KULIAH MCI

ACUTE MYOCARDIAL INFARCTION

Epidemiology Pathology

Pathophysiology
Clinical features Management

Hospital management
Hemodynamic disturbances Arrhythmias

Convalescence, discharge, post-myocardial infarction care

Epidemiology
Acute myocardial infarction (AMI)

Major public health problem in industrialized world and becoming increasingly important problem in developing countries, Indonesia no national data
Death rate from AMI 30% in last decade, but still fatal in 30% of patients 50% within one hour of event mainly due to ventricular fibrillation

Trend Pola Penyakit Penyebab Utama Kematian Dalam Kurun Waktu 10 Tahun di Indonesia, SKRT 1992, 1995, 2001
30 25 20 15 10 5 0
Inf&Parasit Sirkulasi Napas Cer na Neoplasma Kecelakaan Perinatal

1992 1995 2001

Epidemiology
% Mortality (in hospital)

The impact of medical therapy for AMI on shortterm mortality

35 30 25 20 15 10 5 0
1.0

30

Defibrillation Hemodynamic monitoring Beta blockade 15

Thrombolysis/ PTCA ASA 6.5

Pre CCU era

CCU era

Reperfusion era 1950 1969 1970 1979 1980 - 1989

Cumulative incidence of CHD death

0.8 0.6

0.4
0.2 0.0
0 1 2 3 4 5 6 7 8 9 10

Years of follow-up

Pathology
Almost all MIs result from coronary atherosclerosis

AMI part of acute coronary syndrome

A Schematic Life History of an Atherosclerotic Lesion

ATHEROSCLEROSIS (1)
Atheroma Formation
1. Lipoprotein accumulate in intima
Endothelium more permeable to LDL lipoprotein 2. Leucocyte recruitment and accumulation in intima by leucocyte adhesion molecules and chemokines Monocyte accumulate lipids and transform into foam cells T lymphocytes also enter intima

3. Excessive lipid uptake by scavengar receptors ; preferentially oxidized LDL

Foam cells replicate Fatty streak formation

ATHEROSCLEROSIS (2)
Atheroma Formation
4. Smooth muscle cells migrate from media to intima attracted by platelet-derived growth factor (PDGF) Secreted by activated macrophages Smooth muscle cells replicate due to exposure to mitogens (e.g., thrombin) 5. Extracellular matrix make up most of plaque volume : interstitial collagens, proteoglycans, elastin produced by smooth muscle cells Breakdown of these molecules by matric metalloproteinases (MMPs) Luminal stenosis only after plaque burden exceeds 40% of cross-sectional area of artery 6. Endothelial migration and proliferation neovascularization in plaque Plaques often develop areas of calcification

Schematic of the Evolution of the Aterosclerotic Plaque

Nomenclature of acute coronary syndromes

Acute coronary syndrome

Non ST elevation
NSTEMI

ST elevation

Unstable angina

Myocardial infarction NQMI Qw MI

Braunwald E. Heart Disease : a textbook of cardiovascular Medicine,. 6th Ed. 2001

Pathology
Role of acute plaque change Plaque rupture exposure to substances that promote platelet activation and aggregation, thrombin generation and ultimately thrombus formation. Thrombus interrupts blood flow and if imbalance between oxygen supply and demand is severe and persistent it leads to myocardial necrosis

Schematic diagram suggesting probable mechanisms responsible for the conversion from chronic coronary heart disease to acute coronary artery disease syndromes

Schematic representation of the progression of myocardial necrosis after coronary artery occlusion

Plaque rupture common pathophysiological substrate of acute coronary syndromes

Completely occlusive thrombus ST elevation on ECG necrosis of full thickness of ventr. wall 75% - ST elevation diminishes followed by Q-wave development Less obstructive thrombi and/or those that are

constituted by less robust fibrin formation and on greater

proportion of platelet aggregation ST segment depression and/or T wave inversion Relief of transient vasospasm or spontaneous lysis of thrombus within 20 minutes no necrosis, no release of biochemical markers of necrosis no persistent ECG changes

PATHOPHYSIOLOGY
If sufficient quantity of myocardium undergoes ischemic injury LV pump function end-systolic volume Infarct zone thins and elongates infarct expansion Dilatation of ventricle depends on infarct size, patency of infarct-related artery, and activation of local RAS in noninfarcted portion of ventricleultimately : fibrosis stiffness of myocardium Area of infarct : 8% - diastolic compliance > 15% - ejection fraction LV end-diastolic pressure volume > 25% - clinical heart failure > 40% - cardiogenic shock

The vicious circle in cardiogenic shock

CLINICAL FEATURES
PREDISPOSING FACTORS
50% - precipitating factor or prodromal symptoms Unusually heavy exercise Accelerating angina, rest angina

Noncardiac surgical procedures

Respiratory infection, hypoxia, cocain use, stroke, TIA Circadian periodicity Peak incidence between 8 a.m 12 p.m Plasma cathecholamines Cortisol Platelet aggregability

HISTORY
PRODROMAL SYMPTOMS History very valuable to establish discomfort unstable angina 1/3 symptoms for 1 4 wks 20% symptoms for < 24 hrs Malaise, exhaustion D/ Prodoma : chest

NATURE OF PAIN Most patients severe prolonged, > 30 minutes - hours Constricting, crushing, oppressing, compressing heavy weight or squeezing in chest Choking, viselike, heavy pain or stabbing, knifelike, boring or burning discomfort Location : retrosternal, spreading frequently to both sides of the chest with predilection to the left side Often pain radiates down ulnar aspect of left arm, producing tingling sensation in left wrist, hand and fingers

NATURE OF PAIN SOME INSTANCES : pain begins in epigastrium, and simulate abdominal disorder Sometimes pain radiates to shoulders, upper extremities, neck, jaw and interscapular region favoring the left side

Elderly : no chest pain but acute left ventricular failure and chest tightness or marked weakness or syncope
Pain arises from nerve endings in ischemic or injured, but not necrotic, myocardium OTHER SYMPTOMS 50% nausea or vomiting in transmural infarcts Occasionally diarrhea, profound weakness, dizziness, palpation, cold perspiration, sense of impending doom Occasionally : cerebral embolism or systemic arterial embolism

DIFFERENTIAL DIAGNOSIS Acute pericarditis Some pleuritic features : aggravated by resp. movements, often involves shoulder, ridge of trapezius, neck Sharp, knifelike, aggravated by each breath Pulmonary embolism Pain lateral in chest, often pleuritic may be associated with hemoptysis Dissection of aorta In center of chest, extremely severe (ripping, tearing), maximal shortly after onset, persists for many hours, often radiates to back and lower extremities, often one or more arterial pulses absent) Costochondral/and costosternal pain Localized swelling and redness Sharp and darting, marked localized tenderness

Esophagitis, gastroesophageal reflux disease (GERD)

PHYSICAL EXAMINATION
GENERAL APPEARANCE Anxious, considerable distress, restless, fist on chest LV failure & symp. stimulation : cold perspiration, pallor, dyspnea, cough with frothy pink or blood-streaked sputum. Shock : cool, clammy skin, facial pallor, cyanosis, confusion or disorientation
HEART RATE Variable depending on underlying rhythm and degree or ventr. failure Most commonly, HR 100 110/min; > 95% patients : VPBs within first 4 hours

BLOOD PRESSURE Majority normotensive, but syst. BP may decline and diast. BP may rise Half of pts with inferior MI parasympathetic stimulation : hypotension, bradycardia or both half of pts with anterior MI, sympathetic excess : hypertension, tachycardia or both TEMPERATURE AND RESPIRATION Most pts with extensive MI fever within 2448 hrs, fever resolves by 4th or 5th day Respiration due to anxiety and pain, in LV failure : resp. rate correlates with degree of heart failure

JUGULAR VENOUS PULSE JVP usually normal RV infarction : marked jug. venous distension

CAROTID PULSE
Small pulse reduced stroke volume Pulse alternans : severe LV dysfunction

CHEST LV failure : moist rales Severe failure : wheezing 1967 : Killip classification Class I II & Kimball : prognostic

: patients free of rales or S3 : rales < 50% lung fields +/- S3

III : rales > 50% lung fields, frequently pulm. edema IV : cardiogenic shock

CARDIAC EXAMINATION
PALPATION May be normal, but with transmural AMI presystolic pulsation, S4 Abn. systolic pulsation in 3rd, 4th, 5th ics on left of sternum due to dyskinesis

Longstanding hypertension or previous infarction : laterally displaced, sustained apical impulse

AUSCULTATION S1 muffled

S3 reflects severe LV dysfunction with elevated ventr. filling pressure

S4 almost always present in AMI with sinus rhythm due to reduced LV compliance

Commonly andible in most pts with chronic ischemic heart disease and sometimes in normal subjects > 45 years
Murmurs

Systolic
MR : dysfunction of mitral valve, rupture of head of papillary muscle TR Rupture of IV septum

PERICARDIAL FRICTION RUBS

In large transmural infarcts 24 hrs 2 weeks, most commonly after 2nd or 3rd day Delayed onset of rub characteristic of Dresslers syndrome

LABORATORY EXAMINATION
MARKERS OF CARDIAD DAMAGE ST elevation and Q wave (highly indicative of AMI) only in 50% of pts on presentation 30% AMI no classic chest pain 50% AMI nondiagnostic ECG Chest pain in EMG < 20% develop AMI Periodic determination of serum cardiac markers necessary

AMI myocytes necrotic intracellular macromolecules (serum cardiac markers) microvasculature systemic circulation

Creatine Kinase (CK) Exceeds normal in 4 8 hours, normal in 2 3 days; not specific

CK isoenzymes : CKMB
Myoglobin Peak level in 1 4 hours Cardiac-specific troponins : Troponin I

Troponin T

Criteria for the Diagnosis of Acute Myocardial Infarction (AMI)

Increased biomarkers plus one or more of the following Pathological findings of AMI Typical symptoms of AMI plus one of the following ST segment elevation in the ECG Increased levels of cardiac biomarkers Procedural myocardial damage Increased levels of cardiac biomarkers to prespecified levels; symptoms may be absent; ECG changes may be absent or nonspecific

Typical symptoms of myocardial ischemia Q waves in the ECG

No other findings required

ST segment elevation or depression in the ECG

Plot of the appearance of cardiac markers in blood versus time after onset of symptoms

ELEKTROKARDIOGRAM
Current-of-injury patterns with acute ischemia

Hyperacute phase of extensive anterior-lateral MI

Sequence of depolarization and repolarization changes with (A) acute anterior-lateral and (B) acute inferior wall Q infarctions

IMAGING
Rntgenography Degree of congestion and size of left side of heart useful for risk determination Echocardiography Region of wall motion abnormality LV function Doppler echocardiography Assessing severity of MR, TR Identifying side of acute ventr. or septal rupture & quantification of shunt flow Other : nuclear imaging, computed tomography, magnetic resonance imaging

MANAGEMENT
Prehospital care Management in emergency department Reperfusion of myocardial infarction Hospital management

Convalescence, discharge, postmyocardial

infarction care

PREHOSPITAL CARE
Major components of time delay between onset of infarction and restoration of flow in the infarct-related artery

PREHOSPITAL CARE
Time = muscle in first hour of AMI due to ventr. fibrillation factors, known CAD, symptoms of AMI

Patient education most important, pts with risk

Prehospital thromboliysis (?)

17% reduction of mortality

MANAGEMENT IN EMERGENCY DEPARTMENT

Possible Acute Coronary Syndrome (ACS) Rapid triage to urgent care room Obtain baseline sserum cardiac marker levels Assess initial 12-lead ECG

ECG diagnostic of ACS ASA Beta blockade Antithrombin therapy

Nondiagnostic ECG

Continue evaluation in observation unit

Obtain follow-up ECGs and serum marker levels

ST elevation

ECG strongly suspicious for ischemia (ST depression, T wave inversion)

Admit, Initiate anti-ischemic therapy, Initiate reperfusion strategy if ST elevation develops

Consider 2D echo Evidence of ischemia/infarction ?

Routine blood tests on admission: CBC, lipid profile, electrolytes

Yes

No Discharge (goal =8-12h)

MANAGEMENT IN EMERGENCY DEPARTMENT

ASA Beta blockade Antithrombin therapy

ST elevation

12 h

> 12 h Not a candidate for reperfusion therapy Persistent symptoms ?

Eligible for thrombolytic therapy

Thrombolysis therapy contraindicated

No Administer thrombolytic Primary PCI : consider IV GP IIb/IIIA inhibitor and stent as needed

Yes Consider reperfusion therapy

Other medical therapy : ACE inhibitors; ? Nitrates; correc metabolic and electrolyte deficits

Routine blood tests on admission: CBC, lipid profile, electrolytes

 Brief, targeted history 12-lead ECG immediately Bedside ECG monitor Iv access D5W

If ST elevation 1 mm in 2 contiguous leads or new BBB screen immediately for contraindication to thrombolysis thrombolysis < 30 minutes, if longer; mortality rises; max. allowed interval : 12 hours AMI without ST elevation (40 50%) repeat ECG & cardiac markers, treat as non STelevation MI

GENERAL TREATMENT MEASURES

Aspirin : inhibition of cyclooxygenase block thromboxane A2 formation Effective for acute coronary syndromes Part of initial management of pts with suspected AMI 160 325 mg chewed in EMG dpt
Control of cardiac pain Combination of nitrates , analgesics (e.g. morphine), oxygen, beta-adrenoceptor blockers Morphine Drug of choice 4 8 mg i.v, 2 8 mg repeated at intervals of 5 15 minutes Some pts may need 2 3 mg/kg BW

Nitrates : coronary dilatation and increase of venous capacitance No hyportension sublingual nitroglycerin Beta-adrenoceptor blockers : No heart failure, hypotension or heart block metoprolol iv 3 x 5 mg i.v, then continued orally Oxygen : no hypoxemia 2 4 l/min for 6 12 hrs

REPERFUSION OF MYOCARDIAL INFARCTION

Thrombolysis Streptokinase 1.5 mill u/60 minutes Tissue plasminogen activation 100 mg/90 minutes Reteplase Tenacteplase PCI (Percutaneous Coronary Intervention) Primary angioplasty Adjunctive th/with thrombolysis Subacute phase (days 2-7) in pts who do not receive thrombolysis Coronary artery bypass surgery Recurrent/persistent chest pain after thrombolysis/ PCI LM stenosis Ventr. Septal rupture/severe MR

ANTITHROMBOTIC AND ANTIPLATELET THERAPY

Heparin probably of no benefit as adjunct to streptokinase, but may be helpful in pts receiving tPA Newer agents : hirudin, efegatran, hirulog, lowmolecular-weight heparins Antiplatelet therapy Aspirin loading dose 160 325 mg (chewed) maintenance 75 mg Pts who cannot tolerate aspirin : clopidogrel 75 mg GPIIb/IIIa inhibitors useful to support primary PCI

HOSPITAL MANAGEMENT
Coronary Care Unit Prevention of death from VF Hemodynamic monitoring Th/of serious complications of AMI

Intermediate Coronary Care Unit CHF Recurrent VT, VF AF Heart block Anterior MI + recurrent angina + marked ST segment abnormality

SAMPLE ADMITTING ORDERS (1)

Condition IV : Serious NS or D5W to keep vein open

Vital signs q hr until stable, then q 4 h and prn. Notify if HR < 60 or > 110; BP < 90 or > 150; RR < 8 or > 22. Pulse oximetry x 24 hr Activity Bed rest with bedside commode and progress as tolerated after approximately 12 hr

SAMPLE ADMITTING ORDERS (2)

Diet NPO until pain free, then clear liquids. Progress to a heart-healthy diet (complex carbohydrates = 50-55% of kilocal.), monounsaturated and unsaturated fats (30% of kilocal.), including foods high in potassium (e.g., fruits, vegetables, whole grains, dairy products), magnesium (e.g., green leafy vegetables, whole grains, beans, seafood), and fiber (e.g., fresh fruits and vegetables, whole-grain breads, cereals). Nasal O2 L/min x 3 hr Enteric-coated ASA daily (164 mg) Stool softener daily Beta-adrenoceptor blockers ? Consider need for analgesics, nitroglycerin, anxiolytics

Medicatio ns

PHARMACOLOGICAL Th/
Betablockers Pts without a contraindication, betablockers Ace-inhibitors All considered for ACE-inhibition th/ esp CHF, ST segment elevation or LBBB Nitrates Persistent chest pain, LV failure, large anterior transmural AMI Ca-antagonists Verapamil or diltiazem not recommended as routine th/ in AMI May be used for AF or ongoing ischemia for whom blockers ineffective or contraindicated

HEMODYNAMIC DISTURBANCES
LV failure Cardiogenic shock RV infarction Mechanical causes of heart failure Free wall rupture Pseudo aneurysm Rupture of interventricular septum Papillary muscle rupture

Cardiac Arrhythmias and Their Management During Acute Myocardial Infarction (1)
CATEGORY 1. Electrical instability ARRHYTHMIA Ventricular premature beats Ventricular tachycardia OBJECTIVE OF TREATMENT Correction of electrolyte deficits and increased sympathetic tone Prophylaxis against ventricular fibrillation, restoration of hemodynamic stability Urgent reversion to sinus rhythm Observation unless hemodynamic function is compromised Search for precipitating causes (e.g. digitalis intoxication); suppress arrhythmia only if hemodynamic function is compromised THERAPEUTIC OPTIONS Potassium and magnesium solutions, beta blocker Antiarrhythmic agents; cardioversion/defibrill ation Defibrillation, bretylium tosylate Increase sinus rate (atropine, atrial pacing); antiarrhythmic agents Atrial overdrive pacing agent; cardioversion relatively contraindicated if dititalis intoxication present

Ventricular fibrillation Accelerated idioventricular rhythm

Nonparoxysmal atrioventricular junctional tachycardia

Cardiac Arrhythmias and Their Management During Acute Myocardial Infarction (2)
CATEGORY ARRHYTHMIA OBJECTIVE OF TREATMENT Reduce heart rate to diminish myocardial oxygen demand THERAPEUTIC OPTIONS Antipyretics; analgesics, consider beta blocker unless congestive heart failure present; treat latter if present with anticongestive measures (diuretics, afterload reduction) Verapamil, digitalis glycosides; anticongestive measures (diuretics, afterload reduction); cardioversion; rapid atrial pacing (for atrial flutter)

2. Pump failure/ Sinus tachycardia excessive sympathetic stimulation

Atrial fibrillation and/or atrial flutter

Reduce ventricular rate; restore sinus rhythm

Paroxysmal supraventricular tachycardia

Reduce ventricular rate; restore sinus rhythm

Vagal maneuvers; verapamil, cardiac glycosides, beta-adrenergic blockers; cardioversion; rapid atrial pacing

Cardiac Arrhythmias and Their Management During Acute Myocardial Infarction (3)
CATEGORY
3. Bradyarrhythmias and conduction disturbances ARRHYTH MIA Sinus bradycardia OBJECTIVE OF TREATMENT Acceleration of heart rate only if hemodynamic function is compromised Acceleration of sinus rate only if loss of atrial kick causes hemodynamic compromise THERAPEUTIC OPTIONS Atropine; atrial pacing

Junctional escape rhythm

Atropine; atrial pacing

Atrioventricular block and intraventricular block

Insertion of pacemaker

CONVALESCENCE, DISCHARGE, POST-MI CARE Timing of discharge 5 6 days after admission for pts without complications Counseling
Instruction concerning physical activity Use of medication Behavioral alteration Rehabilitation program physical psychological

RISK STRATIFICATION
Poor prognosis : female, age > 70 years, DM, prior angina pectoris, previous MI Anterior MI

AV block, AF
Large MI, recurrent ischemia and reinfarction Assessment at hospital discharge

Assessment of LV function : LV ejection fraction

Assessment of myocardial ischemia

Assessment for electrical instability

MANAGEMENT ALGORITHM FOR RISK STRATIFICATION AFTER ACUTE MYOCARDIAL INFARCTION (1)
Clinical Indications of High Risk at Predischarge Present Strategy I Strategy II Symptom-limited exercise test at 14-21 days Absent Strategy III

Markedly abnormal

Mildly abnormal

Negative

Exercise imaging study

Reversible ischemia

No reversible ischemia Medical treatment

Cardiac catheterization

MANAGEMENT ALGORITHM FOR RISK STRATIFICATION AFTER ACUTE MYOCARDIAL INFARCTION (2)
Absent

Strategy II

Strategy III Submaximal exercise test at 5-7 days Markedly abnormal Mildly abnormal Exercise imaging study Negative

Reversible ischemia

No reversible ischemia Strenuous leisure activity or occupation

Cardiac catheterization

MANAGEMENT ALGORITHM FOR RISK STRATIFICATION AFTER ACUTE MYOCARDIAL INFARCTION (3)

Strenuous leisure activity or occupation

Symptom-limited exercise testing at 3 6 wk Cardiac catheterization Markedly abnormal Mildly abnormal Exercise imaging study Negative

Reversible ischemia

No reversible ischemia Medical treatment

SECONDARY PREVENTION OF RECURRENT ACUTE MYOCARDIAL INFARCTION

Life style modification Cessation of smoking, control of hypertension, diabetes mellitus Modification of lipid profile LDL cholesterol < 100 mgL HDL cholesterol > 40 mgL Triglycerides < 150 mg% Antiplatelet agents, aspirin 80-325 mg or Ticlopidine, Clopidogrel ACE inhibitors, -adrenoceptor blockers, nitrates Ca antagonists, only in pts who cannot take blockers Antiarrhythmics routine use not recommended

UNSTABLE ANGINA
Definition and classification

Pathophysiology
Clinical presentation

Diagnosis of UA / NSTEMI
Risk stratification Medical therapy

Treatment strategies and interventions

DEFINITION
STABLE ANGINA PECTORIS
deep, poorly localized chest or arm discomfort that is reproducibly associated with physical exertion or emotional stress and relieved within

515 minutes by rest and or sublingual

nitroglycerine

DEFINITION
UNSTABLE ANGINA PECTORIS : angina pectoris (or equivalent type of ischemic discomfort) with at least one of three features 1. It occurs at rest (or with minimal exertion) usually > 20 min 2. It is severe and described as frank pain and of new onset (i.e., within one month) 3. It occurs with a cressendo pattern (e.g., more severe, prolonged, or frequent than previously). Some with prolonged chest pain myocardial necrosis NSTEMI (non ST segment elevation myocardial infarction)

Braunwald Clinical Classification of Unstable Angina (1)

CLASS DEFINITION New onset of severe angina or accelerated angina; no rest pain Angina at rest within past month but not within preceding 48 hr (angina at rest, subacute) DEATH OR MI TO 1 YEAR 7.3% 10.3%

Severity
Class I Class II

Class III

Angina at rest within 48 hr (angina at rest, subacute)

10.8%

Braunwald Clinical Classification of Unstable Angina (2)

CLASS DEFINITION
DEATH OR MI TO 1 YEAR

Clinical Circumstances
A (secondary angina) B (primary angina) C (postinfarction angina) Intensity of treatment Develops in the presence of extra-cardiac condition that intensifies myocardial ischemia Develops in the absence of extra-cardiac condition Develops within 2 weeks after acute myocardial infarction Patients with UA may also be divided into three groups depending on whether UA occurs (1) in the absence of treatment for chronic stable angina, (2) during treatment for chronic stable angina, or (3) despite maximal antiischemic drug therapy. The three groups may be designated subscripts 1, 2, or 3, respectively. Patients with UA may be further divided into those with or without transient ST-T wave changes during pain 14.1% 8.5% 18.5%

Electrocardiographic changes

5 pathophysiological processes that may contribute to the development of unstable angina

1. Plaque rupture with superimposed nonocclusive thrombus 2. Dynamic obstruction (i.e., coronary spasm of an epicardial artery or constriction of the small muscular arteries) 3. Progressive mechanical obstruction 4. Inflammation and/or infection 5. Secondary unstable angina, precipitated by increased oxygen demand or decreased supply (e.g., thyrotoxicosis or anemia) Individual patients may have several processes coexisting

PATHOPHYSIOLOGY
Plaque rupture, fissure, or erosion By far more common cause of UA/NSTEMI Vulnerable plaque < 50% stenosis, high lipid content, local inflammation causing breakdown of thin shoulder of plaque, coronary artery constriction at site of plaque, local shear stress forces, platelet activation and prothrombotic stage formation of platelet-rich thrombi at site of plaque rupture/erosion acute coronary syndrome

Inflammation and/or infarction Key role in development of atherosclerosis and in development and recurrence of UA Chlamydia pneumonia ? Helicobacter pylori ? Cytomegalovirus ? Thrombosis many observations support the central role of coronary artery thrombosis in the pathogenesis of unstable angina Platelet aggregation, secondary hemostasis, coronary vasoconstriction and progression of mechanical obstruction all play an important role in the pathogenesis of UA

CLINICAL PRESENTATION

30 45% UAP
25 30% NSTEMI 20% STEMI 80% UAP : history of CAD

History & physical examination

Ischemic pain

Chest discomfort on exertion or at rest severe enough to be considered painful

Physical examination

May be unremarkable or may support diagnosis of cardiac ischemia

Ischemia of large fraction of LV : transient diaphoresis, pale cool skin, sinus tachycardia, 3rd or 4th heart sound, basilar rates, rarely hypotension

ECG UAP : ST segment depression (or transient ST segment elevation) and T wave changes in 50% patients. Continuous ECG monitoring more sensitive than symptoms Cardiac markers If positive CK-MB, troponin T or I diagnosis NSTEMI Cor. arteriography 15% 3VD 30% 2VD 40% 1VD 20% no significant stenosis coronary microvascular dysfunction Angioscopy & intravascular ultrasound

Features associated with higher likelihood of CAD among pts presenting with symptoms suggestive of UA

History
Chest pain as chief complaint similar to prior ACS symptoms Known history of coronary artery disease, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft History of angina Age > 60 Male gender More than two major cardiac risk factors Diabetes Extracardiac vascular disease (carotid or peripheral) Physical Examination Pulmonary rales, hypotension Transient mitral regurgitation Diaphoresis Electrocardiogram New/presumably new ST deviation > 0.05 mV T wave inversion 0.1 mV Q waves, left bundle branch block Cardiac Markers Elevated CK-MB, troponin I or T

Natural History
by 30 days : 3.5 4.5%

new/recurrent MI 6 12%

Indicators of increased risk in unstable angina

History
Advanced age (> 65 years) Diabetes mellitus Post-myocardial infarction angina Prior peripheral vascular disease Prior cerebrovascular disease Clinical Presentation Braunwald Class II or III (acute or subacute rest pain) Braunwald Class B ( secondary unstable angina) Electrocardiogram New/ST segment deviation 0.05 mV T wave inversion 0.3 mV Left bundle branch block Cardiac Markers Increased troponin T or I or CK-MB Increased C-reactive protein (CRP) Angiogram Thrombus

General measures
Bedrest 12 24 hrs Monitoring ECG Oxygen Relief of chest pain : nitrates betablockers morphine sulfate

Nitrates
Sublingual / buccal spray, 3x, 5 minutes apart If pain persists : i.v. nitroglycerin 5-10 ug/min; max 200 ug/min

Betablockers
Recommended when no contraindication Atenolol 5-10 mg iv bolus followed by 100 mg orally

Metoprolol 5 mg iv bolus, 3x given 2-5 minutes apart followed by 50 mg orally 2x daily, titrated to 2x/100 mg daily

Ca channel blockers
3rd drug after nitrates & betablocker or if c.i. to betablocker

ACE inhibitors
Shortterm no benefit when LV not impaired

Lipid-lowering th/
Statins costeffective longterm

ANTITHROMBOTIC THERAPY IN UA/NSTEMI

Aspirin
50% in risk of death Clopidogrel and ticlopidine Inhibits platelet aggregation for pts who can not tolerate aspirin Heparin Low-Molecular-Weight heparins

Direct thrombin inhibitors : hirudin

Oral anticoagulation : warfarin Glycoprotein IIb/IIIa inhibitors High risk pts : IV glycoprotein IIb/IIIa inhibitor + aspirin + heparin

Standardized nomogram for titration of heparin

Initial Dose : 60 U/kg bolus and 12 U/kg/hr infusion. Activated partial thromboplastin time (APTT) should be checked and infusion adjusted at 6, 12, and 24 hours after initiation of heparin, daily thereafter, and 5 to 6 hours after any adjustment in dose. APTT < 35 35 49 50 70 71 90 > 100 CHANGE 70 U/kg bolus 35 U/kg bolus 0 0 Hold infusion for 30 min IV INFUSION (U/kg/hr) +3 +2 0 - 2 - 3

Algorithm for risk stratification and treatment of patients with UA/NSTEMI

CHRONIC CORONARY ARTERY DISEASE

Stable angina pectoris Other manifestations Prinzmetals (variant) angina Silent myocardial ischemia Ischemic cardiomyopathy

STABLE ANGINA PECTORIS

Clinical manifestations Differential diagnosis of chest pain Physical examination Pathophysiology Noninvasive testing Catheterization, angiography, coronary arteriography

Medical management
Percutaneous coronary interventions and coronary artery surgery

CARDIOVASCULAR CAUSES OF CHEST PAIN

CONDITION
Angina

(1)

LOCATION
Retrosternal region: radiates to or occasionally isolated to neck, jaw, epigastrium, shoulder or armsleft common

QUALITY

DURATION

Pressure, burning, < 210 min squeezing, heaviness, indigestion

Rest or UA
Myocardial infarction

Same as angina
Substernal and may radiate like angina

Same as angina but may be more severe

Heaviness, pressure, burning, constriction

Usually <20 min

Sudden onset, 30 min or longer but variable

CARDIOVASCULAR CAUSES OF CHEST PAIN

CONDITION Pericarditis LOCATION QUALITY Usually begins over Sharp, stabbing, sternum or toward knifelike cardiac apex and may radiate to neck or left shoulder; often more localized than the pain of myocardial ischemia Anterior chest; may radiate to back Excruciating, tearing, knifelike

(2)

DURATION Lasts many hours to days; may wax and wane

Aortic dissection

Sudden onset, unrelenting

CARDIOVASCULAR CAUSES OF CHEST PAIN

CONDITION Pulmonary embolism (chest pain often not present) LOCATION Substernal or over region of pulmonary infarction QUALITY Pleuritic (with pulmonary infarction) or angina-like

(3)

DURATION Sudden onset; minutes to <1 hr

Pulmonary Substernal hypertension

Pressure, oppressive

CARDIOVASCULAR CAUSES OF CHEST PAIN

CONDITION Angina AGGRAVATING OR RELIEVING FACTORS

(4)

ASSOCIATED SYMPTOMS OR SIGNS

Precipitated by exercise, S4, or murmur of papillary cold weather or muscle dysfunction during emotional stress; relieved pain by rest or nitroglycerin; atypical (Prinzmetals) angina may be unrelated to activity, often early morning Same as angina, with decreasing tolerance for exertion or at rest Unrelieved by rest or nitroglycerin Similar to stable angina, but may be pronounced. Transient cardiac failure can occur Shortness of breath, sweating, weakness, nausea, vomiting

Rest or UA

Myocardial infarction

CARDIOVASCULAR CAUSES OF CHEST PAIN

CONDITION Pericarditis AGGRAVATING OR RELIEVING FACTORS Aggravated by deep breathing, rotating chest, or supine position; relieved by sitting up and leaning forward Usually occurs in setting of hypertension or predisposition such as Marfans syndrome

(5)

ASSOCIATED SYMPTOMS OR SIGNS Pericardial friction rub

Aortic dissection

Murmur of aortic insufficiency, pulse or blood pressure asymmetry; neurological deficit

CARDIOVASCULAR CAUSES OF CHEST PAIN

CONDITION
Pulmonary embolism (chest pain often not present)

(6)

AGGRAVATING OR RELIEVING FACTORS

May be aggravated by breathing

ASSOCIATED SYMPTOMS OR SIGNS

Dyspnea, tachypnea, tachycardia; hypotension, signs of acute right-sided heart failure, and pulmonary hypertension with large emboli; rales, pleural rub, hemoptysis with pulmonary infarction Pain usually associated with dyspnea; signs of pulmonary hypertension

Pulmonary hypertension

Aggravated by effort

Pain Patterns with Myocardial Ischemia

PHYSICAL EXAMINATION
General examination
Corneal arcus sometimes correlates with elevated cholesterol, low-density cholesterol and prognosis Xanthelasma appears to be promoted by increased levels of triglycerides and a relative deficiency of high-density lipoprotein Retinal arteriolar changes in diabetes mellitus or hypertension Blood pressure may be elevated Peripheral vascular disease in strongly associated with CAD

Cardiac examination
Examination during chest pain transient left ventricular dysfunction (S3, S4, pulmonary rales), softening of mitral component

of S1 > paradoxical spliting of S2.

Sustained apical cardiac impulse, displaced ventricular impulse LV dysfunction Transient apical systolic murmur reversible papillary muscle dysfuntion

Pathophysiology

Pathophysiology
Angina pectoris caused by imbalance between oxygen demand and supply
Angina caused by increased myocardial O2 requirements O2 requirement increased in face of constant, restricted O2 supply. Exertion, emotion, mental stress Rate - increased hemodynamic and catecholamine responses to stress Chills, fever, thyrotoxitosis, tachycardia, hypoglycemia, precipitants of ischemia

Angina caused by transiently decreased O2 supply

UAP and stable angina may be caused by vasoconstriction Platelet thrombi and leucocytes may cause release of vasoconstrictor substances : serotonin, thromboxane A2 Endothelial damage causes decreased production of vasodilatior substances Without organic obstruction lesions, severe dynamic obstruction at rest alone myocardial ischemia (Prinzmetals angina)

CLASS I

II

CANADIAN CARDIOVASCULAR SOCIETY FUNCTIONAL CLASSIFICATION Ordinary physical activity, such as walking and climbing stairs, does not cause angina. Angina with strenuous or rapid or prolonged exertion at work or recreation Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, in cold, in wind, or when under emotional stress, or only during the few hours after awakening. Walking more than two blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions

CLASS
III

CANADIAN CARDIOVASCULAR SOCIETY FUNCTIONAL CLASSIFICATION

Marked limitation of ordinary physical activity. Walking one to two blocks on the level and climbing more than one flight in normal conditions Inability to carry on any physical activity without discomfort anginal syndrome may be present at rest

IV

Noninvasive testing
Biochemical tests

Risk factors : dyslipidemia, CHD intolerance, insulin resistance (CRP, Lp(a), homocysteine)
Resting ECG

Exercise EKG
Stress myocardial perfusion imaging Pharmacological nuclear stress testing adenosine, dipyridamole Stress echocardiography Pharmacological stress echocardiography -dobutamine

High-Risk Findings on Noninvasive Stress Testing (1)

EXERCISE ELECTROCARDIOGRAPHY 2.0 mm or greater ST segment depression 1.0 mm or greater ST segment depression in stage 1 ST segment depression for longer than 5 min during the recovery period Achievement of a workload of less than 4 METs or a low exercise maximal heart rate Abnormal blood pressure response Ventricular tachyarrhythmias MYOCARDIAL PERFUSION IMAGING Multiple perfusion defects (total plus reversible defects) in more than one vascular supply region (e.g., defects in coronary supply regions of the left anterior descending and left circumflex vessels) Large and severe perfusion defects (high semiquantitative defect score) Increased lung thallium-201 uptake reflecting exercise-induced left ventricular dysfunction Postexercise transient left ventricular cavity dilatation Left ventricular dysfunction on gated single-photon emission computed tomography

High-Risk Findings on Noninvasive Stress Testing (2) STRESS ECHOCARDIOGRAPHY Multiple reversible wall motion abnormalities Severity and extent of these abnormalities (high global wall motion score) Severe reversible cavity dilation Left ventricular systolic dysfunction at rest

Angiographic Views of the Left Coronary Artery

Angiographic Views of the Left Coronary Artery

Angiographic Views of the Left Coronary Artery

Medical management
1. Identification and treatment of associated diseases that can precipitate or worsen angina
2. Reduction of coronary risk factors 3. Application of general and nonpharmacological methods (adjustments in lifestyle) 4. Pharmacological management 5. Revascularization (PCI or CABG)

Reduction of Coronary Risk Factors

Hypertension Predisposes to vascular injury Accelerated development of aterosclerosis Increase myocardial O2 demand Intensifies ischemia Antihypertensive th/ mort. and CV events by 16%

Dietary and life style modification

obese Cigarette smoking Predisposis to atherosclerotic plaque erosion and acute thrombosis Increases myocardial O2 demand and coronary tone

Dyslipidemia NCEP guidelines

Pharmacological Therapy
Aspirin
Betablocker Angiotensin converting enzyme (ACE) inhibitors Nitrates

Ca antagonists

Approach to patients with chronic stable angina (1)

1. Identify and treat precipitating factors : anemia, hypertension, thyrotoxicosis, tachyarrhythmias, congestive heart failure, concomitant valvular heart disease 2. Initiate risk factor modification, physical exercise life style counseling. Initiate therapy with HMGCoA reductase inhibitor, as needed to reduce LDL cholesterol < 100 mg/dl 3. Initiate therapy with aspirin and a betablocker. Strongly consider an ACE inhibitors as first-line th/ in chronic CAD 4. Use sublingual nitroglycerine for alleviation of symptoms and prophylactically

Approach to patients with chronic stable angina (2)

5. If episodes occur more than 2-3 x/week add ca antagonists 6. If angina persists, add third antianginal agent 7. Cor angiography with view to consider coronary revascularization indicated if symptoms or ischemia persists despite optimal medical therapy. Also consider in high-risk pts and those with occupations/life style that require a more aggressive approach

Indication for coronary revascularization

1. Significant left main CAD Most pts with three vessel disease that included proximal LAD especially were LV dysfunction CABG 2. Heart failure + severe ischemia especially if significant extent of potentially viable dysfunctioning myocardium 3. Single vessel disease + severe ischemia PCI 4. Angina without high risk similar survival for medically or surgically treated pts

COR PULMONALE CHRONICUM (CPC)

Hipertrofi & dilatasi ventrikel kanan sebab hipertensi pulmonal akibat peny. parenkim dan/atau vaskuler paru (antara a. pulmonal utama dan masuknya vv pulmonal ke atrium kiri)

Etiologi Utama
Penyakit paru obstruktif khronis (PPOK) akibat bronkhitis khronis atau emfisema paru

ETIOLOGY OF PULMONARY HEART DISEASE (1)

I. DISEASES AFFECTING THE PULMONARY VASCULATURE A. Primary diseases of the arterial wall (1) Primary pulmonary hypertension (2) Granulomatous pulmonary arteritis (3) Toxin-induced pulmonary hypertension a. Aminorex fumarate b. Intravenous drug abuse (4) Chronic liver disease (5) Peripheral pulmonic stenosis B. Thrombotic disorders (1) Sickle cell diseases (2) Pulmonary microthrombi C. Embolic disorders (1) Thromboembolism (3) Other embolism (amniotic fluid, air) (2) Tumor embolism (4) Schistosomiasis and other parasitic diseases II. PRESSURE ON PULMONARY ARTERIES BY MEDIASTINAL TUMORS, ANEURYSMS, GRANULOMATA, OR FIBROSIS III. DISEASES OF THE NEUROMUSCULAR APPARATUS AND CHEST WALL A. Neuromuscular weakness D. Pleural fibrosis B. Kyphoscoliosis E. Sleep apnea syndromes C. Thoracoplasty F. Idiopathic hypoventilation

ETIOLOGY OF PULMONARY HEART DISEASE (2)

IV. DISEASES AFFECTING AIR PASSAGES OF THE LUNG AND ALVEOLI A. Chronic obstructive pulmonary diseases B. Cystic fibrosis C. Congenital development defects D. Infiltrative or granulomatous diseases (1) Idiopathic pulmonary fibrosis (2) Sarcoidosis (3) Pneumoconiosis (4) Scleroderma (5) Mixed connective tissue disease (6) Systemic lupus erythematosus (7) Rheumatoid arthritis (8) Polymyositis (9) Eosinophilic granuloma (10) Malignant infiltration (11) Radiation E. Upper airways obstruction F. Pulmonary resection G. High-altitude disease

PATHOGENESIS OF COR PULMONALE

Chronic lung disease
Reduction in pulmonary vascular bed Acidosis and hypercapnia Polycythemia and hyperviscosity Pulmonary hypertension

Hypoxia

Hypertrophy and dilatation of the right ventricle Right ventricular failure

PEMERIKSAAN PENDERITA CPC

Klinis : Pemeriksaan fisik susah karena emfisema pulm pada PPOK Systolic parasternal heave Tricuspid regurgitation P2 > Tanda gagal jantung kanan

EKG : Sangat spesifik, kurang sensitif

ELECTROCARDIOGRAPHIC CHANGES IN COR PULMONALE (1)

ECG CRITERIA FOR COR PULMONALE WITHOUT OBSTRUCTIVE DISEASE OF THE AIRWAYS 1. Right-axis deviation with a mean QRS axis to the right of + 110 o 2. R/S amplitude ratio in V1 > 1 3. R/S amplitude ratio in V6 < 1 4. Clockwise rotation of the electrical axis 5. P-pulmonale pattern 6. S 1Q3 or S 1S 2S 3 pattern 7. Normal voltage QRS

ELECTROCARDIOGRAPHIC CHANGES IN COR PULMONALE (2)

ECG CHANGES IN CHRONIC COR PULMONALE WITH OBSTRUCTIVE DISEASE OF THE AIRWAYS 1. Isoelectric P waves in lead I or right-axis deviation of the P vector 2. P-pulmonale pattern (an increase in P-wave amplitude in II, III, AVf) 3. Tendency for right-axis deviation of the QRS 4. R/S amplitude ratio in V6 < 1 5. Low-voltage QRS 6. S1Q3 or S1S2S3 pattern 7. Incomplete (and rarely complete) right bundle branch block 8. R/S amplitude ratio in V1 > 1 9. Marked clockwise rotation of the electrical axis 10. Occasional large Q wave or QS in the inferior or midprecordial leads, suggesting healed myocardial infarction

X-Thorax Jantung dapat normal, atau membesar dengan apeks terangkat Dilatasi konus pulmonal + cabang besarnya, sedangkan cabang-cabang kecil tak terlihat karena vasokonstriksi PPOK : kelainan paru-paru terlihat Ekhokardiografi Doppler - ekho : - Tek. a. pulmonalis - TR - RV dilatasi

HIPOKSIA
Sebab terpenting hipertensi pulmonal pada PPOK Vasokonstriksi pulmonal (langsung atau lewat pelepasan zat vasoaktif) Proliferasi sel endotel dan penebalan intima arteriol Hipertrofi tunica media a. pulmonal Vasodilatasi terhambat

PENGELOLAAN
OKSIGEN Diberikan kontinu 1-2 l/menit, dapat memperbaiki prognosis karena mengurangi vasokonstriksi pulmonal dan memperbaiki hipoksia DIGITALIS Hanya bila juga ada gagal jantung kiri atau pada gagal jantung kanan akut THEOPHYLLINE Bronkhodilatasi, fungsi RV - LV membaik BETA-ADRENERGIC AGONISTS Bronkhodilator VASODILATOR ? Atasi penyakit paru penyebabnya !!!

Mechanisms of salt and water disturbance in patients with COPD

RBF Effective renal plasma flow Dopamine Filtration fraction Peritubular oncotic pressure PCO 2 Tubular Na +- H + exchange PCO 2

Dopamine ANP PRA ANP ANG II

Plasma renin activity

Angiotensin II Na + retention: edema Plasma aldosterone Natriuresis ANP Dopamine

ANP AVP

Arginine vasopressin level

H 2O retention; hyponatremia