Diagnosis of Ischemic Heart Disease

Anamnesis

Anamnesis represents the first step in the diagnosis of ischemic heart disease.

The hallmark symptom common to all ischemic cardiac conditions is ischemic chest pain, described as a sensation of tightness, pressure, or heaviness, often localized retrosternally 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 manifest with atypical symptoms, including isolated dyspnea, marked fatigue, or syncopal episodes without evident chest pain.

General characteristics of ischemic pain

• Duration: Ischemic pain typically lasts between 2 and 10 minutes in stable angina. In unstable angina, duration varies, with episodes that may exceed 10-15 minutes but do not persist like in myocardial infarction. In myocardial infarction, however, pain lasts for more than 20-30 minutes and is resistant to nitrates. Chest pain lasting longer than 20 minutes suggests possible irreversible myocardial necrosis, with irreversible cell damage usually occurring after 30-40 minutes of untreated ischemia.
• Triggering factors: In chronic conditions such as stable angina, pain is predictably induced by physical exertion, emotional stress, cold exposure, or large meals. In acute syndromes such as unstable angina and myocardial infarction, pain may occur spontaneously, without evident precipitating factors.
• Resolution: In stable angina, pain subsides with rest or sublingual nitrate administration. Vasospastic angina (Prinzmetal’s) also responds well to nitrates. In other acute forms, such as unstable angina and myocardial infarction, pain is more resistant to therapy and tends to persist, requiring more aggressive interventions.

Specific characteristics in different ischemic conditions

• Stable angina: Predictable pain, triggered by physical exertion or emotional stress, resolving with rest or nitrates. It does not cause irreversible myocardial damage since ischemia is transient and does not extend beyond the critical time for cell necrosis.
• Unstable angina: Sudden-onset pain, more intense and prolonged than stable angina, occurring even at rest or with minimal exertion. It may be the prodromal phase of myocardial infarction and, if untreated, can progress to myocardial necrosis. It can also be associated with silent ischemic episodes and ventricular arrhythmias.
• Myocardial infarction (STEMI/NSTEMI): Intense, oppressive, and persistent pain (>20 minutes), typically unrelieved by nitrates and associated with systemic symptoms such as sweating, nausea, vomiting, and dyspnea. It leads to irreversible myocardial necrosis, with the loss of functional cardiac cells and subsequent ventricular remodeling.
• Silent ischemia: Absence of chest pain, often diagnosed incidentally through ECG or functional tests. More frequent in diabetic patients due to autonomic neuropathy, it can still cause progressive ventricular dysfunction if unrecognized and untreated.
• Vasospastic angina (Prinzmetal’s): Anginal episodes at rest, often occurring at night or early in the morning, due to transient coronary spasms. It is not necessarily associated with significant coronary stenosis. Severe ischemia may occur with transient ST-segment elevation and, in some cases, life-threatening ventricular arrhythmias.

Physical Examination

Physical examination is often normal in the early stages of chronic ischemic conditions, but during an acute ischemic event, signs indicative of reduced myocardial perfusion and neurovegetative response may emerge.

Common findings in ischemic heart disease

Physical examination varies between intercritical phases (at rest) and acute ischemic episodes.

• In the intercritical phase: The physical examination is often normal, especially in patients with stable angina or silent ischemia. However, in advanced ischemic heart disease, signs of ventricular dysfunction such as a fourth heart sound (B4) or mild pulmonary congestion may be present.
• During an ischemic episode: Signs of sympathetic activation and reduced myocardial perfusion may appear:
• Tachycardia or bradycardia: Tachycardia secondary to adrenergic activation or reflex bradycardia due to vagal stimulation, more frequent in inferior infarctions.
• Blood pressure changes: Reactive hypertension in the early phases of ischemia or hypotension in severe cases with reduced cardiac output.
• Pallor and sweating: Manifestations of adrenergic activation and vasomotor response to ischemia.
• Dyspnea: A sign of increased left ventricular filling pressure and possible incipient pulmonary edema.

Specific findings in 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 severe cases, while others may have a myocardial infarction without evident clinical signs, as seen in oligosymptomatic or silent forms (more frequent in diabetics and the elderly).
• Stable angina: The physical examination is generally normal during the intercritical period between episodes. During an anginal episode, tachycardia, increased blood pressure, and sweating may occur due to sympathetic activation secondary to reduced myocardial perfusion.
• Unstable angina: During episodes, sympathetic hyperactivity 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 cases of chronic reduced perfusion.
• Silent ischemia: Absence of identifiable clinical signs, necessitating diagnosis through instrumental tests such as ECG, provocative testing, or myocardial perfusion imaging.
• Vasospastic angina: The physical examination is generally normal during the intercritical period between episodes. During coronary vasospasm, transient hypertension, reflex bradycardia, and ventricular arrhythmias may occur, with possible acute myocardial perfusion impairment.

Findings of ischemic complications

In 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 (B4): A sign of reduced ventricular compliance, more frequent in patients with diastolic dysfunction and left ventricular hypertrophy.
• Systolic murmurs: Possible in ischemic mitral regurgitation due to papillary muscle dysfunction.
• Pulmonary crackles: Indicative of pulmonary congestion in cases of advanced left ventricular failure.
• Jugular venous distension and peripheral edema: Signs of right heart failure in advanced disease stages.

Instrumental Investigations

The diagnosis of ischemic heart disease relies on instrumental tests that detect myocardial ischemia, assess cardiac function, and identify coronary stenosis. A stepwise diagnostic approach is followed, beginning with first-level tests and proceeding to advanced investigations when further characterization is required.

Basic Tests

Electrocardiography evaluates the heart’s electrical activity, which characteristically changes in ischemic conditions. These tests are used as the initial diagnostic approach to identify electrical abnormalities and indirect signs of ischemia:

• Resting ECG: May appear normal during the intercritical phase. In active ischemia, inverted T waves and ST-segment depression may be observed, suggesting ongoing ischemia. The presence of pathological Q waves indicates prior myocardial necrosis and is not a marker of acute ischemia.
• 24-48h Holter ECG: Detects transient ischemic episodes, such as intermittent ST-segment depression, and ischemic arrhythmias, particularly useful in patients with atypical symptoms or silent ischemia.
• Exercise Stress Test: Evaluates cardiac response to exertion. It is considered positive if ST-segment depression ≥1 mm, angina, or inducible arrhythmias occur. It is less useful in patients with an already altered resting ECG.

Advanced Diagnostics

These tests are used to confirm ischemia, quantify its severity, and stratify risk.

• Stress Echocardiography: A dynamic ultrasound test that evaluates myocardial contractility under physical or pharmacological stress (dobutamine or vasodilators). Useful in patients with an altered resting ECG or those unable to perform an exercise test. Detects segmental wall motion abnormalities (hypokinesia, akinesia, dyskinesia) indicative of inducible ischemia.
• Myocardial Perfusion Scintigraphy: A nuclear imaging technique using radiotracers (e.g., Tc99-sestamibi) to assess myocardial perfusion. Differentiates between reversible ischemia (transient perfusion defects) and irreversible myocardial necrosis (fixed perfusion defects).
• Cardiac MRI with Stress: An advanced imaging test that, using vasodilators or inotropic agents, simulates cardiac stress. The Late Gadolinium Enhancement (LGE) technique distinguishes viable myocardium from fibrotic tissue, providing an accurate assessment of myocardial viability and ischemic severity.
• Coronary Angiography: An invasive procedure performed via cardiac catheterization, injecting contrast into coronary arteries to visualize their lumen directly. It is the gold standard for assessing coronary anatomy, identifying critical stenosis, and guiding therapeutic decisions on revascularization (angioplasty or coronary bypass surgery).

Specific Findings in Different Ischemic Conditions

Each ischemic condition presents specific diagnostic features across various instrumental tests:

• Stable Angina: Inducible ischemia on provocative tests, with ST-segment depression and perfusion abnormalities on scintigraphy. Coronary angiography reveals ≥50% stenosis.
• Unstable Angina: Transient ECG changes with ST-segment depression and T-wave inversion. Provocative tests are often avoided, while coronary angiography may show unstable atherosclerotic plaques.
• STEMI: Persistent ST-segment elevation in ≥2 contiguous leads, pathological Q waves in late phases, and perfusion abnormalities on scintigraphy.
• NSTEMI: ST-segment depression or persistent inverted T waves without ST elevation. Cardiac MRI can confirm myocardial necrosis without total coronary occlusion.
• Silent Ischemia: Absence of symptoms but evidence of perfusion abnormalities on advanced imaging (scintigraphy, cardiac MRI) or episodic ECG changes on Holter monitoring.
• Vasospastic Angina: Transient ST-segment elevation during ischemic episodes, with normal coronary angiography. The ergonovine or acetylcholine test can induce coronary spasm during angiography.

Differential Diagnosis

The symptoms of ischemic heart disease, particularly chest pain, can be mimicked by several cardiovascular and non-cardiovascular conditions.
Differential diagnosis is based on careful clinical evaluation 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. Confirmed by thoracic CT angiography.
• Myocarditis: Angina-like chest pain associated with fever, fatigue, and diffuse ECG changes. Cardiac enzymes may be elevated without evidence of coronary artery disease. Cardiac MRI reveals myocardial edema.
• Pericarditis: Pleuritic chest pain, worsened by deep inspiration and relieved when sitting forward. ECG shows diffuse ST-segment elevation without reciprocal depression.
• Mitral Valve Prolapse: Atypical chest pain unrelated to exertion, sometimes accompanied by palpitations. Confirmed by echocardiography.

Pulmonary Conditions

• Pulmonary Embolism: Sudden-onset chest pain, dyspnea, tachycardia, and desaturation. Can mimic myocardial infarction, but ECG often shows sinus tachycardia and right axis deviation. Diagnosis confirmed by pulmonary CT angiography.
• Pneumothorax: Unilateral, acute chest pain associated with reduced breath sounds. Diagnosed by chest X-ray.
• Pleuritis: Pleuritic chest pain, worsened by deep breathing, with pericardial rubs on auscultation. Confirmed by chest X-ray or ultrasound.

Gastrointestinal Conditions

• Gastroesophageal Reflux Disease (GERD): Burning retrosternal pain, worsened in a supine position and after meals, relieved by antacids. Upper endoscopy is indicated for persistent symptoms.
• Esophageal Spasm: Constrictive chest pain that may mimic angina but is unrelated to exertion. Triggered by cold food or emotional stress. Diagnosed by esophageal manometry.
• Acute Pancreatitis: Epigastric pain radiating to the back, associated with nausea and vomiting. Diagnosis is based on elevated lipase levels and abdominal ultrasound.

Musculoskeletal Conditions

• Costochondritis: Localized chest pain worsened by sternal palpation and movement. Absent during exertion.
• Muscular Chest Pain: Often secondary to physical exertion or trauma, can be reproduced by palpation or chest movement.

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 testing and advanced imaging, while coronary angiography remains the definitive test in doubtful or high-risk cases.

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