MODULE PATHOLOGY OF CARDIOVASCULAR SYSTEM

ACUTE CORONARY SYNDROME

KELOMPOK 2.03
SEMESTER VI
TANGGAL 13 APRIL 2011
DR. MOH. SAIFUL ROHMAN,SP.J
DANIEL ALEXANDER
HARTADI TANJOYO
NIDA TSANIA
AYU SEKARANI
CHRISTIAN SURYA EKA PUTRA
DESY KARTIKASARI
DIAN ROSALIA
DIMAS BAGUS RESPATI
ELDWIN SUPUTRO
FITRI YULIANI AZIZ
GRACE SETIAWAN
IRENE CLARA K.
IRENE HERDIANTO
IRENE LAMPITA
JAMES KLEMENS PHIETER PHIE
JEREMY TOBIAS
JONATHAN HARTANTO
LISAWATI SUTRISNO
NURHIDAYATI
MIRSA ARISTA
MAULANA HASYMI
1. Define the term acute coronary syndrome!

Suatu kondisi di mana adanya suplai darah dan oksigen yang tidak adekuat pada satu
bagian dari miokardium, hal ini terjadi karena adanya ketidakseimbangan antara suplai
dan kebutuhan oksigen dari miokardium. Penyebab utama iskemi miokardial ini adalah
aterosklerotik pada arteri coronaria di epikardial yang menyebabkan nutrisi regional
pada aliran darah miokardium dan perfusi yang tidak adekuat dari miokardium yang
disuplai oleh arteri tersebut.
2. Explain the definition of unstable angina pectoris!
Unstable angina pectoris harus memiliki satu
a. tipikal chest pain cardiac
b. resting pain >20 menit/crescendo angina (progresif)
c. new onset (paling tidak CCS level III)
d. angina pasca infark

3.

dari

empat

ciri

berikut

During diagnostic evaluation for chest pain patient, we should make risk
stratification for patient with suspected of having acute coronary syndrome. What
factors that include a high likelihood of ACS?
History Symptoms same as prior angina. History of CAD, MI, sudden death. Variant angina
(pain with reversible ST-segment elevation). Transient hemodynamic or ECG changes during
pain.
Exam Hypotension, diaphoresis, pulmonary edema, transient MR
ECG ST-segment depression 1 mm depression from baseline
Marked symmetrical T-wave in-version in multiple leads
Cardiac markers Elevated TnT (troponin T),TnI (troponin I), CK-MB (creatine kinase muscle
and brain subunits)

4. Describe the pathophysiology of UA/NSTEMI!

UA/NSTEMI is most commonly caused by a reduction in oxygen supply and/or by an

increase in myocardial oxygen demand superimposed on an atherosclerotic coronary
plaque, with varying degrees of obstruction. Four pathophysiologic processes that may
contribute to the development of UA/NSTEMI have been identified: (1) plaque rupture or
erosion with superimposed nonocclusive thrombus, believed to be the most common
causeNSTEMI may occur with downstream embolization of platelet aggregates and/or
atherosclerotic debris; (2) dynamic obstruction [e.g., coronary spasm, as in Prinzmetal's
variant angina (p. 238-4)]; (3) progressive mechanical obstruction [e.g., rapidly
advancing coronary atherosclerosis or restenosis following percutaneous coronary
intervention (PCI)]; and (4) secondary UA related to increased myocardial oxygen
demand and/or decreased supply (e.g., tachycardia, anemia). More than one of these
processes may be involved.

Among patients with UA/NSTEMI studied at angiography, approximately 5% have left

main stenosis, 15% have three-vessel CAD, 30% have two-vessel disease, 40% have
single-vessel disease, and 10% have no critical coronary stenosis; some of the latter
have Prinzmetal's variant angina (see below). The "culprit lesion" on angiography may

show an eccentric stenosis with scalloped or overhanging edges and a narrow neck.
Angioscopy may reveal "white" (platelet-rich) thrombi, as opposed to "red" thrombi,
more often seen in patients with acute STEMI. Patients with UA/NSTEMI often have
multiple plaques vulnerable to disruption.

5. Mention independent risk factors used to make risk stratification among patients
with UA/NSTEMI!
Usia >65 tahun
3 faktor resiko cardiovascular (hipertensi, DM, obesitas, perokok, family history first
degree, menopause)
Riwayat CAD
Severe angina symptoms (1 episode dalam 24 jam sebelumnya)
Penggunaan aspirin dalam 7 hari terakhir
Deviasi segment ST >0.05 mV
Significant pain
Peningkatan serum cardiac marker necrosis
CK-MB subforms for Dx within 6 hrs of MI onset
cTnI and cTnT efficient for late Dx of MI
CK-MB subform plus cardiac-specific troponin best combination
Do not rely solely on troponins because they remain elevated for 7-14 days and
compromise ability to diagnose recurrent infarction
6. Describe the appropriate use of antithrombotic therapy during treatment for
UA/NSTEMI!
Oral
antiplatelet
therapy
Aspirin
Intial dose of 162-325 mg nonenteric formulation followed by 75-162
mg/d of an enteric or a nonenteric formulation
Clopidegrol
Loading dose of 300 mg followed by 75 mg/d
Intravenous
antiplatelet
therapy
Abciximab (ReoPro)
0,25 mg/kg bolus followed by infusion of 0,125 mikrogram/kg per
min (max 10 mikrogram/min) for 12-24 hr
Eptifibatide
180 mikrogram/kg bolus followed by infusion of 2,0 mikrogram/kg
(Integrilin)
per min for 72-96 hr
Tirofiban (Aggrastat) 0,4 mikrogram/kg per min for 30 min followed by infusion of 0,1
mikrogram/kg per min for 48-96 hr
Heparin
Heparin (UFH)
Bolus 60-70 U/kg (maximum 5000 U) IV followed by infusion of 12-15
U/kg per h(initial maximum 1000 U/h) titrated to a PTT 50-70 s
Enoxaparin
1 mg/kg SC every 12 h; the first dose may be preceded by a 30 mg
(Lovenox)
IV bolus; renal adjustment to 1 mg/kg once daily if creatinr CI
>30cc/min
Fondaparinux
2,5 mg SQ once daily
Bivalirudin
Initial bolus intravenous bolus of 0,1 mg/kg and an infusion of 0,25
mg/kg per hour. Before PCI, an additional intravenous bolus of 0,5
mg/kg was administered, and the infusion was increased to 1,75
mg/kg per hour
7. What is the pathophysiology of ST elevation myocardial infarction?

STEMI usually occurs when coronary blood flow decreases abruptly after a thrombotic
occlusion of a coronary artery previously affected by atherosclerosis. Slowly developing,

high-grade coronary artery stenoses do not typically precipitate STEMI because of the
development of a rich collateral network over time. Instead, STEMI occurs when a
coronary artery thrombus develops rapidly at a site of vascular injury. This injury is
produced or facilitated by factors such as cigarette smoking, hypertension, and lipid
accumulation. In most cases, STEMI occurs when the surface of an atherosclerotic plaque
becomes disrupted (exposing its contents to the blood) and conditions (local or
systemic) favor thrombogenesis. A mural thrombus forms at the site of plaque
disruption, and the involved coronary artery becomes occluded. Histologic studies
indicate that the coronary plaques prone to disruption are those with a rich lipid core and
a thin fibrous cap (Chap. 235). After an initial platelet monolayer forms at the site of the
disrupted plaque, various agonists (collagen, ADP, epinephrine, serotonin) promote
platelet activation. After agonist stimulation of platelets, thromboxane A 2 (a potent local
vasoconstrictor) is released, further platelet activation occurs, and potential resistance
to fibrinolysis develops.

In addition to the generation of thromboxane A 2, activation of platelets by agonists

promotes a conformational change in the glycoprotein IIb/IIIa receptor (Chap. 109). Once
converted to its functional state, this receptor develops a high affinity for amino acid
sequences on soluble adhesive proteins (i.e., integrins) such as fibrinogen. Since
fibrinogen is a multivalent molecule, it can bind to two different platelets simultaneously,
resulting in platelet cross-linking and aggregation.

The coagulation cascade is activated on exposure of tissue factor in damaged

endothelial cells at the site of the disrupted plaque. Factors VII and X are activated,
ultimately leading to the conversion of prothrombin to thrombin, which then converts
fibrinogen to fibrin (Chap. 110). Fluid-phase and clot-bound thrombin participate in an
autoamplification reaction leading to further activation of the coagulation cascade. The
culprit coronary artery eventually becomes occluded by a thrombus containing platelet
aggregates and fibrin strands.

In rare cases STEMI may be due to coronary artery occlusion caused by coronary emboli,
congenital abnormalities, coronary spasm, and a wide variety of systemicparticularly
inflammatorydiseases. The amount of myocardial damage caused by coronary
occlusion depends on (1) the territory supplied by the affected vessel, (2) whether or not
the vessel becomes totally occluded, (3) the duration of coronary occlusion, (4) the
quantity of blood supplied by collateral vessels to the affected tissue, (5) the demand for
oxygen of the myocardium whose blood supply has been suddenly limited, (6) native
factors that can produce early spontaneous lysis of the occlusive thrombus, and (7) the
adequacy of myocardial perfusion in the infarct zone when flow is restored in the
occluded epicardial coronary artery.

Patients at increased risk of developing STEMI include those with multiple coronary risk
factors (Chap. 235) and those with unstable angina (Chap. 238). Less common
underlying medical conditions predisposing patients to STEMI include hypercoagulability,
collagen vascular disease, cocaine abuse, and intracardiac thrombi or masses that can
produce coronary emboli.

8. Describe clinical presentation of acute ST elevation myocardial infarction and its

differential diagnosis!
Clinical presentation :

Hingga separuh kasus faktor presipitasi yang menyebabkan STEMI seperti exercise
fisik berlebihan, stress emosional, penyakit medis/operatif
Meski STEMI dapat terjadi sewaktu-waktu baik siang maupun malam variasi circadian
telah dilaporkan bahwa cluster dapat dilihat pada pagi hari dalam beberapa jam bangun
pagi
Nyeri presentasi klinis paling sering nyeri dalam dan visceral sering
dideskripsikan dengan nyeri berat, mengikat, dan menghancurkan (crushing), meski
kadang dideskripsikan sebagai nyeri menusuk atau membakar secara karakter mirip
dengan ketidaknyamanan pada angina pectoris namun terjadinya saat istirahat,
biasanya lebih parah, dan berlangsung lebih lama
Nyeri secara khusus meliputi bagian central dada dan/atau epigastrium (lokasi
nyeri yang sering: di bawah xiphoid dan epigastrium), dan kadang menyebar ke
lengan; penyebaran yang lebih jarang meliputi abdomen, punggung, rahang bawah,
dan leher
Sering ada penolakan pasien bahwa mereka terkena serangan jantung sering
terjadi salah dugaan adanya gangguan GI
Nyeri pada STEMI dapat menyebar hingga area occipital namun tidak pernah hingga
ke bawah umbilicus sering disertai weakness, berkeringat, nausea, vomiting,
anxiety, dan perasaan akan kematian yang segera dating
Nyeri dapat muncul saat istirahat, namun bila muncul saat exercise, biasanya tidak
hilang meski aktivitas sudah dikurangi (berkebalikan dari angina pectoris)
Nyeri pada STEMI dapat mirip dengan nyeri karena acute pericarditis, emboli paru,
diseksi aorta akut, costochondritis, dan gangguan GI bisa jadi differential
diagnosis namun pada acute pericarditis, nyeri menyebar hingga trapezius
Nyeri tidak secara seragam muncul pada pasien STEMI proporsi STEMI tanpa nyeri
lebih besar pada pasien DM dan naik seiring usia Pada orang tua, STEMI dapat
muncul dengan onset tiba-tiba berupa breathlessness yang dapat berkembang
menjadi pulmonary edema
Presentasi klinis lain yang lebih jarang, baik dengan/tanpa nyeri hilang kesadaran
tiba-tiba, status konvulsi, sensasi weakness parah, tampakan arrhythmia, adanya emboli
perifer, atau jatuhnya tekanan arteri tanpa sebab
Sebagian besar pasien anxious (cemas) dan restless (agitasi) berusaha
menghilangkan rasa sakit dengan bergerak-gerak di tempat tidur, mengubah posisi, dan
stretching
Pucat karena prespirasi dan dingin di ektremitas
Kombinasi substernal chest pain >30 menit dan diaphoresis dugaan kuat STEMI
Meski banyak pasien punya HR dan BP normal dalam 1 jam pertama STEMI sekitar
pasien dengan anterior infarct punya manifestasi hiperaktivitas simpatis takikardia
dan hipertensi; dan hingga pasien dengan inferior infarct menunjukkan hiperaktivitas
parasimpatis bradikardi dan/atau hipotensi
Precordium biasanya tenang, dan impulse apical mungkin sulit dipalpasi
Pada pasien dengan infarct dinding anterior pulsasi sistolik abnormal karena bulging
diskinetik dari myocardium pada area periapical dalam hari pertama sakit kemudian
membaik
Tanda fisik karena disfungsi ventrikel meliputi suara jantung keempat dan ketiga,
penurunan intensitas suara jantung pertama, dan splitting paradoksikal pada suara
jantung kedua
Disfungsi mitral valve apparatus transient midsystolic murmur atau late systolic dan
apical systolic murmur
Pericardial friction rub bisa terdapat pada banyak pasien transmural STEMI saat
perjalanan penyakit (bila sering diperiksa)
Denyut carotis sering turun volumenya karena penurunan stroke volume
Dalam minggu pertama setelah STEMI peningkatan suhu hingga 380C dapat terjadi
Arterial pressure bervariasi pada sebagian besar pasien dengan infarct transmural,
systolic pressure turun hingga mendekati 10-15mmHg dari status pre-infarct (Harrison)
Diferential diagnosis :
Pericarditis (terjadi ST elevation di semua tempat)

9. What are the goals for the management of patients with suspected STEMI in the
emergency ward?

In the Emergency Department, the goals for the management of patients with suspected
STEMI include control of cardiac discomfort, rapid identification of patients who are
candidates for urgent reperfusion therapy, triage of lower-risk patients to the appropriate
location in the hospital, and avoidance of inappropriate discharge of patients with STEMI.
Many aspects of the treatment of STEMI are initiated in the Emergency Department and
then continued during the in-hospital phase of management.

Aspirin is essential in the management of patients with suspected STEMI and is effective
across the entire spectrum of acute coronary syndromes (Fig. 239-1). Rapid inhibition of
cyclooxygenase-1 in platelets followed by a reduction of thromboxane A 2 levels is
achieved by buccal absorption of a chewed 160325 mg tablet in the Emergency
Department. This measure should be followed by daily oral administration of aspirin in a
dose of 75162 mg.

In patients whose arterial O2 saturation is normal, supplemental O 2 is of limited if any

clinical benefit and therefore is not cost-effective. However, when hypoxemia is present,
O2 should be administered by nasal prongs or face mask (24 L/min) for the first 612 h
after infarction; the patient should then be reassessed to determine if there is a
continued need for such treatment.

10.

Explain how to control chest discomfort in patients with STEMI!

Sublingual nitroglycerin can be given safely to most patients with STEMI. Up to three
doses of 0.4 mg should be administered at about 5-min intervals. In addition to
diminishing or abolishing chest discomfort, nitroglycerin may be capable of both
decreasing myocardial oxygen demand (by lowering preload) and increasing
myocardial oxygen supply (by dilating infarct-related coronary vessels or collateral
vessels). In patients whose initially favorable response to sublingual nitroglycerin is
followed by the return of chest discomfort, particularly if accompanied by other
evidence of ongoing ischemia such as further ST-segment or T-wave shifts, the use of
intravenous nitroglycerin should be considered. Therapy with nitrates should be
avoided in patients who present with low systolic arterial pressure (<90 mmHg) or in
whom there is clinical suspicion of right ventricular infarction (inferior infarction on
ECG, elevated jugular venous pressure, clear lungs, and hypotension). Nitrates should
not be administered to patients who have taken the phosphodiesterase-5 inhibitor
sildenafil for erectile dysfunction within the preceding 24 h since it may potentiate the
hypotensive effects of nitrates. An idiosyncratic reaction to nitrates, consisting of
sudden marked hypotension, sometimes occurs but can usually be reversed promptly
by the rapid administration of intravenous atropine.

Morphine is a very effective analgesic for the pain associated with STEMI. However, it
may reduce sympathetically mediated arteriolar and venous constriction, and the
resulting venous pooling may reduce cardiac output and arterial pressure. These
hemodynamic disturbances usually respond promptly to elevation of the legs, but in
some patients volume expansion with intravenous saline is required. The patient may
experience diaphoresis and nausea, but these events usually pass and are replaced by
a feeling of well-being associated with the relief of pain. Morphine also has a vagotonic
effect and may cause bradycardia or advanced degrees of heart block, particularly in

patients with posteroinferior infarction. These side effects usually respond to atropine
(0.5 mg intravenously). Morphine is routinely administered by repetitive (every 5 min)
intravenous injection of small doses (24 mg) rather than by the subcutaneous
administration of a larger quantity, because absorption may be unpredictable by the
latter route.

Intravenous beta blockers are also useful in the control of the pain of STEMI. These
drugs control pain effectively in some patients, presumably by diminishing myocardial
O2 demand and hence ischemia. More important, there is evidence that intravenous
beta blockers reduce the risks of reinfarction and ventricular fibrillation (see "BetaAdrenoceptor Blockers," below). A commonly employed regimen is metoprolol, 5 mg
every 25 min for a total of 3 doses, provided the patient has a heart rate >60 beats
per minute (bpm), systolic pressure >100 mmHg, a PR interval <0.24 s, and rales that
are no higher than 10 cm up from the diaphragm. Fifteen minutes after the last
intravenous dose, an oral regimen is initiated of 50 mg every 6 h for 48 h, followed by
100 mg every 12 h.

Unlike beta blockers, calcium antagonists are of little value in the acute setting, and
there is evidence that short-acting dihydropyridines may be associated with an
increased mortality risk.