Evaluation of ventricular arrhythmia in children with Wilson's disease; cardiac electrophysiological balance index (iCEB)

Öz

Aim: To evaluate cardiac involvement in Wilson's disease (WD) noninvasively by electrocardiography and to analyze it with the cardiac electrophysiological balance index (iCEB). Method: Eighteen Wilson patients and 18 healthy child patients who were followed up in the Pediatric Gastroenterology department between 2022-2023 were included in the study. Results: Wilson disease patients had normal ventricular and autonomic functions. QT-dispersion (QT-d) (22.61 (±11.47), p=0.000) and Tpe (66.50 (40-78), p=0.02) were found to be significantly higher in the WD group. QRS, QRS-dispersion (QRS-d), QT, QTc, Tpe/QT ratio, Tpe/QTc ratio, QT/QRS ratio, QTc/QRS ratio, Tpe/QRS ratio, Tpe/(QT*QRS) ratio both had similar values in the groups. Heart rate variability parameters (SDNN, SDNN-i, SDANN, rMSSD, pNN50, LF/HF ratio) were at similar values in both groups. rMSSD, pNN50, which indicates parasympathetic activity, was lower in Wilson patients than in the control group, but no statistical difference was detected. LF/HF ratio was significantly higher in WD patients. Conclusions: Despite normal ventricular function and autonomic function in WD patients, they have an increased risk of ventricular arrhythmia. Although the cardiac electrophysiological balance index (iCEB) can provide useful information in the follow-up of WD patients, we recommend that depolarization, repolarization times, and repolarization dispersion times be evaluated separately in addition to iCEB.

Anahtar Kelimeler

• Wilson disease
• index of cardiac electrophysiological balance
• autonomic dysfunction
• Heart rate variability; repolarization dispersion

Kaynakça

1. 1.Rosencrantz R, Schilsky M. Wilson disease:pathogenesis and clinical considerations in diagnosisand treatment. Semin Liver Dis. 2011; 31: 245-59.
2. 2.Gaetke LM, Chow CK. Copper toxicity, oxidativestress, and antioxidant nutrients. Toxicology. 2003;189: 147-63.
3. 3.Quick S, Weidauer M, Heidrich FM, et al. Cardiacmanifestation of Wilson’s Disease. J Am Coll Cardiol.2018; 72: 2808-9.
4. 4.Kuan P. Cardiac Wilson’s disease. Chest. 1987; 91:579-583.
5. 5.Factor SM, Cho S, Sternlieb I, Scheinberg IH,Goldfischer S. The cardiomyopathy of Wilson's disease.Myocardial alterations in nine cases. Virchows Arch APathol Anat Histol. 1982; 397: 301-311.
6. 6.Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML.Wilson's disease. Lancet. 2007; 369: 397-408.
7. 7.Lang RM, Bierig M, Devereux RB, et al.Recommendations for chamber quantification: areport from the American Society ofEchocardiography’s Guidelines and StandardsCommittee and the Chamber Quantification WritingGroup, developed in conjunction with the EuropeanAssociation of Echocardiography, a branch of theEuropean Society of Cardiology. J Am SocEchocardiogr. 2005; 18: 1440-63.
8. 8.Nagueh SF, Appleton CP, Gillebert TC, et al.Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur JEchocardiogr. 2009; 10: 165-93.

9. 9.Chávez-González E, Jiménez AR, Moreno-MartínezFL. QRS duration and dispersion for predictingventricular arrhythmias in early stage of acutemyocardial infraction. Med Intensiva. 2017; 41: 347-55.
10. 10.Bednar MM, Harrigan EP, Anziano RJ, Camm AJ,Ruskin JN. The QT interval. Prog Cardiovasc Dis. 2001;43: 1-45.
11. 11.Yamaguchi M, Shimizu M, Ino H, et al. T wave peak-to-end interval and QT dispersion in acquired long QTsyndrome: a new index for arrhythmogenicity. Clin Sci(Lond). 2003; 105: 671-6.
12. 12.Kors JA, van Eck HJR, van Herpen G. The meaning of the Tp-Te interval and its diagnostic value. JElectrocardiol. 2008; 41: 575-80.
13. 13.Bazett HC. An Analysis of the Time-Relations ofElectrocardiograms. Ann Noninvasive Electrocardiol.1997; 2: 177-94.
14. 14.De Bruyne MC, Hoes AW, Kors JA, et al. QTcdispersion predicts cardiac mortality in the elderly: the Rotterdam Study. Circulation. 1998; 97: 467-72.
15. 15.Lu HR, Yan G-X, Gallacher DJ. A new biomarker–index of Cardiac Electrophysiological Balance (iCEB)–plays an important role in drug-induced cardiacarrhythmias: beyond QT-prolongation and Torsadesde Pointes (TdPs). J Pharmacol Toxicol Methods. 2013;68: 250-9.
16. 16.Tse G. (Tpeak− Tend)/QRS and (Tpeak−Tend)/(QT× QRS): novel markers for predictingarrhythmic risk in the Brugada syndrome. Europace.2017; 19: 696.
17. 17.Robyns T, Lu HR, Gallacher DJ, et al. Evaluation ofindex of cardio‐electrophysiological balance (iCEB) asa new biomarker for the identification of patients atincreased arrhythmic risk. Ann NoninvasiveEletrocardiol. 2016; 21: 294-304.
18. 18.Stein PK. Assessing heart rate variability from real-world Holter reports. Card Electrophysiol Rev. 2002; 6: 239-44.
19. 19.Bernardi l, Valle F, Coco M, Calciati A, Sleight P.Physical activity influences heart rate variability andvery-low-frequency components in Holterelectrocardiograms. Cardiovasc Res. 1996; 32: 234-7.
20. 20.Bhattacharya K, Velickovic M, Schilsky M,Kaufmann H. Autonomic cardiovascular reflexes inWilson's disease. Clin Auton Res. 2002; 12: 190-2.
21. 21.Meenakshi-Sundaram S, Taly AB, Kamath V, et al.Autonomic dysfunction in Wilson's disease–a clinicaland electrophysiological study. Clin Auton Res. 2002;12: 185-9.
22. 22.Chu EC, Chu NS, Huang CC. Autonomic involvementin Wilson's disease: a study of sympathetic skinresponse and RR interval variation. J Neurol Sci. 1997;149: 131-7.
23. 23.Buksińska-Lisik M, Litwin T, Pasierski T,Członkowska A. Cardiac assessment in Wilson’sdisease patients based on electrocardiography andechocardiography examination. Arch Med Sci. 2019;15: 857-64.
24. 24.Amoozgar H, Azadi S, Zahmatkeshan M, SafarpourAR. Electrocardiographic and EchocardiographicFindings in Pre-Liver Transplant Pediatric and YoungAdult Patients With Wilson’s Disease: A Case-ControlStudy. Iranian Heart J. 2022; 23: 118-28.
25. 25.Karhan AN, Aykan HH, Gümüş E, et al. Assessmentof cardiac function and electrocardiographic findingsin patients with Wilson’s disease. Cardiol Young. 2019; 29: 1183-8.
26. 26.Ozturk S, Gurbuz AS, Efe SC, et al. QTc interval isprolonged in Wilson’s disease with neurologicinvolvement. Acta Clin Belg. 2018; 73: 328-32.
27. 27.Antzelevitch C, Fish J. Electrical heterogeneitywithin the ventricular wall. Basic Res Cardiol. 2001;96: 517-27.
28. 28.Gondim FA, Araújo DF, Oliveira IS, Vale OC. Smallfiber dysfunction in patients with Wilson's disease. Arq Neuropsiquiatr. 2014; 72: 592-5.
29. 29.Sturniolo GC, Lazzarini D, Bartolo O, et al. Smallfiber peripheral neuropathy in Wilson disease: an invivo documentation by corneal confocal microscopy.Invest Ophtalmol Vis Sci. 2015; 6: 1390-5.
30. 30.Antzelevitch C, Sicouri S, Di Diego JM, et al. DoesTpeak–Tend provide an index of transmuraldispersion of repolarization? Herat Rhythm. 2007; 4:1114-6.