UA /NSTEMI is defined as the non-overlapped ST coronary syndrome. Intravascular, angiographic and angiographic ultrasound studies suggest that UA / NSTEMI clinical pictures are caused by the presence of complicated atherosclerotic plaques that trigger a cascade of events with consequent reduction of coronary flow. Mortality during UA / NSTEMI is mainly due to sudden death or the development of a new or recurrent myocardial infarction. The formulation of a certain diagnosis and the possibility of optimal management of these patients are based on the initial information collected at the onset of symptoms, updated with the data acquired during the evolution of the clinical picture.
The correct diagnosis of acute coronary syndromeNSTEMI or STEMI is important for the treatment of the case. In fact, the initial management of the patient with UA / NSTEMI differs from the treatment reserved for patients with STEMI, based on an early reperfusion therapy (see Myocardial infarction stemi). The patient with symptoms suggestive of acute coronary syndrome should be placed in an environment that offers the possibility of continuous electrocardiographic (ECG) and defibrillation monitoring and where a 12-lead ECG can be obtained quickly and accurately interpreted within 10 minutes. The main priority is to identify patients with STEMI, which should be considered for immediate reperfusion therapy.
Each patient should have a temporary diagnosis of inclusion
or exclusion of:
(1) acute coronary syndrome (ACS), which can be classified as STEMI, NSTEMI or
unstable angina (UA);
(2) a cardiovascular condition other than ACS;
(3) a specific non-cardiac disorder (eg, esophageal spasm (see Manometry);
(4) an indefinite non-cardiac condition.
This first examination is important for risk stratification and treatment of
life-threatening events!
The UA and NSTEMI are characterized by the imbalance between myocardial oxygen supply and demand.
The most common cause of UA / NSTEMI is the reduction of myocardial perfusion due to the narrowing of the coronary arterial lumen caused by a non-occlusive thrombus that develops following rupture or erosion of an atherothrombotic plaque. In general, the thrombus is not occlusive and, in most patients, the presence of markers of myocardial damage in the circulation is due to microemboli of platelet aggregates or fragments that have detached from the complicated plaque. Secondly, but not less frequently, a dynamic obstruction may occur following an acute and focal spasm of an epicardial coronary artery, such as Prinzmetal's angina or variant angina. Thirdly, the clinical picture of UA / NSTEMI can be caused by the presence of a thrombus associated with coronary spasm. Particularly in subjects with progressive atherosclerotic disease or with restenosis after PCI (coronary angiography, see the treatment of infarction Myocardial infarction stemi). Regardless of the cause, the UA / NSTEMI framework is characterized by the presence of vascular inflammation, which seems to play a decisive role in plaque rupture. The clinical picture of secondary UA / NSTEMI is due to the presence of extrinsic causes in the coronary circulation. These patients have an underlying coronary atherosclerotic narrowing that limits myocardial perfusion; they also often have a previous chronic stable angina. UA and NSTEMI occur following a sudden increase in myocardial oxygen demand (eg, fever, tachycardia), reduction of myocardial blood flow (eg, hypotension), or decreased myocardial oxygen distribution (for eg, severe anemia).
There are three main manifestations of UA and NSTEMI:
(see angina pectoris)
(1) angina at rest;
(2) severe angina of new onset;
(3) angina in crescendo.
The diagnostic criteria of UA / NSTEMI are based on the duration and intensity
of angina evaluated according to the Canadian Cardiovascular Society
classification. The definition of three specific forms of UA / NSTEMI is useful
because the pathophysiology, prognosis and treatment are different. The new
onset forms resulting from the development of an unstable coronary plaque are
the most disruptive for acute coronary syndrome with STEMI described above.
Other scenarios include UA / NSTEMI within 6 months after PCI (coronarography
and angioplasty), almost invariably caused by restenosis. Intravenous
nitroglycerin represents effective therapy; it is usually used to repeat the
PCI. UA and NSTEMI in a patient with prior coronary artery bypass often involve
advanced atherothrombosis of venous grafts and a low probability of long-term
symptomatology compared to other patients with UA. "Non-specific" symptoms of
ACS include: acute dyspnea, epigastralgia, atypical chest pain per seat,
agitation, altered state of consciousness, marked asthenia, syncope. These
symptoms are more common in women, the elderly, and patients with long-standing
diabetes mellitus and are associated with a higher risk of death and major
complications.)
Over the last few years, a number of mechanical, cellular and molecular factors have been identified that contribute to plaque rupture (cf. atheromasic plaque). Most of the times, plaque rupture occurs at the edge ("shoulder region") of the plate, ie in the region of contact ("shoulder") between the plate and the wall of the adjacent vessel; this area, in fact, is rich in inflammatory cells and is also more subject to the forces of stress linked to the flow (tangential stress, shear stress). The plaque that tends to break (plaque at high risk of rupture or "vulnerable") is characterized by a thin fibrous capsule and a high lipid content, which influence the biomechanical properties of the plaque itself, increasing the possibility of breakage. In contrast, fibrosis and calcification appear to decrease the risk of rupture. Erosion gives rise less frequently to a clinical picture of ACS and usually occurs centrally through a thinned cap rather than at the shoulders of the plaque. Erosion seems to be more common among women smokers, while plaque rupture occurs more frequently in dyslipidemic men.
The inflammatory process plays a central role in the genesis of plaque and ACS rupture. Macrophages and T lymphocytes accumulate within the atherosclerotic plaque as a result of the expression of adhesion molecules on monocytes, endothelial cells and leukocytes; furthermore, the release of proinflammatory cytokines and chemokines (such as monocyte-chemo-1 protein-1) promotes the accumulation of other inflammatory cells in the plaque. Matrix metalloproteinases - which include collagenase and gelatinase - are released from macrophages and degrade collagen which provides resistance to the fibrous cap. Tissue metalloproteinase tissue inhibitors are normally expressed by vascular smooth muscle cells. However. at the vulnerable area of the fibrous cap, macrophages predominate, while smooth muscle cells are scarce, creating an imbalance between the enzymes responsible for degradation of the cell matrix and their inhibitors. These findings indicate that an inflammatory stimulus causes a biochemical storm "within the high-risk plaque, leading to rupture of its fibrous cap. Currently it is believed that inflammation, at least in some of the patients with UA / NSTEMI, may be a very It has been shown that in patients with unstable angina there is widespread neutrophil activation in the coronary tree, even distance from the stenotic lesion.It is believed that the clinical picture of the expression such phenomenon includes the presence of complex coronary plaques, multiple and simultaneous at the onset of symptoms in some patients with UA / NSTEMI.
Although the stable plaques may be associated with a noticeable narrowing of the
vascular lumen, they are characterized by a thick fibrous cap, a low lipid
content and inflammatory cells. In contrast, unstable plaques are characterized
by a rich lipid core and a thin fibrous cap. The inflammatory cells, accumulated
or level of the edge of the plate, the "shoulder region", which is the region
most exposed to the stresses of the tangential stress, contribute to the plaque
rupture and to the consequent thrombotic phenomena. In human atherosclerotic
lesions, germs such as Chlamydia pneumoniae, Helicobacter pylori, and antibody
movements against them have been identified. There is a correlation between
cardiovascular risk factors, endothelium dysfunction, inflammation and acute
coronary syndromes. Many proinfiommotor atherogenic factors can cause
endothelium dysfunction and, consequently, endothelial cells increase the
expression of adhesion molecules. ACE, angiotensin converting enzyme; CNP,
C-type natriuretic pepfide; ICAM, molecule of intracellular adhesion; MCP-1,
monocytic chemiotactic protein-1; NFκB, kappa-B nucleus factor; PDGF, a growth
factor derived from platelets; PGl2, prostagland 12; TGF, transformative growth
factor: VCAM. adhesion molecule of vascular cells. The stimulus that activates
the process of acute inflammation in the AU has not yet been clearly defined.
Atherothrombosis itself, as defined by the hypothesis of "damage response", is a
chronic low-grade inflammation condition. There are differing opinions about
whether infectious agents can play a primary role in both atherothrombosis and
in the transformation of a stable CAD into an unstable form.
Activation and platelet aggregation at the thrombogenic plaque rupture area play
an important role in the pathogenesis of AU / NSTEMI. In fact, it has been shown
that the thrombotic process that occurs at an arterial level differs from that
at a venous level, due to the crucial role played by platelet activation. When
the platelets are activated by collagen, adrenaline, adenosine diphosphate (ADP)
and thrombin, they undergo a structural change and release the substances
contained in the α granules, including those with a vasoconstrictive action,
such as the thromboxane A2 and serotonin and others with prothrombotic action
such as fibrinogen and von Willebrand factor. Furthermore, platelet activation
causes an increase in their surface of the expression and binding affinity of
the GPIIb / IIIa receptors, whose binding with the fibrinogen with the von
Willebrand factor leads to platelet aggregation. Activated platelets also
release the soluble factor CD40 ligand (CD40L), which appears to play an
important role as an immunomodulator and proinflammatory molecule, acting as a
link between the activated platelets and the inflammatory process. Platelet
activation and leukocytes interact in the acute phase of the AU / NSTEMI
facilitating the deposition of the platelet thrombus. The interaction between
platelets and activated leukocytes stimulates the coagulation system. The
monocytes release the tissue factor (tissue factor), a small glycoprotein that
triggers the extrinsic coagulation cascade, leading to an increase in thrombin
generation. Tissue factor is also present in the lipid core of atherothrombotic
plaques and is probably one of the main determinants of the thrombogenicity of
broken plaques. The tissue factor initiates the extrinsic coagulation cascade,
activating factor X in factor Xa, which in turn is able to transform prothrombin
into thrombin. Using the phospholipids from the activated platelet membrane,
thrombin catalyzes the conversion of fibrinogen into fibrin, favoring the
formation of fibrin-platelet clots that impede coronary flow in the ACS. The
emboli deriving from platelet thrombus or plaque material at the site of rupture
can cause an obstruction of the microcirculation and initiate a cascade of
events that include local inflammatory processes, tissue damage,
vasoconstriction, recall and aggregation of leukocytes and platelets. All of
these factors contribute to aggravate the patient's prognosis with UA / NSTEMI
and may become a target of drug therapy.