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PRINCIPLES OF MODERN STUDY OF ISCHEMIC HEART DISEASE
Haydarov Navro’zbek Furqat o’g’li
Asian International University, Bukhara, Uzbekistan
https://doi.org/10.5281/zenodo.15023250
Abstract.
Ischemic Heart Disease (IHD), also known as Coronary Artery Disease (CAD),
is a leading cause of morbidity and mortality worldwide. It occurs due to atherosclerosis, a
condition characterized by the buildup of plaque within the coronary arteries, leading to
reduced blood flow to the myocardium. The clinical manifestations of IHD range from
asymptomatic cases to angina pectoris, myocardial infarction, heart failure, and sudden cardiac
death. Risk factors include hypertension, diabetes, dyslipidemia, smoking, obesity, and a
sedentary lifestyle.
Diagnosis is based on clinical evaluation, electrocardiography (ECG), cardiac
biomarkers, echocardiography, stress testing, and coronary angiography. Treatment strategies
include lifestyle modifications, pharmacological therapy (antiplatelet agents, beta-blockers,
statins, nitrates), and invasive interventions such as percutaneous coronary intervention (PCI)
or coronary artery bypass grafting (CABG). Preventive measures play a crucial role in reducing
the incidence and severity of IHD, emphasizing the importance of early detection and risk factor
management. Continued research is essential for improving therapeutic approaches and patient
outcomes.
Key words:
Coronary Artery Disease,
Atherosclerosis
Myocardial Infarction (MI)
Angina Pectoris,
Ischemia
Plaque, Thrombosis, Stenosis.
ПРИНЦИПЫ СОВРЕМЕННОГО ИЗУЧЕНИЯ ИШЕМИЧЕСКОЙ БОЛЕЗНИ
СЕРДЦА
Аннотация.
Ишемическая болезнь сердца (ИБС), также известная как
ишемическая болезнь сердца (ИБС), является основной причиной заболеваемости и
смертности во всем мире. Она возникает из-за атеросклероза, состояния,
характеризующегося накоплением бляшек в коронарных артериях, что приводит к
снижению притока крови к миокарду.
Клинические проявления ИБС варьируются от бессимптомных случаев до
стенокардии, инфаркта миокарда, сердечной недостаточности и внезапной сердечной
смерти. Факторы риска включают гипертонию, диабет, дислипидемию, курение,
ожирение и малоподвижный образ жизни. Диагноз ставится на основании клинической
оценки, электрокардиографии (ЭКГ), сердечных биомаркеров, эхокардиографии, стресс-
тестирования и коронарной ангиографии.
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Стратегии лечения включают изменение образа жизни, фармакологическую
терапию (антиагрегантные препараты, бета-блокаторы, статины, нитраты) и
инвазивные вмешательства, такие как чрескожное коронарное вмешательство (ЧКВ)
или аортокоронарное шунтирование (АКШ). Профилактические меры играют
решающую роль в снижении заболеваемости и тяжести ИБС, подчеркивая важность
раннего выявления и управления факторами риска. Продолжение исследований имеет
важное значение для улучшения терапевтических подходов и результатов лечения
пациентов.
Ключевые слова:
ишемическая болезнь сердца, атеросклероз, инфаркт миокарда
(ИМ), стенокардия, ишемическая бляшка, тромбоз, стеноз.
Pathogenesis
Atherosclerosis is a multifactorial, immunoinflammatory disease of the arteries driven by
lipids. Risk factors, such as smoking, hypertension, diabetes mellitus, male gender and
inflammation accelerate the process where lipids enter the intima and atherosclerotic plaque
develop in the coronary arteries.
Reduced blood flow in the coronary arteries due to
atherosclerotic luminal narrowing and endothelial dysfunction creates an imbalance between
oxygen demand and supply in the myocardium causing ischemia. In the event of plaque rupture
acute coronary thrombosis may occur and cause partial or complete occlusion of the artery and
abrupt hypoperfusion and myocardial infarction.
Nonatherosclerotic causes of myocardial ischemia include primary or induced coronary
artery vasospam, impaired microcirculation or arteriolar dysregulation, coronary emboli, decreased
coronary perfusion due to hypotension, decreased blood oxygen content, significant increased
myocardial oxy- gen demand (eg, severe aortic stenosis, tachyarrhythmia).
Symptoms
Chronic Coronary Syndrome
In the 2019 ESC Guidelines on CCS,
six clinical scenarios are most frequently encountered
among patients with suspected CAD: (i) ‘stable’ angina symptoms, and/or dyspnea; (ii) patients
with new onset of heart failure or left ventricular (LV) dysfunction; (iii) asymptomatic and
symptomatic patients with stabilized symptoms <1 year after an ACS event or patients with
recent revascularization; (iv) asymptomatic and symptomatic patients >1 year after initial
diagnosis or revascularization; (v) patients with angina and suspected vasospastic or microvascular
disease; (vi) asymptomatic subjects in whom CAD is detected at screening. The likelihood of
CAD increases with typical presentation although presentation is not a specific determinant.
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Many patients suspected for CCS present atypical or nonanginal symptom
characteristics. Patients with obstructive CCS may even be asymptomatic, in particular among
patients with diabetes mellitus, or solely manifest as heart failure. Severity of angina is clinically
graded by the Canadian Cardiovascular Society classification (CCS-class), where the angina
threshold is quantified according to the relation to physical activity.
Intensity.
Acute Coronary Syndrome
ACS covers acute myocardial infarction and unstable angina pectoris. Acute myocardial
infarction is defined as myocardial injury and necrosis due to myocardial ischemia with a
subsequent elevation in cardiac troponin,
while unstable angina pectoris represents the unstable
clinical manifestation of CAD with longer lasting angina pectoris at rest without evidence of
necrosis and therefore no elevation of cardiac troponin. Symptoms of ACS are acute onset of
angina pectoris that is prolonged ongoing for >20 minutes. Like CCS accompanying symptoms
of nausea, fatigue, and dyspnea may occur. Unstable angina pectoris can also present as
crescendo angina, that is, worsening of angina in intensity, severity, and activity threshold for
onset.
Diagnosis
Diagnosis of CCS
The general approach for initial diagnostic management of patients suspected of CCS is
based on selecting the most suit- able noninvasive functional or noninvasive anatomical test from
the given patient’s characteristics in order to qualify the risk of obstructive CAD and indication for
revascularization. Only if the risk of obstructive CAD is very high or obstructive CAD is not ruled-
out by clinical assessment or by noninvasive testing invasive coronary angiography is
recommended. The initial diagnostic work-up can be summarized in 5 steps: Assessment of the
symptoms and excluding ACS; Clinical cardiac examination including resting electrocar- diogram
(ECG) and echocardiography; (3) Evaluation of coexisting cardiac and medical conditions that
may influence the symptoms, the choice of further testing, or potential treatment; and from this;
Evaluate probability and clinical likelihood of CCS; and finally from this; Decide whether further
testing is needed and, if so, decide between noninvasive anatomical test coronary computed
tomography angiography (CTA) or noninvasive functional tests including stress ECG, stress
echocardiography, single-photon emission computed tomography (SPECT) or positron emission
tomography (PET) perfusion imaging, stress cardiac magnetic resonance (CMR) perfusion
imaging, or coronary computed tomography angiography derived fractional flow reserve (FFR-
CT) for further cardiac imaging and testing.
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Diagnosis of ACS
Acute myocardial infarction is diagnosed by the presence of elevation of cardiac troponin
values, and at least one of the following: symptoms compatible with angina, new ischemic ECG
changes, development of pathological Q-wave in ECG, imaging evidence of new loss or reduced
function of viable myocardium, or identification of coronary thrombus by ICA.
Unstable angina
pectoris is diagnosed as the same clinical presentation as ACS but with no troponin elevation.
Noninvasive and Invasive Tests for CAD
Coronary Computed Tomography Angiography (CTA)
Coronary CTA is recommended in suitable patients with low to intermediate clinical
likelihood of CCS. To obtain optimal and sufficient image quality a minimum of a 64- slice scanner
and optimal scanning protocol including ECG- triggering and ECG gated 3D reconstruction are
required.
Furthermore, patient characteristics should be taken into account. Preferable patients
should have adequate breath holding abilities, sinus rhythm <60 bpm, BMI <30 kg/m
2
, and
absence of severe calcification.
High calcium score compromises the image quality with a significant
reduction in specificity in terms of stenosis evaluation.
While regular coronary CTA does not
allow stenosis evaluation in such patients, FFR- CT may provide high diagnostic performance and
identification of hemodynamically significant stenosis over a wide range of coronary calcification
scores. Meta-analysis evaluating the diagnostic accuracy of coronary CTA for >50% coronary
stenosis, when compared to invasive angiography demonstrated 96.4% pooled sensitivity and
80.5% pooled specificity.
In head-to-head comparison of [
15
O]H
2
O PET and technetium
99m/tetrofosmin-labeled SPECT with invasive coronary angiography and FFR≤0.80 defined as
significant obstructive CAD, coronary CTA had better sensitivity, 90% (95%CI, 83%-94%) but
lower specificity 63% (95%CI, 52%-68%) than PET and SPECT. Prospective registry studies
have shown that exclusion of obstructive CAD by coronary CTA is associated with a favor- able
prognosis similar to exclusion by functional testing.
Also randomized trials with up to 5 years
follow-up
and a meta-analysis have demonstrated that exclusion of CAD by coronary CTA is safe
with similar
or superior
cardiac outcome compared to initial noninvasive functional testing.
Consequently, coronary CTA is now a class IB recommendation in the 2019 ESC
guidelines.
The favorable long-term outcome may be caused by identification of nonobstructive
CAD and a resultant initiation of preventive therapies
that is not achievable by noninvasive
functional testing modalities. While coronary CTA seems to be associated with increased overall
catheterizations,
it is associated with reduced catheterizations showing no functional obstructive
CAD compared to functional tests,
increased revascularization and reduced myocardial infarction.
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The use of computational fluid dynamics and image based modeling allow estimation of
coronary flow and calculation of FFR from derived coronary CTA images, increasing the
sensitivity and specificity of evaluation of obstructive CAD.
When compared with invasive FFR measurement with a cut off of ≤0.80 the accuracy is
about 87%.
FFR-CT >80% and no need for further diagnostic testing are associated with a
favorable prognosis.
In patients with multivessel disease FFR-CT can distinguish functionally
significant from nonsignificant lesions with similar results as obtained by invasive
measurements.
Cardiac Magnetic Resonance (CMR)
CMR with gadolinium contrast yields information about cardiac function and anatomy,
including prior myocardial infarction and fibrosis, and myocardial perfusion. Performing imaging
under rest and stress with adenosine or dobutamine, semiquantitative assessment of regional
reversible and irreversible ischemia can be obtained. CMR has the advantage that patients are not
exposed to ionizing radiation or x-ray. Evaluation of patients with known CAD is obtainable.
In a
meta-analysis of diagnostic studies with FFR ≤ 0.80 defining significant CAD pooled sensitivity
and specificity was 88% (95%CI, 85%-92%), and 89% (95%CI, 83%-91%) respectively.
A
normal stress CMR is associated with a low risk of cardiac events (<1% per year) and a favorable
prognosis.
CMR is unable to identify hibernation per se but by CMR with gadolinium contrast
the ischemic pattern of myocardial infarction can be determined. There is a continuous and
inverse correlation between the extent of infarct transmurality and the probability of recovery of
contractile function following revascularization. In clinical practice a threshold of<50% infarct
transmurality is used to define viability.
Disadvantages CMR include lower equipment and
expertise availability worldwide. Potential toxicity of gadolinium-based contrast is a concern
though limited clinical data exists.
Exercise Electrocardiogram
The diagnostic endpoint of an exercise ECG test is ischemic ECG changes defined as ≥1
mm horizontal or down-sloping ST-segment depression at peak exercise. Resting ECG abnor-
malities preclude accurate interpretation and exercise ECG tests are not recommended in such
patients. They include abnormalities affecting the ST segment, such as LV hypertrophy, LBBB,
ventricular-paced rhythm, or any resting ST-segment depression ≥0.1 mV. Pooled sensitivity and
specificity when compared to invasive anatomically significant CAD exercise ECG only
performs 56% (95% CI, 46%-69%) and 62% (95% CI, 54%-69%), much lower than functional
and anatomic testes,
and the test has the least favorable ruling- out profile of the noninvasive tests
and is rarely recommended.
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Addition of coronary CTA in CCS diagnosing com- pared to exercise ECG alone not only
qualifies the diagnosis but also significantly reduced death from CAD and nonfatal myocardial
infarction.
Invasive Coronary Angiography (ICA)
Invasive coronary angiography provides anatomical evaluation of the coronary artery
anatomy, including presence and severity of atherosclerosis by determining lesion location,
luminal obstruction, lesion length, and the presence of collateral flow. Historically, an
angiographic stenosis of >70% (>50% for left main) was considered significant, but angiographic
evaluation of stenosis severity is not objective and severity can be difficult to evaluate such that a
suspected significant may not be physiologically significant.
The functional severity of a stenosis
can be evaluated by invasively determination of myocardial FFR. FFR is defined as the maximal
blood flow through a coronary artery, divided by the theoretical normal maximal flow through
the same artery
and is derived from the mean distal coronary artery pressure to the aortic pressure
during maximal vasodilatation. An alternative modality is instantaneous wave-free ratio (iFR),
which is a resting distal-to-proximal pressure ratio over a coronary stenosis. It is measured
during a period in diastole
when intracoronary resistance is constant. FFR <0.75-0.80 and iFR
≤0.89 are associated with reversible ischemia in noninvasive functional tests.
In particular,
angiographical stenoses of 55%-90% are subject to reclassification by invasive functional testing
by FFR or iFR.
Evaluation of stenosis severity in angiographically intermediate lesions can also be obtained
by intravascular imaging by intravascular ultrasound imaging (IVUS) or optical coherence
tomography (OCT). IVUS is an ultrasound-based modality of intravascular imaging while OCT is
a light-based modality with a higher resolution compared with IVUS but that requires complete
blood clearance of the vessel. Intravascular imaging can assess vessel size, lumen area, plaque
composition and volume, stent malapposition, residual thrombus, and dissections. It can as such
be useful in evaluating stenosis severity, especially left main intermediate stenosis, lesion
morphology, provide valuable intravascular information to guide in PCI, and evaluate pathology
in stent failure.
Treatment
Overall treatment for ischemic heart disease consists of antithrombotic medication,
antianginal medication, cardio- vascular risk factors modification, and revascularization when
indicated.
Antithrombotic Therapy
Antiplatelet therapy reduces the risk of serious vascular events as myocardial infarction,
stroke, and vascular death in moderate to high-risk patient at an increased risk of bleeding.
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In patients with previous myocardial infarction or revascularization the beneficial effect of
low dose aspirin 75- 100 mg daily substantially exceeds the bleeding risks and is a Class I, Level
A recommendation.
The evidence for primary prevention is not similarly well founded. In
patients with evidence of CAD on imaging without previous myocardial infarction or PCI
and in patients with moderate risk of CAD, aspirin is recommended preventively.
In patients
intolerant to aspirin, clopidogrel can be used instead. In patients with previous stroke or peripheral
artery disease clopidogrel is preferred. In patients with CCS treated with PCI, dual antiplatelet
therapy (DAPT) with clopidogrel 75 mg daily on top of aspirin is recommended. Duration of
DAPT has been reduced over the last 10 years as randomized clinical trials
and meta-analyses
have demonstrated no overall additional beneficial effect of 12 months vs 6 months DAPT post-
PCI.
In patients with high bleeding risk shorter DAPT duration must be considered. Post-PCI
antiplatelet therapy in ACS patients DAPT is recommended for 12 months. Ticagrelor or prasugrel
is first choice as they are superior to clopidogrel in these patients.
Long-term (<1 year) DAPT or
combination of aspirin and low-dose rivaroxaban may reduce cardiovascular events in high-risk
patients but with an increased risk of bleeding.
These combinations may therefore be considered in high-risk patients with low bleeding
risk, but are not recommended as standard treatment.
Patients with indication for oral anticoagulants, for example due to atrial fibrillation or
mechanical heart valve, have increased bleeding risk after addition of antiplatelet therapy after
PCI. As the effect of combing anticoagulants to ticagrelor or prasugrel has not been studied, this
combination should be avoided and clopidogrel is recommended. The individual patient bleeding
and cardiovascular risk should be taken into careful consideration when deciding the duration of
double and triple therapy. In the ISAR-TRIPLE trial there was difference in the primary endpoint
in patients treated with 6-week vs 6-month triple therapy, and no difference in TIMI major
bleeding.
Antianginal Therapy
Short-acting nitroglycerin sublingual is the cornerstone of acute symptom relief from
angina. Antianginal medications that reduce and prevent angina symptoms include beta-
blockers, calcium channel blockers, and long-acting nitrates.
In symptomatic patients with reduced ejection fraction beta- blockers are indicated as they
reduce mortality and morbidity.
Beta-blockers and calcium channel blockers effectively reduce
symptoms but have not been shown to improve patient outcome in CCS patients without heart failure
or prior myocardial infarction.
According to European and American guidelines beta-blockers
and calcium channel blockers in monotherapy or in combination is first line in treating angina,
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even though no randomized trial has investigated these medications against other antianginal
medications,
but only against each other.
Current guidelines recommend addition of other
antianginal drugs to beta-blockers and/or calcium channel blockers when residual angina is
present.
These include long-lasting nitrates, ivabradine, nicorandil, ranolazine, or tri- metazidine.
No trial has shown effect on mortality or morbidity, but these compounds may provide
symptom relief. Ranolazine, long-lasting nitrates, and trimetazidine not only yield symptom relief
but also improve exercise duration and time to angina during exercise test.
Ivabradine has a similar
effect but failed to demonstrate reduction in angina attacks.
The recommended medical treatment for microvascular angina are beta-blockers, calcium
channel blockers and long- lasting nitrates and for vasospastic angina calcium channel blockers
and long-lasting nitrates.
Revascularization
Revascularization in CCS
While optimal medical therapy is crucial for reducing symptoms, counteracting progression
of atherosclerosis, and preventing atherothrombotic events, myocardial revascularization has a central
role in the management of CCS as an adjunct to medical therapy. The two objectives of
revascularization are symptom relief in patients with angina and/or improvement of prognosis.
Revascularization by PCI or coronary artery bypass grafting (CABG) may effectively relieve
angina, eliminate myocardial ischemia and its adverse clinical manifestations, and reduce the risk of
major acute cardiovascular events including myocardial infarction and cardiovascular death.
Therefore, revascularization should be considered in the presence of symptoms and objective
evidence of ischemia by functional testing or diameter stenosis >90%, FFR ≤ 0.80 or iFR ≤ 0.89 in
major vessel and LVEF ≤ 35% due to CAD.
Even in asymptomatic patients, revascularization may
be considered if the same criteria are fulfilled and also when functional testing reveals large areas of
reversible ischemia, that is, ≥10% of the left ventricle.
The choice of revascularization modality
depends on anatomical coronary pathophysiology. Accordingly, the 2019 ESC guidelines
recommend FFR- or iFR-guided revascularization as a Class I recommendation in CCS patients,
unless a >90% diameter stenosis is evident, in which case revascularization can be performed
upfront. iFR
is closely related to FFR, and iFR-guided PCI (iFR≤0.89) is noninferior to FFR-
guided PCI (FFR≤0.80) with respect to the risk of major adverse cardiac events.
FFR and iFR ratios are continuous variables and the exact cut-point for revascularization
is not firmly settled. It is discussed whether the optimal cut-off is FFR≤0.75 or FFR≤0.80. In
randomized clinical trials and metaanalysis PCI in patients with FFR≤0.80 reduced primary
endpoints, mainly driven by reduced need for urgent revascularization but not reduced mortality.
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Optimal medical treatment alone in patients with FFR > 0.80 is associated with favorable
prognosis with very low event rate.
Other observational studies
and a randomized trials
have demonstrated that deferral of PCI in patients with FFR ≥
0.75 is also safe, though not
unambiguous.
Furthermore it should be taken into account that around the cut-off values FFR ≤
0.80 or iFR ≤ 0.89 the FFR and iFR measurements are less precise.
Outside the range of FFR = 0.75-0.85 the measurement certainty of a FFR result is >95%,
while close to this cutoff the certainty is less than 80%.
Close to the cut-off FFR and iFR can
complement each other,
but the decision about treatment strategy should always be combined
with a thorough clinical evaluation.
In patients with multivessel disease or left main CAD revascularization by CABG rather
than PCI should be considered. PCI still seems to be inferior to CABG in patients with multivessel
disease
or left main CAD,
although some studies have indicated that PCI is noninferior to CABG
in terms of mortality and stroke. PCI is associated with increased need for revascularization.
The
outcome is dependent on the complexity of the coronary lesions esti- mated by SYNTAX score.
In patients with low anatomical complexity (SYNTAX score ≤22) subsequent primary
end- point major adverse cardiac and cerebrovascular events (MACCE), composite endpoint
defined as all-cause mortality, stroke, myocardial infarction, and repeat revascularization), and
secondary endpoint death, myocardial infarction or repeated revascularization were not
significantly different in PCI and CABG treated patients. In patients with intermediate SYNTAX
score (SYNTAX 23-32) event rates in terms of myocardial infarction and repeated
revascularization were increased in the PCI group, whereas death and stroke were not. High
SYNTAX score ≥33 was associated with a significant increase in MACCE, cardiac death, and
myocardial infarction following PCI compared to CABG.
As a consequence, revascularization
of patients with multivessel disease or left main CAD and a low syntax score ≤22 can be done
either by PCI or CABG depending on other clinical conditions of the patient. In patients with
intermediate-to- high SYNTAX complexity CABG should be chosen. Patients with reduced EF <
35 due to obstructive CAD gain a prognostic effect of revascularization. Viability of
myocardium can be assessed by FDG-PET, CMR and stress echocardiography. While some
studies have failed to demonstrate a correlation between myocardial viability and benefit from
revascularization,
selection of patients that gain most benefit from revascularization in terms of
improvement of left ventricular function depends on evaluation of the extend of viability of
dysfunctional myocardium. Evaluation often requires investigation by a combination of PET,
CMR, and stress echocardiography to determine the extent of dysunction, the degree of
transmural affection, and the potential for regaining function in reversibly affected areas.
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Conclusion
Noninvasive anatomic imaging with coronary CCA or noninvasive functional test with
myocardial PET, SPECT, or CMR is recommended as the initial test to diagnose CAD in
symptomatic patients where obstructive disease cannot be excluded by clinical assessment alone.
Coronary CCA is first line in suitable patients, while noninvasive nuclear or magnetic
resonance technology can be used to further qualification of the diagnosis when coronary CCA is
inconclusive, or in patients not suitable for coronary CCA.
Optimal medical treatment remains paramount, while FFR-guided myocardial
revascularization in patients that are not responsive to antianginal treatment provides further
symptom relieve as well has prognostic impact on prevention of spontaneous myocardial infarction.
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Jamshidovich, A. S. (2024). FITOTERAPIYANING AKUSHER-GINEKOLOGIYADA
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