Prospective Study of Adenosine on Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After Heart Transplantation

Abstract

Background Supraventricular tachycardia (SVT) is common after heart transplant. Adenosine, the standard therapy for treating SVT in children and adults without transplant, is relatively contraindicated post-transplant due to a presumed risk of prolonged atrioventricular (AV) block in denervated hearts. This study tested whether adenosine caused prolonged asystole after transplant and if it was effective in blocking AV nodal conduction in these patients. Methods This was a single center prospective clinical study including healthy heart transplant recipients ages 6 months – 25 years presenting for routine cardiac catheterization during 2015 – 2016. After catheterization, a transvenous pacing catheter was placed and adenosine was given following a dose escalation protocol until AV block was achieved. The incidence of clinically significant asystole (≥ 12 seconds following adenosine) was quantified. The effects of patient characteristics on adenosine dose required to produce AV block and duration of effect were also measured. Results Eighty patients completed adenosine testing. No patient (0%; 95% CI 0–3%) required rescue ventricular pacing. AV block was observed in 77 patients (96%; 95% CI 89–99%). The median longest AV block was 1.9 seconds (IQR 1.4–3.2) with the mean duration of adenosine effect 4.3 seconds (±2.0). No patient characteristic significantly predicted adenosine dose to produce AV block or duration of effect. Results were similar across patient weight categories. Conclusion Adenosine induces AV block in healthy pediatric and young adult heart transplant recipients with minimal risk when using low initial doses (25mcg/kg, or 1.5mg if ≥ 60kg) and gradually escalating therapy.

Extracellular nucleotide signaling in solid organ transplantation

“…In addition to promising preclinical research to decipher the complex role of nucleotide signaling in solid organ transplantation, several clinical trials are ongoing or have concluded that address purinergic signaling in the context of transplantation (see Table ). To date, only one study (NCT02462941) has been published whereby Flyer et al showed that adenosine induces atrioventricular block in healthy pediatric and young adult heart transplant recipients with minimal risk when low initial doses are used . Another study (NCT03231371) is currently evaluating the potential protective role of adenosine treatment in vasculopathy in heart transplantation, and another ongoing study (NCT03072589) is evaluating the maximum safe dose and duration of regadenoson (an A2AR agonist) in lung transplant patients as a means to prevent primary graft dysfunction.…”

“…Flyer et al showed that adenosine induces atrioventricular block in healthy pediatric and young adult heart transplant recipients with minimal risk when low initial doses are used. 64 Another study The authors also acknowledge the many excellent papers in the field that, due to space constraints, could not be directly referenced in the current review.…”

Unmasking Adenosine: The Purinergic Signalling Molecule Critical to Arrhythmia Pathophysiology and Management

“…However, a recent case series of patients in sinus rhythm following cardiac transplant given adenosine showed no major adverse events, including asystole, or need for pacing, which calls these views into question. [ 167 ]…”

MiR-33a-5p targets NOMO1 to modulate human cardiomyocyte progenitor cells proliferation and differentiation and apoptosis

“…Moreover, the NOMO1 gene has also been identified that it is evidently down-regulated in human ventricular septal defect myocardium, and it was found that knockdown of NOMO1 gene inhibited the differentiation of P19 cells into cardiomyocytes [17]. Nodal is a member of transforming growth factor-b (TGF-b), which acts as an essential role on heart development and formation of other visceral organs [18]. Nodal is also important for the maintenance of pluripotency of embryonic stem cells and germ layer specification [19].…”