Chronic%20coronary%20syndromes Diagnosis

• A good history and clinical examination is the key first step in the evaluation of a patient with chest pain

• Typical angina (definite or stable)
  • Has substernal chest discomfort with a characteristic quality and duration provoked by exertion and/or emotional stress and relieved by rest and/or Nitroglycerin within minutes
• Atypical angina (probable) has two of the characteristics of typical angina
• Noncardiac/anginal chest pain only has one or none of the characteristics of typical angina

• Helps determine the functional impairment, response to therapy and prognosis of the patient
  • Eg Canadian Cardiovascular Society Classification, Duke Specific Activity Index and Seattle Angina Questionnaire

• Based on the different presentations of patients with suspected or established CCS by the European Society of Cardiology (ESC)
  • Category 1: Patients with suspected coronary artery disease (CAD) and “stable” anginal symptoms; angina may present as dyspnea
  • Category 2: Patients with new onset of heart failure or left ventricular (LV) dysfunction and suspected CAD
  • Category 3: Asymptomatic and symptomatic patients <1 year after an acute coronary syndrome or recent revascularization
  • Category 4: Patients >1 year after being diagnosed with angina or >1 year after revascularization
  • Category 5: Patients with angina and suspected vasospastic or microvascular disease
  • Category 6: Asymptomatic patients in whom CAD is detected at screening
• Presence of these scenarios may increase or decrease patient’s risk for future cardiovascular (CV) events
  • Insufficiently controlled CV risk factors, ineffective lifestyle modifications and/or medical therapy, or unsuccessful revascularization may increase the risk for CV events
  • Appropriate secondary prevention and successful revascularization have been shown to reduce risk for major CV events

• Clinician’s pre-test estimates of disease along with the results of diagnostic tests to generate individualized post-test disease probabilities for a given patient
• Influenced by the prevalence of the disease in the population studied, as well as clinical features including the presence of CV risk factors of an individual
• Major determinants are age, gender and the nature of symptoms
  • Likelihood of CAD is increased with the following: Presence of risk factors for CVD [eg smoking, hypertension, diabetes mellitus (DM), dyslipidemia, family history of CVD], Q-wave or ST-segment/T-wave changes from a resting ECG, LV dysfunction suggestive of CAD, abnormal exercise ECG and presence of coronary calcium by CT
• According to the 2013 ESC guidelines, PTP of CAD are as follows:
  • Low PTP <15%: Patients can be managed without further non-invasive stress testing but it is recommended to exclude other causes of chest pain (eg pulmonary, gastrointestinal, musculoskeletal)
  • Intermediate PTP ≥15-≤85%: An exercise ECG may be considered in patients with 15-65% PTP while a non-invasive imaging is preferred in those with 66-85% PTP
  • High PTP >85%: Patients can be assumed to have stable CAD and an invasive coronary angiography (ICA) may be considered for risk stratification

• Presence of IHD risk factors should be assessed
  • Eg smoking, dyslipidemia (eg familial hypercholesterolemia), DM, hypertension, obesity, metabolic syndrome, chronic kidney disease, physical inactivity, old age and family history of premature cardiovascular disease
• History of cerebrovascular disease, peripheral artery disease (PAD), MI or coronary revascularization also increases the likelihood of IHD

• Risk refers to the risk of CV event (eg death)
  • Low risk has an annual mortality of <1%, intermediate risk 1-3% and high risk >3%
• Uses clinical findings, resting ECG, response to stress testing, quantification of LV function and extent of CAD to determine the level of risk 
• Assists in deciding the appropriate therapy and determines prognosis of the disease
  • Low-risk patients are managed with risk factor reduction with or without anti-anginal therapy while intermediate to high-risk patients are referred to specialists for further evaluation and possible revascularization
• Thrombotic risk is high in a CCS patient in the presence of any 1 of the following:  
  • Coronary: Previous coronary event, high-risk coronary anatomy [eg bifurcation percutaneous coronary intervention (PCI), left main PCI, multivessel PCI, >3 stents], or documented multivessel coronary disease
  • Vascular: Established peripheral artery disease (eg carotid stenosis >50%, renal artery stenosis, mesenteric artery disease, claudication or previous peripheral intervention) or cerebrovascular disease (eg transient ischemic attacks or ischemic stroke from atherosclerosis)
  • Disease: Heart failure from CAD, diabetes on therapy, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², micro- and macroalbuminuria

• Thorough history is the cornerstone of the diagnosis of angina pectoris
• Stable CAD may also present as dyspnea and palpitations; occasionally, patients with CAD may also present with syncope and near syncope
• In many cases, it is possible to make a diagnosis based on the history of chest pain alone but physical exam and diagnostic tests are necessary to confirm the diagnosis, determine the cause and assess the severity of the underlying disease

• It is usually normal or nonspecific in stable angina patients
• Exam during or immediately after an episode of pain may be beneficial since S₄ or S₃ heart sound or gallop, mitral regurgitation murmur, paradoxically split S₂, basilar rales or chest wall heave that dissipates when pain decreases are all predictive of IHD
• Careful CV exam may reveal other related conditions such as heart failure, valvular heart disease or hypertrophic cardiomyopathy
• Audible rub suggests pericardial or pleural disease
• Presence of carotid bruit, renal artery bruit, diminished pedal pulse or palpable abdominal aneurysm are evidences of vascular disease
• Elevated blood pressure (BP), xanthomas and retinal exudates are signs which suggest the presence of IHD risk factors
• Chest pain elicited by pressure on the chest wall can be caused by musculoskeletal syndromes but does not eliminate the possibility of angina due to IHD
• Body mass index (BMI), waist circumference and waist-to-hip ratio should also be taken to determine possible metabolic syndrome, non-coronary vascular disease and other signs of comorbid conditions

• Provide information related to the possible causes of ischemia, establish cardiovascular risk factors and determine prognosis
• Fasting lipid profile
  • To determine the presence of dyslipidemia, establish the patient’s risk profile and help determine the need for treatment
• Fasting blood glucose and glycated hemoglobin (HbA1c)
  • To identify undiagnosed DM and establish patient’s risk profile
  • An oral glucose tolerance test is recommended if both tests are inconclusive
•  Complete blood count (CBC) that includes hemoglobin and white cell count
  • To check underlying anemia and/or infection
  • For prognostic information
•  Serum creatinine
  • To assess renal function
•  Cardiac enzymes (troponins, creatine kinase)
  • To rule out myocardial injury/necrosis
  • Creatine kinase measurement may be decreased for patients on statin therapy with accompanying symptoms of cardiac injury
•  Liver function tests
  • Recommended prior to initiation of statin therapy
•  Thyroid function test
  • To identify other causes of ischemia

Chest X-ray

• Commonly used to evaluate patients with suspected heart disease but does not provide the exact diagnosis nor classify risk group
• Recommended for patients with signs and symptoms of heart failure, atypical presentation or suspicion of pulmonary disease
• Presence of cardiomegaly, pulmonary congestion, atrial enlargement and cardiac calcifications have been related to poor outcome

Non-invasive Cardiac Investigations

• Used in the assessment of angina, in diagnosis, evaluation of treatment efficacy and risk stratification 
• Imaging tests are recommended for patients with clinical pre-test probability (PTP) of 65-85%, ejection fraction of >50% without typical angina or ECG abnormalities
• The choice for the initial non-invasive test should be based on the PTP, availability of the test, the test’s performance in diagnosing obstructive CAD, patient characteristics and local expertise

Resting Electrocardiogram (ECG)

• Recommended in all patients with suspected angina pectoris
• Should be done during or immediately after an episode of chest pain to detect ST-segment changes in the presence of ischemia
• Also used in patients without an obvious noncardiac cause of chest pain
• Normal resting ECG is common even in patients with severe angina which does not exclude the possibility of ischemia
• Assists in clarifying the differential diagnosis if taken in the presence of pain which can detect dynamic ST-segment changes in the presence of ischemia or by identifying features of pericardial disease
• ECG during an episode of chest pain is useful if vasospasm is suspected
• ECG abnormalities indicating a worse prognosis:
  • Evidence of prior myocardial infarction (MI), especially Q waves in multiple leads or an R wave in V1
  • Persistent ST-T wave inversions, particularly in leads V1 to V3
  • Left bundle branch block (LBBB), left anterior hemiblock, bifascicular block, second- or third-degree atrioventricular (AV) block or ventricular tachyarrhythmia/atrial fibrillation
  • LV hypertrophy 

Resting Echocardiography 

• Recommended in the initial evaluation of all patients with symptoms suggestive of SIHD
• Resting 2-dimensional and Doppler echocardiography are useful to evaluate ventricular function and regional wall motion abnormalities and detect or rule out other CV disorders (eg valvular heart disease, hypertrophic cardiomyopathy)
• Estimation of LV ejection fraction (LVEF) and LV diastolic function which are very important in risk stratification
• Not indicated for repeated use on a regular basis in patients with uncomplicated stable angina in the absence or change in clinical condition
• Carotid artery ultrasonography may be done afterwards to assess for presence of plaque or narrowing

Exercise ECG or ECG Stress Test

• Commonly used diagnostic test for IHD
• Evaluates exercise tolerance, symptoms, BP response, arrhythmias and event risk in some patients
• Preferred test to determine inducible ischemia for patients with suspected stable angina, PTP of 15-60% and LVEF ≥50%
• Alternative test to diagnose CAD when other invasive or non-invasive imaging tests are unavailable
• Only for diagnostic confirmation in patients with an intermediate PTP of IHD who have an interpretable ECG and at least moderate physical functioning or no disabling comorbidity
  • Should only be done on high-risk populations for determination of prognosis [ie, a high event risk in a patient with established CCS is a CV mortality of >3% per year based on the Duke Treadmill Score] 
• Should be done only after clinical examination and resting ECG under careful monitoring
• Complications during exercise testing are few but severe arrhythmia and sudden death may occur
• Absolute contraindications to exercise ECG are:
  • MI within the last 2 days, cardiac arrhythmias causing symptoms or hemodynamic compromise, symptomatic and severe aortic stenosis, hypertrophic cardiomyopathy, symptomatic heart failure, pulmonary embolism, pulmonary infarction, myocarditis, pericarditis and acute aortic dissection
• More sensitive and specific than resting ECG for detecting myocardial ischemia
• Test should be standardized using nomograms taking into account age, gender and body size
• No diagnostic value in patients with LBBB, paced rhythm and Wolff -Parkinson-White (WPW) syndrome
• Normal test in patients taking anti-ischemic drugs does not rule out significant coronary disease
  • Withhold beta-blockers for 24-48 hours prior to testing to prevent false-negative findings
• In patients unable to perform adequate amount of treadmill or bicycle exercise, various types of pharmacological stress tests can be useful (eg Adenosine, Dipyridamole)
  • Selection and type of pharmacological stress will depend on individual patient factors
• Treatment can be initiated without stress test if patient has high probability of CAD but the test is contraindicated because of comorbidity or patient preference
• Can be useful for prognostic stratification, to assess the efficacy of medical therapy or revascularization or to assist prescription of exercise after control of symptoms
  • Prognostic value is increased by considering heart rate (HR) variability, predicted maximum HR and HR recovery index

Stress Testing in Combination with Imaging

• Most well-established stress imaging modalities that may be used with either exercise test or pharmacological stress tests are:
  • Stress echocardiography
  • Myocardial perfusion scintigraphy [single photon emission computed tomography (SPECT), positron emission tomography (PET)]
  • Stress cardiac magnetic resonance (CMR)
  • Others [hybrid SPECT and computed tomography (CT), PET and CT, PET and CMR]
    • Further studies are needed to prove the accuracy of hybrid techniques for CAD imaging
• Recommended for patients within the higher range of PTP, or LVEF<50% without typical angina and in patients with resting ECG abnormalities, especially symptomatic patients with previous PCI or coronary artery bypass graft (CABG)
  • Also for patients with intermediate PTP with inadequate ability to exercise, uninterpretable resting ECG and/or exercise stress ECG with equivocal or abnormal results at moderate to high workloads depending on patient’s clinical condition 
• May be performed after an inconclusive CCTA in intermediate- to high-risk patients with stable chest pain  
• Helps in the diagnosis of myocardial ischemia, estimation of major adverse CV events (MACE) risk and guidance of treatment decisions in patients with obstructive CAD
• Exercise imaging is preferable if possible because it allows more physiological reproduction of ischemia and assessment of symptoms
• A high event risk in a patient with established CCS includes a finding of ≥3 of 16 segments with stress-induced hypokinesia or akinesia on stress echocardiography and ≥10% ischemic area on the LV myocardium on SPECT or PET perfusion imaging
• Pharmacological stress testing is indicated in patients who are not able to exercise adequately or may be used as an option to exercise stress tests
  • Two approaches are used:
    • Infusion of short-acting sympathomimetic drugs (eg. Dobutamine) in an incremental dose which increases myocardial oxygen consumption and mimics the effect of physical exercise
    • Infusion of coronary vasodilators (eg Adenosine and Dipyridamole) which provide a contrast between regions supplied by non-diseased coronary arteries where perfusion increases and regions supplied by significant stenotic coronary arteries where perfusion will increase less or even decrease (steal phenomenon)
• Advantages of stress imaging over conventional exercise ECG testing:
  • Superior diagnostic performance for detecting obstructive coronary disease
  • Ability to quantify and localize ischemic areas
  • Ability to provide diagnostic information if there are resting ECG abnormalities or the patients are unable to exercise
  • Ability to establish the functional significance of lesions in patients with confirmed lesions by ICA 
  • Ability to show myocardial viability

Computed Tomography (CT)

• Ultra-fast or electron beam CT and multi-detector or multi-slice CT are two modalities of CT imaging that were developed to improve spatial and temporal resolution in CT
• Recommended in patients with a low clinical PTP (15-50%) of disease, and with intermediate to high PTP with non-conclusive exercise ECG or stress imaging test
• Effective in detecting coronary calcium and quantifying the extent of coronary calcification
  • Calcium is deposited in atherosclerotic plaques within the coronary arteries
  • Coronary calcification increases with age
  • Extent of coronary calcification correlates more closely with the overall burden of plaque than with the location or severity of stenoses
• Detection of coronary calcium may identify those at higher risk of significant coronary disease, but assessment of coronary calcification is not recommended routinely for the diagnostic evaluation of patients with stable angina

Cardiac Magnetic Resonance Imaging (CMR) 

• Used to define structural cardiac abnormalities and evaluate ventricular function
• In conjunction with Dobutamine or adenosine infusion, CMR stress testing can be used to detect wall motion abnormalities or perfusion defect induced by ischemia
• A high event risk in a patient with established CCS includes a finding of ≥2 of 16 segments with stress perfusion defects or ≥3 Dobutamine-induced dysfunctional segments

Ambulatory Electrocardiogram (Holter) Monitoring

• A diagnostic monitoring option for patients suspected of having arrhythmia or vasospastic angina

Coronary Computed Tomography Angiography (CCTA) 

• Radiographic visualization of the coronary vessels after injection of radiopaque contrast material
• Identifies the presence or absence of coronary lumen stenosis, stratifies patient’s risk, provides therapeutic options (eg medical therapy or revascularization) and helps determine prognosis
• CCTA or a non-invasive functional imaging for myocardial ischemia may be used as an initial test to diagnose CAD in symptomatic patients in whom clinical evaluation alone cannot rule out an obstructive CAD
• Extent and severity of angiographic CAD are the most important prognostic factors and essential for revascularization decision making
• Has high sensitivity and specificity for detecting obstructive CAD
  • Sensitive to heart rate, body weight and the presence of calcification
• A very high negative predictive value for obstructive CAD is an advantage of CCTA over standard functional testing
  • If CCTA demonstrated CAD of uncertain functional significance or is non-diagnostic, it is recommended to perform functional imaging for myocardial ischemia
• May be considered in patients with low-intermediate risk PTP with exercise stress test or stress imaging tests showing mild or equivocal ischemic changes and are asymptomatic or mildly symptomatic with good exercise capacity
  
  • Should not be performed in patients who are at high risk for CAD or have extensive calcification because the presence of significant calcification can preclude the accurate assessment of lesion severity or may result to a false-positive study
  • Not advisable for patients unwilling to undergo invasive procedures and revascularization, not candidates for PCI, CABG and those with low probability of recovering even after revascularization
• Indications for coronary angiography:
  • Severe stable angina with a high PTP of disease, particularly if the symptoms are inadequately responding to medical therapy
  • Survivors of cardiac arrest
  • Serious ventricular arrhythmias
  • Previously treated by myocardial revascularization (PCI, CABG) who developed early recurrence of moderate or severe angina pectoris
  • Inconclusive diagnosis on non-invasive testing or discordant test results from different non-invasive modalities at intermediate to high risk of coronary level
  • High risk of restenosis after PCI if PCI has been performed in a prognostically important site

Invasive Cardiac Investigation

Invasive Coronary Angiography (ICA) 

• It is recommended to perform ICA as an alternative test in diagnosing CAD and for guidance during treatment decisions in patients with a high clinical likelihood and moderate to severe symptoms unresponsive to medical therapy, or typical angina with low-level exercise and clinical evaluation showing a high event risk  
• ICA is recommended for the following:  
  • CV risk stratification of symptomatic patients with high-risk clinical profile with symptoms not responding adequately to medical therapy and revascularization is considered to improve prognosis
  • Patients with mild or no symptoms receiving medical therapy with a non-invasive risk stratification showing a high event risk and revascularization is considered to improve prognosis
• Considered for confirmation of CAD diagnosis (together with invasive functional evaluation) when non-invasive testing reveals uncertain diagnosis  
• A high event risk in a patient with established CCS includes a finding of 3-vessel disease with proximal stenoses, left main disease or proximal anterior descending disease (findings which may also be seen with CCTA)