Repolarization parameters and ventricular arrhythmias in Takotsubo syndrome: A substudy from the RETAKO national registry.

Ventricular arrhythmias (VA) occur in about 10% of Takotsubo syndrome (TTS) patients (1Möller C. Eitel C. Thiele H. Eitel I. Stiermaier T. Ventricular arrhythmias in patients with takotsubo syndrome.J Arrhythmia. 2018; 34: 369-375Crossref PubMed Scopus (0) Google Scholar) and comprise: ventricular tachycardia: monomorphic or polymorphic and ventricular fibrillation. All of them have been linked to reduced survival in TTS. ECG abnormalities as: lengthening of QT interval (QTi) corrected for heart rate (QTc) using Bazett’s formula and prolongation of Tpeak-Tend (Tpe) interval have also been associated with major adverse cardiovascular events and worse prognosis (2Braschi A, Frasheri A, Lombardo RM, Abrignani MG, Lo Presti R, Vinci D, et al. Association between Tpeak-Tend/QT and major adverse cardiovascular events in patients with Takotsubo syndrome. Acta Cardiol [Internet]. 2021;76(7):732–738. Available from: https://doi.org/10.1080/00015385.2020.1776012Google Scholar), although some studies do not report an association with VA (3Mugnai G. Vassanelli F. Pasqualin G. Benfari G. Rebonato M. Pesarini G. et al.Dynamic changes of repolarization abnormalities in takotsubo cardiomyopathy.Acta Cardiol. 2015; 70: 225-232Crossref PubMed Google Scholar,4Matsuoka K. Okubo S. Fujii E. Uchida F. Kasai A. Aoki T. et al.Evaluation of the arrhythmogenecity of stress-induced “takotsubo cardiomyopathy” from the time course of the 12-lead surface electrocardiogram.Am J Cardiol. 2003; 92: 230-233Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar). Our purpose was to investigate whether there is an association between electrocardiographic repolarization parameters and VA in 106 patients with TTS in the RETAKO registry. TTS definition and the diagnostic protocol have been previously described (5Núñez Gil I.J. Andrés M. Almendro Delia M. Sionis A. Martín A. Bastante T. et al.Characterization of Tako-tsubo Cardiomyopathy in Spain: Results from the RETAKO National Registry.Rev Española Cardiol (English Ed. 2015; 68: 505-512PubMed Google Scholar): transient hypo/akinesis of the ventricle with typical or atypical patterns, new ECG abnormalities or modest elevation in cardiac troponin, coronary angiography without significant obstructive lesions and recovery of the contractility abnormalities and ejection fraction, with absence of pheochromocytoma or myocarditis. The first ECG obtained upon admission was used. The exclusion criteria were: pacemaker rhythm, left or right bundle branch block (2Braschi A, Frasheri A, Lombardo RM, Abrignani MG, Lo Presti R, Vinci D, et al. Association between Tpeak-Tend/QT and major adverse cardiovascular events in patients with Takotsubo syndrome. Acta Cardiol [Internet]. 2021;76(7):732–738. Available from: https://doi.org/10.1080/00015385.2020.1776012Google Scholar). We produced two groups. The case group included 13 consecutive patients with at least one VA during hospital stay. The control group was composed by 65 patients without VA. The mean corrected QTc measured across all leads was used. The QT-d, was calculated as the difference between the maximum and the minimum QTi. The Tpe interval was measured in precordial leads from the peak to the end of the T wave. The longest interval obtained in all precordial leads was used. SPPSv24 was used for statistical comparisons. The measurements were carried out by two professionals blinded to the presence of VA, with intra and interobserver variability using Cohen´s kappa of 1 in both cases. Clinical and electrocardiographic characteristics are depicted in Table 1. Compared to controls, VA cases consulted more frequently for syncope, and had a higher prevalence of cardiogenic shock on arrival.Table 1Prevalence and electrocardiographic measurements of life-threatening arrhythmias in Takotsubo syndromeAll patients (n=79)Case (n=13)Control (n=66)p valueClinical characteristicsClinical characteristics10 (12.82%)5 (38.5%)5 (7.6%)0.02MaleMean agen/a65.92±17.9468.88±11.200.577Syncope on arrival4 (5.1%)3 (23.1%)1 (1.5%)0.01Killip IV on arrival10 (12.82%)5 (38.5%)5 (7.7%)0.01Onset ECG ST-segment elevation56 (70.9%)6 (7.6%)50 (63.3%)0.032Onset ECG ST-segment depression15 (19%)1 (1.3%)14 (17.7%)0.443Left ventricular ejection fraction on arrivaln/a41.12±15.9345.12±12.960.3461-year mortality4 (5.1%)2 (15.4%)2 (3%)0.0631-year recurrence1 (1.3%)0 (0%)1 (1.5%)0.431Ventricular arrhythmiasMonomorphic ventricular tachycardia8 (10.3%)8 (61.5%)n/an/aPolymporphic ventricular tachycardia2 (2.6%)2 (16.7%)n/an/aVentricular fibrillation3 (3.8%)3 (21.1%)n/an/aECG REPOLARIZATION ANALYSISElectrocardiographic characteristicsCase (mean ± SD)Control (mean ± SD)AUC (area and 95%CI)p valueHeart rate78±18.2784.50±23.820.348 (0.203-0.493)0.326cQT in V3528.20±108.64424.28±51.400.710 (0.540-0.880)<0.001cQT in III461.23±50.12430.55±45.000.673 (0.483-0.863)<0.001QT dispersion91.6±5162.71±30.910.674 (0.524-0.825)<0.001Mean cQT495.18±79.92429.95±44.770.732 (0.565-0.899)<0.001Longest TpTe170.77±34.51102.94±23.050.946 (0.885-1.000)<0.001Heart rate corrected TpTe179.93±58.55109.65±31.510.870 (0.782-0.959)<0.001cQT corrected TpTe0.296±0.090.242±0.060.771 (0.637-0.906)<0.05Values are n (%) or n/N (%). Baseline clinical characteristics. clinical status on arrival and the type of ventricular arrhythmias. Each patient contributed only once to the prevalence of ventricular arrhythmias. in case various types of arrhythmias occurred in the same patient. In the electrocardiographic characteristics section. the AUC for the occurrence of ventricular arrhythmias is provided for each parameter.AUC=area under the curve; CI=confidence interval; cQT=corrected QT interval; n/a=non-applicable; SD= Standard Deviation; TpTe= T-peak to T-end interval. * Percentages provided over available cases in each variable Open table in a new tab The longest Tpeak-Tend (170 vs 103ms, p<0.001) and Tpeak-Tend corrected both by heart rate (179.93 vs 109.65ms, p<0.001) were higher in VA cases. The cQT and cQT dispersion were also higher in the VA case group. The areas under the curve in the Receiving Operator Characteristics (ROC) curve for the longest Tpeak-Tend in the precordial leads were 0.946 (95% Confidence Interval: 0.885-1.0) and 0.732 (95% Confidence Interval: 0.565-0.899) for the cQT. Two patients from the case group received de novo treatment with amiodarone for the VA: one of them was excluded due to bundle branch block, the other one had normal cQT and Tpeak-Tend. Two patients from the case group received vasoactive support and had prolonged cQT and Tpeak-Tend. None of the patients had prior treatment with beta-blockers. None of the patients had neither previous VAs nor predisposing factors. There is greater prevalence of monomorphic over polymorphic ventricular tachycardia, even in the setting of prolonged cTQ and Tpeak-Tend. This could be due to focal gadolinium enhancements (1Möller C. Eitel C. Thiele H. Eitel I. Stiermaier T. Ventricular arrhythmias in patients with takotsubo syndrome.J Arrhythmia. 2018; 34: 369-375Crossref PubMed Scopus (0) Google Scholar) which might represent a substrate for VAs. There is a greater prevalence of ST-segment elevation in the control group as well (p=0.032). This study sheds light into the usefulness of the ECG repolarization parameters for predicting VAs in TTS. TpTe corresponds with transmural dispersion of repolarization in the ventricular myocardium; likely corresponding to an extended vulnerable period that could increase the risk of ventricular arrhythmogenesis. The longest Tpeak-Tend in the precordial leads appears to be an easier and more reliable measurement than the classical cQT for the prediction of VAs in TTS. This could be of paramount importance to make therapeutic decisions or prolong monitorization. Further evaluation of these repolarization parameters in different populations and other prospective studies is needed. All patients provided written informed consent. The research protocol used in this study was approved by the institutional review board and adhered to the Helsinki Declaration guidelines.