Continuing Education Activity

Coronary artery disease (CAD) is a prevalent heart condition characterized by the buildup of atherosclerotic plaque within the arterial lumen. Blood flow impairment reduces oxygen delivery to the myocardium. CAD is the most common cause of major morbidity and mortality in the US and worldwide. Prompt diagnosis and treatment improve outcomes.

The evaluation of CAD typically involves a combination of clinical assessment and diagnostic tests such as electrocardiography, stress testing, and echocardiography. Coronary angiography helps assess the extent of coronary blockages.

Treatment options for CAD range from lifestyle changes and medications to more invasive procedures. Medications like statins, antiplatelet agents, and β-blockers aim to manage symptoms and reduce further plaque buildup. In severe cases, interventions such as percutaneous coronary intervention and the more invasive coronary artery bypass grafting may be necessary. Complications of untreated or poorly managed CAD include heart failure, arrhythmias, and sudden cardiac death.

This activity for healthcare professionals is designed to enhance learners' proficiency in evaluating and managing CAD. Participants gain a deeper insight into the condition's risk factors, pathogenesis, and evidence-based diagnostic and therapeutic strategies. Greater competence enables clinicians to collaborate within an interprofessional team caring for patients with CAD.

Objectives:

• Identify the etiology of coronary artery disease.
• Create a clinically guided strategy for evaluating coronary artery disease.
• Implement individualized therapeutic plans for patients with coronary artery disease.
• Collaborate with the interprofessional team to educate, treat, and monitor individuals with coronary artery disease to improve health outcomes.

Introduction

Coronary artery disease (CAD) is characterized by the development of atherosclerosis in the coronary arteries, which can sometimes be asymptomatic. Coronary heart disease (CHD), also known as ischemic heart disease (IHD), encompasses conditions such as stable angina, acute coronary syndrome (ACS), and silent myocardial ischemia. Mortality associated with CHD is mainly due to CAD. ACS is typically symptomatic and includes conditions like unstable angina and myocardial infarction. For clarity, we will refer to CHD as "CAD" throughout this discussion. 

CAD is the leading single cause of death and disability-adjusted life years (DALYs) lost worldwide. This burden disproportionately affects low- and middle-income countries, contributing to approximately 7 million deaths and 129 million DALYs annually. In 2015, CAD was responsible for 8.9 million deaths and 164.0 million DALYs globally. Individuals who survive myocardial infarction face a significantly higher risk of recurrent events and have an annual mortality rate 5 to 6 times higher than people without CAD.[1]

CAD is marked by an inadequate supply of blood and oxygen to the myocardium. The condition arises from occlusion of the coronary arteries and results in a demand-supply mismatch of oxygen. CAD typically involves the formation of plaques in the lumen of coronary arteries that impede blood flow.

CAD is the major cause of death in the US and worldwide. CAD was an uncommon cause of death at the beginning of the 20th century. Deaths due to CAD peaked in the mid-1960s and then decreased. However, This disease is still the leading cause of death worldwide.[2] The likelihood of death from CAD increases substantially with age. Among the modifiable risk factors, systolic blood pressure plays a crucial role, accounting for a portion of the heightened CAD risk associated with aging.[3]

The term stable ischemic heart disease (SIHD) often is used synonymously with chronic coronary artery disease (CAD) and encompasses a variety of conditions where the end result is a repetitive mismatch between myocardial oxygen supply and demand. This most frequently is seen when long-standing atherosclerotic obstruction within the epicardial coronary arteries results in poor flow and ischemia distally. However, this is not the only mechanism. Various pathophysiologic processes such as coronary artery vasospasm, microcirculation dysfunction, or congenital anomalies can cause the same supply-demand mismatch and result in chronic repetitive ischemia.

Per the American College of Cardiology (ACC)/American Heart Association (AHA) 2012 guidelines, stable ischemic heart disease includes adults with known ischemic heart disease (IHD), who have stable pain syndromes (i.e., chronic angina), or those with new-onset, low-risk chest pain (i.e., low-risk, unstable angina or UA). Asymptomatic patients who were diagnosed through non-invasive methods or who have had their symptoms adequately controlled medically or the following revascularization are also considered to have stable ischemic heart disease.

A distinction should be made between stable ischemic heart disease and acute coronary syndrome (ACS), where a more acute presentation with troponin elevation (i.e., myocardial infarction) or high-risk chest pain without troponin elevation (i.e., high-risk, UA) is required for the diagnosis. It also bears mentioning that stable ischemic heart disease patients can develop chronic, slow worsening of their angina symptoms, which is often managed medically, or may go on to develop ACS and require urgent intervention. Therefore, the ability to distinguish stable ischemic heart disease from ACS within the spectrum of atherosclerotic CAD is paramount.

19858499

18412271

Etiology

CAD is multifactorial. Etiologic factors can be broadly categorized into nonmodifiable and modifiable. Nonmodifiable factors include gender, age, family history, and genetics. Modifiable risk factors include hypertension, smoking, obesity, lipid levels, and psychosocial variables.[4] In the Western world, a faster-paced lifestyle has led people to eat more fast foods and unhealthy meals, which has paved the way for the increased prevalence of IHD. In the US, better primary care in the middle and higher socioeconomic groups has pushed the incidence toward the later part of life. Smoking remains the number one cause of cardiovascular disease. In 2016, the prevalence of smoking in the United States among adults was found to be 15.5%.[5] 

Men are more predisposed to CAD than women. Hypercholesterolemia remains an important modifiable risk factor for CAD. Increased low-density lipoproteins (LDL) raise CAD risk, and elevated high-density lipoproteins (HDL) decrease CAD incidence. An individual's 10-year risk of atherosclerotic cardiovascular disease can be calculated using the atherosclerotic cardiovascular disease equation on the American Heart Association (AHA) portal.[6][7] Markers of inflammation are also substantial risk factors for CAD. High-sensitivity C-reactive protein (hs-CRP) is considered the best predictor of CAD in some studies, although its practical uses are controversial.[8]

Research indicates that obesity is linked to increased cardiovascular disease risk and a higher prevalence of cardiovascular conditions.[9][10] Waist circumference indicates abdominal fat accumulation better than body mass index (BMI). Individuals with a normal BMI but increased waist circumference are at greater risk for developing CAD. The current obesity guidelines do not provide specific recommendations for waist circumference cut-off values in patients with CAD and a normal BMI. Sharma et al examined data from 7,057 patients with CAD across 5 cohort studies. The group found that a higher waist circumference or waist-to-hip ratio, despite having a normal BMI, was associated with an increased risk of mortality in patients with CAD.[11]

The most common cause of chronic ischemia is coronary artery obstruction secondary to atherosclerotic disease. A newly recognized entity, more frequently described in female patients, is endothelial dysfunction or microcirculatory dysregulation, resulting in similar symptoms but without the presence of significant stenosis on angiography. Less common etiologies include coronary vasospasm (Prinzmetal angina) and coronary anomalies which may rarely present with a similar picture.

Epidemiology

Although the incidence of CAD has been declining in developed nations, the overall number of coronary events is not expected to decrease due to factors like immigration and aging. These factors may lead to a transient increase in CAD prevalence. In contrast, developing countries show significant variability in CAD incidence. The spread of Western dietary habits and a more sedentary lifestyle will likely contribute to a sharp rise in CAD cases in these regions.

The continued reduction in CAD mortality rates in developed countries over recent decades can be attributed to advancements in acute treatment and the success of both primary and secondary preventive strategies. However, outcomes may still vary based on ethnic differences, social inequalities, and disparities in access to effective treatments and preventive measures within different regions of the same country. This variation underscores the need for further research and evaluation across various areas.[12]

One study estimated that CAD represented 2.2% of the global disease burden and 32.7% of cardiovascular diseases. The condition costs over 200 billion dollars annually to the health care system in the United States. An estimated 7.6% of men and 5.0% of women in the US lived with CAD from 2009 to 2012, based on the national health survey conducted by the AHA. Thus, about 15.5 million Americans are afflicted with the disease during this time.[13][4] In 2020, an estimated 19.05 million deaths worldwide were attributed to CVD, indicating an 18.71% rise since 2010. The age-standardized death rate per 100,000 people was 239.80, reflecting a 12.19% decrease over the same period. The overall crude prevalence of CVD reached 607.64 million cases in 2020, representing a 29.01% increase compared to 2010.[14]

The incidence of CAD rises with age, regardless of gender. In France's ONACI registry, the incidence of CAD was about 1% in individuals aged 45 to 65, increasing to about 4% in people aged 75 to 84 years.[15]

Multiple studies have demonstrated that the presence of cerebral (CeVD) and peripheral vascular disease (PVD) significantly increases the risk, morbidity, and mortality associated with CAD. For instance, the Gulf Registry of Acute Coronary Events, which included 7,689 patients with ACS, highlighted that polyvascular disease is linked to higher in-hospital and 1-year mortality rates, as well as a decrease in the prescription of dual antiplatelet therapy (DAPT).[16]

Similarly, the MASCARA registry, a multicenter study conducted across 32 hospitals in Spain, found that CeVD and PVD independently predicted increased in-hospital and 6-month mortality following ACS.[17] Ferreira-González et al also observed more severe CAD in patients with CeVD or PVD.[18] These findings are supported by additional studies, including one in Sweden involving 544 postmyocardial infarction patients, where individuals with severe CAD and polyvascular disease exhibited particularly high rates of cardiovascular death and hospital readmission.[19][20]

It is difficult to ascertain the exact prevalence of stable ischemic heart disease due to the heterogeneity of its patient population and the variable definitions that physicians use. Nonetheless, CAD remains a major public health concern nationally in many regards. An estimated 10 million adults in the United States carry the diagnosis, and despite mortality-reducing therapy, IHD was alone responsible for nearly 380,000 deaths within the United States in 2010. In that approximation, it remains the number one cause of death for male as well as female patients. Furthermore, the increasing survival with the use of modern therapies has produced an aging population where more than 20% of women and 35% of men above the age of 80 have coronary artery disease.

Pathophysiology

The hallmark of the pathophysiology of CAD is atherosclerotic plaque formation. Plaque is a buildup of fatty material that narrows the arterial lumen and impedes blood flow. The first step in the process is the formation of a "fatty streak" by subendothelial deposition of lipid-laden macrophages, also called "foam cells." When a vascular insult occurs, the intima layer breaks, and monocytes migrate into the subendothelial space, where they become macrophages. These macrophages take up oxidized LDL particles, leading to foam cell formation. T cells get activated, and cytokines are released to aid in the inflammatory process. Growth factors activate smooth muscles, which also take up oxidized LDL particles and collagen, deposit along with activated macrophages, and increase the population of foam cells. Subendothelial plaque subsequently develops.

The plaque could grow or become stable over time if no further endothelial insult occurs. A fibrous cap forms if the plaque becomes stable and the lesion calcifies over time. The lesion can become hemodynamically significant as time passes. Myocardial tissue perfusion can become insufficient, triggering angina symptoms during times of increased demand (eg, exercise) if the lumen has at least 70% obstruction. Symptoms often abate at rest as the oxygen requirement falls. Angina may occur at rest if the coronary artery is 90% stenosed. Some plaques can rupture and expose tissue factor, culminating in thrombosis that can cause subtotal or total occlusion of the lumen. Severe, acute obstruction typically results in ACS in the form of unstable angina, NSTEMI, or STEMI, depending on the level of insult.[21]

CAD is typically classified as follows (see Image. Classification of Coronary Artery Disease):

• Stable ischemic heart disease (SIHD)
• ACS

  • ST-elevation myocardial infarction (STEMI)
  • Non-ST elevation myocardial infarction (NSTEMI)
  • Unstable angina

Key stages involved in atherosclerotic plaque formation include the following (see Image. Atherosclerotic Plaque Formation): 

Plaque Initiation and Progression

During atherosclerosis, vascular smooth muscle cells (SMCs) proliferate and migrate, forming a fibrous cap that stabilizes the plaque. These SMCs can undergo transdifferentiation, giving rise to various cell types within the plaque core, including osteoblast-like, myofibroblast-like, foam-like, and mesenchymal-stem-like cells. As SMCs release calcifying extracellular vesicles and undergo apoptosis, small calcified deposits, known as microcalcifications, form.

Monocytes enter the thickened intima via the endothelium, absorb lipids, and transform into foam cells, which can also die and release extracellular vesicles and apoptotic bodies, further contributing to calcification. Over time, these microcalcifications develop into more significant calcium deposits, or macrocalcifications, which may evolve into calcified sheets and plates. These sheets can fracture, leading to nodular calcification, which increases the risk of plaque rupture and subsequent thrombosis. Macrocalcifications within a thin fibrous cap can also contribute to plaque rupture.

Plaque Stability and Calcification

Plaque stability is intimately linked with the type of calcification present. Stable plaques are often characterized by macrocalcifications and a thick, collagen-rich extracellular matrix within the fibrous cap, providing structural stability. In contrast, unstable plaques tend to have microcalcifications and a thin fibrous cap, heightening the risk of plaque rupture. Microcalcifications increase mechanical stress within the fibrous cap, making it more prone to rupture, potentially leading to myocardial infarction or stroke.[22]

History and Physical

Pain caused by CAD is known as angina pectoris, typically presenting as a gradual onset of discomfort in the chest, particularly behind the sternum. This discomfort can be triggered by physical exertion or emotional stress and may also occur at rest in cases of ACS. The pain often radiates to the left arm, neck, jaw, teeth, and ear, which may be explained by the convergence of signals from the vagus, trigeminal, and cervical spinal nerves (C2-C3). In addition to chest discomfort, patients frequently experience symptoms such as shortness of breath, nausea, and dizziness.

Research has shown that both men and women with CAD commonly experience chest pain, with this symptom being more prevalent than atypical presentations. Atypical pain is often described as pain in the epigastric region or back or as sensations of burning, stabbing, or indigestion. Women may complain of shortness of breath, easy fatigability, and back pain.[23] 

Angina pectoris may be classified into 2 types: stable and unstable. Stable angina is generally triggered by physical activity, whereas unstable angina can occur suddenly, even at rest. Patients with unstable angina have a poorer prognosis and a higher risk of progressing to myocardial infarction. Individuals with CAD may exhibit either typical (classic) or atypical (nonclassic) pain. Classic pain generally presents as midsternal discomfort, sometimes radiating to the left neck, shoulder, or arm. However, in some cases, the only symptom may be craniofacial pain during an ischemic event. Please see our companion topic on Stable Angina.

Patients experiencing atypical pain are less likely to receive an accurate diagnosis, which is associated with a threefold increase in mortality compared to those with classic angina symptoms. Moreover, a significant proportion of myocardial infarction cases present either asymptomatically or with subtle, nonclassic symptoms, often identified incidentally during routine electrocardiography (ECG) that reveals abnormal Q waves. In some instances, patients may report pain in areas of the body other than the heart, a condition known as heterotopic pain, which can lead to misdiagnosis and unnecessary medical procedures.

Physical examination should include inspection, palpation, and auscultation. During inspection, one must look for acute distress, jugular venous distention, and peripheral edema. During palpation, one should feel a fluid thrill or heave. The severity of peripheral edema or jugular vein distension, if present, should be evaluated. During auscultation, the heart must be examined in all 4 locations, and the lungs should be assessed with a particular focus on the lower zones.

Many individuals with CAD present with nonclassic symptoms that may not be detected during standard emergency department assessments, including history taking, physical examination, and 12-lead ECG. The diagnosis may be overlooked if these patients are not admitted for further evaluation. Studies have shown that 2% to 5% of patients with myocardial infarction who are mistakenly sent home from the emergency department experience poor outcomes, making these individuals a significant source of malpractice claims in emergency medicine. Misdiagnosis often occurs due to the absence of chest pain and lack of ST-segment elevation on the ECG.[24]

The most classic presentation is with reported angina pectoris (commonly referred to as angina) where patients endorse chest discomfort, often left-sided and substernal, that occurs with exertion or emotion and is relieved with rest or nitroglycerin. The description of the chest discomfort itself can vary from heaviness to pressure, squeezing or tightness. Radiation to the left arm, neck, or jaw is also fairly common. The presence of chest “pain” per se, reproducibility with palpation, variation with respiration, or pinpoint localization by the patient makes ischemia less likely.

Patients also may present with “angina-equivalent” symptoms where chest discomfort is never quite present, but instead, exertional dyspnea or more atypical symptoms occur during exercise and limit their functionality. Older age, female gender, and diabetes are typical risk factors. In fact, silent ischemia (or silent myocardial infarction) is not a rare occurrence in the latter population.

Temporally, stable angina is differentiated from unstable angina by its chronicity and reproducibility with exertion. Symptoms will typically last for minutes (not seconds or hours) and after a predictable amount of exertion before being relieved with rest. If the stable, chronic nature of angina changes, where it occurs with less exertion, last for a longer duration of time, or becomes more severe, then urgent evaluation for unstable angina needs to be performed.  

Clinically, if all three criteria are met (substernal chest pain, occurring with exertion and emotion, relieved by rest or nitroglycerin), then it is considered typical angina. This definition is meant to imply a high likelihood of ischemic heart disease as the cause of chest discomfort in the right clinical context. Frequently, patients will not fulfill all three criteria and will be further stratified into atypical angina or non-cardiac chest pain, depending on how many criteria they meet and the overall description of their symptoms.

Stable ischemic heart disease also may be completely asymptomatic, and in fact, studies have proven that atherosclerotic disease, the most common precursor to IHD, starts in childhood and develops over decades, during which patients are completely asymptomatic. It is only after the disease reaches a critical proportion, with coronary artery obstruction amounting to at least 50% of the vessel lumen, that symptoms, if any, may develop. During that period, clinicians will need to be proactive in screening patients at intermediate or higher risk in order to start therapy early.

17487580

9547449

30659365

Evaluation

Several modalities are highly useful in evaluating CAD, including ECG, echocardiography, chest radiography, stress testing, cardiac catheterization, and serum markers. Patient presentation dictates how these tests are utilized. Below are details on different diagnostic modalities available for the evaluation of CAD.

Electrocardiogram

ECG is a fundamental yet enormously helpful test in evaluating CAD. ECG measures electrical activity in the cardiac conduction system, measured by 10 leads attached to the skin at standardized locations. This modality provides information about the heart's anatomy and physiology. ECG tracings typically report cardiac activity on 12 leads, with each lead correlating with a specific cardiac location.

Vital information to note on an ECG tracing includes the heart's rate, rhythm, and axis, the interpretation of which can help identify ongoing acute or chronic pathologic processes. ACS may present with ST-segment and T-wave changes. ACS-related arrhythmias may also be detected. In chronic settings, ECG can provide clues to abnormalities like axis deviation, bundle branch blocks, and ventricular hypertrophy. ECG is also a cost-effective and readily available testing modality that is not user-dependent.

Notably, symptoms help patients detect the presence of a health issue. These symptoms prompt clinicians to perform ECGs, which are essential for making informed clinical decisions, such as activating the cardiac catheterization laboratory for an urgent percutaneous coronary intervention (PCI). When patients arrive at the emergency department, their condition is often undiagnosed, and the final diagnosis is only determined after thorough testing.

Emergency medical services (EMS) personnel can now perform prehospital ECGs. However, a recent study revealed that only 44.6% of patients with ACS reached the emergency department via EMS. Furthermore, only a small percentage (24.6%) of these patients experienced STEMI, and only 56.3% of individuals with STEMI called EMS. Consequently, many patients with ACS symptoms arrive at the emergency department without a diagnosis.[25]

Additionally, patients with chest pain are more likely to receive a prehospital ECG compared to those with other symptoms. Therefore, even though prehospital ECG technology is more widely available, patients who do not report chest pain are less likely to receive this diagnostic test. Including STEMI patients in studies is essential to accurately assess symptom differences and similarities between female and male patients, especially since STEMI requires time-sensitive reperfusion therapy.[26]

Echocardiography

Echocardiography is essentially cardiac ultrasound. This valuable and noninvasive mode of testing may be performed in acute, chronic, inpatient, and outpatient settings. Echocardiography detects wall motion, valvular regurgitation and stenosis, infective or autoimmune lesions, and chamber sizes in acute settings. This tool is also helpful in diagnosing acute pulmonary pathologies like pulmonary embolism. Additionally, echocardiography evaluates the pericardial cavity. In chronic settings, echocardiography can be performed to visually monitor cardiac activity and response to therapy. The test is also used outpatient as part of stress testing.

Echocardiography also has a role in therapeutics. For example, pericardiocentesis may be performed with the needle guided by ultrasound. This test is user-dependent and often more expensive than ECG.[27]

Until recently, the evaluation of regional wall motion abnormalities was the primary focus of stress echocardiography. The European Society of Cardiology advocates the advanced ABCDE protocol, and this assessment remains the core component of step A. However, the protocol has expanded to include additional assessments.

Regional perfusion using ultrasound contrast agents may also be evaluated in step A. Step B evaluates diastolic function and pulmonary B-lines, while step C assesses left ventricular contractile and preload reserve using volumetric echocardiography. Step D focuses on Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery, and step E measures ECG-based heart rate reserve in a nonimaging format. These 5 biomarkers are integrated within the ABCDE protocol, providing a comprehensive approach to risk stratification for patients with chronic coronary syndromes.[28]

Stress Test

The stress test is a relatively noninvasive test for CAD. This modality is used in the setting of suspected angina or angina equivalent and is helpful in identifying coronary pathology when interpreted in the appropriate setting. The heart is artificially exposed to stress during the test. The test is aborted if the patient develops anginal symptoms or abnormal ECG changes, particularly in ST segments, and CAD is diagnosed. ECGs are obtained before, during, and after the procedure, and the patient is continuously monitored for any symptoms.

The stress echocardiography laboratory utilizes various methods, such as exercise, dobutamine, vasodilators like dipyridamole or adenosine, and external pacing for patients with permanent pacemakers. This range of stress-inducing techniques allows for selecting the most suitable test tailored to each patient's needs. In exercise stress tests, the patient has to run on a treadmill until 85% of the age-predicted maximal heart rate is achieved. The test is aborted if a patient develops exertional hypotension, hypertension (>200/110 mm Hg), ST-segment elevations or depression, or ventricular or supraventricular arrhythmias.[29]

Chest Radiography

Chest radiographs are an essential component of the initial evaluation of cardiac disease. The standard imaging films include standing posteroanterior and left lateral decubitus views. Anteroposterior projection is occasionally obtained, especially in inpatient settings, with the patient lying down. However, this interpretation of anteroposterior films is significantly limited. Proper analysis of posteroanterior and anteroposterior views provides valuable and cost-effective information about the heart, lungs, and vasculature. Interpretation should be completed stepwise so that important information is not overlooked. 

Serum Markers

Blood work aids in establishing the diagnosis and assessing therapeutic responses. In acute settings, cardiac enzymes and B-type natriuretic peptides (BNP) are often taken along with complete blood counts and metabolic panels. BNP provides information about volume overload of cardiogenic origin. However, this marker has limitations. BNP can be falsely elevated in kidney disease and falsely low in obesity.

Cardiac enzymes like creatine kinase and troponin provide information about an acute ischemic event. In chronic settings, lipid panels offer important prognostic information. C-reactive protein and erythrocyte sedimentation rate aid in assessing diseases like acute pericarditis. Liver function tests may be taken to evaluate for an infiltrative process that can affect the liver and heart simultaneously, like hemochromatosis. Liver tests also assess increased right heart pressures, especially in chronic settings.

Cardiac Catheterization

Cardiac catheterization is the gold standard and most accurate modality for evaluating ischemic coronary heart disease. Coronary angiography is used to assess the type and number of affected vessels and the severity of stenosis, which are essential in determining the appropriate approach for coronary intervention. However, this invasive procedure has potentially serious complications, and not everyone is a candidate for it.

Patients with intermediate pretest probability for CAD are suitable cardiac catheterization candidates in non-ACS settings. If ACS is diagnosed, all patients with STEMI and selected individuals with NSTEMI should receive an emergent cardiac catheterization. This procedure is performed in a cardiac catheterization laboratory. It is expertise-dependent and accomplished under moderate sedation. Cardiac catheterization requires contrast exposure, which may cause severe allergic reactions and kidney injury.[30]

As an indicator of clinical flow impairment, the extent of stenosis in a lesion is assessed by comparing the maximum stenotic diameter to the diameter of adjacent, typically normal, arterial segments. Coronary flow reduction starts with stenosis exceeding 50% and accelerates once it surpasses 70%. Measuring the percent diameter of stenosis is clinically valuable for evaluating obstruction to blood flow, especially for stenoses below 50% or above 70%.[31]

Coronary Calcium Score and Computed Tomography Angiography

Between 2013 and 2020, 10,857 patients at Haukeland University Hospital in Norway underwent coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA). Obstructive CAD was diagnosed on CCTA if 1 or more vessels with at least 50% stenosis were identified. High-risk CAD included obstructive stenoses in the left main stem, proximal left anterior descending artery, or all 3 major coronary territories, with involvement of at least 1 proximal segment.

A CAC score of 0 in symptomatic patients effectively excluded obstructive CAD and high-risk CAD in 98.2% and 99.4% of cases, respectively. This extensive registry-based study supports using CAC testing for initial patient assessment and as a preliminary step before further cardiac evaluation. However, a full CCTA might be necessary in patients younger than 45 to rule out obstructive CAD safely.[32]

Primary screening for stable ischemic heart disease starts with identifying risk factors associated with the development of atherosclerosis. Older age, male gender, smoking, hypertension, diabetes mellitus, and hyperlipidemia, as well as family history of premature coronary artery disease (defined as an occurrence in a first-degree relative at the age of less than 55 for males or less than 65 for females), are among the strongest risk factors. Obesity, limited physical activity, psychosocial factors such as stress and depression, as well as co-existing chronic kidney disease or another atherosclerotic cardiovascular disease (ASCVD) such as stroke, or peripheral vascular disease (PVD) are also associated with ischemic heart disease.

The "2010 ACC/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults" recommended the use of global risk scores, such as the Framingham Risk Score (FRS), to risk assess all adults. 

The "2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk” added the pooled cohort ASCVD risk equation as a reliable tool for non-Hispanic African American or non-Hispanic white patients who are 40 to 79 years of age. Both global risk score calculators (as well as several others) rely on similar risk factors known to be associated with IHD as mentioned prior, though certain risk factors like positive family history are difficult to quantify and should be accounted for by the physician for every individual patient.

The ASCVD pooled cohort equation was also used in the “2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults” to risk stratify all adults over the age of 21. Patients with known ASCVD, LDL greater than 190mg/dL, diabetes mellitus or 10-year ASCVD calculated risk estimated at greater than 20% are considered high-risk. For this group of patients, high intensity (or maximally tolerated) statin therapy is recommended.

Patients are further stratified into those with intermediate-risk if their ASCVD risk is calculated at 7.5% to 20%, or borderline if their ASCVD risk is 5% to 7.5%. For this group, it is advised to initiate a discussion with the patients regarding their individual risk factors before making a decision to start statin therapy. Further risk stratification using coronary artery calcium (CAC) score could also be helpful. In general, patients with CAC score more than 100, or higher than 75th percentile for their age-matched cohorts are considered at higher risk. Other risk enhancers include hs-CRP of at least 2.0 mg/L, ABI < 0.9 and elevated Lp(a) or apoB levels.

The newer 2017 guidelines also rely on global risk calculators such as the Reynold Risk Score or the MESA (Multi-Ethnic Atherosclerosis Study), but add an LDL-C target instead of an intensity-based approach to statin therapy and/or lipid management strategy. Amidst all of these sequential guidelines, what remains constant is an emphasis on screening for higher risk patients and beginning therapy with lifestyle modification as well as lipid-lowering agents (statins being the cornerstone) while patients are still asymptomatic.

For patients known or suspected to have stable ischemic heart disease, initial evaluation should begin with a thorough history and physical examination, along with a baseline ECG to look for signs of ischemia or previous infarction. Stress testing, as well as an assessment of functional capacity is often necessary, particularly if the patients have active symptoms or evidence of ischemia such as ST changes on ECG. All patients diagnosed with stable ischemic heart disease should have an echocardiogram to assess for ventricular dysfunction because it directly affects management. This is especially true if it shows reduced LVEF. It may also show regional wall motion abnormalities suggestive of ischemia or an old infarction within a specific coronary artery territory. Laboratory tests such as a lipid panel, HbA1c, and renal function are routinely obtained as well. Troponin enzyme levels, brain natriuretic peptide (BNP) or NT-proBNP are not necessary for the diagnosis but may be useful in the right clinical setting.

After the clinical history and non-invasive testing are used to define patient risk, the decision to pursue invasive testing can be made. This is done through cardiac catheterization, where a coronary angiogram can define coronary anatomy with the aim of identifying flow-limiting atherosclerotic lesions. However, the indications to perform such a procedure largely depend on whether or not the information obtained is likely to affect management. While a coronary angiogram may occasionally be used to diagnose IHD in a patient with an atypical clinical presentation or indeterminate stress test results, it is often not done for purely diagnostic reasons. The primary benefit for the majority of patients is in providing another layer of risk-stratification that can direct revascularization-eligible patients towards that route, where they may receive primary cutaneous intervention (PCI) or be referred for coronary artery bypass graft (CABG) surgery.

In that respect, the 2014 ACC/AHA focused update for the diagnosis and management of stable ischemic heart disease guidelines recommend coronary angiography in patients with high-risk of severe IHD (as determined by the clinical setting and stress test results) who are amenable to revascularization (Class IIA recommendation) or patients with refractory ischemic symptoms despite goal-directed medical therapy (Class I recommendation). It is also reasonable to perform in patients with suspected stable ischemic heart disease, where diagnostic tests, including stress test results, are indeterminate.

Coronary angiography is not recommended to assess risk in asymptomatic patients or those at low-risk according to clinical criteria prior to noninvasive stress testing. It also is not recommended in patients with preserved LV function (ejection fraction greater than 50%) and low risk on non-invasive testing. Higher risk patients should also not undergo angiography if they are not candidates for revascularization because of comorbidities or individual preference since it exposes them to the risks of the procedure without affecting future management or improving outcomes.

Treatment / Management

CAD could present either as SIHD or ACS. The management depends on the particular disease type, as discussed below.

Stable Ischemic Heart Disease

SIHD is a chronic condition that primarily presents as stable angina, manifesting with substernal chest pain or pressure that worsens with exertion or emotional stress and gets relieved with rest or nitroglycerin treatment. Duration is at least 2 months. Note that classic anginal symptoms could be absent in some patients, and SIHD may manifest with atypical symptoms and exertional dyspnea in certain demographic groups, including women, older individuals, and people with diabetes mellitus. Management of SIHD includes both nonpharmacologic and pharmacologic interventions. Lifestyle modifications include smoking cessation, regular exercise, weight loss, reasonable control of diabetes and hypertension, and a healthy diet. Pharmacologic interventions include cardioprotective and antianginal medications.

Every patient should get guideline-directed medical therapy (GDMT), which includes low-dose aspirin, β-blocker, as-needed nitroglycerin, and moderate-to-high-intensity statin. If symptoms are not controlled despite GDMT, β-blocker therapy should be titrated up to achieve heart rates between 55 and 60. Adding calcium channel blockers and long-acting nitrates should also be considered.[33] Ranolazine may also be added to relieve refractory anginal symptoms. Failure of maximal GDMT to relieve angina warrants cardiac catheterization to visualize coronary anatomy. A decision on PCI or coronary artery bypass graft (CABG) should also be made based on patient profile.[34]

Acute Coronary Syndrome

ACS presents as sudden-onset substernal chest pain or pressure, typically radiating to the neck and left arm, and may be accompanied by dyspnea, pal pitations, dizziness, syncope, cardiac arrest, or new-onset congestive heart failure. Prompt ECG testing is necessary for all patients with ACS to assess for STEMI. EMS personnel may obtain an ECG in the prehospital setting. STEMI is recognized by ST elevation in contiguous leads of 1 mm in limb or precordial leads except V2 and V3. A STEMI diagnosis in leads V2 and V3 requires 2-mm elevations in men and 1.5-mm elevations in women. Please see our topic Acute Coronary Syndrome for additional discussion.

A new-onset left bundle branch block (LBBB) is considered a STEMI equivalent. A STEMI warrants an emergency PCI, preferably performed in a PCI-capable facility within 2 hours. If the PCI-capable facility is more than 2 hours away, intravenous thrombolytic therapy is indicated after ensuring no contraindications.

A true STEMI must be differentiated from mimics (based on ECG), such as acute pericarditis, Brugada syndrome, early repolarization, and left ventricular hypertrophy-associated changes. Upon presentation, all patients should get a full dose of sublingual aspirin (324 mg). Nitrates should be given for pain relief after ensuring that the patient has no contraindications, such as hypotension, right ventricular failure, and intake of phosphodiesterase inhibitors in the past 24 to 48 hours. High-dose statin therapy and β-blockers should also be initiated early. P2Y12 inhibitors (prasugrel, ticagrelor, or prasugrel) should be considered based on patient profile.

Individuals with non-ST-elevation ACS should receive anticoagulation, typically with heparin or enoxaparin. For NSTEMI, early invasive therapy within 24 hours is advised for patients with intermediate-to-high TIMI scores (>2).[35][36]

Regular visits with cardiologists and family physicians are critical to the long-term management of CAD. Medication adherence and lifestyle modification are also essential.

A systematic review following stenting conducted for the 2016 Americal College of Cardiology/AHA DAPT guidelines analyzed the outcomes of death, major bleeding, myocardial infarction, stent thrombosis, and major adverse cardiac events in 33,051 patients across 11 randomized controlled trials. These trials compared prolonged DAPT to short-course DAPT as a regimen following a drug-eluting stent (DES) procedure and as an agent for secondary prevention after a myocardial infarction episode. The review found that, in patients treated with DES, extended DAPT reduced the incidence of stent thrombosis and myocardial infarction but led to an increased risk of significant bleeding. Additionally, patients with a history of myocardial infarction showed a reduction in cardiovascular events, although this benefit came with a higher risk of bleeding.[37]

Several trials have provided evidence supporting DAPT for 6 months, followed by continued aspirin use beyond this period. The largest of these trials, ISAR-SAFE (a randomized, double-blind trial of 6 versus 12 months of DAPT after DES implantation), involved 4,005 patients, 60% of whom had stable CAD. In these studies, patients continued taking aspirin throughout the 12-month trial period.[38]

However, data is limited on whether aspirin or clopidogrel is the preferable antiplatelet agent for indefinite use after the initial 12 months post-PCI. The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Extended Antiplatelet Monotherapy) trial, which included 5,530 East Asian participants who had tolerated DAPT for 6 to 18 months without ischemic or major bleeding complications, compared the effects of continuing with either clopidogrel (75 mg daily) or aspirin (100 mg daily) for an additional 24 months.[39]

The goals of treatment are to limit atherosclerotic disease progression, prevent or reduce complications including death, and to near-completely eliminate ischemic symptoms with the aim of improving quality of life, and restoring functional capacity. In order to achieve that, three aspects must be addressed: (1) risk-modification, (2) guideline-directed medical therapy (GDMT), and (3) revascularization.

Risk modification begins with individualized life-style changes such as dietary modification, weight reduction, smoking cessation, and frequent exercise. It is also reasonable to counsel patients to avoid stressors and develop coping mechanisms for depression and anxiety where applicable. Education regarding medication adherence and careful self-monitoring also is vital. Importantly, much attention should be directed towards optimizing hypertension, diabetes, and dyslipidemia management since they can directly affect stable ischemic heart disease outcomes, and increase risk of future events.

Guideline-directed medical therapy (GDMT) itself can be split into two categories. The first includes therapies that slow down the atherosclerotic disease, decrease future events of myocardial infarction, and longitudinally decrease mortality. They include anti-platelet agents, beta blockers, renin-angiotensin-aldosterone blockers and lipid-lowering drugs. The second category directly addresses symptoms, and attempts to eliminate angina (or angina-equivalent symptoms) through use of nitrates, beta blockers, calcium channel blockers, and novel therapies. We will discuss the former category of GDMT first, then go through available anti-anginal therapies, and lastly address revascularization.

Medical Therapy to Prevent Myocardial Infarction and Death

Antiplatelet therapy is recommended for secondary prevention in patients with stable ischemic heart disease. The most commonly used agent is aspirin, which irreversibly acetylates platelet cyclooxygenase, and limits thromboxane A2 production thereby decreasing platelet aggregation. Studies have shown that aspirin use following acute coronary syndrome can decrease mortality, and improve outcomes in several trials such as CLARITY-TIMI (which studied patients post-fibrinolysis), and CURRENT OASIS which compared high-dose to low-dose therapy. Consequently, guidelines recommend aspirin 81 to 162 mg daily indefinitely to all patients who can tolerate it.

Controversy remains regarding the use of aspirin for primary prevention in patients at variable risk of coronary CAD. Major recent trials have shown no significant reduction in cardiovascular events, often with an increased risk of bleeding. The ARRIVE trial identified patients at moderate risk who received aspirin for primary prevention, and demonstrated no reduction in the primary outcomes of CV death, MI, unstable angina, stroke or transient ischemic attack. Furthermore, there was an increase in gastrointestinal bleeding (HR = 2.11, CI 95%, 1.36 - 3.28). Similar findings were found in the ASCEND trial, which studied diabetic patients, and the ASPREE trial which followed more than 19,000 patients at least 65 years of age, who were free from CVD or dementia. These findings may suggest that aspirin should not be routinely prescribed for the sole purpose of primary prevention, and that a careful risk-benefit assessment - as pertains to cardiovascular outcomes versus bleeding - needs to be performed before initiation of life-time therapy.

A relative contraindication exists for patients with an NSAIDs allergy and the Samter triad (asthma, nasal polyps, and aspirin sensitivity). In those circumstances, clopidogrel 75 mg daily, which works through irreversibly inhibiting P2Y12 receptors and has demonstrated favorable outcomes in the CAPRIE trial as compared to aspirin, can be used instead. Newer anti-platelet agents such as ticagrelor and prasugrel are not currently recommended for the treatment of stable ischemic heart disease unless patients have had a recent acute coronary event, due to unacceptably elevated risk of bleeding as compared to more traditional therapy in this cohort.

Beta blockers are the only anti-anginal drugs known to prevent infarction and impact mortality in ischemic cardiomyopathy as demonstrated in multiple studies. This is particularly true for patients with reduced LVEF, where trials such as CIBIS II and MERIT-HF showed improved survival. The CAPRICORN trial also studied patients with ischemic cardiomyopathy post myocardial infarction with LVEF less than 35% and showed similar outcomes. Subsequently, current guidelines recommend beta blocker use for at least 3 years after a myocardial infarction and indefinitely for all patients with LVEF of less than 40%, and heart failure symptoms.

The selective use of renin-angiotensin-aldosterone inhibitors is also recommended, and the strongest evidence exists for patients with reduced LVEF as well as those with high risk features. The 1992 survival and ventricular enlargement trial (SAVE), for example, demonstrated decreased mortality with use of captopril in patients with asymptomatic reduced LVEF after an acute myocardial infarction. While the more recent HOPE trial showed improved outcomes with the use of ramipril in patients with established CAD or known atherosclerotic risk factors. However, this is not universal to all patients with stable ischemic heart disease since several studies were unable to demonstrate the same benefits in lower risk populations. As it currently stands, ACE inhibitors are recommended for stable ischemic heart disease patients with reduced LVEF less than 40% and those with high-risk features such as hypertension, diabetes and chronic kidney disease. Angiotensin-receptor blockers (ARBs) also can be used for similar indications in ACE intolerant patients.

Mineralocorticoid antagonists also were studied post myocardial infarction in the EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival) trial, where patients with LVEF less than 40% were started on eplerenone and showed decreased cardiovascular mortality. Per current guidelines, spironolactone or eplerenone are recommended in the subset of patients with reduced LVEF after acute myocardial infarction if they have heart failure or DM.

The national recommendations regarding lipid-lowering therapy have generated much controversy in the past several years, but an agreement exists regarding the need for all patients to be on statin therapy if tolerated. The “2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults” recommended an intensity-based approach, where all patients with established ASCVD (including SIHD) should be on high-intensity statin therapy, or the highest-intensity therapy tolerated, regardless of LDL target. Newer publications advocate a risk-assessment algorithm, where individual patient risk is assessed, and most patients with stable ischemic heart disease are targeted for an LDL less than 70 (or less than 55 for patients with the highest risk). The “2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk” also advocates the selective use of PCSK9 inhibitors, ezetimibe, bile acid sequestrants, nicotinic acid, and fibrates for patients who are intolerant of or have an inadequate response to statin therapy.

Currently, patients with very high ASCVD risk (those with recurrent events, or one ASCVD event in addition to multiple risk factors) are recommended to maintain an LDL level < 70. If patient are unable to achieve their LDL target goal, then Ezetimibe should be added. If goal target is still not achieved, or if patients are intolerant to statin therapy, then PCSK inhibitors should be initiated.

Medical Therapy for Relief of Symptoms

Beta blockers are considered first-line agents, as they are the only anti-anginal medication proven to impact survival. Past the initiation of beta-blocker therapy, the treatment strategy requires escalation of administered dosage or addition of second-line agents until complete or near-complete symptom relief is achieved. If medical therapy fails due to medication intolerance or intractable pain, then revascularization is pursued.

Nitrates are potent vasodilators and cause a combination of venodilation (decreasing preload), arterioral dilation (decreasing afterload), as well as coronary dilation. It is the decreased preload and ventricular wall stress, with resultant decreased oxygen demand that primarily mediates its anti-anginal effects, however. Nitrates are available in sublingual form, which bypasses the first-pass effect and can be used acutely, while more sustained oral or transdermal formulations may be added to beta-blocker therapy for prolonged anti-anginal effect. This requires that a nitrate-free interval of at least 10 to 12 hours be maintained, usually overnight, to prevent tachyphylaxis and diminishing effect.

Calcium channel blockers (CCB) are considered second-line therapy and can be used to augment beta-blocker therapy or as a substitute in patients who are intolerant to them. They are only recommended for uncontrolled ischemic symptoms since they do not affect long-term survival or reduce mortality. Nondihydropyridine CCB agents, such as verapamil and diltiazem, should be used with caution when combined with beta blockers, since that may cause combined negative inotropic and chronotropic effect, with severe hypotension and/or atrioventricular block. This is especially true in patients with reduced systolic function or baseline conduction impairment. Therefore, dihydropyridine agents such as amlodipine are more commonly used in this setting.

Ranolazine, a sodium-channel blocker, is a newer medication that may be used if all the former agents are unsuccessful in controlling chest pain. It may be used in combination with beta-blockers and CCBs. Rarely, alternative therapies such as enhanced external counterpulsation (EECP) or spinal stimulation may be utilized. However, the majority of patients that fail medical therapy would qualify for revascularization, if feasible, to improve symptoms.

Revascularization

In stable ischemic heart disease, there are two main aims of revascularization. The first is to improve symptoms and would require that angina be present despite optimal GDMT in a patient with favorable coronary anatomy for revascularization. The second aim is to improve survival, which is reliant on the presence of high risk anatomy often in the setting of high-risk clinical features. In that regard, revascularization is indicated in left-main (or left-main equivalent) disease, three-vessel disease, or two-vessel disease, including proximal left anterior descending (LAD) coronary artery stenosis. Similar recommendations do not apply to single-vessel disease or two-vessel disease not including the proximal LAD in the absence of refractory symptoms.

While both CABG and primary cutaneous intervention (PCI) are reasonable for the intent of revascularization; the presence of complex anatomy, LV dysfunction, diabetes mellitus, anticipated low-surgical risk and/or high PCI procedural risk are indications to choose CABG over PCI. The literature evidence showing improved survival has also traditionally favored CABG, particularly where left internal mammary grafts were used to bypass proximal LAD stenosis. Clinically, less complex coronary anatomy in association with ischemic symptoms is often treated with PCI to achieve symptom relief. Several studies, including the landmark COURAGE and BARI 2D trials, failed to show mortality benefit in the latter population however.  Despite benefits of symptom relief, no evidence to date has shown survival benefit for revascularization in single-vessel disease, not including the proximal LAD.

Differential Diagnosis

CAD has a wide range of differential diagnoses because of the heart's proximity to adjacent organs, including the lungs, stomach, prominent vessels, and musculoskeletal organs. Acute anginal chest pain can mimic acute pericarditis, myocarditis, Prinzmetal angina, pericardial effusion, acute bronchitis, pneumonia, pleuritis, pleural effusion, aortic dissection, gastroesophageal reflux disease, peptic ulcer disease, esophageal motility disorders, and costochondritis. SIHD may also mimic gastroesophageal reflux disease, peptic ulcer disease, costochondritis, and pleuritis. History taking, physical examination, and diagnostic studies should be diligently conducted to narrow the differential diagnosis and reach an accurate diagnosis.

• Acute pericarditis

• Angina pectoris

• Atherosclerosis

• Coronary artery vasospasm

• Dilated cardiomyopathy

• Familial hypercholesterolemia

• Giant cell arteritis

• Hypertension

• Hypertensive heart disease

• Kawasaki disease

Toxicity and Adverse Effect Management

Both medical and surgical management for IHD have potential side effects and complications. Careful selection, physician expertise, and patient education can mitigate these undesirable effects. Aspirin therapy may cause bleeding, idiosyncratic, and allergic drug reactions.[40] Statin therapy may produce myalgias, diarrhea, and arthralgia.[41] 

β-blocker use can result in bradycardia and hypotension. Angiotensin-converting enzyme inhibitor intake may result in hypotension, dizziness, creatinine elevation, cough, and allergic reactions, including angioedema.[42] PCI can cause coronary artery perforation and stent thrombosis acutely and instent restenosis chronically.[43] CABG's potential complications include but are not limited to arrhythmias, cardiac tamponade, postoperative bleeding, infection, renal impairment, and phrenic nerve injury.

Prognosis

CAD's prognosis depends on multiple factors, some of which are modifiable. The patient's age, gender, family history and genetics, ethnicity, dietary and smoking habits, medication compliance, availability of healthcare and financial status, and the number of arteries involved are some factors. Comorbid conditions, including diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease, also have a role in the overall outcome.[44]

Complications

Arrhythmias, congestive heart failure, mitral regurgitation, mechanical complications, pericarditis, aneurysm formation, and mural thrombi are the main complications associated with CAD.[45][46] These complications are discussed below.

Arrhythmias

Numerous arrhythmic complications can arise in the early period following a myocardial infarction episode. The appropriate management of these arrhythmias depends on several patient-specific factors, including the timing of symptom onset, left ventricular function, overall clinical condition, and the presence of comorbidities.

Certain peri-infarct arrhythmias, such as ventricular arrhythmias, atrial fibrillation, and persistent high-grade atrioventricular block, necessitate immediate intervention. Other arrhythmias, such as sinus bradycardia and tachycardia and transient high-grade atrioventricular block, may require urgent treatment but often resolve on their own following reperfusion and as time progresses. Recognizing these arrhythmias, understanding their likelihood, and being aware of the associated risks are crucial for improving preparedness and outcomes in these vulnerable patients.[47]

Congestive Heart Failure

Investigating cardiac biomechanics is crucial for evaluating the overall cardiovascular function in patients with myocardial infarction, as this population is at a heightened risk of developing chronic heart failure (CHF) due to pathological left ventricular remodeling. Monitoring left ventricular ejection fraction (LVEF) is particularly important in managing CHF, as a reduced LVEF is linked to a poor prognosis, diminished quality of life, and higher mortality and hospitalization rates.

An LVEF decline during follow-up is a clear indicator of CHF progression. A decreased LVEF, signaling the transition from heart failure with preserved ejection fraction (HFpEF) to heart failure with mid-range ejection fraction (HFmrEF) or reduced ejection fraction (HFrEF), is typically seen as a sign of CHF progression in the postinfarction period. Additionally, many studies have identified heart rate variability as a reliable predictor of high mortality risk and CHF progression.[48]

Mitral Regurgitation

A study analyzed 1,000 patients admitted with acute myocardial infarction (AMI) from 2016 to 2017, all of whom underwent PCI followed by predischarge transthoracic echocardiography. Mitral regurgitation was identified in 294 patients (29%) and was categorized as mild in 224 cases (76%), moderate in 61 cases (21%), and severe in 9 cases (3%). Compared to patients without mitral regurgitation, people with this pathology were older (70 ± 12 years vs. 63 ± 13 years; p < 0.001) and exhibited worse LVEF (52 ± 15% vs. 55 ± 11%; p < 0.001) and lower creatinine clearance (69 ± 33 ml/min vs. 90 ± 39 ml/min; p < 0.001).

Additionally, patients with mitral regurgitation had higher rates of hypertension (64% vs. 55%; p = 0.012), heart failure (3.4% vs. 1.1%; p = 0.014), prior myocardial infarction (28% vs. 20%; p = 0.005), and significant flow-limiting lesions in the circumflex artery (50% vs. 33%; p < 0.001) or right coronary artery (51% vs. 42%; p = 0.014). The prevalence and severity of mitral regurgitation were consistent across different AMI subtypes.[49]

Mechanical Complications

During the 13-year study period from 2003 to September 2015, 3,982,655 hospitalizations for STEMI and 5,143,707 hospitalizations for NSTEMI were analyzed. The incidence of mechanical complications, such as papillary muscle rupture (PMR), ventricular septal defects (VSDs), and ventricular free wall rupture (FWR), both overall and individually, remained relatively stable over time in the STEMI and NSTEMI groups.

In the STEMI group, 10,726 patients (0.27%) experienced mechanical complications, including 2,024 cases (0.05%) of PMR, 8,401 cases (0.21%) of VSDs, and 301 cases (0.01%) of FWR. The in-hospital mortality rate for patients with STEMI with mechanical complications was 42.4%. In the NSTEMI group, 3,041 patients (0.06%) experienced mechanical complications, with 628 cases (0.01%) of PMR, 1,943 cases (0.04%) of VSDs, and 470 cases (0.01%) of FWR. The in-hospital mortality rate for patients with NSTEMI with mechanical complications was 25%.[50]

Pericarditis

Postmyocardial infarction pericarditis (PMIP) is an uncommon complication of STEMI in the era of coronary reperfusion. PMIP worsens short-term outcomes but does not affect long-term prognosis. The condition is often associated with larger infarcts.

A retrospective analysis of 6,282 patients with STEMI from the Acute Coronary Syndrome Israeli Survey (2000-2013) found that 76 patients (1.2%) had PMIP. Individuals with PMIP tended to be younger (median age 58 vs. 61; p = 0.045), showed lower rates of hypertension, had elevated cardiac biomarkers, and more frequently had reduced left ventricular ejection fraction (87% vs. 67%; p = 0.001). Patients with PMIP also experienced longer times to reperfusion (225 minutes vs. 183 minutes; p = 0.016) and extended hospital stays (7 vs. 5 days; p < 0.001). However, no significant differences in survival rates were observed at 30 days, 1 year, and 5 years.[51]

Aneurysm Formation

Data on the prevalence and outcomes of left ventricular aneurysms following AMI are limited. A retrospective cohort analysis, using the National Inpatient Sample from 2000 to 2017, evaluated AMI admissions for the presence of left ventricular aneurysms and associated complications, such as ventricular arrhythmias, mechanical complications, cardiac arrest, pump failure, left ventricular thrombus, and stroke. The study reviewed 11,622,528 AMI admissions, of which 17,626 (0.2%) had left ventricular aneurysms.

Patients with left ventricular aneurysms were more frequently female, had higher rates of comorbidities, and were more often admitted to large urban hospitals (all p < 0.001). From 2000 to 2017, a slight increase was observed in the prevalence of left ventricular aneurysms among patients with and without acute STEMI (p < 0.001). Left ventricular aneurysms were more commonly observed with anterior STEMI (31%) compared to inferior (12.3%) and other types (7.9%).[52]

Mural Thrombi

Information on the prevalence of ventricular mural thrombus following AMI is limited. In a study involving 50 patients admitted to a coronary care unit for acute anterior myocardial infarction with ST-segment elevation, coronary arteriography, left ventricular angiography, and revascularization were performed. Transthoracic echocardiography was utilized to evaluate the left ventricular chamber using both fundamental and second harmonic imaging along with contrast agents.

A left ventricular mural thrombus was confirmed in 12% (6 patients) of cases. Among patients with time-to-revascularization exceeding 3 hours, 35% had a left ventricular mural thrombus, compared to none in patients with a time-to-revascularization of 3 hours or less (p = 0.003). Contrast echocardiography emerged as the most accurate method for detecting left ventricular mural thrombus, regardless of the clinician's experience level.[53]

Deterrence and Patient Education

A combination of modifiable and nonmodifiable factors causes CAD. Primary care providers should focus on modifiable risk factor modification on each routine visit. Tight control of diabetes, hypertension, and lipid levels, in addition to smoking cessation, weight loss, and exercise, can make a huge difference. Since CAD is a global public health concern, increasing awareness through school curricula and various media outlets is essential.

Pearls and Other Issues

Several landmark trials have been conducted over the past few decades, and they have changed how we care for patients with CAD. Individual trial results are beyond this article's scope. However, some critical studies include ISIS-2, CURE, CLARITY-TIMI 28, TIRTON-TIMI 38, PLATO, and CURRENT-OASIS 7, which were conducted to help determine guidelines for antiplatelet medications.[54] SYNERGY, ACUITY, ExTRACT-TIMI 25, OASIS-5, and ATLAS ACS/TIMI 52 evaluated the value of anticoagulation in CAD management. ADMIRAL, ACUITY, ISAR-REACT 3, and HORIZONS-AMI were famous trials that investigated GpIIb/IIIa use. COMMIT studied β-blockers, while SHOCK, DANAMI-2, BASKET-LATE, TIMACS, and BASKET-PROVE explored PCI and CABG.

The MIRACL trial investigated statin use. Patients with diabetes or low HDL cholesterol are at a higher risk and gain more significant absolute benefit from early treatment with 80 mg of atorvastatin daily compared to those without these risk factors. In the overall population of the MIRACL study, administering 80 mg of atorvastatin resulted in a 2.6% reduction in the absolute risk of experiencing a primary endpoint event, such as death, nonfatal myocardial infarction, resuscitated cardiac arrest, and recurrent ischemia, compared to placebo. For patients with diabetes or low HDL cholesterol, the reduction in absolute risk was even more significant, at 4.4% and 3.7%, respectively.[55]

Enhancing Healthcare Team Outcomes

IHD frequently presents a diagnostic dilemma. Patients can present with nonspecific symptoms like chest pain or shortness of breath, which may arise from a myriad of diseases, including gastrointestinal, cardiac, musculoskeletal, psychological, and pulmonary causes. While a cardiologist is often a central player in IHD evaluation, taking other team members on board as indicated is essential, including a gastroenterologist, pulmonologist, and psychiatrist. Radiologists are also a vital resource in the whole process. Nurses are an integral part of the diagnostic and therapeutic workup and provide critical bedside information not witnessed by the physicians in their short encounters.

Despite the numerous guidelines on the management of ischemic heart disease, the key is prevention. Healthcare workers including nurse practitioners should educate patients on the benefits of changing their lifestyle and starting and exercise program. Patients should be told to eat healthy and discontinue smoking. Patients should be referred to a dietitian to learn about healthy foods and how to maintain a healthy body weight. There is no substitute for exercise- even walking will suffice as long as it is done on a regular basis.

Review Questions

• Access free multiple choice questions on this topic.
• Click here for a simplified version.
• Comment on this article.

References

1.

Ralapanawa U, Sivakanesan R. Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: A Narrative Review. J Epidemiol Glob Health. 2021 Jun;11(2):169-177. [PMC free article: PMC8242111] [PubMed: 33605111]

2.

Dalen JE, Alpert JS, Goldberg RJ, Weinstein RS. The epidemic of the 20(th) century: coronary heart disease. Am J Med. 2014 Sep;127(9):807-12. [PubMed: 24811552]

3.

Mensah GA, Roth GA, Fuster V. The Global Burden of Cardiovascular Diseases and Risk Factors: 2020 and Beyond. J Am Coll Cardiol. 2019 Nov 19;74(20):2529-2532. [PubMed: 31727292]

4.

Bauersachs R, Zeymer U, Brière JB, Marre C, Bowrin K, Huelsebeck M. Burden of Coronary Artery Disease and Peripheral Artery Disease: A Literature Review. Cardiovasc Ther. 2019;2019:8295054. [PMC free article: PMC7024142] [PubMed: 32099582]

5.

Jamal A, Phillips E, Gentzke AS, Homa DM, Babb SD, King BA, Neff LJ. Current Cigarette Smoking Among Adults - United States, 2016. MMWR Morb Mortal Wkly Rep. 2018 Jan 19;67(2):53-59. [PMC free article: PMC5772802] [PubMed: 29346338]

6.

Petrazzini BO, Chaudhary K, Márquez-Luna C, Forrest IS, Rocheleau G, Cho J, Narula J, Nadkarni G, Do R. Coronary Risk Estimation Based on Clinical Data in Electronic Health Records. J Am Coll Cardiol. 2022 Mar 29;79(12):1155-1166. [PMC free article: PMC8956801] [PubMed: 35331410]

7.

Nasir K, DeFilippis A. Big Data and ASCVD Risk Prediction: Building a Better Mouse Trap? J Am Coll Cardiol. 2022 Mar 29;79(12):1167-1169. [PubMed: 35331411]

8.

Koenig W. High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy. Int J Cardiol. 2013 Oct 15;168(6):5126-34. [PubMed: 23978367]

9.

Klein S, Allison DB, Heymsfield SB, Kelley DE, Leibel RL, Nonas C, Kahn R., Association for Weight Management and Obesity Prevention. NAASO, The Obesity Society. American Society for Nutrition. American Diabetes Association. Waist circumference and cardiometabolic risk: a consensus statement from Shaping America's Health: Association for Weight Management and Obesity Prevention; NAASO, The Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Am J Clin Nutr. 2007 May;85(5):1197-202. [PubMed: 17490953]

10.

Ross R, Neeland IJ, Yamashita S, Shai I, Seidell J, Magni P, Santos RD, Arsenault B, Cuevas A, Hu FB, Griffin BA, Zambon A, Barter P, Fruchart JC, Eckel RH, Matsuzawa Y, Després JP. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020 Mar;16(3):177-189. [PMC free article: PMC7027970] [PubMed: 32020062]

11.

Sharma S, Batsis JA, Coutinho T, Somers VK, Hodge DO, Carter RE, Sochor O, Kragelund C, Kanaya AM, Zeller M, Park JS, Køber L, Torp-Pedersen C, Lopez-Jimenez F. Normal-Weight Central Obesity and Mortality Risk in Older Adults With Coronary Artery Disease. Mayo Clin Proc. 2016 Mar;91(3):343-51. [PubMed: 26860580]

12.

Ferreira-González I. The epidemiology of coronary heart disease. Rev Esp Cardiol (Engl Ed). 2014 Feb;67(2):139-44. [PubMed: 24795124]

13.

Brown JC, Gerhardt TE, Kwon E. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jan 23, 2023. Risk Factors for Coronary Artery Disease. [PubMed: 32119297]

14.

Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, Baker-Smith CM, Beaton AZ, Boehme AK, Buxton AE, Commodore-Mensah Y, Elkind MSV, Evenson KR, Eze-Nliam C, Fugar S, Generoso G, Heard DG, Hiremath S, Ho JE, Kalani R, Kazi DS, Ko D, Levine DA, Liu J, Ma J, Magnani JW, Michos ED, Mussolino ME, Navaneethan SD, Parikh NI, Poudel R, Rezk-Hanna M, Roth GA, Shah NS, St-Onge MP, Thacker EL, Virani SS, Voeks JH, Wang NY, Wong ND, Wong SS, Yaffe K, Martin SS., American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation. 2023 Feb 21;147(8):e93-e621. [PMC free article: PMC12135016] [PubMed: 36695182]

15.

Puymirat É. [Epidemiology of coronary artery disease]. Rev Prat. 2015 Mar;65(3):317-20. [PubMed: 26016186]

16.

Al Thani H, El-Menyar A, Alhabib KF, Al-Motarreb A, Hersi A, Alfaleh H, Asaad N, Saif SA, Almahmeed W, Sulaiman K, Amin H, Alsheikh-Ali AA, Alnemer K, Suwaidi JA. Polyvascular disease in patients presenting with acute coronary syndrome: its predictors and outcomes. ScientificWorldJournal. 2012;2012:284851. [PMC free article: PMC3259691] [PubMed: 22272171]

17.

Ferreira-González I, Permanyer Miralda G, Heras M, Ribera A, Marsal JR, Cascant P, Arós F, Bueno H, Sánchez PL, Cuñat J, Civeira E, Marrugat J., Investigadores del Estudio MASCARA. Prognosis and management of patients with acute coronary syndrome and polyvascular disease. Rev Esp Cardiol. 2009 Sep;62(9):1012-21. [PubMed: 19712622]

18.

Cotter G, Cannon CP, McCabe CH, Michowitz Y, Kaluski E, Charlesworth A, Milo O, Bentley J, Blatt A, Krakover R, Zimlichman R, Reisin L, Marmor A, Lewis B, Vered Z, Caspi A, Braunwald E., OPUS-TIMI 16 Investigators. Prior peripheral arterial disease and cerebrovascular disease are independent predictors of adverse outcome in patients with acute coronary syndromes: are we doing enough? Results from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis In Myocardial Infarction (OPUS-TIMI) 16 study. Am Heart J. 2003 Apr;145(4):622-7. [PubMed: 12679757]

19.

Calais F, Eriksson Östman M, Hedberg P, Rosenblad A, Leppert J, Fröbert O. Incremental prognostic value of coronary and systemic atherosclerosis after myocardial infarction. Int J Cardiol. 2018 Jun 15;261:6-11. [PubMed: 29657058]

20.

Weight N, Moledina S, Zoccai GB, Zaman S, Smith T, Siller-Matula J, Dafaalla M, Rashid M, Nolan J, Mamas MA. Impact of pre-existing vascular disease on clinical outcomes. Eur Heart J Qual Care Clin Outcomes. 2022 Dec 13;9(1):64-75. [PubMed: 35575608]

21.

Nakahara T, Dweck MR, Narula N, Pisapia D, Narula J, Strauss HW. Coronary Artery Calcification: From Mechanism to Molecular Imaging. JACC Cardiovasc Imaging. 2017 May;10(5):582-593. [PubMed: 28473100]

22.

Hashmi S, Shah PW, Aherrahrou Z, Aikawa E, Aherrahrou R. Beyond the Basics: Unraveling the Complexity of Coronary Artery Calcification. Cells. 2023 Dec 12;12(24) [PMC free article: PMC10742130] [PubMed: 38132141]

23.

DeVon HA, Mirzaei S, Zègre-Hemsey J. Typical and Atypical Symptoms of Acute Coronary Syndrome: Time to Retire the Terms? J Am Heart Assoc. 2020 Apr 07;9(7):e015539. [PMC free article: PMC7428604] [PubMed: 32208828]

24.

Abdullatef M, Omran M, Bitar A, Alsaid B. Prevalence of classic and non-classic pain sites of coronary artery disease: a cross-sectional study. BMC Cardiovasc Disord. 2024 Aug 24;24(1):445. [PMC free article: PMC11344326] [PubMed: 39179977]

25.

Mirzaei S, Steffen A, Vuckovic K, Ryan C, Bronas UG, Zegre-Hemsey J, DeVon HA. The association between symptom onset characteristics and prehospital delay in women and men with acute coronary syndrome. Eur J Cardiovasc Nurs. 2020 Feb;19(2):142-154. [PMC free article: PMC7015763] [PubMed: 31510786]

26.

Zègre-Hemsey JK, Patel MD, Fernandez AR, Pelter MM, Brice J, Rosamond W. A Statewide Assessment of Prehospital Electrocardiography Approaches of Acquisition and Interpretation for ST-Elevation Myocardial Infarction Based on Emergency Medical Services Characteristics. Prehosp Emerg Care. 2020 Jul-Aug;24(4):550-556. [PMC free article: PMC7190419] [PubMed: 31593496]

27.

Sicari R, Cortigiani L. The clinical use of stress echocardiography in ischemic heart disease. Cardiovasc Ultrasound. 2017 Mar 21;15(1):7. [PMC free article: PMC5361820] [PubMed: 28327159]

28.

Picano E, Pierard L, Peteiro J, Djordjevic-Dikic A, Sade LE, Cortigiani L, Van De Heyning CM, Celutkiene J, Gaibazzi N, Ciampi Q, Senior R, Neskovic AN, Henein M. The clinical use of stress echocardiography in chronic coronary syndromes and beyond coronary artery disease: a clinical consensus statement from the European Association of Cardiovascular Imaging of the ESC. Eur Heart J Cardiovasc Imaging. 2024 Jan 29;25(2):e65-e90. [PubMed: 37798126]

29.

Bamouni J, Naibe DT, Yameogo RA, Mandi DG, Millogo GRC, Yameogo NV, Kologo JK, Thiam-Tall A, Nébié LAV, Zabsonré P. [Contribution of stress test to the treatment of ischemic heart disease]. Pan Afr Med J. 2018;31:229. [PMC free article: PMC6691289] [PubMed: 31447986]

30.

Meda JR, Kusima HL, Magitta NF. Angiographic characteristics of coronary artery disease in patients undergoing diagnostic coronary angiography at a tertiary hospital in Tanzania. BMC Cardiovasc Disord. 2024 Feb 26;24(1):125. [PMC free article: PMC10898171] [PubMed: 38408906]

31.

Gould KL, Lipscomb K. Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol. 1974 Jul;34(1):48-55. [PubMed: 4835753]

32.

Pedersen ER, Hovland S, Karaji I, Berge C, Mohamed Ali A, Lekven OC, Kuiper KJ, Rotevatn S, Larsen TH. Coronary calcium score in the initial evaluation of suspected coronary artery disease. Heart. 2023 Apr 12;109(9):695-701. [PubMed: 36549683]

33.

Bahit MC, Kochar A, Granger CB. Post-Myocardial Infarction Heart Failure. JACC Heart Fail. 2018 Mar;6(3):179-186. [PubMed: 29496021]

34.

Katz D, Gavin MC. Stable Ischemic Heart Disease. Ann Intern Med. 2019 Aug 06;171(3):ITC17-ITC32. [PubMed: 31382288]

35.

Makki N, Brennan TM, Girotra S. Acute coronary syndrome. J Intensive Care Med. 2015 May;30(4):186-200. [PubMed: 24047692]

36.

Smith JN, Negrelli JM, Manek MB, Hawes EM, Viera AJ. Diagnosis and management of acute coronary syndrome: an evidence-based update. J Am Board Fam Med. 2015 Mar-Apr;28(2):283-93. [PubMed: 25748771]

37.

Virani SS, Newby LK, Arnold SV, Bittner V, Brewer LC, Demeter SH, Dixon DL, Fearon WF, Hess B, Johnson HM, Kazi DS, Kolte D, Kumbhani DJ, LoFaso J, Mahtta D, Mark DB, Minissian M, Navar AM, Patel AR, Piano MR, Rodriguez F, Talbot AW, Taqueti VR, Thomas RJ, van Diepen S, Wiggins B, Williams MS., Peer Review Committee Members. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023 Aug 29;148(9):e9-e119. [PubMed: 37471501]

38.

Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Muñoz D, Smith SC, Virani SS, Williams KA, Yeboah J, Ziaeian B. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Sep 10;140(11):e596-e646. [PMC free article: PMC7734661] [PubMed: 30879355]

39.

Koo BK, Kang J, Park KW, Rhee TM, Yang HM, Won KB, Rha SW, Bae JW, Lee NH, Hur SH, Yoon J, Park TH, Kim BS, Lim SW, Cho YH, Jeon DW, Kim SH, Han JK, Shin ES, Kim HS., HOST-EXAM investigators. Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial. Lancet. 2021 Jun 26;397(10293):2487-2496. [PubMed: 34010616]

40.

García Rodríguez LA, Martín-Pérez M, Hennekens CH, Rothwell PM, Lanas A. Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies. PLoS One. 2016;11(8):e0160046. [PMC free article: PMC4973997] [PubMed: 27490468]

41.

Elam MB, Majumdar G, Mozhui K, Gerling IC, Vera SR, Fish-Trotter H, Williams RW, Childress RD, Raghow R. Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge. PLoS One. 2017;12(8):e0181308. [PMC free article: PMC5542661] [PubMed: 28771594]

42.

Straka BT, Ramirez CE, Byrd JB, Stone E, Woodard-Grice A, Nian H, Yu C, Banerji A, Brown NJ. Effect of bradykinin receptor antagonism on ACE inhibitor-associated angioedema. J Allergy Clin Immunol. 2017 Jul;140(1):242-248.e2. [PMC free article: PMC5705179] [PubMed: 27913306]

43.

Reejhsinghani R, Lotfi AS. Prevention of stent thrombosis: challenges and solutions. Vasc Health Risk Manag. 2015;11:93-106. [PMC free article: PMC4315466] [PubMed: 25657588]

44.

Tabei SM, Senemar S, Saffari B, Ahmadi Z, Haqparast S. Non-modifiable Factors of Coronary Artery Stenosis in Late Onset Patients with Coronary Artery Disease in Southern Iranian Population. J Cardiovasc Thorac Res. 2014;6(1):51-5. [PMC free article: PMC3992733] [PubMed: 24753833]

45.

Michniewicz E, Mlodawska E, Lopatowska P, Tomaszuk-Kazberuk A, Malyszko J. Patients with atrial fibrillation and coronary artery disease - Double trouble. Adv Med Sci. 2018 Mar;63(1):30-35. [PubMed: 28818746]

46.

Nesković AN, Marinković J, Bojić M, Popović AD. Early mitral regurgitation after acute myocardial infarction does not contribute to subsequent left ventricular remodeling. Clin Cardiol. 1999 Feb;22(2):91-4. [PMC free article: PMC6655665] [PubMed: 10068845]

47.

Frampton J, Ortengren AR, Zeitler EP. Arrhythmias After Acute Myocardial Infarction. Yale J Biol Med. 2023 Mar;96(1):83-94. [PMC free article: PMC10052595] [PubMed: 37009192]

48.

Oleynikov VE, Averyanova EV, Oreshkina AA, Burko NV, Barmenkova YA, Golubeva AV, Galimskaya VA. A Multivariate Model to Predict Chronic Heart Failure after Acute ST-Segment Elevation Myocardial Infarction: Preliminary Study. Diagnostics (Basel). 2021 Oct 18;11(10) [PMC free article: PMC8534636] [PubMed: 34679623]

49.

Sharma H, Radhakrishnan A, Nightingale P, Brown S, May J, O'Connor K, Shakeel I, Zia N, Doshi SN, Townend JN, Myerson SG, Kirchhof P, Ludman PF, Adnan Nadir M, Steeds RP. Mitral Regurgitation Following Acute Myocardial Infarction Treated by Percutaneous Coronary Intervention-Prevalence, Risk factors, and Predictors of Outcome. Am J Cardiol. 2021 Oct 15;157:22-32. [PubMed: 34417016]

50.

Elbadawi A, Elgendy IY, Mahmoud K, Barakat AF, Mentias A, Mohamed AH, Ogunbayo GO, Megaly M, Saad M, Omer MA, Paniagua D, Abbott JD, Jneid H. Temporal Trends and Outcomes of Mechanical Complications in Patients With Acute Myocardial Infarction. JACC Cardiovasc Interv. 2019 Sep 23;12(18):1825-1836. [PubMed: 31537282]

51.

Lador A, Hasdai D, Mager A, Porter A, Goldenberg I, Shlomo N, Vorobeichik D, Beigel R, Kornowski R, Iakobishvili Z. Incidence and Prognosis of Pericarditis After ST-Elevation Myocardial Infarction (from the Acute Coronary Syndrome Israeli Survey 2000 to 2013 Registry Database). Am J Cardiol. 2018 Mar 15;121(6):690-694. [PubMed: 29370922]

52.

Vallabhajosyula S, Kanwar S, Aung H, Cheungpasitporn W, Raphael CE, Gulati R, Singh M. Temporal Trends and Outcomes of Left Ventricular Aneurysm After Acute Myocardial Infarction. Am J Cardiol. 2020 Oct 15;133:32-38. [PubMed: 32807388]

53.

Mansencal N, Nasr IA, Pillière R, Farcot JC, Joseph T, Lacombe P, Dubourg O. Usefulness of contrast echocardiography for assessment of left ventricular thrombus after acute myocardial infarction. Am J Cardiol. 2007 Jun 15;99(12):1667-70. [PubMed: 17560872]

54.

James S, Akerblom A, Cannon CP, Emanuelsson H, Husted S, Katus H, Skene A, Steg PG, Storey RF, Harrington R, Becker R, Wallentin L. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2009 Apr;157(4):599-605. [PubMed: 19332184]

55.

Schwartz GG, Olsson AG, Szarek M, Sasiela WJ. Relation of characteristics of metabolic syndrome to short-term prognosis and effects of intensive statin therapy after acute coronary syndrome: an analysis of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial. Diabetes Care. 2005 Oct;28(10):2508-13. [PubMed: 16186288]

Disclosure: Rai Dilawar Shahjehan declares no relevant financial relationships with ineligible companies.

Disclosure: Sanjeev Sharma declares no relevant financial relationships with ineligible companies.

Disclosure: Ehab Dababneh declares no relevant financial relationships with ineligible companies.

Disclosure: Beenish Bhutta declares no relevant financial relationships with ineligible companies.