What are the possible differential diagnoses for a patient presenting with cardiac symptoms and abnormal ECG (electrocardiogram) findings?

Differential Diagnosis for Cardiac Symptoms with Abnormal ECG Findings

Acute Coronary Syndromes

The most critical differential to exclude immediately is acute coronary syndrome (ACS), which includes ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina. 1

Key ECG Features:

• ST-segment elevation indicates transmural ischemia from coronary occlusion and characterizes evolving myocardial infarction 1
• ST-segment depression >1 mm in two or more contiguous leads is highly suggestive of acute coronary syndrome 1
• Deep symmetrical T-wave inversion in anterior chest leads often relates to significant proximal left anterior descending coronary artery stenosis 1
• New or presumed new left bundle branch block should be treated as a STEMI equivalent 2
• Significant Q-waves indicate previous myocardial infarction and presence of significant coronary atherosclerosis 1

Clinical Presentation:

• Prolonged anginal pain at rest (>20 minutes) occurs in 80% of ACS patients 1
• Atypical presentations include epigastric pain, recent onset indigestion, stabbing chest pain, pleuritic features, or increasing dyspnea—particularly in younger patients (25-40 years), elderly (>75 years), diabetics, and women 1
• Physical examination is often normal, but should exclude non-cardiac causes and assess for hemodynamic instability 1

Myocarditis

Myocarditis represents an inflammatory process of the myocardium with histological evidence of myocyte degeneration and necrosis of non-ischemic origin, associated with inflammatory infiltration. 1

Key ECG Features:

• Frequent and/or complex ventricular and/or supraventricular arrhythmias 1
• ST-segment alterations (usually depression; rarely elevation) 1
• T-wave inversion 1
• Occasionally left bundle branch block or atrioventricular blocks 1
• Low QRS voltages particularly with pericardial effusion 1

Clinical Presentation:

• Usually starts with upper respiratory or gastrointestinal symptoms 1
• Palpitations, fatigability, exertional dyspnea, or syncope may be the clinical onset 1
• Evidence of flu-like illness or epidemiological circumstances supporting viral infection 1
• Non-specific symptoms such as fatigue may elude diagnosis 1

Diagnostic Considerations:

• Serum cardiac biomarkers for inflammation are elevated 1
• Echocardiography may show global LV enlargement and dysfunction, localized wall motion abnormalities (usually apex), or modest pericardial effusion 1
• Cardiac MRI can identify hyperemia, inflammation edema, and focal scar with late gadolinium enhancement being crucial for identifying the inflammatory process 1
• Speckle tracking imaging shows reduction in global systolic longitudinal strain correlating with intramyocardial inflammation 1

Pericarditis

Pericarditis is defined as an inflammatory process of the pericardium, which may also affect the subepicardial layers of the myocardium. 1

Key ECG Features:

• ST-T wave alterations mimicking ischemic heart disease 1
• Ventricular or supraventricular tachyarrhythmias 1
• May provide evidence of alternative diagnosis when evaluating suspected ACS 1

Clinical Presentation:

• Usually starts with upper respiratory or gastrointestinal symptoms 1
• Chest pain, increased fatigability, or exertional dyspnea 1
• Onset may be concealed with only transient fever without significant cardiac symptoms 1

Stress-Induced (Takotsubo) Cardiomyopathy

Takotsubo cardiomyopathy mimics ACS with chest pain and ECG changes but no angiographic evidence of ACS, characterized by reversible LV dysfunction with regional wall motion abnormalities that do not correspond to typical coronary artery perfusion territories. 1

Key Features:

• Accounts for approximately 2% of all patients admitted with potential ACS diagnosis 1
• Typically affects perimenopausal females (90%) but can affect all patient groups 1
• Presents with LV apical akinesia in typical cases, but heterogeneous presentations include mid-cavity, LV base, and RV involvement 1
• Biventricular involvement occurs in about one-quarter of patients 1
• Complete recovery of LV function is required to confirm diagnosis, ranging from days to weeks 1

Cardiomyopathies

Hypertrophic Cardiomyopathy (HCM):

• ECG may show left ventricular hypertrophy patterns 1
• Can present with ventricular arrhythmias 1
• Exercise testing may reveal exercise-induced wall motion abnormalities 1

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC):

• May present with ventricular arrhythmias originating from the right ventricle 1
• Electrophysiological study may be considered for differential diagnosis from benign RVOT tachycardia 1

Dilated Cardiomyopathy:

• ECG may show low QRS voltages, bundle branch block, or AV block 1
• Echocardiography demonstrates LV enlargement and dysfunction 1

Pulmonary Embolism

Pulmonary embolism should be considered as an alternative diagnosis when evaluating patients with chest pain and abnormal ECG. 1

• ECG may provide evidence supporting this diagnosis 1
• Physical examination should exclude this as a potential cause 1

Aortic Dissection

Aortic dissection is a life-threatening emergency requiring early diagnosis, as prompt management significantly impacts outcomes. 1

Key Features:

• May present with chest pain and ECG changes 1
• Echocardiography can demonstrate intimal flap in aortic root and arch 1
• Complications include acute aortic regurgitation, pericardial effusion, or regional wall motion abnormalities suggestive of coronary artery involvement 1
• Normal transthoracic echocardiography cannot exclude aortic dissection 1

Supraventricular Tachycardia (SVT)

Wide-complex tachycardia (QRS duration >120 ms) may represent either ventricular tachycardia or a supraventricular rhythm with abnormal conduction. 1

Key ECG Features:

• Presence of AV dissociation (with ventricular rate faster than atrial rate) or fusion complexes provides diagnosis of VT 1
• Concordance of precordial QRS complexes (all positive or negative) suggests VT or pre-excitation 1
• QRS complexes in tachycardia identical to sinus rhythm are consistent with SVT 1
• Irregular ventricular rate suggests atrial fibrillation, multifocal atrial tachycardia, or atrial flutter with variable AV conduction 1

Clinical Presentation:

• Palpitations, light-headedness, syncope, or near-syncope 1
• Syncope should be taken seriously in patients with WPW syndrome 1
• Drop in blood pressure is greatest in first 10-30 seconds of SVT 1

Channelopathies

Resting 12-lead ECG may reveal signs of inherited disorders associated with ventricular arrhythmias and sudden cardiac death. 1

Specific Conditions:

• Long QT syndrome (LQTS): Prolonged QT interval 1
• Short QT syndrome (SQTS): Shortened QT interval 1
• Brugada syndrome: Characteristic ST-segment elevation in right precordial leads 1
• Catecholaminergic polymorphic ventricular tachycardia (CPVT): Exercise testing useful for diagnosis showing adrenergic-dependent polymorphic VT 1

Marfan Syndrome with Cardiac Involvement

The primary cause of mortality in young people and competitive athletes with Marfan syndrome is aortic root dilatation, dissection, and rupture. 1

• Evaluation includes echocardiography to assess aortic root 1
• May present with cardiac symptoms and ECG abnormalities related to aortic complications 1

COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C)

In pediatric patients, MIS-C represents a unique post-infectious hyperinflammatory disorder associated with SARS-CoV-2 that presents with cardiac symptoms and abnormal ECG findings. 3, 4

Key Features:

• Characterized by overwhelming systemic inflammation, fever, hypotension, and cardiac dysfunction 4
• Main cardiac complications include myocarditis and coronary artery aneurysms 4
• Presents with fever plus incomplete Kawasaki clinical features (2-3 features) 3
• ECG abnormalities reflect acute myocarditis 3, 5, 6
• Cardiac biomarkers: Detectable troponin I >10 ng/L has 91% sensitivity and 76% specificity for MIS-C vs Kawasaki disease; NT-proBNP >2000 ng/L has 82% sensitivity and 82% specificity 7
• SARS-CoV-2 PCR often negative but serology positive 5, 6
• Cardiac MRI shows diffuse myocardial edema on T2 sequences and native T1 mapping, typically without late gadolinium enhancement 5

Non-Cardiac Causes

Physical examination should systematically exclude non-cardiac causes of chest pain including pneumothorax, gastrointestinal disorders, and musculoskeletal pain. 1

• Chest pain fully reproduced by palpation had only 7% incidence of acute myocardial ischemia in the Multicenter Chest Pain Study 1
• Sharp or stabbing chest pain had 22% incidence of acute myocardial ischemia 1
• Chest pain with pleuritic features had 13% incidence of acute myocardial ischemia 1