Action Potential Features in Right Ventricular Myectomies from the Pediatric Tetralogy of Fallot Patients

Objectives: The tetralogy of Fallot (TOF) patients are prone to ventricular arrhythmias in adulthood. We investigated action potential (AP) features in right ventricular (RV) myocardium from TOF infants and children with the aim of detecting possible early, predisposing arrhythmogenic factors at cellular level, and relating these to age and TOF severity.

Methods: Intracellular AP were recorded from tissue samples excised intraoperatively from the RV outflow tract of 13 TOF patients at stimulation frequencies of 0.5, 1, 2, 3, and 4 Hz. Arrhythmia susceptibility of the tissue was examined by pharmacological testing with barium chloride and low potassium. AP shape was analyzed with regard to resting membrane potential (RMP), AP amplitude (APA), maximum upstroke velocity (dV/dt maximum), and AP duration at 20, 50, and 90% repolarization (APD20, APD50, and APD90).

Result: Patients under 21 months of age (n = 10) had significantly shorter APD20 than patients aged 9–12 years (n = 3; [Table 1]). There was no difference in AP shape between patients with and without cyanosis, pressure gradient between RV and pulmonary artery &≥60 mm Hg, and medication with &β-blockers. Over all patients, RMP, APA, dV/dt maximum, and rate dependence of both APD and dV/dt maximum ([Table 1]) were similar to previous microelectrode AP studies in healthy adult human RV tissue preparations. 10 patients in total (from both age groups) showed early after depolarizations, AP alternans, and/or abnormal AP features (e.g., extreme AP triangulation/lack of plateau). These patients had significantly longer APD20, APD50, and APD90 at 0.5 Hz compared with patients without any AP abnormalities.

Table 1 Electrophysiologic measurements at different stimulation frequencies

Stim. freq.	RMP (mV)	APA (mV)	dV/dt max (V/s)	APD20 <21 mo (ms)	APD20 9–12 y (ms)	APD90 <21 mo (ms)	APD90 9–12 y (ms)
0.5 Hz	-72 ± 2.6	91 ± 7.3	148 ± 64.0	130 ± 38.5	197 ± 17.5	280 ± 105.2	352 ± 31.2
1 Hz	-72 ± 4.6	92 ± 6.4	124 ± 58.0	120 ± 35.4	182 ± 14.6	262 ± 90.0	318 ± 44.7
2 Hz	-73 ± 4.9	90 ± 4.7	122 ± 42.9	96 ± 31.8	143 ± 12.5	191 ± 45.5	261 ± 35.3

Conclusion: TOF patients under 21 months showed a less pronounced AP plateau than older patients. Further studies are needed to investigate whether this is a TOF-specific or a disease-unrelated maturation effect. Moreover, those samples with abnormal or arrhythmic AP had longer APD at all repolarization levels than those with normal AP, which may reflect a reduced repolarization reserve. Clinical features defining these patients remain to be identified.