Effect of liver transplantation on QT-interval prolongation and impact on mortality

https://doi.org/10.1016/j.ijcard.2020.11.017Get rights and content

Highlights

  • QT-interval prolongation is evident in over half of liver cirrhosis patients.

  • Liver transplantation is a curative procedure for end-stage liver disease.

  • The QT-interval significantly prolongs further in the early post-transplant period.

  • The QT-interval largely resolves to within normal limits on long-term follow-up.

  • QT-interval prolongation is not a predictor of long-term mortality.

Abstract

Background

QT-interval prolongation is considered the electrophysiological hallmark of cirrhotic cardiomyopathy. However, the significance of QT-interval prolongation and how it is affected by liver transplantation (LT) remains unclear.

Methods

Consecutive inpatients undergoing LT between 2010 and 2017 at a state-wide liver transplant center in Australia were included. Preoperative, early postoperative and long-term follow-up corrected QT-intervals (QTc) were manually measured by a cardiologist. QTc was calculated using the Bazett formula and QTc ≥440 milliseconds (ms) was considered prolonged.

Results

Overall, 1111 ECG tracings among 408 patients (mean age 57 ± 12 years) were assessed. Pre-LT, 265 patients (65.0%) had QTc ≥440 ms and 24 patients (5.9%) had QTc ≥500 ms. In the early postoperative period, there was a significant increase in QTc compared to pre-LT (471 ± 39 vs. 452 ± 31 ms, p < 0.001) and 80 patients (20.3%) had QTc ≥500 ms. At a median of six months post-LT, there was significant reduction in mean QTc compared to pre-LT (430 ± 32 vs. 452 ± 31 ms; p < 0.001) with the QTc shortening in 73% of patients. QT-interval prolongation was not associated with postoperative complications or mortality at any time-point.

Conclusion

QT-interval prolongation is common in patients with liver cirrhosis and this metric normalized in the majority within six months post-LT. A significant increase in QTc was noted early post-LT, with over 20% demonstrating QTc ≥500 ms. QT-interval prolongation was not associated with post-transplant complications or mortality. Resolution of QT-interval prolongation suggests that this feature of cirrhotic cardiomyopathy may reverse post-transplantation.

Introduction

Prolongation of the QT-interval is observed in nearly half of patients with end-stage liver disease and is widely recognized as the electrophysiological hallmark of cirrhotic cardiomyopathy [1,2]. Historically, this has been defined as a corrected QT-interval (QTc) ≥440 milliseconds (ms) due to the loss of the usual gender difference in QTc among patients with cirrhosis [[2], [3], [4], [5]]. In the general population as well as in patients with coronary artery disease (CAD), prolongation of the QT-interval has been associated with an increased risk of mortality [6,7]. Our group has previously demonstrated that certain comorbid factors such as hepatorenal syndrome, pulmonary hypertension, and CAD are associated with increased risk of morbidity and mortality post-liver transplantation [8,9]. However, there is a scarcity of research regarding outcomes in end-stage liver disease post-transplant for patients with a prolonged QT-interval.

Liver transplantation (LT) is a curative procedure for patients with end-stage liver disease. Despite the common observation of QT-interval prolongation in patients with liver disease, the effect of LT on QTc remains unclear. Recent consensus statements on cirrhotic cardiomyopathy highlight the gaps in our current understanding of both the significance of a prolonged QTc in patients undergoing transplantation and whether LT can lead to a normalization of the QTc in this patient population [10]. Previous studies that have investigated QT-interval patterns in the cirrhotic population were limited by small sample sizes, a paucity of longitudinal ECG data, and variable follow-up [1,5,10,11].

The aims of this study were twofold. First, we sought to describe temporal changes in QTc in the early and long-term postoperative periods and to determine whether a prolonged QTc is reversed as a result of LT. Second, we examined the effect of the QT-interval on perioperative complications and long-term mortality.

Section snippets

Study population

Consecutive adults (age ≥ 18 years) undergoing LT between 2010 and 2017 at a state-wide liver transplant center in Melbourne, Australia were included in this retrospective study. Patients were excluded if they were undergoing re-transplantation or multi-organ transplantation, had significant CAD without revascularization, cardiomyopathy or valvular heart disease, or if they were transplanted for hemochromatosis or amyloidosis. This project was approved by the Human Research Ethics Committee at

Baseline demographics

A total of 408 patients were initially included in this study, all of whom had pre-transplant ECGs on the day of LT. Subsequently, 394 patients had a postoperative (median day 1 post-LT) ECG and 309 patients had an ECG at long-term follow-up (median six months post-LT). ECGs were not available for all patients at all three time-points (Fig. 1). The mean age was 57 ± 12 years and the majority of patients (67.4%) were male. Hepatitis B or C (32.6%) was the most common etiology of cirrhosis and

Discussion

QT-interval prolongation is considered the electrophysiological hallmark of cirrhotic cardiomyopathy, however its clinical significance and implications for LT are unclear. This large study of consecutive patients undergoing LT has established the following findings:

  • 1.

    In this cohort with a prolonged baseline QTc, there was a significant further prolongation of the QT-interval in the early postoperative period with over one-fifth of patients having a QTc ≥500 ms.

  • 2.

    The QT-interval significantly

Conclusion

QT-interval prolongation is common in patients with end-stage liver disease. Our study demonstrates that the QT-interval becomes further prolonged in the early postoperative period and that LT normalizes this electrocardiographic metric in the majority of patients on long-term follow-up. A prolonged QTc at any time-point was not associated with an increased risk of operative complications or long-term mortality and this may be due to the marked improvement in QTc post-transplant. The resolution

Authorship roles

All authors meet the four criteria for authorship as per the ICMJE recommendations. All authors take full responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Financial support

Dr. Anoop N Koshy is a recipient of the National Health and Medical Research Council of Australia/National Heart Foundation Post-Graduate Scholarship and Royal Australasian College of Physicians Blackburn Scholarship.

Disclosures

The authors of this manuscript have no conflicts of interest to disclose.

Author Statement

Jefferson Ko: Conceptualization, Methodology, Formal Analysis, Investigation, Writing – Original Draft, Writing – Review & Editing, Visualization Anoop N. Koshy: Conceptualization, Methodology, Software, Validation, Formal Analysis, Investigation, Data Curation, Writing – Review & Editing Hui-Chen Han: Methodology, Validation Laurence Weinberg: Resources, Writing – Review & Editing Paul Gow: Resources, Supervision Adam Testro: Resources, Supervision Han S. Lim: Writing – Review & Editing Omar

References (29)

  • Y. Zhang et al.

    Electrocardiographic QT-interval and mortality: a meta-analysis

    Epidemiology

    (2011)
  • A.N. Koshy et al.

    Prediction of perioperative cardiovascular events in liver transplantation [published online ahead of print 2020]

    Transplantation.

    (2020)
  • A.N. Koshy et al.

    Cardiovascular mortality following liver transplantation: predictors and temporal trends over 30 years [published online ahead of print 2020]

    Eur. Heart J. Qual. Care Clin. Outcomes

    (2020)
  • M. Izzy et al.

    Cirrhotic cardiomyopathy after transplantation: neither transient nor innocent bystander

    Hepatology

    (2018)
  • 1

    Jefferson Ko and Anoop N Koshy contributed equally to this paper.

    View full text