Effect of liver transplantation on QT-interval prolongation and impact on mortality
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)
- et al.
Effect of cirrhosis and liver transplantation on the gender difference in QT interval
Am. J. Cardiol.
(2005) - et al.
Cardiac electrophysiological abnormalities in patients with cirrhosis
J. Hepatol.
(2006) - et al.
Incidence and trends of cardiac complications in major abdominal surgery
Surgery
(2018) - et al.
QT interval in patients with non-cirrhotic portal hypertension and in cirrhotic patients treated with transjugular intrahepatic Porto-systemic shunt
J. Hepatol.
(2003) - et al.
Potassium levels after liver reperfusion in adult patients undergoing cadaveric liver transplantation: a retrospective cohort study
Ann. Med. Surg.
(2020) - et al.
Prolongation of QTc interval: relationship with etiology and severity of liver disease, mortality and liver transplantation
Liver Int.
(2003) - et al.
Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors
Hepatology
(1998) - et al.
Q-T interval prolongation in liver cirrhosis: reversibility after orthotopic liver transplantation
Jpn. Heart J.
(1998) Prolonged QT-interval syndromes
J. Am. Med. Assoc.
(1986)- et al.
What clinicians should know about the QT interval
J. Am. Med. Assoc.
(2003)
Electrocardiographic QT-interval and mortality: a meta-analysis
Epidemiology
Prediction of perioperative cardiovascular events in liver transplantation [published online ahead of print 2020]
Transplantation.
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
Cirrhotic cardiomyopathy after transplantation: neither transient nor innocent bystander
Hepatology
Cited by (10)
Prolonged QT-interval in cirrhosis: is it reversible?
2021, International Journal of CardiologyCorrected QT interval in cirrhosis: A systematic review and metaanalysis
2023, World Journal of HepatologyRevisiting the QT Interval: An Old Marker for a New Disease?
2023, Arquivos Brasileiros de CardiologiaProlonged QT Interval in Cirrhosis: Twisting Time?
2022, Gut and Liver
- 1
Jefferson Ko and Anoop N Koshy contributed equally to this paper.