Cardiac stressing agents

1. Introduction

• Cardiac stressing agents are pharmacologic substances used to mimic the effects of exercise on the heart during a cardiac stress test.

• Employed when a patient is unable to perform adequate physical exercise for stress testing due to physical limitations or comorbidities.

• Allow evaluation of myocardial perfusion, ischemia, and functional capacity using imaging modalities such as nuclear scintigraphy, echocardiography, or MRI.

• Main categories:

  • Vasodilator stress agents (increase coronary blood flow).

  • Inotropic/chronotropic stress agents (increase heart rate and contractility).

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2. Pharmacologic Categories and Mechanisms

A. Vasodilator Stress Agents

• Work by dilating coronary arteries, increasing blood flow in healthy vessels.

• Ischemic areas supplied by stenotic arteries receive relatively less flow (coronary steal phenomenon).

• Common agents:

  • Adenosine

    • Nonselective adenosine receptor agonist.

    • Short half-life (~10 seconds).

    • Causes direct coronary vasodilation via A2A receptor activation.

  • Regadenoson

    • Selective A2A receptor agonist.

    • Longer half-life than adenosine.

    • More convenient (single bolus dosing).

  • Dipyridamole

    • Inhibits adenosine reuptake and degradation → increased endogenous adenosine levels → vasodilation.

B. Inotropic/Chronotropic Stress Agents

• Increase myocardial oxygen demand by raising heart rate and contractility.

• Useful in patients with contraindications to vasodilators or when vasodilator tests are inconclusive.

• Common agent:

  • Dobutamine

    • β1-adrenergic agonist (also some β2, α1 activity).

    • Increases heart rate, myocardial contractility, and blood pressure.

    • Mimics physiologic stress of exercise.

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3. Clinical Uses

• Detection of coronary artery disease (CAD) in patients unable to undergo adequate exercise testing.

• Risk stratification in patients with known CAD.

• Assessment of myocardial viability before revascularization.

• Evaluation of valvular heart disease (e.g., low-flow aortic stenosis).

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4. Administration

• Performed in a controlled environment with continuous ECG, blood pressure, and oxygen saturation monitoring.

• Often combined with imaging:

  • Nuclear perfusion imaging (SPECT or PET).

  • Stress echocardiography.

  • Stress cardiac MRI.

• Pre-procedure preparation:

  • Avoid caffeine and methylxanthines (antagonize adenosine) for 12–24 hours.

  • Adjust or hold certain cardiac medications as instructed.

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5. Contraindications

Vasodilator Agents (Adenosine, Regadenoson, Dipyridamole)

• High-grade AV block or sick sinus syndrome (without pacemaker).

• Symptomatic hypotension.

• Severe bronchospastic disease (asthma, severe COPD).

• Unstable acute coronary syndromes or severe hypotension.

• Use of dipyridamole or methylxanthines shortly before testing.

Dobutamine

• Uncontrolled hypertension.

• Severe aortic stenosis or hypertrophic obstructive cardiomyopathy (risk of outflow obstruction).

• Recent myocardial infarction (unstable phase).

• Uncontrolled arrhythmias.

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6. Adverse Effects

Vasodilators

• Flushing, chest discomfort, dyspnea.

• Hypotension.

• AV block, bradycardia.

• Bronchospasm.

• Headache.

Dobutamine

• Palpitations, tachyarrhythmias.

• Angina or myocardial ischemia.

• Hypertension.

• Tremor, anxiety.

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7. Monitoring and Safety

• Continuous ECG and hemodynamic monitoring during infusion.

• Emergency resuscitation equipment must be available.

• Reversal of vasodilator effects:

  • Adenosine/regadenoson: effects wear off quickly; aminophylline can be used if needed.

  • Dipyridamole: aminophylline can reverse prolonged vasodilation.

• Termination criteria:

  • Development of significant arrhythmias.

  • Severe hypotension or hypertension.

  • Severe chest pain or ischemic ECG changes.

  • Intolerable side effects.

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8. Advantages and Limitations

Advantages

• Enables cardiac stress testing in patients unable to exercise.

• Allows controlled titration and quick reversal (especially with adenosine/regadenoson).

• Can be tailored to patient’s condition and contraindications.

Limitations

• Cannot fully replicate physiological exercise capacity.

• Vasodilators unsuitable for patients with bronchospasm or severe conduction disease.

• Dobutamine unsuitable in uncontrolled arrhythmias or severe hypertension.