Drugs & Diseases > Pathology

Pathology of Acute Myocardial Infarction

Updated: Oct 26, 2015

 Author: Allen Patrick Burke, MD; Chief Editor: Allen Patrick Burke, MD more...

Overview
Acute myocardial infarction (MI) indicates irreversible myocardial injury resulting in necrosis of
a significant portion of myocardium (generally >1 cm). The term "acute" denotes infarction less
than 3-5 days old, when the inflammatory infiltrate is primarily neutrophilic. Acute MI may be
either of the nonreperfusion type, in which case the obstruction to blood flow is permanent, or of
the reperfusion type, in which the obstruction or lack of blood flow is long enough in duration
(generally hours) but is reversed or restored after myocardial cell death occurs.

Go to Myocardial Infarction and Right Ventricular Infarction for complete information on these
topics.

Pathophysiology
Acute myocardial infarction (MI) generally refers to segmental (regional) myocardial necrosis,
typically endocardium-based, secondary to occlusion of an epicardial artery. In contrast,
concentric subendocardial necrosis may result from global ischemia and reperfusion in cases of
prolonged cardiac arrest with resuscitation. Areas of myocardial infarction may be subepicardial
if there is occlusion of smaller vessels by thromboemboli originating from coronary thrombi. In
the majority of patients, there is obstructive coronary disease at angiography.

The area of infarct occurs in the distribution of the occluded vessel. Left main coronary artery
occlusion generally results in a large anterolateral infarct, whereas occlusion of the left anterior
descending coronary artery causes necrosis limited to the anterior wall. There is often extension
to the anterior portion of the ventricular septum with proximal left coronary occlusions.

In hearts with a right coronary dominance (with the right artery supplying the posterior
descending branch), a right coronary artery occlusion causes a posterior (inferior) infarct. With a
left coronary dominance (about 15% of the population), a proximal circumflex occlusion will
infarct the posterior wall; in the right dominant pattern, a proximal obtuse marginal thrombus
will cause a lateral wall infarct only, and the distal circumflex is a small vessel.

The anatomic variation due to microscopic collateral circulation, which is not evident at autopsy,
plays a large factor in the size of necrosis and distribution. Unusual patterns of supply to the
posterior wall, such as wraparound left anterior descending or posterior descending artery
supplied by the obtuse marginal artery, may also result in unexpected areas of infarct in relation
to the occluded proximal segment.

A proximal occlusion at the level of an epicardial artery results in a typical distribution that starts
at the subendocardium and progresses towards the epicardium (the so-called wavefront
phenomenon). [1] Therefore, an area of necrosis or scarring is considered to have an "ischemic
pattern" if it is largest at the endocardium, with a wedge-shaped extension up to the epicardial
surface.

Ischemic injury, however, may be located in the mid myocardium or even the subepicardium if
the level of the coronary occlusion is distal within the myocardium. Therefore, in cases of
thromboemboli from epicardial thrombi (especially plaque erosions), there may be patchy
infarction, often associated with visible thrombi within the myocardial vessels, not centered in
the endocardium but occurring anywhere in the myocardium, including midepicardial and
subepicardial locations.

Etiology
Acute myocardial infarction (MI) results from lack of oxygen supply to the working
myocardium. Regional infarcts are due to lack of blood flow that occurs when an epicardial
artery is blocked by atheroma or thrombus, or other obstructions. Global subendocardial infarcts
occur when there is lack of oxygenation despite circulation—for example, when there is a
respiratory arrest followed by prolonged hypoxemia.

Autopsies of hospital inpatients dying of acute regional MI reveal an acute thrombus overlying
atherosclerotic plaque in more than 95% of cases when the coronary arteries are carefully
inspected. [2] In the remaining hearts, there will be severe coronary diseases without thrombus.
Rare causes of acute MI include no apparent cause (usually attributed to coronary spasm),
coronary embolism (varied causes, including valve vegetations and tumors), spontaneous
coronary artery dissections, congenital anomalies of the coronary origins, and thrombosis in
nonatherosclerotic normal coronary arteries (hypercoagulable states).

Risk factors

There is a known genetic predisposition to coronary artery disease that leads to acute MI. In
general, about 50-85% of the risk of coronary atherosclerosis is secondary to acquired
conditions. The remainder is secondary to genetic polymorphisms, which involve pathways of
inflammation, lipid metabolism, coagulation, the renin-angiotensin-aldosterone system, and other
components of atherogenesis. [3, 4]

Epidemiology
Acute myocardial infarctions (MIs) are common. In the United States, they result in the
hospitalization of approximately 4 men and 2 women per 1000 population each year. [5]

Clinical Features
The symptoms of acute myocardial infarction (MI) are chest pain, which may radiate to the arm
or jaw, sweating, nausea, and chest tightness or pressure. The diagnosis rests on laboratory
findings of myocardial necrosis, which causes leakage of myocardial enzymes, such as troponin,
into the circulating blood. Acute infarcts are divided by electrocardiographic findings into ST-
elevation myocardial infarction (STEMI) and non ST-elevation infarction (non-STEMI).

A prospective cohort study of 6304 consecutively enrolled patients with suspected acute
coronary syndrome reported that in patients without myocardial infarction at presentation,
troponin concentrations were less than 5 ng/L in 2311 (61%) of 3799 patients, with a negative
predictive value of 99·6% for the primary outcome. The study concluded that low plasma
troponin concentrations identified two-thirds of patients who were at very low risk of cardiac
events and who could be discharged from the hospital. [6]

STEMI is usually the result of blockage of a coronary artery with large elevations of cardiac
enzymes in the serum and eventually result in Q waves on the electrocardiogram. In contrast,
non-STEMI, which overlaps with the acute coronary syndrome unstable angina, causes modest
elevations of cardiac enzymes in the serum and pathologically shows small or patchy areas of
necrosis. Q waves do not develop in non-STEMI.

Gross Findings
The earliest change that can be grossly discerned in the evolution of acute myocardial infarction
(MI) is pallor of the myocardium, which is visible 12 hours or later after the onset of irreversible
ischemia. The gross detection of infarction can be enhanced by the use of tetrazolium salt
solutions, which form a colored precipitate on gross section of fresh heart tissue in the presence
of dehydrogenase-mediated activity. Myocardial necrosis can be detected as early as 2-3 hours in
dogs and in humans by this method.

In nonreperfused MI, the infarcted area is well defined at 2-3 days, with a central area of yellow
discoloration surrounded by a thin rim of highly vascularized hyperemia (see the first image
below). In reperfused MI, the infarcted region appears red because of trapping of the red cells
and hemorrhage from ruptured necrotic capillaries (see the second image below).

Acute myocardial infarct. At 3 days,

there is a zone of yellow necrosis surrounded by darker hyperemic borders. The arrow points to a
transmural infarct in the posterior wall of the left ventricle, in this short axis slice through the left
and right ventricular chambers.
View Media Gallery

Acute myocardial infarction,

reperfusion type. In this case, the infarct is diffusely hemorrhagic. There is a rupture track
through the center of this posterior left ventricular transmural infarct. The mechanism of death
was hemopericardium.
View Media Gallery
At 5-7 days, the regions are much more distinct, with a central soft area and a depressed
hyperemic border. At 1-2 weeks, the infarct begins to appear depressed, especially at the margins
where organization takes place, and the borders take on a white hue.

Healing may be complete as early as 4-6 weeks for small infarcts or may take as long as 2-3
months for large ones (see the images below). Areas of congestion and vasodilatation within
healed scars may appear hemorrhagic. In these cases, mottled myocardium that gives the gross
appearance of acute MI may, upon histologic examination, demonstrate only old fibrosis.

Healing myocardial infarction, lateral

left ventricle. In this heart, there is a variegated or mottled appearance to the lateral left ventricle
(left). This infarct began 19 days prior to death.
View Media Gallery

Early healed myocardial infarction,

anterior septum. There is a glistening gelatinous appearance to this infarction, that occurred 6
weeks prior to death, from embolization during valve surgery.
View Media Gallery

Healed infarcts are white from the scarring, and the ventricular wall may be thinned
(aneurysmal), especially in transmural infarction (see the image below). In general, infarcts that
occupy more than 50% of the ventricular wall, from the subendocardial to the epicardial surface,
are considered transmural and are associated with Q-wave changes on electrocardiography.

Healed myocardial infarction,

anterior left ventricle. There is diffuse scarring (white) with marked thinning of the ventricle
(aneurysm).
View Media Gallery

Microscopic Findings
Microscopically, the diagnosis of acute myocardial infarction (MI) rests on the presence of
necrotic myocardium, with an interface of acute inflammation separating it from viable
myocardium. Areas of inflammation with a scar or areas of mummified dead myocardium
bordered by granulation tissue do not indicate the presence of acute MI.

The earliest morphologic characteristic of MI occurs between 12 and 24 hours after the onset of
chest pain. Hypereosinophilia of the cytoplasm as assessed by hematoxylin-eosin staining is
characteristic of myocardial ischemia (see the first image below). Neutrophil infiltration is
present by 24 hours at the border areas (see the second image below).
 Acute myocardial infarct. The
earliest change is hypereosinophilia (above) with an intense pink cytoplasm. There is no
inflammation at border between the necrotic myocardium and the viable myocardium (left and
below), indicating that the necrosis is about 12-24 hours in age.
View Media Gallery

Acute myocardial infarct. After 24

hours, there is a neutrophilic infiltrate at the border of the infarct. Viable myocardium is at the
left, and neutrophils with apoptosis (karyorrhexis) are seen infiltrating the necrotic muscle. This
patient experienced abdominal pain 35 hours prior to death.
View Media Gallery

As the infarct progresses between 24 and 48 hours, coagulation necrosis is established, with
various degrees of nuclear pyknosis, early karyorrhexis, and karyolysis. The myocyte striations
are preserved and the sarcomeres elongate. The border areas show prominent neutrophil
infiltration by 48 hours.
At 3-5 days, the central portion of the infarct shows loss of myocyte nuclei and striations; in
smaller infarcts, neutrophils invade the infarct and fragment, resulting in more severe
karyorrhexis (nuclear dust). By 5-7 days, macrophages and fibroblasts begin to appear in the
border areas. By 1 week, neutrophils decline and granulation tissue is established (see the image
below), with neocapillary invasion and lymphocytic and plasma cell infiltration.

Healing myocardial infarct. This

patient died 8 days after experiencing sudden chest pain at rest. There is a large area of necrosis
with hypereosinophilia of myocytes, with a rim of viable myocardium at the very bottom. At the
border, there is chronic inflammation with early granulation tissue, with ingrowth of endothelial
cells.
View Media Gallery

Although lymphocytes may be seen as early as 2-3 days, they are not prominent in any stage of
infarct evolution. Eosinophils may be seen within the inflammatory infiltrate but are present in
only 24% of infarcts. There is phagocytic removal of the necrotic myocytes by macrophages, and
pigment is seen within macrophages. [7]

By the second week, fibroblasts are prominent, but they may appear as early as 1 week at the
periphery of the infarct (see the image below). There is continued removal of the necrotic
myocytes as the fibroblasts are actively producing collagen, and angiogenesis occurs in the area
of healing.
 Healing myocardial infarct. At 10
days to 2 weeks, there is chronic inflammation, hemosiderin-laden macrophages, and early
fibroblasts without significant collagen deposition.
View Media Gallery

Healing continues and, depending on the extent of necrosis, may be complete as early as 4 weeks
or may require 8 weeks or longer to complete (see the image below). The central area of large
infarction may remain unhealed and show mummified myocytes for extended periods, even
though the infarct borders are completely healed.

Healed myocardial infarct. At 3

months, there is dense scar, which is blue on this Masson trichrome stain. This infarct was
subendocardial, in the posterior left ventricle near the ventricular septum.
View Media Gallery

The histologic dating of MI may be important from a medicolegal point of view. There is no way
of determining infarct age exactly, however, both because the histologic features that define the
stages of repair overlap and because infarcts may enlarge, resulting in heterogeneity from one
area to another. The border zone between necrotic myocardium and viable myocardium is the
focus of dating, which depends on the reaction of viable myocardium to the area of infarct.

At 24 hours of occlusion followed by reperfusion after 6 hours in a canine model, myocytes are
thin, hypereosinophilic, and devoid of nuclei or showing karyorrhexis, with ill-defined borders
and interspersed areas of interstitial hemorrhage. There is a diffuse but mild neutrophil
infiltration. Within 2-3 days, macrophage infiltration is obvious and there is phagocytosis of
necrotic myocytes and early stages of granulation tissue.

Infarct healing is more rapid in dogs than in humans, most likely because of nondiseased
adjoining coronary arteries (collaterals) and a lack of underlying myocardial disease. In humans
with acute MI, there is often chronic ischemia secondary to extensive atherosclerotic disease.

In humans, if reperfusion occurs within 4-6 hours after the onset of chest pain or
electrocardiographic (ECG) changes, there is myocardial salvage, and the infarct is likely to be
subendocardial without transmural extension. There will be a nearly confluent area of
hemorrhage within the infarcted myocardium, with extensive contraction band necrosis. Within a
few hours of reperfusion, sparse neutrophils are evident within the area of necrosis, but they are
usually sparse.

Macrophages begin to appear by day 2-3; by day 3-5, fibroblasts appear, with an accelerated rate
of healing as compared with that of nonreperfused infarcts. Subendocardial infarcts may be fully
healed as early as 2-3 weeks. Larger infarcts and those reperfused after 6 hours take longer to
heal. Infarcts reperfused after 6 hours show larger areas of hemorrhage than do occlusions with
more immediate reperfusion.

Immunohistochemistry
Immunohistochemistry is of limited use in the diagnosis of acute myocardial infarction (MI).
Immunolocalization of complement or fibrin may be helpful in identifying areas of myocyte
necrosis, where there is leakage of extracellular proteins into the myocytes. In addition, markers
of ischemia include hypoxia-inducible factor-1, complement leaking into myocytes, and
cyclooxygenase-2, which can be demonstrated immunohistochemically.

Prognosis and Predictive Factors

The morbidity and mortality of myocardial infarction (MI) result from arrhythmias, cardiac
rupture, heart failure, valve insufficiency, and embolization.

Arrhythmias include ventricular tachyarrhythmias, which are the most common cause of sudden
death, especially early after infarction, and various degrees of heart block.

Cardiac rupture occurs in approximately 5% of patients, has a high mortality, and is increased in
frequency in patients experiencing their first infarct, hypertensive patients, and women. [8]
The risk of heart failure is proportional to the size of the infarct and the presence of papillary
muscle necrosis. The size of infarct may be significantly decreased with prompt reperfusion after
the first symptoms, either by thrombolytic treatment or by percutaneous intervention. Stem cell
treatment is an investigative approach to minimizing myocardial infarct size.

Infarction or rupture of the posteromedial papillary muscle causes acute mitral insufficiency,
which greatly worsens cardiac output and which may be treated surgically. The improvement in
prognosis that has occurred in the last decade is due to early treatment with thrombolytic agents
and reperfusion. [9]

Mural thrombosis over the area of infarction may result in embolization and concomitant stroke
but is decreased in incidence with anticoagulation therapy. [10]

Patologi Infark Miokard Akut

Diperbarui: 26 Oktober 2015
• Penulis: Allen Patrick Burke, MD; Pemimpin Redaksi: Allen Patrick Burke, MD lebih ...
•
Ikhtisar
Infark miokard akut (MI) menunjukkan cedera miokard ireversibel sehingga terjadi nekrosis pada
sebagian besar miokardium (umumnya> 1 cm). Istilah "akut" menunjukkan infark kurang dari 3-5 hari,
ketika infiltrasi inflamasi terutama neutrofil. MI akut mungkin salah satu tipe nonreperfusi, dalam hal ini
penyumbatan pada aliran darah bersifat permanen, atau tipe reperfusi, di mana penyumbatan atau
kekurangan aliran darah cukup lama dalam durasi (umumnya jam) namun terbalik atau dipulihkan.
Setelah kematian sel miokard terjadi.
Pergi ke Myocardial Infarction dan Right Ventricular Infarction untuk informasi lengkap mengenai topik
ini.
Patofisiologi
Infark miokard akut (MI) umumnya mengacu pada nekrosis miokard segmentasional (regional), biasanya
berbasis endokardium, sekunder akibat oklusi arteri epikardial. Sebaliknya, nekrosis subendoksi
konsentris dapat terjadi akibat iskemia global dan reperfusi dalam kasus henti jantung berkepanjangan
dengan resusitasi. Area infark miokard mungkin subepicardial jika terjadi oklusi pembuluh darah yang
lebih kecil dengan tromboemboli yang berasal dari trombi koroner. Pada sebagian besar pasien, ada
penyakit koroner obstruktif pada angiografi.
Area infark terjadi pada distribusi bejana yang tersumbat. Oklusi arteri koroner utama pada umumnya
menghasilkan infark anterolateral besar, sedangkan oklusi arteri koroner anterior kiri mengarah
menyebabkan nekrosis terbatas pada dinding anterior. Sering terjadi perpanjangan ke bagian anterior
septum ventrikular dengan oklusi koroner kiri proksimal.
Dalam hati dengan dominasi koroner kanan (dengan arteri kanan yang memasok cabang turun
temurun), oklusi arteri koroner yang tepat menyebabkan infark posterior (inferior). Dengan dominasi
koroner kiri (sekitar 15% dari populasi), oklusi circumflex proksimal akan terjadi pada dinding posterior;
Dalam pola dominan yang tepat, trombus marjinal proksimal tumpul akan menyebabkan dinding infark
lateral saja, dan sirkumfleks distal adalah bejana kecil.
Variasi anatomis karena sirkulasi kolateral mikroskopis, yang tidak terbukti pada otopsi, memainkan
faktor besar dalam ukuran nekrosis dan distribusi. Pola pasokan yang tidak biasa ke dinding posterior,
seperti sampul kiri anterior descending atau arteri turun posterior yang dipasok oleh arteri marjinal
tumpul, juga dapat menyebabkan area infark yang tidak terduga sehubungan dengan segmen proksimal
yang tersumbat.
Oklusi proksimal pada tingkat arteri epikardial menghasilkan distribusi tipikal yang dimulai pada
subendokardium dan berlanjut menuju epikardium (fenomena wavefront yang disebut). Oleh karena itu,
area nekrosis atau jaringan parut dianggap memiliki "pola iskemik" jika terbesar pada endokardium,
dengan ekstensi berbentuk baji sampai ke permukaan epikardial.
Cedera iskemik, bagaimanapun, mungkin terletak di pertengahan miokardium atau bahkan
subepicardium jika tingkat oklusi koroner distal di dalam miokardium. Oleh karena itu, dalam kasus
tromboemboli dari trombi epikardial (terutama erosi plak), mungkin ada infark yang merata, sering
dikaitkan dengan trombi yang terlihat di dalam pembuluh miokard, yang tidak berpusat pada
endokardium namun terjadi di mana saja di miokardium, termasuk di daerah midepicardial dan
subepicardial.

Etiologi
Infark miokard akut (MI) diakibatkan oleh kekurangan suplai oksigen ke miokardium yang bekerja. Infark
regional adalah karena kurangnya aliran darah yang terjadi ketika arteri epikardial diblokir oleh ateroma
atau trombus, atau penghalang lainnya. Infark subendokard global terjadi bila ada kekurangan
oksigenasi meski beredar - misalnya, bila terjadi penghentian pernapasan diikuti dengan hipoksemia
berkepanjangan.
Otopsi pasien rawat inap di rumah sakit karena MI regional akut menunjukkan adanya trombus akut di
atas plak aterosklerotik di lebih dari 95% kasus ketika arteri koroner diperiksa secara hati-hati. [2] Di
jantung yang tersisa, akan ada penyakit koroner yang parah tanpa trombus.
Penyebab langka MI akut termasuk penyebab yang tidak jelas (biasanya disebabkan oleh kejang
koroner), emboli koroner (penyebab bervariasi, termasuk vegetasi katup dan tumor), pembedahan
arteri koroner spontan, anomali kongenital asal koroner, dan trombosis pada arteri koroner normal non-
aterosklerotik keadaan hiperkoagulasi).
Faktor risiko
Ada predisposisi genetik yang diketahui terhadap penyakit arteri koroner yang menyebabkan MI akut.
Secara umum, sekitar 50-85% risiko aterosklerosis koroner sekunder akibat kondisi yang diakibatkan.
Sisanya sekunder terhadap polimorfisme genetik, yang melibatkan jalur peradangan, metabolisme lipid,
koagulasi, sistem renin-angiotensin-aldosteron, dan komponen atherogenesis lainnya. [3, 4]
Epidemiologi
Infark miokard akut (MIs) umum terjadi. Di Amerika Serikat, mereka mengakibatkan rawat inap sekitar 4
pria dan 2 wanita per 1000 penduduk setiap tahunnya. [5]
Fitur Klinis
Gejala infark miokard akut (MI) adalah nyeri dada, yang dapat menyebar ke lengan atau rahang,
berkeringat, mual, dan sesak atau tekanan dada. Diagnosis ditinjau berdasarkan temuan laboratorium
nekrosis miokard, yang menyebabkan kebocoran enzim miokard, seperti troponin, ke dalam darah yang
beredar. Infark akut dibagi dengan temuan elektrokardiografi menjadi ST-elevation myocardial
infarction (STEMI) dan non ST elevation infarction (non-STEMI).
Sebuah studi kohort prospektif terhadap 6.304 pasien yang terdaftar secara berurutan dengan dugaan
sindrom koroner akut melaporkan bahwa pada pasien tanpa infark miokard saat presentasi, konsentrasi
troponin kurang dari 5 ng / L pada 2311 (61%) dari 3799 pasien, dengan nilai prediksi negatif 99 • 6%
untuk hasil utama. Studi tersebut menyimpulkan bahwa konsentrasi plasma troponin yang rendah
mengidentifikasi dua pertiga pasien yang berisiko sangat rendah terhadap kejadian kardiak dan yang
dapat dipulangkan dari rumah sakit. [6]
STEMI biasanya merupakan hasil penyumbatan arteri koroner dengan peningkatan enzim jantung dalam
serum dan pada akhirnya menghasilkan gelombang Q pada elektrokardiogram. Sebaliknya, non-STEMI,
yang tumpang tindih dengan sindrom koroner akut angina tidak stabil, menyebabkan peningkatan
sederhana enzim jantung dalam serum dan secara patologis menunjukkan daerah nekrosis kecil atau
tambal sulam. Gelombang Q tidak berkembang di non-STEMI.
Temuan Kotor
Perubahan paling awal yang dapat sangat dibedakan dalam evolusi infark miokard akut (MI) adalah
pucat miokardium, yang terlihat 12 jam atau lebih setelah timbulnya iskemia ireversibel. Deteksi bruto
infark dapat ditingkatkan dengan penggunaan larutan garam tetrazolium, yang membentuk endapan
berwarna pada bagian kotor jaringan jantung segar dengan adanya aktivitas yang dimediasi
dehidrogenase. Nekrosis miokard dapat dideteksi sejak 2-3 jam pada anjing dan pada manusia dengan
metode ini.
Pada MI yang tidak diulang, daerah yang infark ditentukan dengan baik pada 2-3 hari, dengan daerah
sentral perubahan warna kuning dikelilingi oleh tepi tipis hyperemia yang sangat vaskularisasi (lihat
gambar pertama di bawah). Dalam reperfused MI, daerah yang infarcted tampak merah karena
terperangkapnya sel darah merah dan perdarahan dari kapiler nekrotik yang pecah (lihat gambar kedua
di bawah)