What is the management of upsloping ST (segment) depression indicative of myocardial ischemia?

From the Guidelines

The management of upsloping ST segment depression indicative of myocardial ischemia involves prompt medical intervention with antiplatelet therapy, anticoagulation, and anti-ischemic medications, as outlined in the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1. The initial treatment should include aspirin (325 mg loading dose followed by 81 mg daily), plus a P2Y12 inhibitor such as clopidogrel (300-600 mg loading dose, then 75 mg daily), ticagrelor (180 mg loading dose, then 90 mg twice daily), or prasugrel (60 mg loading dose, then 10 mg daily). Some key points to consider in the management of upsloping ST segment depression include:

• Anticoagulation with unfractionated heparin (60-70 U/kg IV bolus, maximum 5000 U, followed by 12-15 U/kg/hr infusion) or low molecular weight heparin like enoxaparin (1 mg/kg subcutaneously twice daily) should be initiated 1.
• Anti-ischemic therapy includes beta-blockers (metoprolol 25-50 mg orally every 6 hours or 5 mg IV every 5 minutes for 3 doses), nitrates (sublingual nitroglycerin 0.4 mg every 5 minutes for chest pain, or IV nitroglycerin 5-10 mcg/min titrated upward), and high-intensity statins (atorvastatin 40-80 mg daily) 1.
• Oxygen should be administered if saturation is below 90% 1.
• Patients should undergo risk stratification with cardiac biomarkers and be considered for early invasive strategy with coronary angiography, particularly if they have high-risk features or recurrent symptoms 1. It's worth noting that upsloping ST depression during exercise is not usefully predictive for the presence of myocardial ischemia in general populations, as stated in the exercise standards for testing and training: a scientific statement from the American Heart Association 1. However, in the context of real-life clinical medicine, it is essential to prioritize caution and consider the patient's overall clinical presentation and risk factors when making management decisions. Some important considerations in the management of upsloping ST segment depression include:
• The degree, time of appearance, duration, and number of leads with ST-segment depression can provide valuable information about the severity of coronary artery disease 1.
• The anatomic and functional severity of coronary artery disease can also be related to the time of appearance of ischemic ST-segment depression 1.
• The presence of high-risk features, such as recurrent symptoms or significant ST-segment depression, should prompt consideration of early invasive strategy with coronary angiography 1.

From the Research

Management of Upsloping ST Depression

The management of upsloping ST depression indicative of myocardial ischemia involves several considerations, including:

• The presence of active cardiac symptoms, as upsloping ST depression may indicate cardiac ischemia in these cases 2
• The use of beta-blockers, which reduce myocardial oxygen demand, improve flow toward ischemic regions, and have mild antiplatelet and antiarrhythmic effects 3
• The use of calcium channel blockers, which reduce myocardial oxygen demand and improve oxygen supply 3
• The use of ranolazine, a novel antianginal and anti-ischemic agent, which is currently approved for the treatment of angina pectoris either as monotherapy or added to beta-blockers, nitrates, and calcium channel blockers 4

Diagnostic Considerations

When evaluating upsloping ST depression, it is essential to consider the following:

• The sensitivity and specificity of upsloping ST depression in predicting reversible ischemia, which were found to be 82% and 90% compared to myocardial perfusion imaging, and 77% and 92% as assessed by coronary angiography 5
• The association between upsloping ST depression and an increased risk of coronary artery disease 5
• The potential for upsloping ST depression to represent acute ischemia, as seen in a patient with acute coronary syndrome 6

Treatment Options

Treatment options for upsloping ST depression indicative of myocardial ischemia may include:

• Beta-blockers, such as timolol, metoprolol, atenolol, and propranolol, which have cardioprotective effects and reduce overall mortality and the incidence of recurrent myocardial infarction 3
• Calcium channel blockers, such as diltiazem, which can reduce the incidence of reinfarction in patients after non-Q wave myocardial infarction 3
• Ranolazine, which is an effective antianginal and anti-ischemic agent, but its use should be restricted to patients with stable angina pectoris 4