Incidence Of TdP Research Articles

Abstract 9694: Incidence and Outcomes of Hospitalized Patients With Torsades de Pointes

Introduction: TdP is a polymorphic VT that occurs with prolonged QT interval and can cause sudden cardiac death. Trends in incidence and outcomes of TdP during the COVID-19 pandemic are not well-established. We aim to report incidence of intrahospital TdP and VT, baseline characteristics of patients with TdP, and trends in post-TdP recovery and mortality before and during the COVID-19 pandemic. Methods: Patients with diagnoses of VT and TdP from 2016-2020 at our institution were included. The diagnosis was confirmed after analysis of the patients’ ECGs. Demographics, medical history, and hospital course data were collected. Chi-square/Fisher’s exact, one-way ANOVA, and logistic regression analyses were conducted. Results: Seventy-four patients were included in the analysis. Average age was 60 ± 17, and 57% were male. Fifty-two (70%) patients were in the ICU at time of TdP. Co-morbidities included hypertension (53%), atrial fibrillation/flutter (41%), diabetes mellitus (34%), CAD (26%), and CKD (22%). Average LVEF was 39 ± 19%. Forty-two (57%) underwent emergent defibrillation, 19 (26%) required transvenous pacing, and 7 (10%) were administered isoproterenol for acute management of TdP. Median recovery time of QTc interval to <500ms was 3 days. Twenty-two (30%) received an ICD. Follow-up device check data was available for 15 patients; 4 had at least 1 episode of NSVT. Fifteen (20%) patients died during their admissions. The proportion of patients with VT that had TdP increased in 2020 compared to prior years (p<0.001). However, the proportion of patients with TdP that died during admission was not significantly different across 2016-2020. Conclusions: The proportion of patients with TdP relative to those with VT increased significantly in 2020, concurrent with the first wave of the COVID-19 pandemic. The absolute number of hospitalized patients with TdP did not change from 2016-2020. Mortality rate in patients with TdP did not differ significantly from 2016-2020.

TdP Incidence in Methoxamine-Sensitized Rabbit Model Is Reduced With Age but Not Influenced by Hypercholesterolemia.

Metabolic syndrome is associated with hypercholesterolemia, cardiac remodeling, and increased susceptibility to ventricular arrhythmias. Effects of diet-induced hypercholesterolemia on susceptibility to torsades de pointes arrhythmias (TdP) together with potential indicators of arrhythmic risk were investigated in three experimental groups of Carlsson’s rabbit model: (1) young rabbits (YC, young control, age 12–16 weeks), older rabbits (AC, adult control, age 20–24 weeks), and older age-matched cholesterol-fed rabbits (CH, cholesterol, age 20–24 weeks). TdP was induced by α-adrenergic stimulation by methoxamine and IKr block in 83% of YC rabbits, 18% of AC rabbits, and 21% of CH rabbits. High incidence of TdP was associated with high incidence of single (SEB) and multiple ectopic beats (MEB), but the QTc prolongation and short-term variability (STV) were similar in all three groups. In TdP-susceptible rabbits, STV was significantly higher compared with arrhythmia-free rabbits but not with rabbits with other than TdP arrhythmias (SEB, MEB). Amplitude-aware permutation entropy analysis of baseline ECG could identify arrhythmia-resistant animals with high sensitivity and specificity. The data indicate that the TdP susceptibility in methoxamine-sensitized rabbits is affected by the age of rabbits but probably not by hypercholesterolemia. Entropy analysis could potentially stratify the arrhythmic risk and identify the low-risk individuals.

Istaroxime, a positive inotropic agent devoid of proarrhythmic properties in sensitive chronic atrioventricular block dogs

Current inotropic agents in heart failure therapy associate with low benefit and significant adverse effects, including ventricular arrhythmias. Istaroxime, a novel Na+/K+-transporting ATPase inhibitor, also stimulates SERCA2a activity, which would confer improved inotropic and lusitropic properties with less proarrhythmic effects. We investigated hemodynamic, electrophysiological and potential proarrhythmic and antiarrhythmic effects of istaroxime in control and chronic atrioventricular block (CAVB) dogs sensitive to drug-induced Torsades de Pointes arrhythmias (TdP). In isolated normal canine ventricular cardiomyocytes, istaroxime (0.3–10 μM) evoked no afterdepolarizations and significantly shortened action potential duration (APD) at 3 and 10 μM. Istaroxime at 3 μg/kg/min significantly increased left ventricular (LV) contractility (dP/dt+) and relaxation (dP/dt−) respectively by 81 and 94% in anesthetized control dogs (n = 6) and by 61 and 49% in anesthetized CAVB dogs (n = 7) sensitive to dofetilide-induced TdP. While istaroxime induced no ventricular arrhythmias in control conditions, only single ectopic beats occurred in 2/7 CAVB dogs, which were preceded by increase of short-term variability of repolarization (STV) and T wave alternans in LV unipolar electrograms. Istaroxime pre-treatment (3 μg/kg/min for 60 min) did not alleviate dofetilide-induced increase in repolarization and STV, and mildly reduced incidence of TdP from 6/6 to 4/6 CAVB dogs. In six CAVB dogs with dofetilide-induced TdP, administration of istaroxime (90 μg/kg/5 min) suppressed arrhythmic episodes in two animals.Taken together, inotropic and lusitropic properties of istaroxime in CAVB dogs were devoid of significant proarrhythmic effects in sensitive CAVB dogs, and istaroxime provides a moderate antiarrhythmic efficacy in prevention and suppression of dofetilide-induced TdP.

The possible role of propofol in drug-induced torsades de pointes: A real-world single-center analysis

BackgroundTorsades de pointes (TdP) is a polymorphic ventricular tachycardia associated with QT prolongation. Propofol is a sedative-anesthetic with proarrhythmic effects on cardiac myocytes. We performed a retrospective study to determine the incidence of TdP following propofol exposure at Mayo Clinic (Rochester, MN) from 08/11/1998–11/20/2015. MethodsWe queried our database using key search terms to identify patients exposed to propofol who developed TdP perioperatively or during non-surgical sedation. QT intervals were obtained from electrocardiograms (ECGs) performed before propofol exposure and after documented TdP and were corrected using Fridericia and Framingham methods. T wave peak-to-end (Tp-e)/QT ratios were also calculated. ResultsA total of 628,784 patients received propofol over 17.3years. Of these patients, 21 developed TdP (12, postoperatively; 3, intraoperatively; 6, during sedation). There were 17 patients who were exposed to at least one factor associated with QT-prolongation, including QT-prolonging medications in 8 patients, heart rate <60 beats per minute in 8 patients, potassium <3.5mmol/L in 4 patients, magnesium <1.8mg/dL in 2 patients, and subarachnoid hemorrhage in 2 patients. The number of patients with QTc>500ms using Fridericia correction was significantly higher from baseline following exposure to propofol (1 patient vs 6 patients, P=0.04); however no significant difference was observed with Framingham correction. ConclusionIn our study, TdP after propofol administration occurred with an annual incidence of 1.93 per million and was often associated with other risk factors. Nevertheless, propofol should be administered with caution in patients at risk of developing TdP.

Effects of proarrhythmic drugs on relaxation time and beating pattern in rat engineered heart tissue.

The assessment of proarrhythmic risks of drugs remains challenging. To evaluate the suitability of rat engineered heart tissue (EHT) for detecting proarrhythmic effects. We monitored drug effects on spontaneous contractile activity and, in selected cases, on action potentials (sharp microelectrode) and Ca2+ transients (Fura-2) and contraction under electrical pacing. The Ito-blocker inhibitor 4-aminopyridine increased action potential duration and T2 and caused aftercontractions, which were abolished by inhibitors of ryanodine receptors (RyR2; JTV-519) or sodium calcium exchanger (NCX; SEA0400). 77 Drugs were then tested at 1-10-100× free therapeutic plasma concentrations (FTPC): Inhibitors of IKr, IKs, Ito, antiarrhythmics (8), drugs withdrawn from market for torsades des pointes arrhythmias (TdP, 5), drugs with measurable (7) or isolated TdP incidence (13), drugs considered safe (14), 28 new chemical entities (NCE). Inhibitors of IKr or IKs had no effect alone, but substantially prolonged relaxation time (T2) when combined at high concentration. 15/33 drugs associated with TdP and 6/14 drugs considered non-torsadogenic (cibenzoline, diltiazem, ebastine, ketoconazole, moxifloxacin, and phenytoin) induced concentration-dependent T2 prolongations (10-100× FTPC). Bepridil, desipramine, imipramine, thioridazine, and erythromycin induced irregular beating. Three NCE prolonged T2, one reduced force. Drugs inhibiting repolarization prolong relaxation in rat EHTs and cause aftercontractions involving RyR2 and NCX. Insensitivity to IKr inhibitors makes rat EHTs unsuitable as general proarrhythmia screen, but favors detection of effects on Ito, IKs + Ito or IKs + IKr. Screening a large panel of drugs suggests that effects on these currents, in addition to IKr, are more common than anticipated.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-014-0436-7) contains supplementary material, which is available to authorized users.

GW24-e2999 Proarrhythmic window of a drug determines the risk of multiple ion channel inhibitors

ObjectivesThe proarrhythmic risk of QT prolonging drugs varies significantly. However, the mechanisms responsible for the high or low risk of drug-induced arrhythmias remain unknown. In this study, we tested our...

Opioid addiction agonist therapy and the QT prolongation phenomenon: state of the science and evolving research questions

Opioid addiction agonist therapy and the <scp>QT</scp> prolongation phenomenon: state of the science and evolving research questions

Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

BackgroundThe aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle.MethodsIon currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model.ResultsAction potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 µg/kg) significantly lengthened the QTc interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QTc. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 µM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (ICa) was slightly diminished, but the transient outward (Ito) and inward rectifier (IK1) potassium currents were not influenced.ConclusionsDiclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve.

Effects of diclofenac on ventricular muscle repolarization: proarrhythmic implications

Results Diclofenac (30 μM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier and L-type calcium currents (ICa) without influencing transient outward (Ito) and inward rectifier (IK1) potassium currents. The action potential was slightly lengthened in ventricular muscle but shortened in Purkinje fibres by diclofenac (20 μM). The maximum upstroke velocity (Vmax) was decreased in both preparations. Larger repolarization lengthening was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong the QTc interval, while the potassium channel blocker dofetilide (25 μg/kg) significantly lengthened QTc in anaesthetized rabbits. The combination of diclofenac and dofetilide significantly prolonged QTc. Diclofenac alone did not induce torsades de pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide led to a significant increase in the incidence of TdP.

Combined pharmacological block of I(Kr) and I(Ks) increases short-term QT interval variability and provokes torsades de pointes.

Assessing the proarrhythmic potential of compounds during drug development is essential. However, reliable prediction of drug-induced torsades de pointes arrhythmia (TdP) remains elusive. Along with QT interval prolongation, assessment of the short-term variability of the QT interval (STV(QT)) may be a good predictor of TdP. We investigated the relative importance of I(Ks) and I(Kr) block in development of TdP together with correlations between QTc interval, QT interval variability and incidence of TdP. ECGs were recorded from conscious dogs and from anaesthetized rabbits given the I(Kr) blocker dofetilide (DOF), the I(Ks) blocker HMR-1556 (HMR) and their combination, intravenously. PQ, RR and QT intervals were measured and QTc and short-term variability of RR and QT intervals calculated. DOF increased QTc interval by 20% in dogs and 8% in rabbits. HMR increased QTc in dogs by 12 and 1.9% in rabbits. Combination of DOF+HMR prolonged QTc by 33% in dogs, by 16% in rabbits. DOF or HMR given alone in dogs or HMR given alone in rabbits induced no TdP. Incidence of TdP increased after DOF+HMR combinations in dogs (63%) and following HMR+DOF (82%) and DOF+HMR combinations (71%) in rabbits. STV(QT) markedly increased only after administration of DOF+HMR combinations in both dogs and rabbits. STV(QT) was markedly increased by combined pharmacological block of I(Kr) and I(Ks) and may be a better predictor of subsequent TdP development than the measurement of QTc interval prolongation.

Examination of the role of the Na+/Ca2+ exchanger in the genesis of the dofetilide-induced torsades de pointes

Delayed afterdepolarizations (DADs) induced by the electrogenic Na+/Ca2+ exchanger (NCX) play an important role in the genesis of arrhythmias. However, it is not known whether the NCX-induced DADs play any role in the genesis of the repolarization prolonging drug-induced torsades de pointes ventricular tachycardia (TdP). Therefore, the present study examined the effect of the selective inhibition of NCX (by SEA0400) on the occurrence of dofetilide-induced TdP in isolated, Langendorff-perfused, AV-blocked rabbit hearts. A group of hearts was perfused with 100 nM dofetilide, another group was perfused with the combination of 1 μM SEA0400 and 100 nM dofetilide, and a control group of hearts was perfused with the solvent DMSO. Each group contained n=8 hearts. Volume conducted ECG was recorded and the incidence and the onset times of TdPs were analyzed subsequently. The incidence of TdP did not differ between the dofetilide and the SEA0400+dofetilide-perfused hearts, whereas the incidences of TdP were significantly higher in these groups as compared to that in the DMSO control (88% and 100% vs. 13%, respectively, p<0.05). No statistical difference was found in the TdP onset time values of the dofetilide and the SEA0400+dofetilide groups (7.1±0.6 min vs. 5.16±0.9 min, respectively). According to our results the selective inhibition of NCX did not prevent the development of TdP, which implies that NCX does not contribute to the genesis of dofetilide-induced TdP in isolated, AV-blocked rabbit hearts. Funded by: OTKA F046776, ETT 203/2003.

Quinidine-Induced QTc Interval Prolongation and Gender Differences in Healthy Korean Subjects

Background and Objectives: Drug-induced electrocardiographic QT interval prolongation is associated with the occurrence of a potentially lethal form of polymorphic ventricular tachycardia, termed ‘torsades de pointes’ (TdP). Women are at greater risk for the development of drug-induced TdP. To determine whether this may be the result of gender-specific differences in the effect of quinidine on cardiac repolarization, we compared the degree of quinidineinduced QT interval lengthening in young, healthy volunteers. Subjects and Methods: Twelve women and 12 men each received a single intravenous dose of quinidine (4 mg/kg) or placebo in a single-blinded, randomized crossover trial. Total plasma concentrations of quinidine were measured, and QT and corrected QT intervals were analyzed. Results: As expected, the mean QTc interval at baseline was longer for women than for men (443.6±26.9 vs 402.1±31.3 msec, respectively, p=0.037). The mean value of the maximal ΔQTc after quinidine infusion was higher in women (134.4±46.4 vs 117.5±37.7 msec, respectively, p=0.029), and the mean value of the minimal ΔQTc for 1 hour after quinidine infusion was also higher in the female group (47.6±15.7 vs 83.7±25.4 msec, p=0.034). However, there were no significant differences in the time courses of the changes in the quinidine-induced QTc and ΔQTc interval between the two groups (p=0.092, and p=0.305, respectively). Conclusion: Quinidine causes greater QT prolongation in women at equivalent serum concentrations. This difference may contribute to the greater incidence of drug-induced TdP observed in women taking quinidine, and has implications for other cardiac and noncardiac drugs that prolong the QTc interval. (Korean Circ J 2007;37:559-566)

In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation

The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC 50) was: sparfloxacin (44 μM) > telithromycin = moxifloxacin = erythromycin (± 100 μM). 2. Assessing their effects on action potential duration (APD 90) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin > moxifloxacin > telithromycin > erythromycin (prolongation of APD 90 at 100 μM: 83%, 48%, 33% and 17% from baseline compared to + 5% with solvent, P < 0.05, respectively). 3. Assessing the drug effects on the APD 60, triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin > erythromycin > sparfloxacin > telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T p–e, T p–e/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin > erythromycin > moxifloxacin > telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation > the Purkinje fiber > HERG > the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.

Clinical Study of Amiodarone‐Associated Torsade De Pointes in Chinese People

Amiodarone-associated torsade de pointes (Tdp) has been reported increasingly in China in recent years. In this study, we made clinical analysis of amiodarone-associated Tdp in Chinese people. Two major Chinese medical databases were searched to identify articles published during the last 26 years that presented data on amiodarone-associated proarrhythmic events. The articles were divided into two categories: case reports and observational studies. Fifty-two Chinese-language case reports with 98 patients and 2 patients registered in our hospital, total 100 patients about amiodarone-associated Tdp, were enrolled in the study. Amiodarone-associated Tdp occurred more frequently in females (68.0%, 68/100). The major primary disease of females was rheumatic heart disease (40.7%, 24/59), while that of males was coronary heart disease (45.8%, 11/24). In most patients, Tdp occurred repeatedly and terminated in 24-48 hours. Some Tdp worsen to ventricular fibrillation and caused 19 patients' death (mortality rate 21.8%, 19/87). Known predisposing factors to the development of Tdp, such as heart failure, hypokalemia, drugs combination, and bradyarrhythmia, existed in many cases. Tdp also occurred in six patients (4 females, 2 males) without any known predisposing factors except QTc interval prolongation. Fourteen observational studies each reported data from at least 100 patients who were treated with amiodarone for at least 1 month. Of 2,354 patients included in these studies, 455 patients exposed to amiodarone were reported to have proarrhythmic events (an overall incidence of 19.3%), while only 4 patients were reported to have Tdp or ventricular fibrillation (an incidence of 0.17%). In conclusion, approximately one-fifth of the patients have amiodarone-induced proarrhythmic events, while the incidence of Tdp or ventricular fibrillation is remarkably low. Amiodarone-associated Tdp occurred more frequently in Chinese females. Known predisposing factors for occurrence of Tdp prevailed in Chinese patients. QTc interval prolongation may be an independent risk factor of amiodarone-associated Tdp.

Drugs effects on ventricular repolarization: A critical evaluation of the strengths and weaknesses of current methodologies and regulatory practices

A growing number of drugs and drug combinations inhibit cardiac potassium ion conductance and ventricular repolarization, and increase cardiac APD, QT interval, and risk of potentially fatal TdP. The past decade has seen an explosion of research advances into the mechanism of action underpinning these observations, and an unprecedented level of collaboration between academia, industry, and regulatory authorities to define effective strategies for accurate prediction of increased TdP risk (if any) in humans, based upon nonclinical and/or clinical endpoints. Because the incidence of TdP is so very low, even for drugs for which the association is known, the risk can only be assessed based upon surrogate markers (signals) in in vitro and in vivo non-clinical studies as well as in clinical trials. In this article, we review both the strengths and weaknesses of current methodologies and regulatory practices for assessment of TdP risk for pharmaceuticals.

Predictors of in-hospital ventricular fibrillation or torsades de pointes in patients with acute symptomatic bradycardia

Severe bradyarrythmias remain as an important cause for hospital urgent admission and these patients can suffer potentially lethal complications (such as ventricular fibrillation [VF] and Torsades de Pointes [TdP]) between hospital admission and final therapy. Incidence and predictors of these tachyarrhythmias have not been well established. We retrospectively studied all consecutive patients (N = 243, age 75 ± 10 years; 47% men) admitted to the emergency department of a general hospital between January 1998 and July 2000 for symptomatic bradyarrhythmia. Concomitant therapy included diuretics (25%), digitalis (10%), beta-blockers (10%), amiodarone (2%), and verapamil or diltiazem (8%). Syncope was the most frequent symptom at admission (54%). The most prevalent inclusion bradyarrhythmia was ≥second-degree AV block (82%). Eleven patients (4.5%) presented VF or TdP. Univariate predictors for these complications were previous amiodarone or diuretic intake, presentation as syncope, low serum potassium level, and longer QTc at admission. Multivariate analysis with logistic regression showed only therapy with diuretics and/or amiodarone and QTc at admission as significant predictors for TdP or VF development. Incidence of VF or TdP in patients admitted for symptomatic bradyarrhythmia is relatively important. A prolonged QTc interval and/or therapy with amiodarone or diuretics can predict their presentation.

Torsades de pointes: unanswered questions.

Torsade de pointes (Tdp) is a polymorphic ventricular tachycardia (VT) in which the axis of the QRS complex changes direction after a certain number of complexes as if the complex rotated around the baseline. Tdp is usually associated with QT prolongation, and dispersion of ventricular repolarlization (DR). Experimental models of tdp are usually associated with induction of early after depolarizations (EADs). Several aspects of the pathogenesis of tdp are incompletely understood. The purpose of this article is to propose the directions in research that may increase our current understanding of the factors responsible for tdp. The most plausible hypotheses requiring further supporting evidence are: 1. The occurrence of tdp requires the presence of DR i.e. tdp does not occur in the absence of DR. 2. EADs appear to play an important role as a trigger to tdp in the animal models, but more evidence are needed at the clinical level. 3. EADs may be responsible for arrhythmias other than tdp. 4. The greater incidence of tdp in the females than in tha males may be attributed to differences in the duration of the QT interval and different morphology of the ST-segment and the T-wave. The above gender differences may be caused by the effects of gonadal hormones which modulate some of the membrane currents flowing during early ventricular repolarization.

944-68 A Comparison Between the Pro-Arrhythmic Effect of Almokalant and d-Sotalol In an Animal Model of Torsade de Polntes Arrhythmias

Administration of class III agents may promote the development of Torsade de Pointes arrhythmias (TdP). We have developed a chronic AV block dog model in which after d-sotalol (dS) TdP can be reproducibly induced by pacing. The response is also reproducible over weeks. In this model of TdP we compared the proarrhythmic effect of d-sotalol (2 mg/kg) and Almokalant (A, 0.12 mg/kg) in the same dog. In 7 anesthetized dogs with chronic AV block (4 ± 2 wksl dS was administered, and A in a second experiment (4 ± 1.6 wks later). In 517 dogs monophasic action potentials were endocardially recorded in the right and in the left ventricle (RV, LV) to register EADs and to measure the action potential duration (APD). Dispersion of repolarization (ΔAPD) was defined as LV APD – RV APD Baseline conditions were identical in the two experiments in the same dog (cycle length of the idioventricular rhythm, CL-IVR:1620 ± 335 ms. 0T:405 ± 50 ms. LV APD:385 ± 40 ms, RVAPD:340 ± 32 ms, ΔAPD: 45 ± 25 ms). The CL-IVR and OT time increased with resp. 20 and 27% after dS and with 20 and 34% after A. EADs were more frequently observed after A (5151 than after dS (3/5). Induction of TdP was more frequently seen after A: spontaneous TdP was observed in 417 dogs, the incidence increased to 517 after pacing. After dS TdP was only induced by pacing (217). Induction was found to be related to ΔAPD. After both drugs the LV APD increased more than the RV APD. LV APD after A (575 ms) was also longer than OT time (550 ms). The ΔAPD increased more after A than dS (40 ± 18 to 125 ± 95 ms vs 45 ± 30 to 85 ± 70 ms. P &lt; 0.05). Conclusions. A induced more EADs and led to a larger ΔAPD than dS in the same dog. These changes were related to a higher incidence of TdP. The findings show the value of our model to evaluate TdP induction by different drugs.