Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3720_Библиотеки_им_академика_М_И_Перельмана
.pdf
150 Cardiovascular Thrombus
https://t.me/med1917
Data show that CD40L and CD40 can exert several stimuli on endothelial cells to promote the production of cytokines,
chemokines, and angiogenesis factor and mediate contact-dependent expression of MMPs in endothelial cells [45]. These
interactions through CD40/CD40L were associated with an angiogenic response in endothelial cells cultured in 3D fibrin
matrix gels, sensitive to MMP inhibition.
Proteolysis
Studies suggest that the imbalance between synthesis and degradation of collagen of the atherosclerotic plaque could
represent a key determinant of plaque disruption [46,47]. In a stable plaque the presence of interstitial forms of collagen
confers biomechanical strength to the fibrous cap and protects thrombogenic material in the core, avoiding contact with
coagulation factors in blood and preventing the activation of the coagulation cascade [48]. MMPs activated by in flammatory cells (macrophages, foam cells) localized in atherosclerotic plaques could alter and deplete fibrillar collagens from
the fibrous cap, leading to cap thinning and promoting the rupture [49e51]. Moreover, a second mechanism responsible for
this matrix reduction may also be attributed to a reduced collagen synthesis by inhibition of smooth muscle cell proliferation [52] (Fig. 10.2).
VULNERABLE PLAQUE
The term “vulnerable plaque” was used by Muller et al. to identify the main plaque features that trigger the onset of ACS
[53]. Pathology studies have suggested that a coronary atherosclerotic plaque that is prone to rupture or erosion and can
thusly cause an acute myocardial infarction is most frequently characterized by a thin cap, which separates the large lipid or
necrotic core from the coronary arterial lumen [54].
Several clinical investigations aim ed to identify the presence of atheroma with a thin fibrous cap and discover high-risk
patients who might necessitate directed treatment or specific preventative measures [55]. Studies investigating atherosclerotic lesions and these morphologic features used several imaging modalities, such as coronary computed tomography
angiography, magnetic resonance imaging, intravascular ultrasonographyevirtual histology, and optical coherence
tomography.
Plaque rupture is the main cause of luminal thrombosis in ACS [56]; specifically, the rupture of the thin fibrous cap in
vulnerable plaques could allow circulating blood to come in direct contact with the thrombogenic contents of the lipid-rich
core, inducing the rapid activation of the coagulation cascade and leading to acute thrombosis. On the other hand,
epidemiological studies reported that plaque erosion may cause about one-t hird of myocardial infarctions, especially in
young patients, smokers, and women [57,58] (Fig. 10.3).
FIGURE 10.2 Some cytokines and molecules involved in plaque progression from stable plaque to vulnerable plaque. ASK1, apoptosis signal-regulating
kinase 1; CD40L, cluster of differentiation 40 ligand; IL-1R, interleukin 1 receptor; JNK, c-Jun N-terminal kinase; Lp-PLA
phospholipase A
b-activated kinase 1; TNFR1, tumor necrosis factor receptor 1; VCAM1, vascular cellular adhesion molecule 1; VEGF, vascular endothelial growth factor.
, lipoprotein-associated
; MMPs, matrix metalloproteinases; NF-kB, nuclear factor kB; PKC-z, protein kinase C zeta; TAK1, transforming growth factor-
2
2
Acute Coronary Syndrome: Thrombotic Lesions in Patients With Unstable Angina Chapter | 10 151
https://t.me/med1917
FIGURE 10.3 Mechanisms leading to atherosclerotic coronary plaque, thrombosis, and acute coronary syndrome.
Transformation into high-risk plaque implies the modification of structural characteristics of the coronary plaque. Two
types of vascular remodeling were described in coronary occlusive stenosis: a positive remodeling, resulting in expansion
of the external elastic membrane, which initially prevents the reduction of the vessel lumen, and a negative remodeling,
associated with a constriction of the external elastic membrane, which accelerates the reduction of the vessel lumen [59].In
this scenario, experimental studies showed that negative remodeling was the most important determinant of luminal
restenosis. However, plaque morphology is not the only feature determining the transformation in unstable lesions.
Other features were probably associated with rupture in high-risk plaques. In a postmortem study, Narula et al.
evaluated high-risk plaques with similar histological characteristics, showing that ruptured plaques were significantly larger
than plaques that were not ruptu red [60]; in other postmortem studies, macrophage infiltration, microcalcifications, and an
overlying thin fibrous cap, with less collagen and fewer smooth muscle cells, were described in unstable lesions [56,61].
Motoyama et al., evaluating characteristics of atherosclerotic plaques by computed tomographic angiography, reported that
ruptured lesions had a significantly larger remodeling index, high total volume, and large necrotic cores, in comparison
with uneventful atheromas [62].
In a serial computed tomography angiography study, the authors demonstrated that vulnerable plaques with a higher
degree of progression were significantly associated with an acute cardiovascular event [63]. Specifically, unstable lesions,
which are frequently associated with the majority of acute coronary events, are lipid rich and present a thin fibrous cap;
several studies suggested that the rupture of the fibrous cap represents the main element of structural failure of most
atherosclerotic plaques leading to thrombosis [64]. Moreover, local alterations, such as biomechani cal stimuli, can irreversibly alter stable lesions and induce plaques to become unstable [65].
Studies using several invasive imaging modalities confirmed that the greatest progression of plaques and structural
alterations of necrotic cores occurred in vascular regions with a low shear stress [66]. Thus, an increase in structural stress,
during the early stages of positive remodeling, may precipitate the rupture of a plaque with risk features such as a large
necrotic core or a thin fibrous cap. What triggers the formation of a thrombus at the site of plaque erosion and a subsequent
ACS is still being investigated.
CLINICAL PRESENTATION
Ischemic symptoms dominate the clinical presentation in an ACS. Frequently patients complain of chest discomfort or
pressure, not necessarily pain, in the retrosternal area or adjacent areas with or without radiation [67]. Associated symptoms
can be subtle and are variable. They may include fatigue, nausea, vomiting, diaphoresis, dyspnea, lightheadedness, and/or
syncope. Women tend to present with atypical symptoms. Detailed history and physical assessment are very important for
patient risk stratification and accurate diagnosis. Positive risk factors that increase the probability of an ACS include male sex,
152 Cardiovascular Thrombus
https://t.me/med1917
older age, diabetes, hypertension, hyperlipidemia, tobacco abuse, peripheral arterial disease, and family history of premature
coronary artery disease. In the absence of risk factors, ACS is possible but in general less likely.
The pathophysiology behind ACS is characterized by inadequate oxygen and nutrient delivery to the myocardium
perfused by the ischemia-related artery. This is generally precipitated by partial or complete acute coronary obstruction.
Complete occlusions can persist or partially recanalize through innate anticoagulation pathways. This mechanism is not
clearly defined, as some patients may recanalize and others can present with complete obstruction precipitating a transmural infarct without any evidence of spontaneous resolution.
Typically, elevated cardiac biomarkers and abnormal ECG findings are sufficient to diagnose ACS. This, however,
needs to be interpreted in the appropriate context of events. Occasionally, patients are unable to relay an accurate history or
to describe symptoms. Elevations of cardiac biomarkers can be seen also in patients with stable obstructive coronary
lesions hindering sufficient coronary blood flow in the setting of increased demand. These increased oxygen deman d states
can be seen in anemia, sepsis, tachyarrhythmias, congestive heart failure, hypotensive and hypertensive states, and cocaine
abuse. These are the so-called myocardial infarction type 2 [2].
Patients presenting with signs and symptoms of acute heart failure, refractory angina, or ventricular arrhythmias are
considered high-risk patients and should undergo an invasive workup. They usually warrant emergent, rather than urgent,
revascularization. Further risk stratification of individual cases is warranted and is well established through various risk
scores, including but not limited to the thrombolysis in myocardial infarction (TIMI) and global registry of acute coronary
events (GRACE) scores [68,69]. These risk scores have been implicated for prediction of outcomes and short-term
mortality. Acuity and the nature of clinical presentation dictate the timing of revascularization. Coronary angiography
differentiates ACS from other acute coronary pathologies, which may be more prevalent in patients without risk factors.
The term “myocardial infarction with nonobstructive coronary arteries” has been coined for these acute coronary states.
Conditions such as coronary vasospasm, spontaneous coronary artery dissection, Takotsubo cardiomyopathy, or microvascular dysfunction that can mimic an ACS have been described [70].
NONINVASIVE DIAGNOSIS
Electrocardiogram
Obtaining and interpreting an ECG within 10 min of presentation in a patient with suspected ACS has been a quality
measure advocated for by many organizations, including the American Heart Association and the American College of
Cardiology [2]. Myocardial injury pattern on ECG is easily detectable and diagnosed by the presence of >2-mm
ST-segment elevation in two contiguous leads. Although these findings are sensitive for transmural injury, they are not
very specific, as various other myopericardial states can mimic these ECG findings. The absence of persistent ST-segment
elevation is consistent with non-ST-elevation ACS (NSTE-ACS), which can be further de fined as unstable angina or
NSTEMI. Other ECG findings seen in NSTE-ACS can be widely variable, including presence of normal or silent ECG,
diffuse T-wave inversions, or >1-mm ST-segment depression in contiguous leads as a result of subendocardial ischemia
(Fig. 10.4) [71]. Serial ECGs are very important in following the progression of ACS and to increase sensitivity for
detection of an evolving event. In general, patients with ST deviations on ECG (transient ST-segment elevations and/or
ST-segment depressions) have a poorer prognosis than patients with T-wave changes or patients with normal or unchanged
ECGs.
Biomarkers/Laboratory Testing
Cardiac biomarkers for the detection of myocardial necrosis have evolved and have become highly specific over the past
few decades. They tend to rise over a few hours and can remain elevated for up to 2 weeks. Historically, an elevated white
blood cell count and nonspeci fic but sensiti ve markers, such as lactate dehydrogenase, aspartate aminotransferase, and
creatine kinase, have been associated with myocardial injury. Contemporary assays for detection of myocyte necrosis
predominantly measure the presence of cardiac troponin, a myocardial protein, in the peripheral blood, but other assays for
high-sensitivity troponin, myoglobin, copeptin, and heart fatty acid binding protein are also in use or under investigation
[72]. A rise and fall of these biomarkers usually complements the clinical diagnosis of ACS and ECG findings [2]. In the
setting of elevated cardiac biomarkers, NSTEMI is the working diagnosis, unless persistent ST-segment elevations are
present on ECG. As the sensitivity of contemporary troponin assays increases, the likelihood of diagnosing NSTEMI has
increased while the diagnosis of unstable angina has become rarer [4]. In addition, trending these biomarkers helps in
quantifying infarct size and has been shown to predict short- and long-term prognosis [73].
Acute Coronary Syndrome: Thrombotic Lesions in Patients With Unstable Angina Chapter | 10 153
https://t.me/med1917
FIGURE 10.4 ECG of a patient who presented
with chest pain and who was found to have
ST-segment depressions in anterolateral leads
consistent with ischemia.
Noninvasive Imaging
Culprit lesions are often described as atheroma with evidence of superficial plaque erosion or plaque rupture with
superimposed thrombus, where the latter is more common. Plaque rupture portends worse long-term outcomes, including
increase in cardiac death, nonfatal myocardial infarction, unstable angina, and target lesion revascularization, which have
occurred significantly more often in patients with plaque rupture than in those with intact fibrous cap [74].
Plaque morphology, not degree of luminal loss from obstructive stenosis, has been shown to be predictive of the
likelihood of future coronary events. In fact, vulnerable lesions tend to be less obstructive because of positive vascular
remodeling. This has been described on intravascular ultrasound, and is also known as the Glagov phenomenon. Atheromatous lesions consist of inflammatory cells, usually in the form of lipid-filled macrophages, with variable degrees of
calcium deposition. Thin-capped fibroatheromas are less stable, as they tend to have a larger necrotic lipid core and
increased expression of inflammatory mediators.
In practical terms, the patient who presents to the hospital with chest pain can be subjected to noninvasive imaging
tests, which are very good at excluding an ACS caused by coronary atherosclerosis and stenosis and thus allowing for the
triage of patients who need to be admitted and of patients who can safely be discharged. However, more recent data seem
to suggest that in the absence of positive cardiac biomarkers, the deferral of noninvasive testing is reasonable in patients
with chest pain [75].
The utility of echocardiography in the emergency room for the diagnosis of patients with possible myocardial ischemia
was demonstrated in the early 1990s [76] with an absence of regional wall motion abnormalities being able to rule out an
ACS with high specificity. Later studies using myocardial perfusion and strain imaging and stress echocardiography have
confirmed the utility of echocardiography in the triage of these patients [77]. Nuclear myocardial perfusion imaging has an
excellent sensitivity and specificity for ruling out ACS [78], and this was the imaging modality that is predominantly used
in the United States for the triage of patients with suspected ACS. More recently, computed tomography angiography is
becoming more popular, because of its wide availability and excellent resolution, which enables physicians to triage
patients more rapidly and to diagnose coronary disease more accurately [79]. Finally, other imaging modalities such as
positron emission tomography with and without molecular imaging and magnetic resonance imaging [77] can also be used
to rule out or to diagnose an ACS but are not routinely used for this purpose at the moment.
INVASIVE DIAGNOSIS
As mentioned, the diagnosis of unstable angina specifically is a clinical diagnosis but there are certain invasive imaging
modalities that can con firm the diagnosis and that form the basis for choosing the optimal therapy for each patient. The
most recent guidelines from the American Heart Association/American College of Cardiology allow for two strategies to
approach the patient with definite or likely ACS without ST-segment elevation: an ischemia-driven strategy and an early
invasive strategy [80]. The invasive strategy consists of early coronary angiography of patients with ACS without ST
elevation, which has the advantage of a more definitive nature of the evaluation, the option of immediate percutaneous
revascularization, and the earlier discharge of the patient from the hospital [80].
154 Cardiovascular Thrombus
https://t.me/med1917
Coronary Angiography
Coronary angiography as part of the early invasive strategy should be considered in patients with negative cardiac enzymes
and no ECG changes suggestive of ischemia when the pretest probability of finding significant obstructive coronary disease
potentially causing the symptoms is high. This can be due to a clinical history consistent with unstable angina
(e.g., crescendo angina or new onset angina) or due to high-risk scores such as the TIMI risk score for unstable angina and
NSTEMI [68]. However, because of the high prevalence of coronary disease and because of the lack of an independent test
there may be patients who undergo coronary angiography and who have obstructive coronary disease but who have
symptoms that were not caused by the coronary disease. Unfortunately, as of this writing there is no way determine this.
Findings on coronary angiography in patients with unstable angina/NSTE-ACS include normal coronary arteries,
nonobstructive coronary disease, and obstructive coronary disease in one single vessel or in multiple vessels [14]. It is not
quite usual to find a completely occluded coronary vessel in these patients, although it is sometimes encountered in patients
who have had coronary bypass grafting surgery in the past and in whom the ACS is caused by the occlusion of a bypass
graft while the native artery still has antegrade flow or by occlusion of a severe stenosis that was already collateralized [81].
Sometimes the coronary angiogram can provide evidence of a thrombus or a ruptured atherosclerotic plaque [81e83] but
other times it is difficult to identify the culprit lesion [84]. However, in most patients with unstable angina, asymmetric
stenoses with irregular borders and haziness are more frequent than smooth symmetric stenoses [85] on coronary
angiography.
Coronary angiography serves not only as a diagnostic tool but also as critical decision-making point regarding the
therapeutic options available to the patient. While coronary angiography is not the best tool for detailed diagnosis of the
thrombotic process superimposed on a ruptured or eroded plaque, it is the cornerstone for therapeutic decision-making.
The tests that are better at providing a detailed understanding of the severity of ischemia and the pathophysiology of the
ACS as a manifestation of a throm bus occluding the coronary vessel are fractional flow reserve and intravascular coronary
imaging, respectively.
Fractional Flow Reserve
Fractional flow reserve is a measurement that gives information about the physiologic significance of a given coronary
stenosis and that is used mainly as a decision tool for revascularization versus medical therapy. Because the measurement
of fractional flow reserve is predicated on an intact microvascular bed, the test is not recommended in interrogating the
culprit vessel in acute STEMI. However, in NSTEMI the microembolization and disruption of the distal microvascular bed
are less severe and, in fact, similar to those in patients with stable ischemic heart disease [86]. Even though there are some
studies that seem to support the validity of fractional flow reserve in the culprit vessel of patients with unstable angina/
NSTEMI [87,88], the data are not nearly as robust as the data for pati ents with stable ischemic heart disease, and caution is
warranted. Nevertheless, fractional flow reserve remains an invaluable tool to assess the diagnosis and the prognosis of
patients with coronary atherosclerosis who have had or are at risk of developing an ACS [89].
Intravascular Ultrasound, Optical Coherence Tomography, and Coronary Angioscopy
Intracoronary imaging techniques like intravascular ultrasound, optical coherence tomography, and coronary angioscopy
provide the best information about the culprit lesion and the potential cause of an ACS.
Intravascular ultrasound is an imaging method that has proved very useful in characterizing the coronary atherosclerotic
plaque in patients with stable and unstable coronary artery disease. Based on the premise that plaque stability is determined
by its composition, plaque areas that were characterized as fibrous and fibrolipidic, calcified, and calcified necrotic were
mapped with the aid of intravascular ultrasound [90]. On the ultrasound image, these areas largely corresponded to
homoechoic, hypoechoic, and hyperechoic areas, respectively, and provided a way of in vivo analysis of coronary plaques.
These findings were confirmed with findings from directional atherectomy in vivo correlations. The unstable plaque was
found to have more often a larger lipid core and a thin cap, as well as thrombus and rupture, compared with the stable
plaque [91]. Moreover, intravascular ultrasound was shown to be a method that can help predict major adverse cardiac
events in patients with unstable angina [92] . Specifically, adaptive vessel remodeling and plaque area stenosis severity
were associated with major adverse cardiac events. More recently, virtual histology, which is derived from coronary
intravascular images, is becoming a tool used for better understanding of and characterizing the vulnerable plaque [93].
Optical coherence tomography is another intravascular imaging modality that can provide information about plaque
architecture and volume as well as vessel remodeling in patients with ACS [94]. The advantage of optical coherence
Acute Coronary Syndrome: Thrombotic Lesions in Patients With Unstable Angina Chapter | 10 155
https://t.me/med1917
tomography is the great resolution that it provi des, which allows the evaluation of details such as fibrous cap thickness that
are not available with other methods like intravascular ultrasound [95]. Both intravascular ultrasound and optical coherence
tomography have contributed significantly to our understanding of the pathogenesis of the vulnerable plaque and substrate
for thrombus formation in ACS [93].
Finally, the feasibility of coronary angioscopy, which allows the direct visualization of the ruptured atherosclerotic
plaques and the overlying thrombi, including the different iation of red (recent) thrombi and gray-white (older) thrombi in
patients with ACS with and without ST-segment elevation, was demonstrated by Mizuno and colleagues [96]. This method
provides information about the intraluminal surface of the plaque and about the presence or absence of thrombus. More
recent developments of the technique have allowed fluorescent dye staining of different atheroma components such as
apolipoprotein B in coronary plaques [97] but, by and large, the technique remains a research tool.
TREATMENT
Medical Therapy
Treatment of patients with unstable angina and NSTEMI consists of admission to the hospital, usually to a telemetry
or stepdown unit, with the goals to reli eve ischemia and to prevent or limit myocardial infarction, arrhythmia, and
death [80].
Treatment consists of medical therapy with antithrombotic agents, antiplatelet agents, statins, and beta blockers and
other medications as needed as well as revascularization, especially in high-risk patients. The current American Heart
Association/American College of Cardiology guidelines and European Society of Cardiology guidelines provide detailed
recommendations regarding the management of patients with ACS without ST-segment elevation [80,98].
Antithrombotic Agents
The use of parenteral antithrombotic agents is a corner stone of medical therapy in patients with definite or likely unstable
angina and ACS without ST-segment elevation. The recommended agents are low-molecular-weight and unfractionated
heparin, bivalirudin (for patients undergoing invasive strategy only), and fondaparinux. All of these agents have class I
recommendations based on a multitude of trials showing better outcomes if patients with ACS are treated with anticoagulants [99e101]. In general, the recommendation is to give the anticoagulants for 48 h or until percutaneous coronary
intervention (PCI) is performed, highlighting the importance of treating the thrombotic substrate and letting the vulnerable
plaque “cool down” to avoid recurrences, especially in the patients treated with an ischemia-driven strategy. Treatment
with fibrinolytic agents is contraindicated in patients with unstable angina or NSTEMI as it may be more harmful than
beneficial [102].
Antiplatelet Agents
Antiplatelet agents are another cornerstone of therapy in patients with NSTE-ACS and they can be broadly classified into
three categories: aspirin, P2 Y
Aspirin is the mainstay of antiplatelet therapy in these patients, and its beneficial effects were recognized relatively
early [103] compared with the other agents. Aspirin should be started as soon as possible in patients with NSTE-ACS and
continued indefinitely.
As of this writing there are four available P2Y
only the last three are routinely used in practice. The guidelines recommend adding clopidogrel to aspirin for 12 months in
patients with likely or definite NSTE-ACS treated medically and either ticagrelor or clopidogrel in patients treated with an
invasive strategy [80,98]. Because of a lack of data, prasugrel is not recommended as an upfront P2Y
patients but is recommended in patients undergoing PCI with stenting in the setting of an ACS without ST-segment
elevation. Gl ycoprotein IIb/IIIa inhibitors are recommended in patients with high-risk features such as positive troponins, and the preferred upstream agents are tirofiban and eptifibatide [104,105]. The third agent, abciximab, is recommended only in patients undergoing PCI.
In addition to the above therapies, the guidelines also recommend oxygen, nitrates, analgesics, calcium channel
blockers, and angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers for symptom control and risk
factor control, respectively. More recent ly high-intensity statin therapy [106] has also become a staple in the pharmacologic armamentarium for treating patients with NSTE-ACS.
inhibitors, and glycoprotein IIb/IIIa inhibitors.
12
inhibitors: ticlopidine, clopidogrel, prasugrel, and ticagrelor. However,
12
inhibitor in these
12
156 Cardiovascular Thrombus
https://t.me/med1917
Revascularization
The invasive strategy of management for patients with NSTE-ACS consists of obtaining an (invasive) coronary angiography routinely in the first 24e72 h after hospital admission, in contrast to the ischemia-driven strategy, in which only
patients with hemodynamic instability, with refractory angina, or with other high-risk features are referred for coronary
angiography. In general, after coronary angiography at least 50% of patients will get revascularized. The main advantages
of coronary angiography is that it provides a diagnosis of epicardial coronary disease, aides in patient risk stratification, and
helps identify the culprit lesion(s) while establishing the indication and the suitability for coronary revascularization. The
debate about the optimal management strategy of patients with NSTE-ACS is ongoing and different studies and metaanalyses have provided mixed results [107,108]. However, there is consensus that a routine invasive strategy will
benefit most of the patients who are at high risk and that the main benefit is in a reduction of recurrent myocardial
infarction and angina.
The type of revascularization (i.e., PCI vs. coronary artery bypass graft surgery) is a matter of resources available,
suitability of the coronary anatomy for either procedure, patient comorbidities, longer term health goals, and patient
preferences. The guidelines recommend a “heart team approach” to the decision-making process, taking into account the
patient’s SYNTAX [109] and STS scores, especially in the case of patients with left main trunk stenosis or patients with
multivessel disease [98]. About 1 in 10 patients with ACS without ST elevation will have nonobstructive coronary artery
disease on coronary angiography [110].
PCI is the preferred procedure in patients with single-vessel or two-vessel coronary disease, especially when the
proximal segment of the left anterior descending artery is not involved (Fig. 10.5). Despite providing detailed information
about the coronary anatomy, coronary angiography has limitations regarding identification of the culprit lesion [84], but,
while previous guidelines discouraged treatment of nonculprit lesions, this is now viewed as acceptable in the most recent
guidelines [80,98]. Because of the thrombotic pathophysiologic substrate of ACS, antiplatelet and anticoagulant therapy
during percutaneous intervention in these patients is especially important, and American Heart Association/American
College of Cardiology guidelines provide specific recommendations for drugs used for this purpose [80]. Specifically, two
antiplatelet agents, prasugrel and cangrelor, can also be used for patients undergoing percutaneous revascularization and all
three glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, and tirofiban) are recommended in patients with high risk
features. Discontinuing anticoagulant therapy after intervention is a class I indication.
Coronary bypass surgery is the preferred revascularization method in patients with complex anatomy as reflected in a
high SYNTAX score, patients with diabetes, and patients without comorbidities that would put them at high risk for a
protracted postoperative hospital stay. Because the patients with ACS without ST elevation are at high risk of recurrent
ischemia, the guidelines recommend the continuation of aspirin therapy perioperatively. Therapy with clopidogrel or
ticagrelor should be discontinued 24 h before urgent coronary bypass surgery and 7 and 5 days before nonurgent (elective)
coronary bypass surgery, respec tively, although it is reasonable to perform surgery earlier in certain cases.
LONG-TERM THERAPY AND OUTCOMES
Patients with unstable angina and NSTEMI represent a high-risk population, and therapy is aimed at alleviating symptoms,
restoring their state of health, and lowering the risk of recurrence. The patients with protracted clinical course, leftventricular dysfunction, severity of coronary artery disease, atrial fibrillation, incomplete revascularization, and multiple
comorbidities have a higher long-term risk and warrant aggressive medical therapy and close follow-up. In general, after an
NSTE-ACS, the 30-day mortality risk is approximately 2.5% [110] and the 1-year mortality risk is 5%e10%.
Dual antiplatelet therapy for at least 12 months followed by long-term therapy with aspirin, high-dose statin therapy,
and therapy for the control of hypertensio n and dia bete s, if pr esen t, should be routinely incorporated in the therapy
regimen of these patients. Another measure that is probably underutilized and that has been shown to benefitthese
patients is cardiopulmonary rehabilitation [111], which receives a class I recommendation in the current guidelines [80].
Despite the improved outcomes with dual antiplatelet therapy, routi ne platelet activity testing and genotyping are not
recommended because strategies of adjusting antiplatelet therapy based on this infor ma tion co uld n ot sho w be nefit
[112,113].
SUMMARY
In conclusion, unstable angina is a clinical syndrome caused by an obstructive thrombotic lesion in the coronary tree that
impairs flow to the myocardium. It is generally regarded as a precursor to a myocardial infarction as it has a similar
Acute Coronary Syndrome: Thrombotic Lesions in Patients With Unstable Angina Chapter | 10 157
https://t.me/med1917
(A)
(C)
(B)
(D)
(E)
FIGURE 10.5 (A) A 59-year-old man who presented with acute coronary syndrome and had a history of coronary artery bypass surgery 16 years prior
was found to have stenosis and thrombus in his saphenous vein graft to the obtuse marginal (arrow). (B) He underwent successful percutaneous coronary
intervention and stenting with a bare metal stent with an excellent angiographic result. Two years later he underwent coronary angiography for recurrent
chest pain. The stent was almost completely occluded and was treated successfully with drug-eluting stents. (C) A 66-year-old man presented with
stuttering chest pain for several days and underwent coronary angiography, which showed stenosis and thrombus in the left circumflex system (arrow).
(D) He underwent successful intervention with placement of a drug-eluting stent and the symptoms subsided. (E) A 62-year-old man presented with acute
coronary syndrome and had a history of coronary artery bypass surgery 20 years prior. He underwent coronary angiography, which showed thrombus
(arrowhead) and sequential stenoses (arrows) in the saphenous vein graft to the right posterior descending artery. (F) He underwent thrombectomy with
the AngioJet device and successful placement of two drug-eluting stents. Four years later, on repeat coronary angiography, the stents were patent.
(F)
pathology and pathophysiology. The accepted predominant mechanisms, as of this writing, that lead to the formation of a
thrombotic lesion and a subsequent ACS are rupture of a vulnerable plaque and plaque erosion. This is the result of
complex interrelationships between inflammation, thrombosis, and proteolysis probably triggered by the subendothelial
deposit of oxidized low-density lipoproteins. The resulting changes are serious and require inpatient treatment with
158 Cardiovascular Thrombus
https://t.me/med1917
antiplatelet agents and anticoagulants aimed at controlling the thrombotic process. Medical therapy in the acute phase is
followed by revascularization, especially in high-risk patients and then by risk factor control to avoid recurrence. However,
despite significant progress in our understanding and treatment of unstable angina, there is still a way to go in the
prevention and treatment of this prevalent manifestation of coronary artery disease.
REFERENCES
[1] Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey Jr DE, et al. 2012 ACCF/AHA focused update incorporated into the
ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the
American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013;127(23):e663e828.
[2] Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Circulation
2012;126(16):2020e35.
[3] Fowler NO. “Preinfarctional” angina. A need for an objective definition and for a controlled clinical trial of its management. Circulation
1971;44(5):755e8.
[4] Braunwald E, Morrow DA. Unstable angina: is it time for a requiem? Circulation 2013;127(24):2452e7.
[5] Melki D, Lugnegard J, Alfredsson J, Lind S, Eggers KM, Lindahl B, et al. Implications of introducing high-sensitivity cardiac troponin T into
clinical practice: data from the SWEDEHEART Registry. J Am Coll Cardiol 2015;65(16):1655e64.
[6] Meier P, Lansky AJ, Baumbach A. Almanac 2013: acute coronary syndromes. Heart 2013;99(20):1488e93.
[7] Wachira JK, Stys TP. Cardiovascular disease and bridging the diagnostic gap. S D Med 2013;66(9):366e9.
[8] Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statisticse2012 update: a report from the
American Heart Association. Circulation 2012;125(1):e2e220.
[9] Yeh RW, Sidney S, Chandra M, Sorel M, Selby JV, Go AS. Population trends in the incidence and outcomes of acute myocardial infarction.
N Engl J Med 2010;362(23):2155e65.
[10] Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Executive summary: heart disease and stroke Statisticse2016
update: a report from the American Heart Association. Circulation 2016;133(4):447e54.
[11] Pitts SR, Niska RW, Xu J, Burt CW. National Hospital Ambulatory Medical Care Survey: 2006 emergency department summary. Natl Health Stat
Rep 2008;(7):1e38.
[12] Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population.
Am Heart J 1986;111(2):383e90.
[13] Gordon T, Kannel WB, Hjortland MC, McNamara PM. Menopause and coronary heart disease. The Framingham Study. Ann Intern Med
1978;89(2):157e61.
[14] Akhter N, Milford-Beland S, Roe MT, Piana RN, Kao J, Shroff A. Gender differences among patients with acute coronary syndromes undergoing
percutaneous coronary intervention in the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR). Am Heart J
2009;157(1):141e8.
[15] Watkins S, Thiemann D, Coresh J, Powe N, Folsom AR, Rosamond W. Fourteen-year (1987 to 2000) trends in the attack rates of, therapy for, and
mortality from non-ST-elevation acute coronary syndromes in four United States communities. Am J Cardiol 2005;96(10):1349e55.
[16] Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011;473(7347):317e25.
[17] Vischer UM. von Willebrand factor, endothelial dysfunction, and cardiovascular disease. J Thromb Haemost 2006;4(6):1186e93.
[18] Knowles JW, Wang H, Itakura H, Southwick A, Myers RM, Iribarren C, et al. Association of polymorphisms in platelet and hemostasis system
genes with acute myocardial infarction. Am Heart J 2007;154(6):1052e8.
[19] Empana JP, Canoui-Poitrine F, Luc G, Juhan-Vague I, Morange P, Arveiler D, et al. Contribution of novel biomarkers to incident stable angina and
acute coronary syndrome: the PRIME Study. Eur Heart J 2008;29(16):1966e74.
[20] Nieswandt B, Pleines I, Bender M. Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke. J Thromb Haemost
2011;9(Suppl 1):92e104.
[21] McGregor L, Martin J, McGregor JL. Platelet-leukocyte aggregates and derived microparticles in inflammation, vascular remodelling and
thrombosis. Front Biosci 2006;11:830e7.
[22] Trip MD, Cats VM, van Capelle FJ, Vreeken J. Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med
1990;322(22):1549e54.
[23] Parodi G, Marcucci R, Valenti R, Gori AM, Migliorini A, Giusti B, et al. High residual platelet reactivity after clopidogrel loading and long-term
cardiovascular events among patients with acute coronary syndromes undergoing PCI. J Am Med Assoc 2011;306(11):1215e
[24] Tantry US, Bliden KP, Suarez TA, Kreutz RP, Dichiara J, Gurbel PA. Hypercoagulability, platelet function, inflammation and coronary artery
disease acuity: results of the Thrombotic RIsk Progression (TRIP) study. Platelets 2010;21(5):360e7.
[25] Wada R, Rohatagi S, Small D, Winters KJ, Salazar DE. Correlation of inhibition of platelet aggregation with cardiovascular and bleeding outcomes
in acute coronary syndromes. J Clin Pharmacol 2010;50(8):904e13.
[26] Shantsila E, Lip GY. Monocytes in acute coronary syndromes. Arterioscler Thromb Vasc Biol 2009;29(10):1433e8.
[27] Lavi S, Herrmann J, Lavi R, McConnell JP, Lerman LO, Lerman A. Role of lipoprotein-associated phospholipase A2 in atherosclerosis. Curr
Atheroscl Rep 2008;10(3):230e5.
23.
Acute Coronary Syndrome: Thrombotic Lesions in Patients With Unstable Angina Chapter | 10 159
https://t.me/med1917
[28] Teng Z, Brown AJ, Calvert PA, Parker RA, Obaid DR, Huang Y, et al. Coronary plaque structural stress is associated with plaque composition and
subtype and higher in acute coronary syndrome: the BEACON I (Biomechanical Evaluation of Atheromatous Coronary Arteries) study. Circ
Cardiovasc Imaging 2014;7(3):461e70.
[29] Ohayon J, Finet G, Gharib AM, Herzka DA, Tracqui P, Heroux J, et al. Necrotic core thickness and positive arterial remodeling index: emergent
biomechanical factors for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol 2008;295(2):H717e27.
[30] Richardson PD, Davies MJ, Born GV. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques.
Lancet 1989;2(8669):941e4.
[31] Wanjare M, Agarwal N, Gerecht S. Biomechanical strain induces elastin and collagen production in human pluripotent stem cell-derived vascular
smooth muscle cells. Am J Physiol Cell Physiol 2015;309(4):C271e81.
[32] Caro CG, Fitz-Gerald JM, Schroter RC. Arterial wall shear and distribution of early atheroma in man. Nature 1969;223(5211):1159e60.
[33] Davies PF, Civelek M, Fang Y, Fleming I. The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress
regions in vivo. Cardiovasc Res 2013;99(2):315e27.
[34] White SJ, Hayes EM, Lehoux S, Jeremy JY, Horrevoets AJ, Newby AC. Characterization of the differential response of endothelial cells exposed
to normal and elevated laminar shear stress. J Cell Physiol 2011;226(11):2841e8.
[35] Chaudhury H, Zakkar M, Boyle J, Cuhlmann S, van der Heiden K, Luong le A, et al. c-Jun N-terminal kinase primes endothelial cells at athe-
roprone sites for apoptosis. Arterioscler Thromb Vasc Biol 2010;30(3):546e53.
[36] Magid R, Davies PF. Endothelial protein kinase C isoform identity and differential activity of PKCzeta in an athero-susceptible region of porcine
aorta. Circ Res 2005;97(5):443e9.
[37] Warboys CM, de Luca A, Amini N, Luong L, Duckles H, Hsiao S, et al. Disturbed flow promotes endothelial senescence via a p53-dependent
pathway. Arterioscler Thromb Vasc Biol 2014;34(5):985e95.
[38] Sheikh S, Rainger GE, Gale Z, Rahman M, Nash GB. Exposure to fluid shear stress modulates the ability of endothelial cells to recruit neutrophils
in response to tumor necrosis factor-alpha: a basis for local variations in vascular sensitivity to inflammation. Blood 2003;102(8):2828e34.
[39] Cuhlmann S, Van der Heiden K, Saliba D, Tremoleda JL, Khalil M, Zakkar M, et al. Disturbed blood flow induces RelA expression via c-Jun
N-terminal kinase 1: a novel mode of NF-kappaB regulation that promotes arterial inflammation. Circ Res 2011;108(8):950e9.
[40] Papafaklis MI, Takahashi S, Antoniadis AP, Coskun AU, Tsuda M, Mizuno S, et al. Effect of the local hemodynamic environment on the de novo
development and progression of eccentric coronary atherosclerosis in humans: insights from PREDICTION. Atherosclerosis 2015;240(1):205e11.
[41] Samady H, Eshtehardi P, McDaniel MC, Suo J, Dhawan SS, Maynard C, et al. Coronary artery wall shear stress is associated with progression and
transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation 2011;124(7):779e88.
[42] Hansson GK. Immune mechanisms in atherosclerosis. Arterioscler Thromb Vasc Biol 2001;21(12):1876e90.
[43] Barger AC, Beeuwkes 3rd R, Lainey LL, Silverman KJ. Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible
role in the pathophysiology of atherosclerosis. N Engl J Med 1984;310(3):175e7.
[44] Fleiner M, Kummer M, Mirlacher M, Sauter G, Cathomas G, Krapf R, et al. Arterial neovascularization and inflammation in vulnerable patients:
early and late signs of symptomatic atherosclerosis. Circulation 2004;110(18):2843e50.
[45] Mach F, Schonbeck U, Fabunmi RP, Murphy C, Atkinson E, Bonnefoy JY, et al. T lymphocytes induce endothelial cell matrix metalloproteinase
expression by a CD40L-dependent mechanism: implications for tubule formation. Am J Pathol 1999;154(1):229e38.
[46] Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res 2014;114(12):1852e66.
[47] Fukumoto Y, Libby P, Rabkin E, Hill CC, Enomoto M, Hirouchi Y, et al. Statins alter smooth muscle cell accumulation and collagen content in
established atheroma of watanabe heritable hyperlipidemic rabbits. Circulation 2001;103(7):993e9.
[48] Libby P, Aikawa M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med 2002;8(11):1257e62.
[49] Austin KM, Covic L, Kuliopulos A. Matrix metalloproteases and PAR1 activation. Blood 2013;121(3):431
[50] Jovin IS, Muller-Berghaus G. Interrelationships between the fibrinolytic system and lipoproteins in the pathogenesis of coronary atherosclerosis.
Atherosclerosis 2004;174(2):225e33.
[51] Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med 2013;368(21):2004e13.
[52] Fang L, Moore XL, Chan W, White DA, Chin-Dusting J, Dart AM. Decreased fibrocyte number is associated with atherosclerotic plaque instability
in man. Cardiovasc Res 2012;95(1):124e33.
[53] Muller JE, Tofler GH, Stone PH. Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 1989;79(4):733e43.
[54] Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006;47(8 Suppl):C13e8.
[55] Narula J, Garg P, Achenbach S, Motoyama S, Virmani R, Strauss HW. Arithmetic of vulnerable plaques for noninvasive imaging. Nat Clin Pract
Cardiovasc Med 2008;5(Suppl 2):S2e10.
[56] Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med 1984;310(18):1137e40.
[57] Arbustini E, Dal Bello B, Morbini P, Burke AP, Bocciarelli M, Specchia G, et al. Plaque erosion is a major substrate for coronary thrombosis in
acute myocardial infarction. Heart 1999;82(3):269e72.
[58] Farb A, Burke AP, Tang AL, Liang TY, Mannan P, Smialek J, et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of
coronary thrombosis in sudden coronary death. Circulation 1996;93(7):1354e63.
[59] Renker M, Baumann S, Rier J, Ebersberger U, Fuller SR, Batalis NI, et al. Imaging coronary artery disease and the myocardial ischemic cascade:
clinical principles and scope. Radiol Clin North Am 2015;53(2):261e9.
[60] Narula J, Nakano M, Virmani R, Kolodgie FD, Petersen R, Newcomb R, et al. Histopathologic characteristics of atherosclerotic coronary disease
and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J Am Coll Cardiol 2013;61(10):1041e51.
e9.
Соседние файлы в папке Библиотека им академика М.И. Перельмана