertension
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Side effects : Avoid in : 1. Asthmatics 2. Second and Third Degree Heart Block, bradycardia 3. Patients with frank Heart Failure 4. ‘Brittle’ DM (relative) 5. Intermittent Claudication (relative) 6. Raynaud’s Syndrome (relative)
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Cardioselective Beta-blocker
e.g. Atenolol, Acebutalol, Metoprolol 1. Fewer effects on airways resistance 2. Less interference with autonomic and metabolic responses to hypoglycaemia in insulin-dependentdiabetics Dose titration : Symptoms, side effects Resting HR 50-60bpm, exercise HR 100-120bpm
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Nitrate Actions :  Supply :

Dilate coronary arteries Favourably redistribute blood flow from pericardial to endocardial sites  Demand : 1.  Preload 2.  LV size and  LV pressure (by reduction of BP) Mechanism : Nitrates are an exogenous source of nitric oxide (NO), which is an endothelium-derived relaxation factor (EDRF)
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1. 2.

Sublingual nitrate : rapid absorption and short-acting Mononitrates are active without undergoing first pass liver metabolism unlike the dinitrate, bioavailability is more predictable.
Failure of nitrate to relieve angina if : 1. Severe angina pectoris 2. Loss of potency of tablets : shelf life of glyceryl trinitrate is about 6 months (spray : longer shelf life) 3. Incorrect route of administration e.g. sublingual tablets taken orally 4. Tolerance with long-acting nitrate 5. Non-compliant e.g. because of headache

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Side Effects and Contraindications 1. Syncope and hypotension from reduction of preload and afterload, especially in presence of cerebral vascular disease 2. Reflex tachycardia 3. Headache and flushing 4. Contraindicated in hypertrophic obstructive cardiomyopathy and constrictive pericarditis
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Calcium antagonists
Selectively block Ca channel during Phase 2 action potential Tissue Specific Ca channels AV node, sinus node Vascular and intestinal smooth muscle Myocardium (High dose): negative inotropic effect
Action in angina  Supply : Dilate coronary artery  Demand : Lowers BP (after load reduction) Nifedipine : short acting, reflex tachycardia may cause angina

Verapamil and diltiazem : additional rate slowing effect
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Second Generation Ca Blocker
Amiodipine Felodipine Isradipine Lacidipine All are dihydrophyridine derivatives, compared to nifedipne : 1. Longer acting (longer half-life or stronger tissue binding). Once daily use. 2. Less reflex tachycardia and oedema 3. Less negatively inotropic (vascular selective) e.g.

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Calcium antagonists : Side effects
1. 2. 3. 4. 5. 6. Flushing Oedema Headache Palpitations Negative inotropic effects Bradycardia (verapamil, diltiazem)
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Use of Ca Blocker in Angina
1. Short acting Ca blocker e.g. nifedipine should not be used. 2. In patients with a strong component of vasospasm, a Ca blocker is useful 3. Often combined with a beta-blocker 4. Useful agent for concomitant hypertension

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Other Agents
1. Potassium channel openers
e.g nicorandil – vasodilating agent

2. Sinus node inhibitor e.g. ivabradine 3. Metabolic agent – increase glucose / fat
utilisation e.g. trimetazioline
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Guidelines for Medical Treatment of Patient with Stable Angina
Class I advice :  Beta-blockers are first-line therapy  Calcium antagonists or long-acting nitrates as a substitute for beta-blockers if initial treatment with beta-blockers leads to unacceptable side-effects  Calcium antagonists or long-acting nitrates in combination with beta-blockers when initial treatment with beta-blockers is not successful
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Stable Angina
Suboptimal management in clinical practice
Pts receiving drug therapy (%) Pts receiving therapeutic doses (%)
50% 40% 30% 21% 20% 10% 0% BB CCB Nitrate 36% 29% 30% 23% 42%

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Indications for Coronary Angiogram/Revascularisation
1.
2. 3.

Medically refractory angina / Acute coronary syndrome
Post-infarctional angina Prognositically significant ischaemia : 3.1 3.2 Exercise test : significant ST depression at low workload Stress thallium suggestive of large amount or multiple areas of myocardium at risk

3.3 4.
5.

Poor ventricular function with ischaemia

Concomittant cardiac surgery (e.g. Valve operation)
For other patients an initial aggressive medical therapy is an option
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Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial
Pts & Methods : 2287 pts with stable angina and significant coronary artery disease (but excluding ‘high risk’ categories) received OMT vs PTCA

Conclusion : OMT (including LDL ~1.8, HDL ~1, and ABCDE) is a reasonable initial option Perspective : High residual events, Bare-metal stents, 32% cross over to PTCA/CABG

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Coronary Arterial Bypass Grafting
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Venons Conduits Saphenous vein grafts 50% patency at 10 year Arterial Conduits Internal mammary artery Brachial artery Better patency Cardiopulmonary bypass ( bypass with “ beating – heart”) Keyhole surgery vs mid-sternotomy

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

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Arterial access femoral, brachial or radial artery Lesion crossing with guide wire Balloon or stent placement Drug eluting stents sironlimus (cypher) or pracilactal (Taxus) Antiplatelet therapy Dual: aspirin and clopidogrel (longer treatment in drug eluting stents)

Percutaneus Transluminal Coronary Angioplasty (PTCA)

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Lewis Cardiac Cath Laboratory

QMH

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Problems of PTCA
1. Acute closure / Dissection Stent placement 2. Restenosis Drug eluting stents  restenosis rate from 30 to 5-10% 3. Inadequate revascularization Complete occlusion Small vessels
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CABG
Complete Revascularisation

PTCA
Often incomplete

Survival Benefit proven in LM, TVD and poor LV
Angina relief Mortality (1-2%)

Most consider equivalent, less optimal for DM patient
Angina relief Mortality (0.5%-1%)

Morbidity higher (wound, CVA, arrhythmia)
Recovery and hospitalization 1-2 week Failure of grafts

Lower morbidity (contrast nephropathy, wound complications)
Short recovery 1-2 days Restenosis

Repeat CABG is associated with high risk

Re-PTCA at no increase risk
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Blastocyst Bone marrow

Embryonic Stem Cell

Stem cells
In Vitro Reprogramming

Pacemaker cells Cardiomyocytes Endothelial cells

Biological pacemaker Angiogenesis Cellular cardiomyoplasty

Overview of Stem Cell Program for Cardiovascular Diseases Prof HF Tse/ Prof CP Lau Lancet 2003

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Prescription Guidelines in Cardiology Haiat & Leroy 2006

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Prescription Guidelines in Cardiology Haiat & Leroy 2006

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