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Journal of Clinical Medicine Research logoLink to Journal of Clinical Medicine Research
. 2018 Mar 16;10(5):384–390. doi: 10.14740/jocmr3338w

Impact of Drug Induced Long QT Syndrome: A Systematic Review

Karuppiah Arunachalam a,e, Seetha Lakshmanan b, Abhishek Maan a, Narendra Kumar c, Paari Dominic d
PMCID: PMC5862085  PMID: 29581800

Abstract

Background

Drug induced long QT syndrome is quite common in daily clinical practice but its impact is unknown.

Methods

PubMed and EMBASE databases (until May 2, 2017) were searched to identify studies reporting drug induced long QT syndrome and followed the PRISMA guidelines. The main outcomes measured in these studies were QTc prolongation, ventricular arrhythmias, torsade de pointes (TdP) and death.

Results

Out of 176 non-duplicate reports, 36 studies satisfied inclusion criteria and provided data on patients exposed to drugs that can potentially cause long QT. Totally, 14,756 patients were exposed and 930 patients (6.3%) were found to have QTc prolongation. The number of males was 6,400 and females were 5,723 patients. The mean age of the patients was 43.8 ± 9.36 years. Ventricular arrhythmias were found in 379 patients (2.6%), 26 patients were found to have premature atrial contractions (PACs) and premature ventricular contractions (PVCs). TdP was found in 49 patients (0.33 %), sudden cardiac death (SCD) was found in five patients and 586 patients were found to have all-cause mortality.

Conclusions

Around 6% of patients have risk of QT prolongation when exposed but only 0.3% developed TdP and 2.6% developed ventricular arrhythmias. Risk of developing arrhythmias is higher with concomitant use of multiple QT prolonging drugs.

Keywords: QTc prolongation, Torsades de pointes, Sudden cardiac death

Introduction

The QT interval reflects electrical depolarization and repolarization of both ventricles. Rate-corrected QT (QTc) intervals are almost identical in males and females till late adolescence (0.37 - 0.44 s). After which, the normal range of QTc interval is slightly longer in females (< 0.47s) than in males (< 0.45s) [1].

Prolonged QT interval seen on electrocardiogram (EKG) is known as Long QT syndrome. This syndrome is often associated with increased risk of arrhythmias especially torsades de pointes (TdP), a distinctive form of polymorphic ventricular tachycardia characterized by changes in the amplitude and deformation of QRS complexes around the isoelectric line. TdP may potentially degenerate into ventricular fibrillation (VF) and cause sudden cardiac death (SCD), if not treated promptly.

Acquired forms of Long QT syndrome are usually provoked by the presence of extrinsic triggers such as QT-prolonging drugs, hypokalemia or hypomagnesemia, and bradycardia. However, the most common culprit is those associated with QT prolonging drugs which are still regularly being used in clinical practice, namely antihistamines, antibiotics, antidepressants, and prokinetics. In recent days, more and more drugs have started identifying QTc prolongation as their adverse effect. Nonetheless, these drugs are still being prescribed by clinicians probably because they are unaware of the relative risk of QTc prolongations and their impact on patients. There are plenty of case reports and systematic review based on case reports published on drug induced QTc prolongation. In this systematic review of research articles, we have focused on identifying the common drugs that have been known to prolong QTc and analyze their cardiac side effects and their impact on mortality.

Methods

This systematic review was performed according to the PRISMA guidelines [2].

Data sources and searches

Comprehensive search was conducted on PubMed and EMBASE databases by using the term ((drug induced QT syndrome) or (medication induced QT syndrome)) and ((outcome) or (adverse events)) for studies published until May 2, 2017. Two authors independently screened titles and abstracts to identify relevant studies in English and discrepancies were resolved by consensus. Duplicates were removed prior to study selection. Full texts of potentially relevant articles were assessed independently for eligibility by two authors. The search was supplemented by screening the studies included in similar systematic reviews and meta-analysis (Fig. 1).

Figure 1.

Figure 1

Flowchart illustrates the process of including and excluding studies following PRISMA guidelines using PubMed and EMBASE database.

Study selection

Inclusion criteria include: 1) studies analyzing QT prolongation due to medications, 2) more than 10 subjects, 3) studies that identify QT measurement or change in QTc, drug usage, measured outcomes and other cardiac side effects.

Exclusion criteria include: 1) age less than 18 years old, 2) patients with congenital long QT syndrome, 3) case reports, case series, review articles, 4) studies with less than 10 subjects, 5) studies that doesn’t discuss outcomes, 6) articles in language other than English, 8) studies that reports only events without number of patients screened or affected, 9) studies using off market drugs and experimental drugs.

Outcomes of interest

The primary outcome was to identify drugs causing QT prolongation compared to baseline. Secondary outcomes included their impact and other side effects observed among the patients taking these drugs namely, ventricular arrhythmias, TdP and death.

Results

Out of 176 non-duplicate reports, 36 studies satisfied inclusion criteria and provided data on patients exposed to drugs that can potentially cause long QT.

Geographically, 12/36 studies were done in USA, multicenter studies account for 11/36 studies, one study was done in UK/France/Germany/Turkey/Greece/Taiwan/Iran, two studies were done in Switzerland. Study design distributions were: cross sectional studies in 3/36, prospective observational in 3/36, retrospective studies in 10/36 and randomized controlled trials in 19/36 (Table 1, [3-38]).

Table 1. Summary of Studies With Age, Type of Study, Gender, Drugs Used and Distribution of QTc Prolongation.

Author Country Year/ study period Type of study Age M F NT N1 N2 Nc Drug1 Drug2 Poly pills Major diagnosis/ indication Total QTc prolongation
Agusala et al [3] USA n/a Retrospective 63 ± 13 231 98 329 227 102 n/a Sotalol Dofetilide n/a Atrial fibrillation 55
Armahizer et al [4] USA 2009 Retrospective 62 ± 15.2 102 85 501 n/a n/a n/a n/a n/a Ondansetron, amiodarone, metronidazole and haloperidol Drug-drug interaction in CCU/CTICU 187
Cunnington et al [5] UK 2012 Retrospective 76.5 75 37 112 61 n/a n/a n/a n/a Domperidone, citalopram, amitriptyline, hydroxychloroquine, quetiapine, mirtazapine, quinine, olanzapine Parkinson’s disease 20
Hough et al [6] USA 02/2006 - 06/2006 Randomized prospective 37 (18 - 51) 78 31 109 44 43 22 Paliperidone ER Quetiapine n/a Schizophrenia and schizoaffective dis n/a
Letsas et al [7] Greece 02/2004 - 10/2006 Retrospective 64.3 ± 14.1 2 19 21 n/a n/a n/a n/a n/a Amiodarone, sotalol, digoxin, indapamide Multiple n/a
Moffett et al [8] USA 2012 - 2013 Prospective observational 32 ± 5 9 13 22 22 n/a n/a Ondansetron n/a n/a Nausea, vomiting 20
Niedrig et al [9] Switzerland 2012 Retrospective n/a n/a n/a 51 n/a n/a n/a Macrolide and quinolone antibiotics (MQABs) with > 1 QT prolonging drugs n/a Y Bacterial infection requiring systemic MQ antibiotics n/a
Perrin-Terrin et al [10] France Retrospective 34 ± 8 37 5 42 42 n/a n/a Methadone n/a n/a Heroin addiction n/a
Potkin et al [11] USA 2001 - 2002 Randomized prospective n/a n/a n/a 188 113 35 35 Iloperidone (8,12,24mg) Quetiapine n/a Schizophrenia and schizoaffective dis 10
Wieneke et al [12] Germany 24 weeks Randomized prospective 29.5 30 23 53 31 22 n/a Levo-α-Acetylmethadol (LAAM) Methadone n/a Opiate addiction 7
Beyraghi et al [13] Iran 01/2010 - 06/2010 Cross-sectional 35.3 27 47 74 n/a n/a n/a n/a n/a Antipsychotics, anticholinergic, antidepressant, lithium, other mood stabilizer Bipolar, schizo, MDD, others 22
Koca et al [14] Turkey 2009 - 2010 Prospective observational 59 13 39 52 52 0 0 Capecitabine n/a n/a Malignancy 10
Lee et al [15] USA n/a Retrospective 55 ± 19.5 39 61 100 n/a n/a n/a Azithromycin n/a DDI = ondansetron (48%), trazodone (22%), and moxifloxacin (17%) Hospitalized respiratory/gynae infections 29
Pearson et al [16] USA 2 years Retrospective 46 ± 11 23 35 59 n/a n/a n/a Methadone n/a n/a Opiate addiction 16
Price et al [17] USA 1969 - 2002 Retrospective 55.9 481 765 1,246 633 613 n/a Methadone n/a n/a Pain management 249
Van der Sijs et al [18] Netherlands 2010 Retrospective n/a 32 24 56 n/a n/a n/a n/a n/a Haloperidol, amiodarone, sotalol etc. Multiple 25
Azorin et al [19] Multicenter 2006 Randomized prospective n/a n/a n/a 186 97 89 n/a Sertindole Risperidone n/a Schizophrenia 26
Chan et al [20] Taiwan Randomized prospective 35 45 38 83 49 34 n/a Aripiprazole Risperidone n/a Schizophrenia n/a
Beasley et al [21] Multicenter 2004 - 2005 Randomized prospective 36 ± 10 294 41 335 198 69 68 Olanzapine Haloperidol n/a Schizophrenia n/a
Conley et al [22] Multicenter Randomized prospective 40 ± 10.8 274 103 377 188 189 n/a Risperidone Olanzapine n/a Schizophrenia n/a
Feischhacker et al [23] Multicenter Randomized prospective 36.6 399 296 695 350 345 n/a Aripiprazole Olanzapine n/a Schizophrenia 12
Kane et al [24] USA 2000 - 2002 Randomized prospective 38.6 ± 0.5 288 126 414 206 104 106 Aripiprazole Haloperidol n/a Schizophrenia 4
Kane et al [25] USA 1997 - 1998 Randomized prospective 35 ± 8.85 n/a n/a 306 152 154 n/a Ziprasidone Chlorpromazine n/a Schizophrenia n/a
McEvoy et al [26] USA Randomized prospective 40.4 ± 0.5 326 94 420 312 n/a 108 Aripiprazole n/a n/a Schizophrenia 3
Min et al [27] South Korea Randomized prospective 23.5 n/a n/a 35 16 19 n/a Risperidone Haloperidol n/a Schizophrenia n/a
Peuskens et al [28] Multicenter Randomized prospective 38.1 n/a n/a 1,362 1,136 226 n/a Risperidone Haloperidol n/a Schizophrenia n/a
Peuskens et al [29] Multicenter Randomized prospective 36.5 120 108 228 115 113 n/a Amisulpride Risperidone n/a Schizophrenia 4
Potkin et al [30] Multicenter 1995 - 1996 Randomized prospective 39.1 283 121 404 202 99 103 Aripiprazole Risperidone n/a Schizophrenia 3
Sacchetti et al [31] Multicenter Randomized prospective 39.95 ± 10.7 101 45 146 73 73 n/a Ziprasidone Clozapine n/a Schizophrenia 13
Tran et al [32] Multicenter Randomized prospective 36.21 ± 10.73 220 119 339 172 167 n/a Olanzapine Risperidone n/a Schizophrenia 23
Vieta et al [33] Multicenter Randomized prospective n/a 127 207 334 175 169 n/a Aripiprazole Haloperidol ddI = ondansetron (48%), trazodone (22%), and moxifloxacin (17%) Mania 9
Haixu et al [34] China 52 weeks Cross-sectional 66.6 ± 14.4 1,731 2,390 4,121 n/a n/a n/a n/a n/a Multiple Acquired long QT syndrome in hospitalized pts 106
Niedrig et al [35] Switzerland 21 days Cross-sectional n/a n/a n/a 243 186 n/a 57 Citalopram+escitalopram n/a n/a Major depression 15
Van Haelst et al [36] Netherlands 2007 - 2012 Cross-sectional 70 ± 7 154 243 397 n/a n/a n/a SSRI’s n/a Multiple Major depression 44
Manini et al [37] USA 2012 - 2013 Prospective observational 42.3 ± 0.8 255 217 472 n/a n/a n/a n/a n/a Methadone, oxycodone, other opiods, benzodiazepines etc. Acute drug overdose 60
Kasper et al [38] Multicenter 12 weeks Randomized prospective 37.1 ± 10.3 758 536 1,241 810 431 n/a Aripiprazole Haloperidol n/a Schizophrenia 2
Total 43.8 6,554 5,966 15,153 974

M: male; F: female; n/a: unavailability of data; NT: total number of patients in the study; N1: number of patients exposed to drug 1; N2: number of patients exposed to drug 2; Nc: number of patients exposed to control drug; DDI: drug-drug interactions.

Drugs used in studying QTc prolongation were distributed as follows out of 36 studies: multiple drugs in 10/36 studies, haloperidol in 6/36 studies, olanzapine, ziprasidone and quetiapine in 2/36, risperidone in 5/36, methadone in 4/36, aripiprazole in 7/36, Other drugs (clozapine/chlorpromazine/dofetilide/capecitabine/azithromycin/amisulpride/ citalopram/ escitalopram/sotalol/paliperidone ER/ondansetron/fluoroquinolone antibiotics/azithromycin/sertindole/LAAM/iloperidone) one each out of 36 studies. Multiple drugs is designated as a variable when a study uses more than two drugs in the study population or more than two drugs in the same patient.

Totally, 14,756 patients were exposed and 930 patients (6.3%) were found to have QTc prolongation. Males were 6,400, females were 5,723 patients and mean age of the patients was 43.8 ± 9.36 (Table 1). Ventricular arrhythmias were found in 379 patients (2.6%), 26 patients were found to have PACs and PVCs. TdP was found in 49 patients (0.33 %), SCD was found in five patients and 586 were found to have all-cause mortality. Only two studies reported ventricular arrhythmias [3, 36]; two studies reported TdP [9, 19]; one study reported SCD [9]; and four studies reported death [18-20, 36]. Remaining studies either didn’t report ventricular arrhythmias or didn’t have any episodes of ventricular arrhythmias. In one of the studies using methadone, 43 out of 59 patients were found to have TdP [19], remaining six patients who had TdP were result of using multiple drugs [9]. The study is based on 5,503 reported adverse events from MedWatch database (Table 2, [3-38]).

Table 2. Summary of Distribution of Different Types of Arrhythmias Among Qatients With QT Prolonging Drugs.

Author Drug1 Drug2 Poly pills Total Qtc prolongation Mean change in QTc Ventricular tachycardia PVC/NSVT/ECTOPY TdP SCD/cardiac arrest Death
Agusala et al [3] Sotalol Dofetilide n/a 55 n/a 70 23 0 0 0
Armahizer et al [4] n/a n/a Ondansetron, amiodarone, metronidazole and haloperidol 187 n/a n/a n/a 0 n/a n/a
Cunnington et al [5] n/a n/a Domperidone, citalopram, amitriptyline, hydroxychloroquine, quetiapine, Mirtazapine, quinine, olanzapine 20 n/a n/a n/a n/a n/a n/a
Hough et al [6] Paliperidone ER Quetiapine n/a n/a n/a 0 0 0 n/a 0
Letsas et al [7] n/a n/a Amiodarone, sotalol, digoxin, indapamide n/a n/a 0 0 6 5 0
Moffett et al [8] Ondansetron n/a n/a 20 n/a 0 0 0 0 0
Niedrig et al [9] Macrolide and quinolone antibiotics (MQABs) with > 1 QT prolonging drugs n/a Y n/a n/a 0 0 0 n/a 0
Perrin-Terrin et al [10] Methadone n/a n/a n/a 66.0 ± 41.1 0 0 0 0 0
Potkin et al [11] Iloperidone (8,12,24mg) Quetiapine n/a 10 16.97 ± 14.13 0 SVT = 1 0 0 0
Wieneke et al [12] Levo-α-Acetylmethadol (LAAM) Methadone n/a 7 40 ± 13 0 0 0 n/a 0
Beyraghi et al [13] n/a n/a Antipsychotics, anticholinergic, antidepressant, lithium, other mood stabilizer 22 n/a 0 0 0 0 0
Koca et al [14] Capecitabine n/a 10 n/a n/a 2 n/a n/a n/a
Lee et al [15] Azithromycin n/a DDI = ondansetron (48%), trazodone (22%), and moxifloxacin (17%) 29 n/a n/a n/a n/a n/a 4
Pearson et al [16] Methadone n/a n/a 16 n/a n/a n/a 43 n/a 5
Price et al [17] Methadone n/a n/a 249 n/a n/a n/a n/a n/a 42
Van der Sijs et al [18] n/a n/a Haloperidol, amiodarone, sotalol etc. 25 59.76 ± 47.157 n/a n/a n/a n/a n/a
Azorin et al [19] Sertindole Risperidone n/a 26 n/a n/a n/a n/a n/a n/a
Chan et al [20] Aripiprazole Risperidone n/a n/a (-1 ± 39, 8 ± 34) n/a n/a n/a n/a n/a
Beasley et al [21] Olanzapine Haloperidol n/a n/a (-0.62 ± 24.57, 0.97 ± 26.07, -4.71 ± 18.75) n/a n/a n/a n/a n/a
Conley et al [22] Risperidone Olanzapine n/a n/a (-1.3 ± 25.7, 1.2 ± 20.2) n/a n/a n/a n/a n/a
Feischhacker et al [23] Aripiprazole Olanzapine n/a 12 n/a n/a n/a n/a n/a n/a
Kane et al [24] Aripiprazole Haloperidol n/a 4 n/a n/a n/a n/a n/a n/a
Kane et al [25] Ziprasidone chlorpromazine n/a n/a 12(7.5) n/a n/a n/a n/a n/a
McEvoy et al [26] Aripiprazole n/a n/a 3 n/a n/a n/a n/a n/a n/a
Min et al [27] Risperidone Haloperidol n/a n/a 15.0 ± 22.2, 0.9 ± 33.0 n/a n/a n/a n/a n/a
Peuskens et al [28] Risperidone Haloperidol n/a n/a -1.71 ± 24.88, -4.1 ± 24 n/a n/a n/a n/a n/a
Peuskens et al [29] Amisulpride Risperidone n/a 4 n/a n/a n/a n/a n/a n/a
Potkin et al [30] Aripiprazole Risperidone n/a 3 -0.69 ± 22, 6.31 ± 29, -2.18 ± 21 n/a n/a n/a n/a n/a
Sacchetti et al [31] Ziprasidone Clozapine n/a 13 6 ± 43.3,-3.6 ± 39.3 n/a n/a n/a n/a n/a
Tran et al [32] Olanzapine Risperidone n/a 23 -4.9 ± 44.9, 4.4 ± 35.1 n/a n/a n/a n/a n/a
Vieta et al [33] Aripiprazole Haloperidol ddI = ondansetron (48%), trazodone (22%), and moxifloxacin (17%) 9 n/a n/a n/a n/a n/a n/a
Haixu et al [34] n/a n/a Multiple 106 n/a 309 n/a n/a n/a 535
Niedrig et al [35] Citalopram + escitalopram n/a n/a 15 n/a n/a n/a n/a n/a n/a
Van Haelst et al [36] SSRIs n/a Multiple 44 2.83 n/a n/a n/a n/a n/a
Manini et al [37] n/a n/a Methadone, oxycodone, other opiods, benzodiazepines etc. 60 n/a n/a n/a n/a n/a n/a
Kasper et al [38] Aripiprazole Haloperidol n/a 2 n/a n/a n/a n/a n/a n/a
Total 974 379 26 49 5 586

n/a: not available; PVC: premature ventricular contractions; NSVT: non sustained ventricular tachycardia; TdP: torsade de pointes; SCD: sudden cardiac death.

Duration of the prospective studies was mostly 6 months to 2 years where as one of the retrospective study reviewed a database for 33 years. Remaining retrospective study usually lasted from 1 to 5 years. The setting in which patients were studies either inpatient or outpatient except for one study where the setting was ICU and emergency room. QTc interval was measured predominantly by Bazett’s formula except for few using Fridericia’s formula. QTc interval was measured using routine 12-lead EKG in all the studies.

Changes in QTc were discussed only in 11 studies. QTc decreased in risperidone group in a large study of 1,362 patients compared to haloperidol [31]. Same effect with use of risperidone was seen in a study comparing the drug against olanzapine [25]. But the results are not consistent with another two studies where risperidone compared to olanzapine and aripiprazole had prolonged QTc compared to the latter drugs [24, 26]. In a study of patients with methadone, QTc was prolonged nearly by 66 ms [13]. Van der sijs et al studied use of multiple drugs (haloperidol, amiodarone, sotalol), QTc prolongation was found to be 59.76 ms [18].

Discussion

Drug-induced Long QT syndrome holds an undesirable risk of arrhythmias and SCD causing substantial concern to clinicians. Although more than 150 drugs have already been implicated (www.qtdrugs.org), more are continuously being identified by the Food and Drug Administration (FDA). This has led to the withdrawal of many newly developing, otherwise useful drugs after noticing a small number of cases with QT prolongation and arrhythmias in phase 2 and 3 stages of drug trials. Drugs that have been taken off the market in the United States and other countries because of their increased risk of TdP are namely, ondansetron, cisapride, terfenadine, astemizole.

In our qualitative approach, methadone was reported in four studies and found to have highest proportion of patients with QTc prolongation and TdP in single study. Cumulatively, concomitant use of multiple QT prolonging drugs is found to have largest patient population with significant QTc prolongation. Use of multiple QT prolonging drugs was studied most commonly followed by use of drugs such as haloperidol, risperidone and aripiprazole individually. Schizophrenia is the most common diagnosis in which outcomes of QT prolongation was evaluated. Usage of multiple QT prolonging drugs and sertindole is associated with SCD. Researches which studied azithromycin, methadone and sertindole, multiple QT prolonging drugs were found to have reported all-cause mortality. Amiodarone, sotalol and dofetilide are notorious for significant QTc prolongation and especially the risk of ventricular arrhythmias TdP is higher. Most commonly studied non-cardiac drugs are antipsychotics like haloperidol, risperidone, olanzapine and aripiprazole. QTc prolongation doesn’t correspond to ventricular arrhythmias or TdP in non-cardiac drugs.

On a study of 172 patients, the most common cause for QTc prolongation was QTc interval-prolonging medication and was deemed most responsible in 48% of patients, with 25% of these patients taking ≥ two offending drugs [39]. Out of seven patients who died with VF, cause of death was myocardial ischemia in three patients and severe heart failure in three patients and one had VF during seizure. Antidepressants caused QTc prolongation in 53 patients and amiodarone in 36 patients [39].

TdP was reported in less than 1% with use of amiodarone though it is one of the most common QTc prolonging cardiac drugs [40]. There were no significant differences in mean QTc interval duration in users of citalopram and paroxetine and their corresponding reference patients according to study by Van Haelst et al. The use of an SSRI by elderly surgical patients was not associated with the occurrence of QT interval prolongation [36]. Hasnain et al in their comprehensive review reported 28 cases of TdP, six (21.4 %) experienced it with QTc interval < 500 ms; 75 % of TdP cases occurred at therapeutic doses [41].

Acquired QTc interval prolongation is more common than congenital and is typically ascribed to drugs that incidentally block the IKr current or systemic illness that indirectly prolongs the QTc interval through ill-defined mechanisms. Drugs block the delayed rectifier potassium channel which is coded by human ether-a-go-go-related gene (hERG). The distinct molecular structure of hERG channel makes it more susceptible to medications. IKr current plays an important role in phase 3 of ventricular action potential (ventricular repolarization) [42]. Prolongation of ventricular action potential due to blockage of delayed rectifier potassium channel leads to fluctuation in membrane potential leading to development of early after depolarization (EAD). After reaching a certain threshold with wider heterogeneity, EADs can lead to reentrant excitation and TdP which can result in SCD [43].

Strengths and limitations

There is significant number of randomized control trials which increases the strength of this systematic review. Baseline QTc and measured QTc after the use of specific QT prolonging drug was either not reported or discussed in a large number of studies. There is an inconsistency in measuring the risk of QTc prolongation in most of the studies. There are also unclear reports of ventricular arrhythmias or TdP studied in the included articles.

Conclusions

Acquired QTc prolongation due to drugs is the most common cause for QTc prolongation observed in clinical practice. Caution should be exercised in case of usage of cardiac drugs like amiodarone, sotalol and dofetilide as they are increasingly associated with fatal arrhythmias. Though antipsychotics and antibiotics could cause significant QTc prolongation, ventricular tachycardia or TdP is more common with simultaneous use of two or more other QT prolonging drugs. More detailed randomized controlled studies with accurate description of baseline QTc, change in QTc interval and appropriate report of any significant ventricular arrhythmias with usage of multiple QTc prolonging drugs should be performed in future.

Conflict of Interest

The authors have no conflict of interest to disclose.

Grant Support

None.

Author Contributions

KA: design of the study, data collection, preparation of manuscript and review; SL: design of the study, data collection; AM, NK: review of manuscript; PD: critical and final review of manuscript.

Disclosure

None

Abbreviations

TdP

torsades de pointes

EAD

early after depolarization

PAC

premature atrial contraction

PVC

premature ventricular contraction

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