Risk Factors For QT Prolongation Research Articles

A prospective study on change of QTc interval with antipsychotic medications in patients of schizophrenia and related psychotic disorder

Background: Sudden unexplained death in individuals with mental health problems was described in 1960 and a link with antipsychotic drugs was postulated over 40 years ago. Down the years, a clear relation between electrocardiography (ECG) abnormalities and antipsychotic use was observed with special emphasis on QT prolongation. Various factors modulate the risk of QT prolongation including gender, age, race, and drug choice. An evaluation of antipsychotic use-induced QT changes in Eastern Indian population is the dire need of the hour. Aims and Objectives: The aim and objective are to study the effects of risperidone, olanzapine, and aripiprazole on QT interval after a period of 4 weeks of usage in previously drug-naïve Eastern Indian psychotic patients. Materials and Methods: A total of 78 drug-naïve patients fulfilling inclusion and exclusion criteria were randomly assigned to receive risperidone, olanzapine, and aripiprazole after a baseline ECG. A repeat ECG after 4 weeks of drug usage was done and compared using standard protocols with respect to QT interval. Findings were tabulated and statistical analysis was done using SPSS 25.0 to test for statistical significance at P<0.05. Results: Our study found significant rise in QT values after 4 weeks of using olanzapine and aripiprazole, but not with risperidone. However, none of the patients from either of the groups experienced any incidence of QT prolongation. Rise with olanzapine was significantly higher than that with risperidone. Conclusion: Caution is suggested in patients with risk factors for QT prolongation or a high value of QT during prescribing olanzapine. Studies with larger sample size can be carried out to find genetic predisposition of Indian population to anti-psychotic induced QT interval rise/prolongation.

Incidence and Risk Factors for QT Prolongation associated with Fluoroquinolones

Incidence and Risk Factors for QT Prolongation associated with Fluoroquinolones

Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes

BackgroundQT prolongation increases cardiovascular mortality in diabetes. The risk factors for QT prolongation vary across different studies. There is no data on the QT prolongation in patients with diabetes from the Arab region, where diabetes is highly prevalent. Here we aimed to assess the prevalence of QT prolongation and its associated risk factors in patients with type 2 diabetes from Saudi Arabia.MethodThis was a retrospective, cross-sectional, hospital-based file review study. Data were collected from the medical records of patients with type 2 diabetes aged above 14 years and underwent ECG examination, and laboratory investigations were done within one month of ECG.ResultsThe study included 782 patients with a prevalence of QTc prolongation of 13%. Patients with prolonged QTc interval were characterized by older age, higher BMI, longer diabetes duration, lower total cholesterol and LDL-C, and more diabetic nephropathy, hypertension, and CVD cases. They were also more in insulin treatment, antihypertensive medications, loop diuretics, and potassium-sparring diuretics. Logistic regression analysis revealed the odds of prolonged QTc interval increased significantly with CVD (OR = 1.761, 95% CI:1.021–3.036, p = 0.042), and usage of loop diuretics (OR = 2.245, 95% CI:1.023–4.923, p = 0.044) after adjusting for age, gender, and duration of diabetes.ConclusionThe risk factors associated with QTc prolongation in patients with type 2 diabetes are CVD, and loop diuretics. Age, BMI, and diabetes duration were more in people with QTc prolongation, whereas total cholesterol and LDL-C levels were lower. More patients had diabetic nephropathy, hypertension, and CVD with prolonged QTc.

Risk Factors for QT Prolongation in Patients with Chronic Hydroxychloroquine Use.

Hydroxychloroquine is used as an antimalarial and immunomodulator, however it can induce QT prolongation that could potentially lead to fatal arrhythmia. We investigated changes in QT interval in long-term hydroxychloroquine users, and identified possible risk factors associated with significant QTc prolongation. We retrospectively enrolled 3603 patients who received long-term hydroxychloroquine treatment from 2009 to 2019, of whom 167 had electrocardiography (ECG) results before and during hydroxychloroquine therapy. Baseline characteristics, laboratory data, comorbidities, concurrent medications, and related clinical outcomes were reviewed. Overall, 225 patients (6.2%) died within the study period, with 50 patients (1.4%) continuously receiving hydroxychloroquine treatment until death. Three patients had fatal ventricular arrhythmia. No significant change in corrected QT interval (QTc) was noted before and during hydroxychloroquine treatment (451.1 ± 39.9 ms vs. 456.0 ± 37.3 ms, P = 0.140) in the ECG cohort. Multivariable logistic regression showed that diabetes mellitus [odds ratio (OR): 9.55, 95% confidence interval (CI): 2.02-45.22; P = 0.005] and use of additional QT-prolonging drugs (OR: 2.89, 95% CI: 1.40-5.94; P = 0.004) were independent risk factors for significant QTc prolongation. Multiple linear regression, with the number of QT-prolonging drugs and comorbidities including diabetes mellitus, hypertension, and atrial fibrillation as explanatory variables, predicted QTc response (adjusted R2 = 0.385) in the long-term hydroxychloroquine users. In the long-term users of hydroxychloroquine, those with diabetes mellitus and concurrent use of additional QT-prolonging drugs were at a higher risk of significant QTc prolongation. Baseline QTc interval, concurrent medications, and comorbidities predicted QTc response.

Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation.

BackgroundHeart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms.MethodsWe investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro.ResultsIn patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (IKr).ConclusionFor the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.

Hydroxyzine Initiation Following Drug Safety Advisories on Cardiac Arrhythmias in the UK and Canada: A Longitudinal Cohort Study.

IntroductionRegulatory advisories on hydroxyzine and risk of QT prolongation and Torsade de pointes (TdP) were issued in the UK in April 2015 and Canada in June 2016. We hypothesized patients with risk factors for QT prolongation and TdP, compared with those without risk factors, would be less likely to initiate hydroxyzine in the UK and in British Columbia (BC), Canada, following advisories.MethodsWe conducted a longitudinal study with repeated measures, and evaluated hydroxyzine initiation in a UK cohort and a concurrent BC control cohort (April 2013–March 2016) as well as in a BC advisory cohort (June 2014–May 2017).ResultsThis study included 247,665 patients in the UK cohort, 297,147 patients in the BC control cohort, and 303,653 patients in the BC advisory cohort. Over a 12-month post-advisory period, hydroxyzine initiation decreased by 21% in the UK (rate ratio 0.79, 95% confidence interval 0.66–0.96) relative to the expected level of initiation based on the pre-advisory trend. Hydroxyzine initiation did not change in the BC control cohort or following the Canadian advisory in the BC advisory cohort. The decrease in hydroxyzine initiation in the UK in the 12 months after the advisories was not significantly different for patients with risk factors compared with those without risk factors.ConclusionHydroxyzine initiation decreased in the UK, but not in BC, in the 12 months following safety advisories. The decrease in hydroxyzine initiation in the UK was not significantly different for patients with versus without risk factors for QT prolongation and TdP.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-022-01175-2.

Risk factors for QT prolongation with atypical antipsychotics

Drug‐induced prolongation of the QT interval can increase risk of developing the life‐threatening, albeit rare, atypical ventricular tachycardia known as torsade de pointes. Research literature, including individual case reports as well as meta‐analyses, suggests that use of atypical antipsychotic agents, especially sertindole and ziprasidone, can prolong the QT interval.

Evaluation of the Citalopram levels on QTc Interval in Rats using with Radio-telemetry

Long QT syndrome is an arrhythmogenic disease characterized by prolonged QT interval. Citalopram (CIT) was reported to prolong QT interval dose-dependently. Omeprazole (OMP), inhibits CIT metabolizing enzyme CYP2C19, thereby increases serum concentrations which may increase the risk of QT prolongation. These are commonly co-prescribed and recent studies have raised the safety concerns about. We aimed to investigate the dose dependent effects of citalopram alone and in combination with OMP. Forty male, Sprague Dawley rats were divided into 5 groups (n=8). CIT (10 mg/kg or 30 mg/kg) was given for 2 weeks alone or in combination with OMP (100 mg/kg) starting from the 2nd week. ECG recordings and blood samples were collected. QT interval significantly increased in all groups compared to control. The plasma level of CIT in the CIT30 group was significantly higher than CIT10 group (p<0.01) and was significantly higher in the CIT10+OMP group than that of the CIT10 group (p<0.01). In treatment groups, the increase in plasma citalopram level correlated positively with the increase in QT (r=0.844, r2=0.713). It was determined that CIT caused prolongation of QT interval, the addition of OMP increased QT interval more, and these increases correlated positively with CIT plasma concentration. Therefore, it would be appropriate to routinely measure CIT plasma levels in addition to ECG, particularly in patients with additional risk factors for QT prolongation.

Changes in QTc interval after hydroxychloroquine therapy in patients with COVID-19 infection: a large, retrospective, multicentre cohort study

ObjectiveTo evaluate the extent of hydroxychloroquine-induced corrected QT (QTc) prolongation and its relation to COVID-19 infection severity and incidence of polymorphic ventricular arrhythmias and sudden arrhythmic deaths.DesignA large-scale cohort study...

Premature atrial contractions with multiple patterns of aberrant conduction followed by torsade de pointes in a patient with polymyalgia rheumatica

Rationale:Recent studies have shown that QT interval prolongation is associated with disease severity and predicts mortality in systemic inflammatory diseases, particularly rheumatoid arthritis. Systemic pro-inflammatory cytokines released from synovial tissues in rheumatoid arthritis, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, could have direct effects on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels, resulting in QT interval prolongation on surface electrocardiogram (ECG) and an increased predisposition to develop lethal ventricular arrhythmias. However, reports on torsade de pointes (TdP) due to acquired long QT syndrome in patients with polymyalgia rheumatica (PMR) are limited.Patient concerns:An 85-year-old Japanese woman with active PMR developed first syncope.Diagnosis:Frequent premature atrial contractions (PACs) with multiple patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP were documented. PACs were the first beat of TdP.Interventions:Amiodarone, together with magnesium and potassium, was intravenously administered. However, TdP resulted in a ventricular arrhythmic storm, for which sedation with mechanical ventilatory support, temporary overdrive cardiac pacing, and intravenous landiolol administration in addition to multiple direct current shocks were effective.Outcomes:Approximately 2 years later, the patient was treated with amiodarone, propranolol, and prednisolone. She did not undergo implantable cardioverter-defibrillator implantation and was quite well, with no recurrence of ventricular tachyarrhythmia.Lessons:IL-6 hyperproduction in inflamed tissues has been widely confirmed in PMR. Frequent PACs with various patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP, for which IL-6-mediated enhancement of L-type Ca2+ current and inhibition of the rapid component of the delayed rectifier K+ current are the most likely mechanisms, were documented in an elderly Japanese woman with PMR. ECG may be recorded once in patients with active PMR even when these patients do not complain of palpitation or syncope. If QT interval prolongation or arrhythmia, including even PACs, is observed, follow-up ECG may be warranted, particularly for patients with some risk factors for QT prolongation that could lead to TdP, such as advanced age, female sex, hypopotassemia, and polypharmacy.

Proton Pump Inhibitors Directly Block hERG-Potassium Channel and Independently Increase the Risk of QTc Prolongation in a Large Cohort of US Veterans

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The Use of QT Prolongation Risk Factor Assessment Tool to Assess the Risk of QT Prolongation in Patients Taking Methadone: An Irish Experience

Currently, no tool exists to assist doctors in estimating their patients’ risk of QT prolongation. Methadone is one of many medications which is known to prolong a patient’s QT, and which can lead to Torsades de Pointes and sudden cardiac death. The aim of the study was to design a QT prolongation risk factor assessment tool, for patients taking methadone, which would allow physicians to objectively assess a patient’s risk of QT prolongation. Following a literature review a QT prolongation risk factor assessment tool was created. An audit was then carried out to see what risk factors for QT prolongation were identified prior to use of the tool, in our practice, and then after the tool had been introduced. The introduction of a dedicated QT risk factor assessment tool led to an 61% (39/100 to 100/100) increase in the documentation of individual QT prolongation risk factors in our patients. There was a 100% (4/4) increase in the documentation of risk of QT prolongation in the patient notes, of discussion that risk with patients (4/4), and of the frequency of repeat ECGS (4/4). The introduction of such a QT prolongation risk factor assessment tool in our practice led to an increased awareness of QT prolonging medications, an improvement in the documentation of QT prolonging risk factors and a change in the culture of the practice around medication prescribing and QT prolongation. In patients who are on methadone, a QT prolongation risk factor assessment tool allows for an objective assessment of each patient’s risk of QT prolongation which then allows for measures to be put in place to monitor and address this risk.

ELECTROCARDIOGRAPHIC CHANGES IN NEWBORNS FROM MOTHERS WITH METABOLIC SYNDROME

The aim: Analysis of electrocardiographic parameters in newborns from mothers with metabolic syndrome. Materials and methods: We conducted a prospective cohort trial of 125 newborns, which included the study of their anthropometric, clinical and laboratory indicators and, in particular, ECG parameters. The main group consisted of 40 children, born from mothers with diagnosed metabolic syndrome, the comparison group included 2 subgroups: 28 term newborn and 57 preterm, from mothers without metabolic syndrome. Results: In newborns from mothers with metabolic syndrome on a fragmentary ECG we revealed abnormal depolarization, manifested by changes in the ventricular complex -QRS expansion (p<0.001), impaired conduction (p = 0.004), changes of T wave (p<0.001) and prolonged QT interval (p<0.001). There are such risk factors for QT prolongation in neonates: disease cardiovascular system and disorders of lipid metabolism in mother, asphyxia at birth and electrolyte disorders (hypernatremia OR 0.97), weight too high to gestational age at birth in newborn (OR 2.97), increased blood pressure in the neonatal period (OR 1.07), artificial feeding (OR 3.01). Conclusions: Metabolic syndrome in women during pregnancy has a pronounced effect on the cardiovascular system of the newborn. The detected signs of cardiac dysfunction on the ECG can serve as early integrated indicators of metabolic syndrome and cardiovascular disease in children.

Effects of Antipsychotics on Arrhythmogenic Parameters in Schizophrenia Patients: Beyond Corrected QT Interval.

PurposeAntipsychotic drugs have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect marker for proarrhythmic risk. Recently, improved methods, namely, QT dispersion (QTD), QTD ratio (QTDR), T wave peak-to-end interval (Tp-e), Tp-e/QT ratio and Tp-e/QTc ratio, have been regarded as proarrhythmic risk markers. We attempted to reevaluate the risk of sudden cardiac death due to antipsychotics use by measuring these improved evaluation methods.Patients and MethodsWe retrospectively evaluated QTc, QTD, QTDR, Tp-e, Tp-e/QT ratio and Tp-e/QTc ratio from the medical records of 410 patients with schizophrenia diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, or 5th Edition. Information on drugs administered was obtained from medical records. We investigated the correlation between each index on ECG and medication, such as antipsychotics, prescribed to participants with linear regression analysis. We also compared each index between 235 healthy controls and 235 patients matched for age and sex.ResultsPositive correlations between QTc and levomepromazine and brexpiprazole were identified. Levomepromazine and lithium were positively correlated with QTD. Levomepromazine, quetiapine, asenapine, clozapine and carbamazepine were positively correlated with QTDR. Levomepromazine, olanzapine, brexpiprazole and lithium were positively correlated with Tp-e. Olanzapine, brexpiprazole and lithium were positively correlated with the Tp-e/QT ratio. Olanzapine, brexpiprazole and lithium were positively correlated with Tp-e/QTc ratio. Significant differences in all indexes were noted between the patients and healthy controls.ConclusionAccording to our results, the prediction of the risk of sudden cardiac death by each index was inconsistent. We should evaluate the predictive factor of ventricular arrhythmia according to various electrocardiogram indexes because QTc alone could not identify the risk of sudden cardiac death.

Prevalence of QTc interval prolongation and its associated risk factors among psychiatric patients: a prospective observational study

BackgroundQT interval prolongation is a growing concern worldwide, posing psychiatric patients to life-threatening fatal arrhythmias i.e., torsade de pointes. This study aimed to identify the prevalence of QT interval prolongation, its associated risk factors and prescribing patterns of QT prolonging drugs among psychiatric patients.MethodA prospective observational study was conducted that included psychiatric patients from a tertiary care hospital and a psychiatry clinic in Peshawar, Khyber Pakhtunkhwa, Pakistan. Electrocardiogram was recorded of those patients who were using psychotropic medications for ≥7 days, aged 18 years or more, and of either gender, male or female. The Fredericia correction formula was used for measuring QTc values (corrected QT). Chi-square test was applied to estimate differences between patients with or without prolonged QTc interval whereas, logistic regression analysis was performed to identify various predictors of QT interval prolongation.ResultsOut of 405 patients, the QTc interval was prolonged in 23 (5.7%) patients including 1 (0.2%) patient with highly abnormal prolonged QTc interval (> 500 ms). QT drugs (91.6%), female sex (38.7%) and hypertension (10.6%) were the most common QT prolonging risk factors. Prolonged QTc interval was significantly higher among male patients (p = 0.007).ConclusionIn the present study, QT interval prolongation was observed in a considerable number of psychiatric patients. While, the high prevalence of QT prolonging risk factors among these patients warrants the increased risk of fatal arrhythmias. Therefore, risk assessment and electrocardiographic monitoring, and prescription of safer alternatives are highly recommended.

QT prolongation in patients with acute leukemia or high-risk myelodysplastic syndrome prescribed antifungal prophylaxis during chemotherapy-induced neutropenia

Benefits of serial electrocardiographic (ECG) monitoring to detect QT prolongation in patients with hematological malignancies remain unclear. This retrospective, single-center, study evaluated 316 adult acute leukemia and high-risk MDS patients who received 11,775 patient-days of voriconazole prophylaxis during induction chemotherapy. Of these, 37 patients (16.2%) experienced QTc prolongation. Medications associated with QTc prolongation included furosemide, haloperidol, metronidazole, mirtazapine, prochlorperazine, and venlafaxine. Hypokalemia and hypomagnesemia were also significantly associated with QTc prolongation (HR 3.15; p = .003 and HR 6.47, p = .007, respectively). Management modifications due to QTc prolongation included discontinuation of QT prolonging medications (n = 25), more aggressive electrolyte repletion (n = 5), and enhanced ECG monitoring (n = 3). One patient with multiple QT prolonging factors experienced possible Torsades de Pointes. Overall mortality was 15% with no cardiac-related deaths. Serial ECG monitoring during induction chemotherapy can be tailored proportionally to QT-prolonging risk factors. Management should include aggressive electrolyte repletion and avoidance of concurrent QT prolonging medications.

165P - Prevalence of risk factors for QT prolongation and torsades de pointes among women with HR+/HER2– advanced or metastatic breast cancer treated in real-world settings in Italy and Germany

165P - Prevalence of risk factors for QT prolongation and torsades de pointes among women with HR+/HER2– advanced or metastatic breast cancer treated in real-world settings in Italy and Germany

Investigation of the Proarrhythmic Effects of Antidepressants according to QT Interval, QT Dispersion and T Wave Peak-to-End Interval in the Clinical Setting.

ObjectiveSome antidepressants have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect biomarker for proarrhythmic risk. Therefore, we reevaluated the risk of sudden cardiac death due to antidepressants using improved methods, namely, QT dispersion (QTD), T wave peak-to-end interval (Tp-e), and Tp-e/QT ratio. MethodsWe compared the effects of antidepressants on QTc (QT/RR1/3), QTD, Tp-e, and Tp-e/QT ratio in 378 patients with mood disorder. We also compared each index between 165 healthy controls and 215 randomly selected age-matched patients. ResultsAge (p<0.01), sex (p<0.05), tricyclic antidepressant (TCA) use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly associated with a prolonged QTc. We also found that age (p<0.01), TCA use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly prolonged QTD. However, there was no correlation between each variable and Tp-e or Tp-e/QT ratio. Significant differences in QTc and QTD were found between the patients and healthy controls. ConclusionFrom our results, prediction of risk of sudden cardiac death by QTD, Tp-e, or Tp-e/QT ratio was inconsistent. Increased QTD may be more suitable for predicting sudden cardiac death due to antidepressants.

High prevalence of the risk factors for QT interval prolongation and associated drug–drug interactions in coronary care units

ABSTRACTObjectives: Patients admitted in coronary care units are susceptible to QT interval prolongation due to numerous risk factors. The purpose of this study was to identify the prevalence of risk factors for QT interval prolongation; QT prolonging medications; drug–drug interactions; their predictors; and torsades de pointes risks of drugs.Methods: After obtaining approval, this cross-sectional study was carried out during one-year period in coronary care units of two major tertiary care hospitals of Khyber Pakhtunkhwa, Pakistan. The Arizona Center for Education and Research on Therapeutics QT drugs lists and Micromedex DrugReax® were used to identify the QT prolonging medications and QT prolonging drug–drug interactions.Results: Total 649 patients were included in this study. The most frequent QT prolonging risk factors included use of ≥ 1 QT prolonging drugs (74.9%) and myocardial infarction (61.3%). Total 181 patients were presented with 361 QT prolonging drug–drug interactions. There was significant association of the occurrence of QT prolonging drug–drug interactions with female gender (p = 0.01), 9–10 prescribed medications (p = 0.001), and > 10 prescribed medications (p < 0.001).Conclusions: The majority of patients presented with multiple risk factors for QT prolongation in coronary care units which may precipitate lethal outcomes.

Drug-physiology interaction and its influence on the QT prolongation-mechanistic modeling study.

The current study is an example of drug-disease interaction modeling where a drug induces a condition which can affect the pharmacodynamics of other concomitantly taken drugs. The electrophysiological effects of hypokaliemia and heart rate changes induced by the antiasthmatic drugs were simulated with the use of the cardiac safety simulator. Biophysically detailed model of the human cardiac physiology-ten Tusscher ventricular cardiomyocyte cell model-was employed to generate pseudo-ECG signals and QTc intervals for 44 patients from four clinical studies. Simulated and observed mean QTc values with standard deviation (SD) for each reported study point were compared and differences were analyzed with Student's t test (α = 0.05). The simulated results reflected the QTc interval changes measured in patients, as well as their clinically observed interindividual variability. The QTc interval changes were highly correlated with the change in plasma potassium both in clinical studies and in the simulations (Pearson's correlation coefficient > 0.55). The results suggest that the modeling and simulation approach could provide valuable quantitative insight into the cardiological effect of the potassium and heart rate changes caused by electrophysiologically inactive, non-cardiological drugs. This allows to simulate and predict the joint effect of several risk factors for QT prolongation, e.g., drug-dependent QT prolongation due to the ion channels inhibition and the current patient physiological conditions.