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QTc prolongation and liver disease – As good as PELD score?

Patients with chronic liver disease often have associated prolongation of their corrected QT intervals (QTc) on electrocardiogram. In adults, the presence of QTc prolongation has been shown to correlate with disease severity, as measured by Child–Pugh scores. In addition, QTc prolongation was associated with lower survival in follow-up (1). To date, pediatric data have shown a correlation between QTc prolongation and the presence of liver failure as well as normalization of QTc interval after liver transplant (2). However, these data have not been corroborated in large-scale pediatric series. In this issue of Pediatric Transplantation, Arikan et al. (3) present a series of 88 patients with chronic liver disease and report on their QTc intervals at diagnosis and follow-up. They found that in pediatric patients, prolonged QTc was correlated with pediatric end-stage liver disease (PELD) scores and was associated with a higher mortality rate. PELD was found to be an independent predictor of survival. In those patients with prolonged QTc who underwent liver transplantation, a significant percentage of them had normalization of their QTc at one year post-transplant follow-up. They postulate that QTc may be useful for the assessment of severity of liver disease in these patients and may be a useful tool for assisting in timing of liver transplantation. Strengths of this study included blinded analysis of ECGs and absence of any QT prolonging drugs or electrolyte abnormalities at time of initial QTc measurement. This allows for methodical analysis of QTc and removes as much variability as possible with this often troublesome measurement (4). Prolongation of QTc was defined as >440 ms, which is a conservative measure. In neonates and adolescent females, QTc of up to 450 ms may be considered normal. With this classification, there is potential for slight overestimation of the true incidence of prolongation of QTc in this patient population. However, given that outcomes were able to be differentiated with this more conservative cutoff of 440 ms suggests a definite effect, since some of the patients in the ‘‘prolonged’’ group truly may have had a ‘‘normal’’ QTc. One potential critique of this study might be the methodology used for QTc calculation. In this study, Bazett s formula for QTc was used, which is the standard methodology used in most pediatric ECGs. In adult patients with liver disease, some authors have suggested that Bazett s formula does not adequately account for heart rate variations, and that other formulas should be considered (5). However, since this has not been independently validated in pediatric patients with liver disease, it would appear that the application of Bazett s formula in this study seems appropriate based on current knowledge. Numerous etiologies have been postulated as possible explanations for this association, including autonomic dysfunction, portal hypertension and the presence of ‘‘cardiotoxic’’ substances entering the systemic circulation (6, 7). Certainly, this retrospective study provides interesting insight into the potential link between QTc prolongation and outcome of liver transplant patients. As PELD undergoes continuing assessment and validation, the use of the QTc interval as an objective predictor of pretransplant mortality is intriguing. Studies indicate significant regional exceptions to PELD and variability in its application in organ allocation (8, 9). In the future, it may be the case that QTc measurements can be employed prospectively as a risk factor for adverse patient outcomes. Clearly, further prospective studies are needed to help delineate the Pediatr Transplantation 2009: 13: 263–264 2008 John Wiley & Sons A/S.