How does Regadenoson (Lexiscan) stress the heart?

How Regadenoson (Lexiscan) Stresses the Heart

Regadenoson is a selective A2A adenosine receptor agonist that causes coronary vasodilation in normal epicardial arteries, creating a heterogeneity of blood flow between normal and stenotic coronary vessels that can be detected during myocardial perfusion imaging. 1

Mechanism of Action

• Regadenoson selectively binds to A2A adenosine receptors, causing coronary vasodilation in normal epicardial arteries 1
• Unlike exercise stress which creates a mismatch between oxygen supply and demand, regadenoson unmasks locally limited capacity for coronary vasodilation 1
• Normal coronary arteries dilate significantly in response to regadenoson, while stenotic arteries that have already recruited vasodilator reserve at rest cannot increase flow to the same extent 1
• This differential response creates a heterogeneity in myocardial perfusion that can be visualized with nuclear imaging agents 1

Pharmacological Properties

• Regadenoson is administered as a fixed-dose intravenous bolus (0.4 mg/5 mL) over 10 seconds, regardless of patient weight 2, 3
• After administration, regadenoson causes:
  • Peak coronary blood flow within 1-4 minutes 2
  • Maximum increase in coronary blood flow of approximately 2.5-3.4 times baseline 4
  • Sustained coronary hyperemia for approximately 2-5 minutes 5, 4
• The pharmacokinetic profile is multi-exponential with:
  • Initial phase half-life of 2-4 minutes 2
  • Intermediate phase half-life of approximately 30 minutes 2
  • Terminal phase half-life of approximately 2 hours 2

Hemodynamic Effects

• Regadenoson typically causes:
  • Increased heart rate (average increase of 21-34 beats per minute) 2, 3, 4
  • Mild decrease in systolic blood pressure (5-24 mmHg) 2, 4
  • Mild decrease in diastolic blood pressure (8-15 mmHg) 2, 4
• In clinical studies, approximately 22% of patients experienced heart rate >100 bpm and 5% had increases >40 bpm 2
• These hemodynamic effects are generally well-tolerated and resolve within approximately 15 minutes 6

Comparison to Other Stress Agents

• Unlike dobutamine (which increases myocardial oxygen demand through increased contractility and heart rate), regadenoson works by directly causing coronary vasodilation 1, 7
• Compared to adenosine:
  • Regadenoson is more selective for A2A receptors, resulting in fewer side effects related to A1, A2B, and A3 receptor activation 5, 8
  • Regadenoson can be given as a single bolus rather than continuous infusion 2, 8
  • Regadenoson produces comparable absolute increases in myocardial blood flow 3
• Despite being administered at a fixed dose, regadenoson produces coronary hyperemia comparable to dipyridamole and is independent of patient body weight or BMI 3

Clinical Applications

• Regadenoson is primarily used for pharmacological stress myocardial perfusion imaging in patients unable to exercise adequately 7, 8
• It is particularly useful for nuclear myocardial perfusion imaging techniques such as SPECT and PET 1
• Regadenoson can also be used with MRI heart function stress testing to diagnose hemodynamically significant coronary artery disease 1
• Unlike adenosine, regadenoson may be used in patients with mild to moderate reactive airway disease due to its selectivity for A2A receptors 5, 8

Safety Considerations

• The effects of regadenoson can be reversed with aminophylline (100 mg administered by slow IV injection) 2, 4
• Caffeine decreases the ability to detect reversible ischemic defects and should be avoided before testing 2
• Common side effects include flushing, chest pain, headache, and dyspnea, but these are generally transient 7, 6
• Regadenoson should be used with caution in patients with severe renal impairment, though no dose adjustment is needed 2

By creating a differential vasodilatory response between normal and stenotic coronary arteries, regadenoson effectively "stresses" the heart by revealing perfusion abnormalities that can be detected through appropriate imaging techniques.