PENYAKIT JANTUNG KORONER

Bahan kuliah mahasiswa FK Unsyiah Tanggal 10 Mei 2008

Clases of Recommendations
Class I Class II Class II a
Evidence and/or general agreement that a given treatment or procedure is beneficial, useful and effective Conflicting evidence and/or a divergence of opinion about the usefullness/efficacy of a given treatment or procedure Weight of evidence/opinion is in favour of usefullness/efficacy

Class II b
Class III

Usefulnes/efficacy is less well estabilished by evidence/opinion

Evidence or general agreement that the treatment is not useful/evidence and in some

Levels of Evidence
Level of Evidence A
Data derived from multiple randomized clinical trials or meta-analyses Data derived from single randomized clinical trial or large non-randimized studies Consensus of the opinion of the experts and/or small studies, restropective studies, registries

Level of Evidence B

Level of Evidence C

Recommendations for diagnosis and risk stratification

Should be based on a combination of

clinical history, symptoms, ECG, biomakers and risk score results

(I-B)

The evaluation of the individual risk is the dynamic process that is to be updated as the clinical situation evolves

continued

A 12 leads ECG should be obtains in 10 minutes of first medical contact and immediately read by an experienced physician (I-C) Blood must be drawn promptly for troponin(cTnT or cTnI) measurement. The should available within 60 minutes (I-C). The test should be repeated after 6-12 hours if the initial test negative (I-A)

Estabilish risk score ( such as GRACE) should be implement ed for initial and subsequent risk assessment (I-B) An Echocardiogram is recommended to rule in/out differential diagnosis (I-C) In patients with recurrence of pain, normal ECG findings, and negative troponins tests, a noninvasive stress test for inducible ischaemia is recommended before disgharge (I-A)

Predictors of long-term Death or MI should be consider in risk stratification (I-B):

Clinical indicators: age, heart rate, BP, Killip class, diabetes, previous MI/CAD ECG markers: ST segment depression A blood markers : troponin, GFR/CrCl/Csystatin C, BNP/NT-proBNP, hsCRP

Imaging finding: low ejection fraction, main stem lesion, 3 VD

Risk score result.

INTRODUCTION
ANGINA NON ST ELEVATION AMI
ST ELEVATION AMI

ANGINA
Clinical syndrome characteristic by discomfort in the chest, jaw, shoulder, back or arms. typically elicited by exertion or emotional stress and relieved by rest or nitroglycerin Less typically epigastric area

DIAGNOSIS AND ASSESSMENT

1. Clinical assessment 2. Laboratory test
3. Specific cardiac investigation

Purpose of investigation
1) Confirmation of the presence of ischaemia in patients w/ suspected stable angina 2) Identification or exclusion of associated conditions or precipitating factors 3) Risk stratification 4) To plan treatment options 5) Evaluation of the efficacy of treatment

Symptoms and Signs

1. History very important 2. Characteristic of discomfort :
a) b) c) d) e) Location Character Duration Relation to exertion Exacerbating or relieving factors

Unstable Angina
1) Rest angina 2) Rapidly increasing or crescendo angina Previously stable w/ rapid prograssive increase in severity 3) New onset angina rcent onset of severe angina w/ marked limitation of ordinary activity witjin 2 mo

Grading system
I. II. Canadian cardiovascular Society Duke Specific Activity Index

III. Seattle angina questionaire

Class I II

Classification of angina severity according to the Canadian cardiovascular Society

Level of symptoms
Ordinary activity does not cause angina. Angina w/ strenuous or rapid or prolonged exertion only
Slight limitation of ordinary activity
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals in cold weather, whwn under emotional stress, or only during the first few hours after awakening

III
IV

Marked limitation of ordinary activity

Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions

Inability to carry out any physical activity w/o discomfort or angina at rest

Definition of myocardial infarction

Criteria for acute myocardial infarction

Evidence of myocardial necrosis in clinical setting consistent w/ myocardial ischemia

Detection of rise and/or fall of cardiac biomarker (troponin) at least one value abovethe 99th percentile URL together w/ myocardial ischaemia w/ at least one of the following : -Symptoms of ischaemia -ECG changes indicative of new ischaemia -Development pathological Q waves in ECG -Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality

Sudden , unexpected cardiac death, involving cardiac arrest,often w/ symptoms suggestive myocardial ischaemia, and accompanied by presumably new STelevation, or new LBBB, and/or evidence of fresh thrombus by coronary angiography and/or at autopsy, but death occuring before blood sample could be obtained,or at time before the appearance cardiac biomarkers in the blood

Criteria for prior myocardial infarction

Any one of the following criteria meets the diagnosis for prior myocardial infarction :
Development the new pathological Q waves w/ or w/ out symptoms Imaging of evidence of a regionof loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause Pathological findings of healed or healing of myocardial infarction

Classification of myocardial infarction

Type 1
Type 2 Type3
Spontaneous MI related to ischaemia due to primary coronary event such as plaque eruption and/ or rupture, fissuring, or dissection MI secondary to ischaemia due to either increased O2 demand or decreased supply e.g. coronary artery spasm, coronary embolism, anemia, arrthythmia, hypertension, or hypotension Sudden unexpected cardiac death, incuding cardiac arrest, often w/ symptoms suggestive of myocardial ischaemia, accompanied by presumably new ST-elevation in coronary artery by angiography and/or pathology, but death occuring before blood samples could be obtained, or at a time before the appearance of cardiac biomarkers in the blood MI associated w/ PCI MI associated w/ stent thrombosis as documented by angiography or autopsy

Type 4a Type 4b

ECG
ST-elevation - New ST-elevation at J-point in two contiguous leads w/ the cut-off points : > 0,2 mV in men or - 0,15 mV in women in leads V2-V3 and/or - > 0,1 mV in other leads

ST-depression and T wave changes

New horizontal or down sloping ST depression >0,05 mV in two contiguous Leads; and/or

T-inversion > 0,1 mV in two contiguous leads w/ prominent R Wave or R/S ratio > 1

ECG changes associated w/ prior MI

1. Any Q wave in V2-V3 > 0.02 sec or QS comp in V2 V3 2. Q wave > 0.03 sec and >0,1 mV deep or QS comp in I, II, aVL, aVF, or V4-V6 in any two leads of contiguous lead grouping ( I, aVL, V6,V4-6, II, III, aVF) 3. R wave > 0.04 sec in V2-3 and R/S >1 w/ concordant positive T-wave in the absence of conduction effect

Common ECG pitfalls in diagnosing MI

False Positive :
Benign early repolarization LBBB Pre-excitation Brugada syndrome Peri-/myocarditis Pulmonary embolism Subarachnoidl haemorrhage Metabolic disturbances such as hyperkalemia Failure to recognize normal limits for J-point displacement Leads transposition or use of modified MasonLikar configuration Cholecystitis

Common ECG pitfalls in diagnosing MI

False Positive :
Benign early repolarization LBBB Pre-excitation Brugada syndrome Peri-/myocarditis Pulmonary embolism Subarachnoidl haemorrhage Metabolic disturbances such as hyperkalemia Failure to recognize normal limits for J-point displacement Leads transposition or use of modified MasonLikar configuration Cholecystitis

DEFINITIONS
1.Patient with typical acute chest pain and persistent (>20 minutes) ST segment elevation (STE ACS ): - reflects an acute total coronary occlusion - theurapeutic is to achieve rapid, complete and sustained reperfusion by primary angioplasty or fibrinolytic therapy

2. Patients with acute chest pain but without persistent ST segmen elevation: - persistent or transient ST Segmen depression or T waves inversion, Flat T waves,pseudo-normalisation of T waves, or no ECG changes at presentation - working diagnosis based on measurement of TROPONINs - qualified as NSTEMI

Admission
Working Diagnosis ECG

Chest pain

Suspicion of Acute Corornary Syndrome Persistent ST- elevation ST/T Abnormalities Normal or Undetermined ECG Troponin Twice negative

Bio chemistry Risk stratification Diagnosis STEMI

Troponin positive

High Risk NSTEMI

Low Risk Unstable Angina

Treatment

Reperfusion

Invasive

Non-invasive

Epidemioloy & Natural History

NSTE ACS is more frequent then STEMI In Hospital mortality STEMI > NSTE-ACS (7%vs5%) In contrast to STEMI, where most events occur before or shortly after presentation, in NSTEACS these events continue overdays and weeks Mortality of STEMI and NSTE ACS after 6 moths are comparable(12% vs 13%) Long term followup showed the death rate higher in NSTEMI ACS

PATHOPHYSIOLOGY
A LIFE THREATING MANIFESTATION OF ATHEROSCLEROSIS Precipated by acute thrombosis Induced by ruptured or eroded athrerosclerotic plaque, w/ or w/o concomittant vasoconstriction sudden and critical reduction in blood flow Inflammation key pathophisiologic el_nt Rare cases : arteritis, trauma, dissection, thromb-embolism, congenital anomalies, cocaine abuse

DIAGNOSIS AND RISK ASSESSMENT

Prolonged(> 20 minutes)anginal pain at rest ( 80% ) New onset( de novo) severe angina class III CCS ( 20% ) Recent destabilisation of previously stable angina w/ at least CCS III angina characteristics(crescendo angin ) Post MI angina

Clinical symptoms
failure or dementia Retrosternal pressure or heaviness radiating to left arm,neck or jaw. Accompanied by diaphoresis, nausea, abdominal pain, dyspnoea, and syncope. Atypical presentation : epigastric pain, recent onset indigestion, stabbing chest pain, chest pain w/pleuritic features, or increasing dyspnoea. often observed in younger(25-4 yo) and older(> 75 yo), women, diabetes, chronic renal

Diagnostic tools
1) 2) 3) 4) 5) Physical examination & clinical history Electrocardiogram Biochemicals markers Echocardiography Imaging of coronary anatomy

Physical examination
Frequently normal. Sign of heart failure Haemodynamic instability An important goal exclude non-cardiac causes

Biomarkers
TROPONINS : initial rise after 3 to 4 hours. Persist elevated for up 2 weeks after MI In NSTE-ACS over 48 to 72 hours Troponin elevation can be encountered in many conditions that do not constitute ACS D-dimer(pulmonary embolism) BNP/NT(dyspnoea, heart failure) Haemoglobin( anaemia), Leucocyte( inflammatory disease ) Markers of renal function

Non-coronary conditions w/ troponin elevations

1. Severe congestive heart failure acute & chronic 2. Aortic dissection, aortic valve disease or hyperthropic cardiomyophaty 3. Cardiac contusion, ablatio, pacing, cardioversion, or myocardial biopsy 4. Inflammatory diseases, eg myocarditis, or myocardial extension of endo-/pericarditis 5. Hypertensive crisis 6. Tachy or bradyarrhythmias

7.Pulmonary embolism, severe pulmonary hypertension 8. Hypothyroidism 9. Apical balooning syndrome 10 Chronic or acute renal dysfunction 11.Acute neurological disease including stroke, or subarachnoidal haemorrhage 12. Infiltrative disease eg amyloidosis, haemochromatosis, sarcoidosis, scleroderma 13. Drug toxicity, eg adriamycin, 5 FU, herceptin, snake venom 14. Burns, if affecting > 30 % of BSA 15.Rhadomyolisis 16.Criticall ill patients, especially w/ respiratory failure, or sepsis

Echocardiography
Recommended to detect wall motion abnormalities To rule out differential diagnosis Can identify ischaemia and myocardial viability Can diagnose healing or healed infarction

Differential diagnoses
Cardiac
Myocarditis Pericarditis Myopericarditis Cardiomyopathy Valvular disease Apical balooning (Tako-Tsubo syndr)

Pulmonary
Pulmonary embolism Pulmonary infarction Pneumonia Pleuritis Pneumothorax

Haematological
Sickle cell anaemia

Vascular
Aortic dissection Aortic aneurysm Aortic coarctation Cerebrovasc. Dis

Gastro-intestinal
Oesophageal spasm Oesophagitis Peptic ulcer Pancreatitis Cholecystitis

Orthopaedic
Cervical discophaty Rir Fracture Muscle injury/inflammation Costochondritis

Mortality in hospital and at 6 months in low, intermediate and high risk categories in registry populations according to the GRACE Risk Score

Risk Category (tertiles)

GRACE Risk Scorre

In-Hospital deaths(%)

Low

< 108

<1

Intermediate
High
Risk category (tertiles)

109-140
>140
GRACE Risk Score

1-3
>3
Post-discharge to 6 mo deaths(%)

Low Intermediate High

< 88 89-118 >118

<3 3-8 >8

Treatment
The management of NSTE-ACS includes five theuraphetic tools : Anti-ichemic agents Anticoagulants Antiplatelet agents Coronary revascularization Long-term management

Recommendations for anti-ischemic drugs:

Beta-blokers are recommended in the abcense of contraindication, particularly in patients w/ hypertension or tachycardia(I-B)

IV or oral nitrates are effective for symptom relief in the acute management of anginal episodes (I-C) CA blokers provide symptoms relief in patients already receiving nitrates and beta-blokers, they are useful in patients w/ contraindication to beta-blokade, and in the subgroup of patients w/ vasospastic angina (I-B) Nifedipine, or other dihydropyridines, should not be used unless combined w/ betablokers (III-B)

Recommendations of anticoagulan
Anticoagulan is recommended for all patients in addition to antiplatelet theraphy (I-A) Anticoagulan should be selected according to the risk of ischaemic and bleedings events (I-B) The choice depends in initial strategy urgent invasive, early invasive, or conservative strategies (I-B) In an urgent invasive strategy UFH (I-C), or enoxaparin (IIa-B) or bivaluridin (I-B) should be immediately started

Anti coagulant can be stopped within 24 hours of the invasive prosedure(IIa-C) . In a conservative strategy, fondaparinux, enoxaparin or other LMWH may be maintained up to hospital discharge (I-B)

Continued. In non-urgent situation, when decision whether to follow early invasive or conservative strategy is pending :
Fondaparinux is recommended on the basis of the most favorable efficacy/safety profile (I-A) Enoxaparin with less favourable/safety profile than fondaparinux should b use only if the bleeding risk is low (IIa-B) As efficacy/safety profile of LMWH (other than enoxaparin) or UFH relative to fondaparinux is unknown, these anticoagulantsncannot be recommended over fondaparinux (IIa-B) At PCI procedures the the initial anticoagulan should be mainted also during the procedure regarless whether this treatment is UFH (I-C), enoxaparin (IIa-B) or bivalurudin (I-B), while additional UFH in standart dose ( 50-100 IU/kg bolus) is necessary in case of fondaparinux (IIa-C)

Recommendations for oral antiplatelet drugs

Aspirin is recommended for all patients presenting w/ NSTE-ACS w/ out contraindication at an initial loading dose of 160-325 mg(non-enteric) (I-A) and at a maintenance dose of 75 to 100 mg long-term (I-A)

For all patients, immediate 300 mg loading dose of clopidrogel is recommended, followed by 75 mg clopidrogel daily (I-A). Clopidrogel should be maintained for 12 months unless there is an excessive risk of bleeding (I-A) For all patients w/ contraindication to aspirin, clopidogrel should be given instead (I-B)

continued

In patients considered for an invasive procedure/PCI, a loading dose of 600 mg of clopidrogel may be used to achieved more rapid inhibition of platelet function (IIa-B) In patients pre-treated w/ clopidrogel who need to undergo CABG, surgery should be postponed for 5 days for clopidrogel withdrawl if clically feasible (IIa-C)

Recommendation for GP IIb/IIIa inhibitors

In patients at intermediate to high risk, particularly patients w/ elevated troponin, ST-depression, or diabetes, either eptifibatide, or tiroffiban for initial early treatment are recommended in addition to oral anti platelet agents (IIa-A) The choice of combination of antiplatelet agents and anticoagulans should be made in relation to risk of ischaemic and bleeding events (I-B) Patients who reeived initial treatment w/ eptifibatide or tirofiban prior to angiograpfy, should be maintained on the same drug during and after PCI (IIa-B) In high risk patients not pre-treated w/ GP IIb/IIIa inhibitors and proceeding to PCI, abciximab is recommended immediately following angiography (I-A). The use of eptifibatide or tirofiban in this setting is less well establiished (IIa-B)

continued

GP IIb/IIIa inhibitors must be combined w/ an anticoagulan (I-A) Bivalirudin may be used as an alternative to GP IIb/IIIa inhibitors plus IFH/LMWH (IIa-B) When the anatomy is known and PCI is planned to be performed within 24 hours and using GP IIb/IIIa inhibitors, most secure evidence is for abciximab (IIa-B)

Emergency Care
Inial diagnosis of AMI :
History of chest pain/discomfort St segmen elevation or (presumed) new LBBB on admission ECG.Repeated ECG recordings often needed Elevated markers of myocardial necrosis ( CK-MB, troponins) Do not wait for the results to initiate reperfusion treatment 2D echo and perfusion scintigraphy helpful to rule out AMI

Relief of pain, breathlessness and anxiety

IV opoids ( e.g. 4 to 8 mg morphine ) w/ additional doses of 2 mg at 5 min intervals O2(2-4 l,min) if breathlessness or heart failure Consider IV B blockers or nitrate if opoids fail to relieve pain Tranquilizers may be helpful

Recommendations for reperfusion theraphy

Class Level of evidence

I
Reperfusion is indicated in all patients w/ history of chest pain/discomfort of < 12 hours and associated w/ ST_segment elevation or(presumed) new LBBB on the ECG

IIa

IIb

III
A

Primary PCI
Preferred treatment if performed by experienced team < 90 min after first medical contact Indicated for patients in shock and those w/ contraindication to fibrinolytic theraphy GP IIb/IIIa antagonist and primary PCI no stenting w/ stenting

X X

A C

X X

A A

Class
Fibrinolytic treatment
In the abcense of contraindication and if PCI can be performed in 90 minutes of first medcal contact by an experienced team, pharmacological reperfusion should be initited as soon as possible Choice of fibrinolytic agentsdepends on individual assessment of benefit and risk, avaiilability and cost In patients presenting late(> 4-8 hours after symptoms onset) a more fibrin spesific agent such astenecteplase or ateplase is preferred prehospital initiation of fibrinolytic theraphy if appropriate facillities exist Readministration of a non-immunogenic lytic agent if evidence of reocclusion and mechanical reperfusion not available If not already on aspirin 150 325 mg chewable aspirin ( no enteric coated tablets) w/ ateplase and reteplase a weight a djusted dose of heparin should be given w/early and

Level of Evidence
III

IIa

IIb

X
X X X X

B
B B A B

Contraindications to fibrinolytic therapy

Absolute :
- Haemorrhagic stroke or unknown origin at any time - ischemic stroke in preceding 6 months - CNS damage or neoplasma - Recent major trauma/surgery/head injury (w/ preceding 3 weeks ) - GE bleedings within the last month - Known bleeding disorder - Aortic dissection

Relative TIA in preceding 6 month Oral anticoagulant theraphy Pregnancy or within 1 weekspost partum Non-compressible punctures Traumatic resuscitation Refractory hypertension( systolic BP > 180 mmHg) Advanced liver disease Infective endocarditis Active peptic ulcer

Initial treatment Antithrombin Spec contr co-theraphy indications

Streptokinase
1,5 millions units in 100 ml of 5% dextrose or 0,9% saline over 30-60 min None or iv heparin for 24 to 48 h Prior SKS or anistreplase

Alteplase

15 mg iv bolus 0,75 mg/ kg over 30 min Then 0,5 mg/ kg Over 60 min iv. Total dose dosage not to exceed 100 mg
10 U + 10 U iv bolus given 30 min apart Single iv bolus 30 mg if < 60 kg 35 mg if 60 to <70 kg 40 mg if 70 to <80 kg 45 mg if 80 to <90 kg 50 mg if >90 kg

Iv heparin For 24 to 48 h

Reteplase

Iv heparin for 24 to 48 h Iv heparin for 24 to 48 h

Tenecteplase (TNK-tPA)

Heparin co-theraphy
Heparin : iv bolus 60 U/kg w/ a max of 4000 U

______________________________
Iv infusion 12 U ./kg for 24 to 48 h w/ a max of 1000 U/h. Target a PTT : 50-70 ms
____________________________________ aPTT to be moitored at 3, 6, 12, 24 h after starting treatment

Treatment of pump failure and shock

Diagnosis :
CXR, echocardiography, RH catheterisation ___________________________________________

Treatment of mild and moderately severe heart failure

O2 Furosemide 20-40 mg iv repeated at 1-4 h interval if necessary Nitrates : if no hypotension ACE inhibitors : in absenceof hypotension, hypovolemia or renal failure ____________________________________________

Treatment of severe heart failure

O2 Furosemide: 20-40 mg iv repeated at 1-4 hourly interval if necessary Nitrates : if no hypotension Inotropic agents : dopamine and/or dobutamine Haemodynamic assessment w/ balloon floating catheter Ventilatory support : if inadequate oxygen tension consider early revascularisation

Treatment of Shock
O2 Haemodynamic assessment w/ ballon floating catheter Inotropic agents : dopamine and dobutamine Ventilatory support if adequate oxygen tension Intraaortic balloon pump Consider left ventricular assist devices and early revascularisation

Recomm. for routine prophylactic therapies in acute phase

Class Level of evidence

I
Aspirin : 150-325 mg( no enteric coated formulation) IV B Bloker: for all patients for whom it is not contraindicated Oral B-blokers ACE Inhitor : oral formulation on first day: -To all patients for whom it is not - contraindicated - To high-risk patients - Nitrates - Ca antagonist & Lidocaine

IIa

IIb

III
A

X X

X X X X

A A A B

Management of the later in-hospital course

Myocardial infarction Clinical risk assessment

High Risk Coronary angiogram Suitable anatomy + Viable myocardium

Yes Yes

Medium or low risk Assess LV function

High risk

Medium risk Significant angina

No

Low risk Medical Rx

Revascularise
No

Recommendations for secondary prevention

I
Stop smoking Optimal glycemic control in diabetic patients Blood pressure control in hypertensive patients Mediteranean-type diet Supplementation w/ 1g fish oil n-3 polyunsaturated fatty acids Aspirin: 75 to 160 mg daily. If aspirin is not tolerated Clopidrogel (75 mg daily) Oral anticoagulant Oral Beta bloker: to all patients if no contraindication Continuation of ACE-inhibition started on the first day

Class IIa IIb III

Level of evi dence

C B C B B A C B A A A X X B A

X X

x x x x
X

x
X X X

Statins : I in spite of dietary measures total choletsterol > 190 mg/dl (5,06 mmol/l) and/or LDL cholesterol > 115 mg/dl (2,98 mmol/l)
Ca antagonist ( diltiazem or verapamil). If contraindication t betablokers and no heart failure Nitrates in absence of angina