Ischemic Heart Disease and Angina Pectoris

• In 1772, William Heberden described angina pectoris, a chest discomfort during walking that disappears with rest, linking it to ischemic heart disease.
• Ischemic heart disease is an imbalance between myocardial oxygen supply and demand, commonly due to coronary artery atherosclerosis.
• Ischemic heart disease affects millions in the US and is a leading cause of death in industrialized nations.
• Ischemia may present with exertional symptoms or as silent ischemia without clinical manifestations.
• Angina pectoris, which is the most common ischemic heart disease manifestation, refers to chest discomfort arising from myocardial oxygen supply and demand imbalance.

Clinical Definitions (Table 6-1)

• Ischemic heart disease involves an imbalance between myocardial oxygen supply and demand, leading to myocardial hypoxia and waste metabolite accumulation.
• Angina pectoris involves uncomfortable sensations in the chest and surrounding areas due to myocardial ischemia.
• Stable angina is a predictable pattern of transient angina, triggered by physical activity or stress, and relieved by rest, without permanent myocardial damage.
• Variant angina is usually a discomfort at rest, which is due to coronary artery spasm rather than increased oxygen demand, and it is often associated with ST-segment changes.
• Silent ischemia is an asymptomatic episode of myocardial ischemia, detectable through ECG or lab tests.
• Unstable angina presents as increased frequency and duration of angina episodes with less exertion or rest, and a high risk of progressing into myocardial infarction.
• Myocardial infarction is a region of myocardial necrosis typically from prolonged blood supply cessation and acute thrombus at the site of coronary atherosclerosis.

Myocardial Oxygen Supply and Demand

• Myocardial oxygen requirements are normally met continuously by coronary arterial supply.
• Oxygen supply and demand is balanced even during exercise due to increased oxygen delivery.
• Myocardial oxygen supply depends on blood oxygen content and coronary blood flow.
• Oxygen content is determined by hemoglobin concentration and systemic oxygenation.
• Coronary blood flow is dynamic and responsible for matching oxygen supply with metabolic needs.
• Coronary artery flow (Q) is directly proportional to perfusion pressure (P) and inversely proportional to coronary vascular resistance (R): Q ∝ P/R.
• Coronary perfusion occurs predominantly during diastole, unlike other arterial systems.
• Systolic flow compression is caused by small coronary branches during myocardial contraction
• Diastolic flow is uninhibited because relaxed myocardium doesn't compress coronary vasculature.
• In coronaries, perfusion pressure is approximated by the aortic diastolic pressure minus the left ventricular diastolic pressure.
• Conditions lowering aortic diastolic pressure can decrease myocardial oxygen supply.
• Coronary vascular resistance is primarily modulated by external compressive forces and intrinsic coronary tone factors.

External and Intrinsic Control

• External compression is exerted on coronary vessels by surrounding myocardium contraction during the cardiac cycle.
• Subendocardium is more vulnerable to ischemic damage due to greater force during myocardial contraction.
• Unlike most tissues, the heart cannot increase oxygen extraction on demand because in its basal state, it removes nearly as much oxygen as possible from its blood supply.
• Autoregulation of coronary vascular resistance facilitates increased blood flow for additional oxygen requirements.
• Local metabolites, endothelium-derived substances, and neural innervation regulate coronary vascular resistance.
• Metabolite accumulation affects coronary tone, modulating myocardial oxygen supply to meet changing metabolic demands.
• During tissue hypoxia, ATP production is impaired, leading to ADP and AMP accumulation, which degrade into adenosine.
• Adenosine, lactate, acetate, hydrogen ions, and carbon dioxide act as vasodilators.
• The arterial wall’s endothelial cells produce vasoactive substances that regulate vascular tone.
• NO, prostacyclin, and EDHF act as vasodilators produced by the endothelium.
• Endothelin 1 is an example of an endothelium-derived vasoconstrictor.
• NO regulates vascular tone by diffusing into and relaxing arterial smooth muscle through a cGMP-dependent mechanism.
• Normal endothelium produces NO in basal state, stimulated by substances like acetylcholine, thrombin, aggregating platelets products, or shear stress of blood flow.
• Prostacyclin, also released from endothelial cells, causes vasodilation via a cAMP-dependent mechanism.
• EDHF is a diffusible substance that hyperpolarizes neighboring vascular smooth muscle cells, leading to relaxation. Endothelin 1 partially counteracts the actions of endothelial vasodilators and its expression is stimulated by factors such as thrombin, angiotensin II, epinephrine, and shear stress of blood flow.
• In healthy endothelium, vasodilators outweigh vasoconstrictors, but dysfunctional endothelium secretes fewer vasodilators.
• Neural control of vascular resistance involves sympathetic and parasympathetic components.
• Sympathetic nervous system plays a role, whereas the parasympathetic nervous system contribution is minor under normal circumstances.
• Coronary vessels have α-adrenergic receptors (vasoconstriction) and β2-adrenergic receptors (vasodilation).
• Metabolic, endothelial, and neural factors interplay to determine net impact on coronary vascular tone.

Oxygen Demand

• Myocardial oxygen demand is determined by ventricular wall stress, heart rate, and contractility.
• Small oxygen amounts are used for basal cardiac metabolism and electrical depolarization.
• Ventricular wall stress is the tangential force acting on myocardial fibers; related to intraventricular pressure, ventricular radius, and wall thickness.
• Wall stress ∝ (P x r) / (2 x h), where P is intraventricular pressure, r is ventricular radius, and h is wall thickness.
• Increased pressure in the left ventricle elevates wall stress and myocardial oxygen consumption.
• Greater ventricular filling increases wall stress and oxygen consumption, while decreased filling reduces them.
• A hypertrophied heart has lower wall stress because force is spread over a greater muscle mass.
• Heart rate increases the number of contractions and ATP consumption rises which increases oxygen consumption.
• Contractility measures the contraction force, and it can be directly augmented, which increases oxygen consumption.
• Autoregulatory mechanisms match coronary tone to myocardial oxygen supply and demand, but this is impaired in advanced coronary atherosclerosis.

Pathophysiology of Ischemia

• Myocardial ischemia in CAD traditionally occurs due to fixed atherosclerotic plaques narrowing the vessel lumen.
• Reduced blood flow in CAD results from fixed vessel narrowing and endothelial cell dysfunction.
• Hemodynamic significance of fixed atherosclerotic coronary artery stenoses relates to fluid mechanics and vascular supply anatomy.
• Poiseuille's law explains flow (Q) through a vessel: Q = (ΔPπr⁴) / (8ηL).
• The geometric component L/r⁴ governs vascular resistance, so stenotic lesion significance depends on length and degree of narrowing.
• Coronary arteries include large epicardial segments and smaller, distal "resistance vessels".
• Proximal vessels undergo stenosis and the distal vessels adjust vasomotor tone.
• Stenosis significance relies on narrowing degree of vessel’s epicardial portion and compensatory vasodilatation.
• When stenosis narrows <60%, the resistance vessels can compensate.
• Above ~70% diameter reduction, maximal blood flow decreases.
• Resting blood flow may be compromised if stenosis narrows the vessel more than ~90%.
• Collateral connections may buffer the fall in myocardial oxygen supply, but they are often insufficient to prevent ischemia during exertion.
• Endothelial dysfunction contributes to reduced myocardial oxygen supply by inappropriate vasoconstriction and loss of antithrombotic properties.

Endothelial Dysfunction and Other Causes

• In normal cases, physical activity/stress causes coronary artery vasodilatation, mediated by endothelial-derived vasodilators like NO.
• Vasodilatation reduction is as a result of direct catecholamine effect which occurs in dysfunctional endothelium, leading to vasoconstriction and ischemia.
• Impaired vasodilatation is noted in those with CAD risk factors before visible lesions which suggests endothelial dysfunction is an early atherosclerotic process indicator.
• In acute coronary syndromes, products from platelet aggregation induce local NO release, but cause vasoconstriction and therefore dysfunction in endothelial cells.
• Factors released from endothelial cells have antithrombotic properties, but are attenuated in endothelial cell dysfunction.
• Other causes of ischemia are, decreased perfusion pressure from hypotension, reduced oxygen content and increased myocardial oxygen demand.

Consequences of Ischemia

• The consequences of ischemia include inadequate myocardial oxygenation and accumulation of metabolic waste products.
• Myocytes switch to anaerobic pathways during ischemia which impairs contractile proteins and systolic/diastolic function.
• Elevated LV pressure causes pulmonary congestion and dyspnea, while metabolic products activate pain receptors and cause angina.
• The ultimate fate of affected myocardium depends on the severity and duration of oxygen supply and demand imbalance.
• An ischemic cardiac episode results in irreversible myocardial necrosis or full myocyte function recovery.
• After severe acute transient ischemia, stunned myocardium demonstrates prolonged reversible systolic dysfunction when blood flow returns.
• Hibernating myocardium tissue manifests chronic ventricular contractile dysfunction due to reduced blood supply, which promptly recovers with restored blood flow via revascularization.
• Viability imaging studies differentiate hibernating from infarcted myocardium to guide revascularization decisions.

Ischemic Syndromes

• Distinct clinical syndromes result from pathophysiologic process and severity of the ischemic insult.
• Stable angina manifests as predictable chest discomfort brought on by exertion/stress due to plaque in coronary arteries.
• Reduced flow capacity meets low oxygen needs at rest, but physical exertion causes O2 demand to exceed supply.
• Imbalances are contributed to with inappropriate coronary vasoconstriction from atherosclerosis.
• Stenosis may change or remain constant.
• Patients may experience sudden increases in tempo and duration of ischemic episodes, which may be a precursor to acute MI.
• Ruptured plaques cause platelet aggregation and thrombosis.
• Variant angina cases cause spasm in focal arteries in absence of lesions, and thus reduced oxygen and thus angina.
• This may involve with endothelial dysfunction.
• Silent ischemia occurs without pain at 20-50% in those with normal angina, in this case the discomfort is a concern. Silent ischemia is common in diabetic patients, the elderly, and in women.
• Coronary stenoses are absent, microvascular angina is in presence of angina pectoris.
• Related to resistance vessel reserve and may improve as well as prognosis.

Clinical Features of Chronic Stable Angina

• The main part of the clinical evaluation is the history described by the patient and differentiates the myocardial ischemia from other discomfort conditions.
• Angina is typically described as pressure, tightness, burning, or heaviness, lasts a few minutes and is neither sharp nor stabbing.
• The Levine sign has a patient place a clenched fist over sternum defining constricting discomfort.
• Angina discomfort is diffuse, located in the retrosternal area/left precordium, in the chest, back, arms, neck, lower face or upper abdomen.
• Generalized sympathetic and parasympathetic stimulation results in tachycardia, diaphoresis, nausea.
• Dyspnea, transient fatigue, and weakness result.
• Symptoms such as these symptoms without chest discomfort occur when the symptom isn't typical (angina equivalents).
• Can happen after emotional excitement, physical exertion, anger
• Additional CAD discomfort can occur due to large meals (increase wall stress) or cold weather.
• Generally relieved within minutes by sublingual nitroglycerin or cessation if triggered.
• Varies because patients learn and avoid situations.
• Important to inquire on any reductions from activities to daily living or other risk factors for atherosclerosis and CAD.

Differential Diagnosis and Examination

• Various disorders mimic transient chest discomfort of angina pectoris such as cardiac causes and musculoskeletal conditions.
• In contrast to angina pectoris, GI causes for pain are often precipitated by some foods but exertion unrelated
• History is critical is used in distinguishing such other causes listed in table 6-2 including differentiation from pericarditics which argues against because the symptom of more likely result of pericarditics of acute pulmonary.
• ECG are common, with examination, increased heart rate and blood pressure because of adrenergic responses.
• Palpation is related and important to examine and abnormalities can be detected on palpation of the Left chest if indicated due to ischemia during such exam such as the carotid.

Diagnostic Studies

• Angina must be suspected and then confirmed as the correct diagnostic cause and several procedures and helpful confirming as such but importantly the proper studies and procedures need to be selected for which patient is correct.
• Electrocardiogram is that One of the most important and the more useful procedures which can determine heart episodes are occurring.
• In patients with cardio ischemia or the ECG segments and T segment and Wavy changes can take place usually the the acute episodes generally result in segments horizontal changes and the T waves inversion or flatter.
• The segments elevations on more severe forms of patients acute in contrast The elevation of the symptoms it normalizes patients ECG and when the symptoms are alleviated so do its readings and ECG.
• ECG during the period are free of the episodes are generally free and normal as well and In others some type
• Not to fully rule the heart's problems out and need further testing stress testing.

Stress and Imaging Studies

• Stress testing and provocative exercising is recommended for heart disease.
• Exercise or pharmacologic testing is very valuable at helping with the prognosis.
• Treadmill or stationary testing in which exercise causes a development or observations, regular ECG and checking for any other problems but is stopped if angina happens or heart issues get worse to achieve targeted heart rate.
• Standard is if reproduced typical chest pain with significant cadmium test.
• It's 68% sensitivity and 77 specificity from significant cads which means its likely is severe and patients will be given medication.
• Stress may affect the patient depending to determined the presence and those medic is typically what for testing.
• In some patients with no problems like those that have normal basic segments less useful
• There can be some situations the suspicion is low.
• Nuclear or radionuclide can be combined to beat these.
• Radu injected after peak and then will be seen in the degree of areas of it because it helps determine viable
• It provides the specific significant for ischemial and helps define which tests are the significant.

Additional Tests

• Tests of other methods such as cardio version as well and helps reduce sensitive CAD.
• Other cardio are to those that may benefit include those unable to which includes vaso direct, and this helps see the amount such as adensosine
• Some of these such help because some cannot compensate increase.
• Others are not well and thus the study to make su there is is that vessel and for such
• CAD is visualizated coronary or injection and helps.
• CAD is what that make there is such cases for testing it is important or such.
• Catheter the measurement the catheter helps or the measure and how good the value is
• FFR helps there if is less if than it there is is such.
• CT angiogram or help for the testing because such other problems affect those of it.

Coronary Arterial Disease

• CAD shows significant arteries, heart will also be effected and should know how and test for it which are the common and important concepts to be noted in study.

Natural History and Treatment

• Some of those with Cad can show no change, but there can be many years long for it as well but the other problems can exist such as problems which heart rates or death
• Likely with disruption, and death rates because of it.
• The mortality related because the Cad reduced because of it. .The main goal should be to reduce attacks as well.
• Is the prevent the for is in addition to problems from such.
• To lower the risk for CAD and so the many should take actions such as cessation cholesterol diet.