What are the possible causes of diffuse ST segment depression on an electrocardiogram (EKG)?

Causes of Diffuse ST Segment Depression on EKG

Diffuse ST segment depression on EKG has multiple etiologies including acute myocardial ischemia (particularly subendocardial ischemia or left main/multivessel disease), reciprocal changes from ST elevation in opposite leads, left ventricular hypertrophy, cardioactive drugs (especially digitalis), electrolyte abnormalities (particularly hypokalemia), and supraventricular tachyarrhythmias. 1, 2

Cardiac Ischemic Causes

Acute Coronary Syndromes

• Subendocardial ischemia causing diffuse ST depression across multiple leads represents injury currents directed toward the ventricular chamber, reflecting endocardial ischemia without transmural involvement 1
• Left main coronary artery disease or severe multivessel disease classically presents with diffuse ST depression accompanied by ST elevation in lead aVR 3, 4
• ST depression indicates more severe coronary disease: patients with ST depression have 100% increased occurrence of three-vessel or left main disease compared to those without 4
• The severity correlates with the number of leads showing depression, the magnitude of depression, and earlier appearance during stress 1, 2

Reciprocal Changes

• ST depression may represent reciprocal changes from ST elevation in anatomically opposite leads rather than primary ischemia 1
• For example, ST depression in V1-V2 commonly indicates posterior or lateral wall ST elevation myocardial infarction 1, 5
• ST depression in leads II, III, aVF may be reciprocal to anterior wall ST elevation 5

Non-Ischemic Cardiac Causes

Structural Heart Disease

• Left ventricular hypertrophy produces secondary ST-T wave changes with ST depression, particularly in lateral leads 1, 6
• Severe aortic stenosis can cause diffuse ST depression with ST elevation in aVR, mimicking left main disease, even without significant coronary stenosis 3

Arrhythmias

• Supraventricular tachycardias can produce diffuse ST depression that may persist briefly after conversion to sinus rhythm, reflecting global ischemia in small intracardiac vessels 7
• The tachycardia-induced ischemia occurs despite normal coronary arteries on angiography 7

Conduction Abnormalities

• Left bundle branch block causes secondary ST-T wave changes with ST depression 1, 6
• Intraventricular conduction disturbances produce secondary repolarization abnormalities that can obscure or mimic ischemic changes 1, 2

Metabolic and Pharmacologic Causes

Electrolyte Abnormalities

• Hypokalemia is a primary cause of ST segment depression by affecting the plateau phase of the ventricular action potential 1, 2
• Lowered serum potassium should always be considered in the differential diagnosis 1

Medications

• Cardioactive drugs, particularly digitalis, commonly cause ST depression with characteristic "scooped" or "sagging" appearance 1, 2, 6
• Various cardiac and non-cardiac medications can affect ventricular repolarization and produce ST changes 2

Other Causes

• Acute myocarditis can produce diffuse ST segment changes 1
• Pericarditis may cause confounding ST changes, though typically presents with ST elevation 1
• Neurological events can produce ST depression through autonomic effects 2

Critical Diagnostic Considerations

Pattern Recognition

• Horizontal or downsloping ST depression ≥0.5-1.0 mm in two or more contiguous leads is most specific for myocardial ischemia 1, 2
• Upsloping ST depression is considered "equivocal" and not reliably predictive of ischemia in general populations 1, 2

High-Risk Features

• Diffuse ST depression with ST elevation in aVR strongly suggests left main or severe multivessel disease and warrants urgent evaluation 3, 4
• Earlier appearance during stress testing and longer duration in recovery indicate more severe coronary disease 1, 2

Common Pitfalls to Avoid

• Do not overlook non-ischemic causes such as LVH, LBBB, digitalis effect, or electrolyte abnormalities when evaluating ST depression 2, 6
• Avoid misinterpreting reciprocal changes as separate ischemic territories—always look for corresponding ST elevation in opposite leads 1, 5
• Remember that upsloping ST depression should not be considered definitive evidence of ischemia despite its presence 1, 2
• Consider that confounding ECG abnormalities (LVH, conduction disturbances, pericarditis) may mask or alter the expected ischemic pattern 1