Anamnesis represents the first step in the diagnosis of ischemic heart disease.
The cardinal symptom, common to all ischemic cardiac conditions, is ischemic chest pain, described as a sensation of tightness, pressure, or weight, often retrosternal and radiating to the left arm, neck, or jaw.
However, ischemic pain may also present in atypical locations, such as the epigastric region, back, or right arm, making clinical recognition more difficult, especially in diabetic and elderly patients.
In some cases, myocardial ischemia may present with atypical symptoms, including isolated dyspnea, marked asthenia, or syncopal episodes without obvious chest pain.
General characteristics of ischemic pain
Duration: Ischemic pain typically lasts between 2 and 10 minutes in stable angina. In unstable angina, the duration is variable, with episodes that may last more than 10-15 minutes but do not reach the persistence typical of infarction. In myocardial infarction, however, the pain persists for more than 20-30 minutes and is resistant to nitrates. Prolonged chest pain lasting more than 20 minutes suggests possible irreversible myocardial necrosis, with irreparable cellular damage generally beginning after 30-40 minutes of untreated ischemia.
Triggering factors: In chronic forms such as stable angina, pain is predictably induced by physical exertion, emotional stress, exposure to cold, or large meals. In acute syndromes such as unstable angina and myocardial infarction, pain can arise spontaneously, without evident precipitating factors.
Resolution: In stable angina, pain subsides with rest or with sublingual nitrate administration.
Vasospastic angina (Prinzmetal’s), also responds well to nitrates.
In other acute forms, such as unstable angina and myocardial infarction, the pain is more resistant to therapy and tends to persist, requiring more aggressive interventions.
Specific characteristics in the different forms of ischemia
Stable angina: Predictable pain, related to physical exertion or emotional stress, with remission at rest or after nitrates. It does not cause irreversible myocardial damage as the ischemia is transient and does not exceed the critical time for cellular necrosis.
Unstable angina: Sudden pain, more intense and prolonged than in stable angina, occurring even at rest or with minimal effort. It can represent the prodromal phase of myocardial infarction and, if left untreated, can evolve into myocardial necrosis. It may also be associated with silent ischemic episodes and ventricular arrhythmias.
Myocardial infarction (STEMI/NSTEMI): Intense, oppressive, and persistent pain (>20 minutes), typically not relieved by nitrates and associated with systemic symptoms such as sweating, nausea, vomiting, and dyspnea. It results in irreversible myocardial necrosis, with functional loss of cardiac cells and consequent ventricular remodeling.
Silent ischemia: Absence of chest pain, often diagnosed incidentally via ECG or functional tests. More common in diabetic patients due to autonomic neuropathy, it can nevertheless cause progressive ventricular dysfunction if unrecognized and untreated.
Vasospastic angina (Prinzmetal’s): Anginal episodes at rest, often during the night or early morning, due to transient coronary spasms. It is not necessarily associated with significant coronary stenosis. It can cause severe ischemia with transient ST-segment elevation and, in some cases, dangerous ventricular arrhythmias.
Physical Examination
The physical examination is often normal in the early stages of chronic ischemic disease, but during an acute ischemic event, signs indicative of reduced myocardial perfusion and neurovegetative response may emerge.
Common findings in ischemic heart disease
The physical examination varies between intercritical phases (at rest) and acute ischemic episodes.
During the intercritical phase: The physical examination is often normal, especially in patients with stable angina or silent ischemia. However, in advanced cases of ischemic heart disease, signs of ventricular dysfunction such as a fourth heart sound (S4) or mild pulmonary congestion may be present.
During an ischemic episode: Signs of sympathetic activation and reduced myocardial perfusion may occur:
Tachycardia or bradycardia: Tachycardia secondary to adrenergic activation, or reflex bradycardia due to vagal stimulation, more frequent in inferior infarctions.
Blood pressure alterations: Reactive hypertension in the early stages of ischemia or hypotension in more severe cases with reduced cardiac output.
Pallor and sweating: Manifestations of adrenergic activation and vasomotor response to ischemia.
Dyspnea: Sign of increased left ventricular filling pressure and possible incipient pulmonary edema.
Specific signs for different ischemic conditions
STEMI/NSTEMI: Clinical signs can vary widely. Some patients present with hypotension, cold sweating, tachycardia, polypnea and signs of cardiogenic shock in the most severe cases, while others may have myocardial infarction without obvious clinical signs, as occurs in paucisymptomatic or silent forms (more frequent in diabetics and the elderly).
Stable angina: The physical examination is generally normal in the intercritical period between episodes. During an anginal episode, tachycardia, increased blood pressure, and sweating may occur, related to sympathetic activation secondary to reduced myocardial perfusion.
Unstable angina: During episodes, adrenergic hyperactivation with tachycardia, sweating and pallor may be present, generally more pronounced than in stable angina. In the intercritical period, the physical examination may be normal or show signs of residual ischemia in the case of chronic reduced perfusion.
Silent ischemia: Absence of objective clinical signs, making diagnosis through instrumental tests such as ECG, provocative tests, or myocardial perfusion imaging necessary.
Vasospastic angina: The physical examination is generally normal in the intercritical period between episodes. During coronary vasospasm, transient hypertension, reflex bradycardia and ventricular arrhythmias may occur, with possible acute impairment of myocardial perfusion.
Findings of ischemic complications
In the advanced stages of ischemic heart disease or in the presence of structural myocardial damage, signs of heart failure and ischemic valvular dysfunction may emerge:
Fourth heart sound (S4): Sign of reduced ventricular compliance, more frequent in patients with diastolic dysfunction and left ventricular hypertrophy.
Systolic murmurs: Possible in the case of ischemic mitral regurgitation secondary to papillary muscle dysfunction.
Pulmonary crackles: Indicative of pulmonary congestion in the presence of advanced left ventricular failure.
Jugular distension and peripheral edema: Signs of right heart failure in the advanced stages of the disease.
Instrumental Investigations
The diagnosis of ischemic heart disease relies on instrumental tests that allow the detection of myocardial ischemia, assessment of cardiac function, and identification of any coronary stenoses.
The diagnostic approach involves a gradual pathway, with first-level tests followed by advanced tests when further characterization is needed.
Basic tests
The electrocardiogram evaluates the heart's electrical activity, which characteristically changes in ischemic conditions.
These tests are used as the first diagnostic approach to identify electrical abnormalities and indirect signs of ischemia:
Resting ECG: May be normal during the intercritical phase. In the presence of active ischemia, T wave inversion and ST-segment depression may appear, suggestive of ongoing ischemia. The presence of pathological Q waves, on the other hand, indicates previous myocardial necrosis and is not a sign of acute ischemia.
24-48 hour Holter ECG: Identifies transient ischemic episodes, such as intermittent ST-segment depressions, and ischemic arrhythmias, particularly useful in patients with atypical symptoms or silent ischemia.
Stress test: Assesses the cardiac response to exercise. It is considered positive if ST-segment depression ≥1 mm, angina, or inducible arrhythmias occur. It is less useful in patients with an already abnormal baseline ECG.
Advanced diagnostics
These tests are used to confirm the presence of ischemia, quantify its extent and stratify risk.
Stress echocardiography: A dynamic echocardiographic examination that assesses myocardial contractility under physical or pharmacological stress (dobutamine or vasodilators). It is useful in patients with an abnormal baseline ECG or who cannot perform the stress test. It allows the identification of segmental wall motion abnormalities (hypokinesia, akinesia, dyskinesia), indicative of inducible ischemia.
Myocardial scintigraphy: A nuclear imaging technique using radiopharmaceuticals (e.g. sestamibi-Tc99) to assess myocardial perfusion. It distinguishes between reversible ischemia (transient reduction in perfusion) and irreversible myocardial necrosis (fixed perfusion defect).
Cardiac Magnetic Resonance Imaging with stress: An advanced imaging test that, through vasodilator or inotropic drugs, simulates stress on the heart. The Late Gadolinium Enhancement (LGE) technique distinguishes viable from fibrotic tissue, enabling an accurate assessment of myocardial viability and ischemia severity.
Coronary angiography: An invasive test performed by cardiac catheterization, with injection of contrast medium into the coronary arteries for direct lumen visualization. It is the gold standard for the evaluation of coronary anatomy, enabling the identification of critical stenoses and guiding therapeutic decisions on revascularization (angioplasty or coronary bypass).
Specific findings in different forms of ischemia
Each ischemic condition presents specific diagnostic features in the various instrumental tests:
Stable angina: Inducible ischemia in provocative tests, with ST-segment depression and perfusion abnormalities on scintigraphy. Coronary angiography shows coronary stenoses ≥50%.
Unstable angina: Transient ECG changes with ST-segment depression and T wave inversion. Provocative tests are often avoided, while coronary angiography may reveal unstable atherosclerotic plaques.
STEMI: Persistent ST-segment elevation in ≥2 contiguous leads, presence of pathological Q waves in the late phases and perfusion abnormalities on scintigraphy.
NSTEMI: ST-segment depression or persistent T wave inversion, without ST-segment elevation. Cardiac MRI can confirm the presence of myocardial necrosis without total coronary occlusion.
Silent ischemia: Absence of symptoms, but evidence of perfusion abnormalities on advanced imaging tests (scintigraphy, cardiac MRI) or episodic ECG changes on Holter.
Vasospastic angina: ECG with transient ST-segment elevation during ischemic episodes, with coronary angiography showing no significant stenosis. The ergonovine or acetylcholine test can induce vasospasm during coronary angiography.
Differential Diagnosis
The symptoms of ischemic heart disease, particularly chest pain, can be mimicked by numerous cardiovascular and non-cardiovascular conditions.
The differential diagnosis is based on careful clinical assessment and the use of specific instrumental tests.
Cardiovascular conditions
Aortic dissection: Acute, tearing chest pain radiating to the back, often associated with hypertension and pulse asymmetry. Diagnosis is confirmed by thoracic CT angiography.
Myocarditis: Angina-like chest pain, associated with fever, asthenia, and diffuse ECG changes. Cardiac enzymes may be elevated without evidence of coronary artery disease. Cardiac MRI shows areas of myocardial edema.
Pericarditis: Pleuritic chest pain, worsened by deep inspiration and improved by sitting forward. The ECG shows diffuse ST-segment elevation without reciprocal depression.
Mitral valve prolapse: Atypical chest pain, not related to exertion, sometimes associated with palpitations. Echocardiography confirms the valve prolapse.
Pulmonary conditions
Pulmonary embolism: Sudden chest pain, dyspnea, tachycardia, and desaturation. It can mimic myocardial infarction, but the ECG often shows sinus tachycardia and right axis deviation. Diagnosis is confirmed by pulmonary CT angiography.
Pneumothorax: Unilateral, acute chest pain associated with reduced breath sounds. Diagnosis is made by chest X-ray.
Pleuritis: Pleuritic chest pain, worsened by deep breathing and accompanied by pericardial rubs on auscultation. Diagnosis is confirmed by chest X-ray or ultrasound.
Gastrointestinal conditions
Gastroesophageal reflux: Burning retrosternal pain, worsened in the supine position and after meals, improved by antacids. Upper endoscopy is indicated in case of persistent symptoms.
Esophageal spasm: Constrictive chest pain that can mimic angina, but is not related to exertion. It can be triggered by cold foods or emotional stress. Esophageal manometry is the diagnostic test of reference.
Acute pancreatitis: Epigastric pain radiating to the back, associated with nausea and vomiting. Diagnosis is based on lipase measurement and abdominal ultrasound.
Musculoskeletal conditions
Costochondritis: Localized chest pain, worsened by palpation of the sternum and by movements. Absent during exertion.
Muscular chest pain: Often secondary to physical exertion or trauma, it can be reproduced by palpation or movement of the chest.
Conclusion
The diagnosis of ischemic heart disease requires an integrated approach based on anamnesis, physical examination, and instrumental tests. Diagnostic confirmation is achieved through provocative tests and advanced imaging, while coronary angiography remains the definitive test in doubtful or high-risk cases.
References
Byrne RA et al. ESC Guidelines 2023 for the treatment of acute coronary syndromes. G Ital Cardiol. 2024;25(2 Suppl. 2):e1-e112.
Pizzi C et al. Ischemic heart disease and depression: an underestimated reality. G Ital Cardiol. 2013;14(7):526-537.
Temporelli PL et al. Is there still a role today for exercise ECG testing in ischemic heart disease? Beyond ST-segment depression. G Ital Cardiol. 2025;26(2):85-89.
Coli S et al. Guidelines and daily clinical practice in the diagnosis of coronary artery disease. Cardiologia. 2024;12(3):45-67.
Silveri G et al. Identification of Ischemic Heart Disease by using machine learning technique based on parameters measuring Heart Rate Variability. arXiv. 2020;2010.15893.
Silveri G et al. Novel Classification of Ischemic Heart Disease Using Artificial Neural Network. arXiv. 2020;2011.09801.
ARCA Lazio. Guidelines for ischemic heart disease. 2024.
SIPREC. Chronic ischemic heart disease: evolution in personalized approach. 2022.
Gruppo San Donato. Ischemic heart disease: what it is, diagnosis and treatment. 2023.
