Analysis of Adenosine on Sinus and Atrioventricular Nodal Conduction in the Pediatric Transplanted Heart

After cardiac catheterization, the study protocol will begin with 12.5µg/kg of adenosine (one eighth the recommended starting clinical dose), and will double to 25µg/kg, 50µg/kg, 100µg/kg and finally 200µg/kg (not to surpass the total maximum dose of 12mg). A pacing catheter will be placed within the right ventricle prior to medication administration. Escalating doses will stop if ventricular pacing is required due to a ventricular pause greater than 12 seconds or if atrioventricular block is demonstrated with a ventricular pause less than 12 seconds. If there is no prolonged pause requiring pacing and no demonstration of medication effect the subsequent dose will be given.

Progression to the next dose of the adenosine will depend on both the primary and secondary study outcomes. If the adenosine dose produces clinically significant bradycardia (> 12 seconds), ventricular pacing will be used to maintain cardiac output, and the dose will be considered unsafe to use clinically and testing will end for that patient. If the adenosine dose produces atrioventricular block but with a pause of less than 12 seconds (thus does not require pacing), the dose will be considered effective and the study will terminate as well. However, if the adenosine dose does not produce atrioventricular block or require pacing intervention, the dose will be considered safe but ineffective and the study will progress to the next higher dose. Before dose progression, the study will pause for additional 30 seconds to ensure complete adenosine metabolism, as the half-life of adenosine is less than 10 seconds and does not exhibit cumulative effects. The subsequent dose will then be administered and the ECG observed for clinically significant bradycardia and atrioventricular block. This will be repeated until clinically significant bradycardia and/or atrioventricular block is observed, or up to the final 200μg/kg (not to surpass the total maximum of 12mg) dose.

The same study protocol is being utilized to retest the subset of patients in whom dipyridamole was discontinued prior to the initial testing to further understand the safety of administering adenosine to heart transplant patients chronically maintained on dipyridamole.

Inclusion criteria

• Patients who have undergone a heart transplantation and who receive their routine care at the Morgan Stanley Children's Hospital of New York, Columbia University Medical Center

Exclusion criteria

• Patients admitted to the inpatient heart failure team
• Patients present for their first outpatient catheterization after new transplant
• Abnormal hemodynamics concerning for acute rejection
• Patients present for follow up of rejection (last biopsy positive)
• Ingested methylxanthine-containing foods that day
• Patients taking oral dipyridamole and did not discontinue it 3 days prior to testing
• Prior transplant history of coronary artery vasculopathy with this allograft or concern for abnormal coronary vasculature by angiography on the day of the catheterization
• Patients taking carbamazepine (may potentiate adenosine effect)
• Patients with known conduction disease (first, second or third degree atrioventricular block) and/or with pre-existing sinus node dysfunction (based on pre-existing ECG, Holter or inpatient telemetry)
• Patients/guardians unable to give consent in English