Increase In QTc Interval Research Articles

Evaluation of Electrocardiographic Repolarization Parameters in Patients who Received Ribociclib and Palbociclib Therapy

Abstract Introduction: Ribociclib and palbociclib are the inhibitors of cyclin-dependent kinase (CDK) 4/6 activity which have been used in the treatment of metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative breast cancer. QT interval prolongation has been the main reported adverse effect in Phase III trials of ribociclib and palbociclib therapy. In the present study, we aimed to evaluate electrocardiographic (ECG) changes in patients who received palbociclib and ribociclib therapy. Materials and Methods: Sixty women with metastatic HR-positive, human epidermal growth factor-2-negative breast cancer were included in the study. Baseline ECG and echocardiographic examinations of these patients were done. Second control electrocardiogram was obtained on the 14th day of first-cycle therapy. PR interval, corrected QT (QTc) interval, QT dispersion (QTD), and QRS duration were calculated. Results: Heart rate, PR interval, QRS, QT, QTc, QTD, and corrected QTD duration did not differ before and after CDK 4/6 treatment. Two patients who received ribociclib and palbociclib treatment had basal QTc duration higher than 450 ms (458 ms and 465 ms, respectively). The 14th-day QTc intervals of these patients were found to be 318 ms and 406 ms, respectively. After CDK 4/6 treatment, only two patients had QTc interval of 469 ms and 507 ms. The mean change of QTc interval before and during the 14th day of CDK 4/6 therapy was 7.38 ± 35.049 ms. When palbociclib and ribociclib treatments were analyzed separately, the baseline and 14th day of QTc interval were 415 ± 31.5 versus 428.11 ± 24.52 and 416.13 ± 26.05 versus 420.07 ± 31.32 ms, respectively. Conclusions: Ribociclib and palbociclib treatment was associated with a small statistically insignificant increase in QTc interval. Physicians should be aware of the side effect of these treatments.

Association between corrected QT interval and long-term cardiovascular outcomes in elderly patients who had undergone endovascular therapy for lower extremity arterial disease.

Population-based studies have reported the association between prolonged corrected QT (QTc) intervals and an increased risk of adverse cardiovascular events. Data regarding the association between longer QTc intervals and incident cardiovascular outcomes in patients with lower extremity arterial disease (LEAD) are scarce. To examine the impact of QTc interval on long-term cardiovascular outcomes in elderly patients with symptomatic LEAD. This cohort study extracted data from the Tzu-chi Registry of ENDovascular Intervention for Peripheral Artery Disease (TRENDPAD) and enrolled 504 patients aged ≥ 70 treated with endovascular therapy for atherosclerotic LEAD from July 1, 2005, to December 31, 2019. The main outcomes of interest were all-cause mortality and major adverse cardiovascular events (MACE). Multivariate analysis was conducted using the Cox proportional hazard model to determine independent variables. We performed interaction analysis between corrected QT and other covariates and Kaplan-Meier analysis to compare the outcome of interest among the groups stratified by the tercile of QTc intervals. A total of 504 patients [235 men (46.6%); mean age, 79.9 ± 6.2 years; mean QTc interval, 459 ± 33 msec] entered the final data analysis. We categorized the baseline patient characteristics according to terciles of QTc intervals. During the median follow-up time of 3.15 (interquartile ranges, 1.65-5.42) years, we noted 264 deaths and 145 MACEs. The 5-year rates of freedom from all-cause mortality (71% vs. 57% vs. 31%, P < 0.001) and MACEs (83% vs. 67% vs. 46%, P < 0.001) were significantly different among the tercile groups. Multivariate analysis showed that a 1-SD increase in the QTc interval increased the risk of all-cause mortality [hazard ratio (HR) 1.49, P < 0.001] and MACEs (HR 1.59, P < 0.001) after adjusting for other covariates. The interaction analysis showed that QTc interval and C-reactive protein levels were most strongly associated with death (HR = 4.88, 95% CI 3.09-7.73, interaction P < 0.001) and MACEs (HR = 7.83, 95% CI 4.14-14.79, interaction P < 0.001). In elderly patients with symptomatic atherosclerotic LEAD, a prolonged QTc interval is associated with advanced limb ischemia, multiple medical comorbidities, increased risk of MACEs, and all-cause mortality.

Which anti-nausea medications are more likely to increase QTc interval?

Which anti-nausea medications are more likely to increase QTc interval?

Hinokitiol for hypertensive emergencies: effects on peripheral resistance, cardiac load, baroreflex sensitivity, and electrolytes balance

Hinokitiol, a natural monoterpenoid, has been shown previously to possess a potent vasodilating activity in vitro in both control and hypertensive aortae. Here, the antihypertensive and cardioprotective effects of an intravenous hinokitiol injection were fully investigated in angiotensin II-induced hypertensive emergency in rats. Hinokitiol intravenous injection was prepared in the form of self-nanoemulsifying drug delivery system. Rat’s arterial and ventricular hemodynamics were measured in real-time recordings in addition to surface electrocardiogram while slow injection of cumulative doses of hinokitiol or vehicle as well as time control. Hinokitiol at dose 10 mg/kg showed a considerable reduction in the raised systolic blood pressure (30 mmHg) within only 30 min. The decrease in blood pressure seems to be mediated through a reduction in peripheral resistance, as appears from the decreases in diastolic pressure, dicrotic notch pressure, and pulse pressure. In addition, hinokitiol injection reduced heart load due to the decrease in heart rate, increases in cycle duration (particularly the non-ejection duration) and diastolic duration, and decreases in end-diastolic pressure. An effect most likely mediated via prolongation of ventricular repolarization as appears from the increases in PR, QTc, and JT intervals. However, acute intravenous injection of hinokitiol neither affected the baroreflex sensitivity nor sodium/potassium balance. In conclusion, acute hinokitiol intravenous injection markedly reduced severe hypertension in rats. This effect seems to be mediated through decreasing peripheral resistance and decreasing cardiac load, suggesting that it is an effective treatment in hypertensive emergencies after clinical evaluation.

Changes of electrocardiograms and heart morphology of animals with different resistance to hypoxia under influences of stress

Stress is a process that increases a person’s adaptive capacity and leads to the various diseases, such as hypertension, coronary artery disease, heart attack, cardiac arrest, stroke, mental disorders such as depression and anxiety and even sudden death. Individual response to stress may depend on age, gender, features of autonomic regulation, state of the central nervous system, endocrine systems, higher nervous activity. With excessive stress, the work of internal organs is disturbed, in particular, the cardiovascular system. Determination of the damaging effect of stress on the cardiovascular system in individuals with different reactivity will contribute to the development of individual correction methods. The aim of the study was to analyze the changes in electrocardiograms (ECG) and morphological feachers after stress in animals with different resistance to hypoxia. Material and methods of investigation. Experiments were performed on 48 Wistar rats, with high and low resistance to hypoxia (HRH, LRH), aged 5–6 months. Animals were divided into two groups – control and experimental (after immobilization stress). Individuals with different resistance to hypoxia were selected by method of V. Ya. Berezovsky. Stress was modeled by three one-hour immobilization of rats, which were immobilized on their backs with an interval of 24 hours between each stressful episode. Investigation we did after 24 hours after third immobilization. Under anesthesia were registrated ECG and taken heart for morphological investigation. Sections were stained with hematoxylin and eosin. Results. In examining the ECG in control HRH and LRH animals, no significant difference in the analyzed ECG indicators was established. 24 hours after the last 1 hour three-time immobilization in HRH rats were noted an increase in heart rate, a decrease of the duration of the RR interval, a decrease of the amplitude of the R wave, an increase of QTc interval, an increase of the amplitude of the T wave, an increase in the deviation of the ST segment from the isoline. In LRH rats, stress caused an increase in heart rate, a decrease in the duration of the RR interval, a decrease in the duration of the PQ interval, a decrease in the amplitude of the R wave, an increase in the amplitude of the T wave, an increase in the deviation of the ST segment from the isoline. When comparing the parameters of НRH and LRH rats, in LRH were found a smaller amplitude of the P wave, a smaller amplitude of the R wave, a smaller value of the QTc interval, greater deviation of the ST segment from the isoline. Physiological changes on ECG can also connected with morphological feaches. Conclusions. Stress leads to changes in functional and histological properties of heart, which depends on resistance to hypoxia. In the ECG 24 hours after the last 1 hour three-time immobilization in HRH and LRH rats were noted an increase in heart rate, a decrease of the duration of the RR interval, a decrease of the amplitude of the R wave, an increase of the amplitude of the T wave, an increase in the deviation of the ST segment from the isoline. In HRH rats were also an increase of QTc interval, in LRH rats – a decrease in the duration of the PQ interval. Indxes changes were grater in LRH rats. Mophological changes was higher also in LRH animals.

Inter-sleep stage variations in corrected QT interval differ between obstructive sleep apnea patients with and without stroke history.

Obstructive sleep apnea (OSA) is related to the progression of cardiovascular diseases (CVD); it is an independent risk factor for stroke and is also prevalent post-stroke. Furthermore, heart rate corrected QT (QTc) is an important predictor of the risk of arrhythmia and CVD. Thus, we aimed to investigate QTc interval variations in different sleep stages in OSA patients and whether nocturnal QTc intervals differ between OSA patients with and without stroke history. 18 OSA patients (apnea-hypopnea index (AHI)≥15) with previously diagnosed stroke and 18 OSA patients (AHI≥15) without stroke history were studied. Subjects underwent full polysomnography including an electrocardiogram measured by modified lead II configuration. RR, QT, and QTc intervals were calculated in all sleep stages. Regression analysis was utilized to investigate possible confounding effects of sleep stages and stroke history on QTc intervals. Compared to patients without previous stroke history, QTc intervals were significantly higher (β = 34, p<0.01) in patients with stroke history independent of age, sex, body mass index, and OSA severity. N3 sleep (β = 5.8, p<0.01) and REM sleep (β = 2.8, p<0.01) increased QTc intervals in both patient groups. In addition, QTc intervals increased progressively (p<0.05) towards deeper sleep in both groups; however, the magnitude of changes compared to the wake stage was significantly higher (p<0.05) in patients with stroke history. The findings of this study indicate that especially in deeper sleep, OSA patients with a previous stroke have an elevated risk for QTc prolongation further increasing the risk for ventricular arrhythmogenicity and sudden cardiac death.

Abstract 15510: Big Heart Problems: A Case of Reversible Nonischemic Cardiomyopathy Due to Severe Hypothyroidism

Introduction: Cardiomyopathy is a heterogeneous group of myocardial diseases that can result in mechanical and electrical dysfunction. Thyroid insufficiency can increase the risk of cardiovascular abnormalities through multiple mechanisms including ventricular arrhythmias, hypertension, and heart failure. Case Presentation: Our patient is a 40-year-old Hispanic female with a past medical history of papillary thyroid carcinoma with a right-sided hemithyroidectomy in 2019 who presented to the emergency department with a 1-week history of dyspnea and peripheral edema. She has a family history of sudden cardiac death in her father. She discontinued her levothyroxine 75 mcg once daily dose 6 months ago as she believed this was causing her headaches. Her vital signs were significant for a heart rate of 117 beats per minute and a blood pressure of 185/147 mmHg. Her lab work showed a thyrotropin level of 94.6 uIU/mL, free thyroxine of 0.57 ng/dL, troponin T of 22 ng/L, and proBNP of 2660 pg/mL. A transthoracic echocardiogram (TTE) demonstrated global left ventricular hypokinesis with a left ventricular ejection fraction (LVEF) of 30-35%. Her electrocardiogram (EKG) showed normal sinus rhythm and corrected QTc of 494 ms. She received levothyroxine and furosemide and was discharged with guideline directed medical therapy (GDMT). Her outpatient TTE demonstrated improved LVEF of 40-45% after two months of levothyroxine use and GDMT. Discussion: Hypothyroidism has many cardiometabolic effects that directly impact cardiac function. Impairments in cardiac contractility can result in diastolic heart failure leading to low cardiac output, low heart rate, and low stroke volume. Increased vascular permeability results in protein-rich pericardial and pleural effusions. Myxedema, or non-pitting edema can be seen in long-standing, severe hypothyroidism. An increased QTc interval occurs due to prolonged cardiac action potentials which predispose the heart to ventricular irritability. Treatment with levothyroxine can improve cardiac output and contractility, however this carries increased risk of cardiac arrhythmias and myocardial ischemia. Conclusion: Severe hypothyroidism should be considered in cases of isolated nonischemic cardiomyopathy.

FLUOROQUINOLONES EFFECT ON THE QTC INTERVAL IN PATIENTS WITH DRUG-RESISTANT TB

FLUOROQUINOLONES EFFECT ON THE QTC INTERVAL IN PATIENTS WITH DRUG-RESISTANT TB

MATE1 Deficiency Exacerbates Dofetilide-Induced Proarrhythmia.

Dofetilide is a rapid delayed rectifier potassium current inhibitor widely used to prevent the recurrence of atrial fibrillation and flutter. The clinical use of this drug is associated with increases in QTc interval, which predispose patients to ventricular cardiac arrhythmias. The mechanisms involved in the disposition of dofetilide, including its movement in and out of cardiomyocytes, remain unknown. Using a xenobiotic transporter screen, we identified MATE1 (SLC47A1) as a transporter of dofetilide and found that genetic knockout or pharmacological inhibition of MATE1 in mice was associated with enhanced retention of dofetilide in cardiomyocytes and increased QTc prolongation. The urinary excretion of dofetilide was also dependent on the MATE1 genotype, and we found that this transport mechanism provides a mechanistic basis for previously recorded drug-drug interactions of dofetilide with various contraindicated drugs, including bictegravir, cimetidine, ketoconazole, and verapamil. The translational significance of these observations was examined with a physiologically-based pharmacokinetic model that adequately predicted the drug-drug interaction liabilities in humans. These findings support the thesis that MATE1 serves a conserved cardioprotective role by restricting excessive cellular accumulation and warrant caution against the concurrent administration of potent MATE1 inhibitors and cardiotoxic substrates with a narrow therapeutic window.

C-reactive Protein Elevation Is Associated With QTc Interval Prolongation in Patients Hospitalized With COVID-19.

BackgroundThe relationship between inflammation and corrected QT (QTc) interval prolongation is currently not well defined in patients with COVID-19.ObjectiveThis study aimed to assess the effect of marked interval changes in the inflammatory marker C-reactive protein (CRP) on QTc interval in patients hospitalized with COVID-19.MethodsIn this retrospective cohort study of hospitalized adult patients admitted with COVID-19 infection, we identified 85 patients who had markedly elevated CRP levels and serial measurements of an ECG and CRP during the same admission. We compared mean QTc interval duration, and other clinical and ECG characteristics between times when CRP values were high and low. We performed mixed-effects linear regression analysis to identify associations between CRP levels and QTc interval in univariable and adjusted models.ResultsMean age was 58 ± 16 years, of which 39% were women, 41% were Black, and 25% were White. On average, the QTc interval calculated via the Bazett formula was 15 ms higher when the CRP values were “high” vs. “low” [447 ms (IQR 427–472 ms) and 432 ms (IQR 412–452 ms), respectively]. A 100 mg/L increase in CRP was associated with a 1.5 ms increase in QTc interval [β coefficient 0.15, 95% CI (0.06–0.24). In a fully adjusted model for sociodemographic, ECG, and clinical factors, the association remained significant (β coefficient 0.14, 95% CI 0.05–0.23).ConclusionAn interval QTc interval prolongation is observed with a marked elevation in CRP levels in patients with COVID-19.

Influence of NOS1AP Risk Variants on the Corrected QT (QTc) Interval in the Pharmacotherapy of Schizophrenia.

The variants of the gene for nitric oxide synthase 1 adaptor protein (NOS1AP) are associated with schizophrenia and cardiovascular deficits involving corrected QT (QTc) interval prolongation. Here, we investigated a possible pharmacogenetic effect of antipsychotic treatment on QTc length in interaction with two NOS1AP variants (rs12143842 and rs10494366) whose minor alleles are associated with increased QTc interval length. We conducted a retrospective analysis of electrocardiographic (ECG) and genotype data of 239 patients diagnosed with schizophrenia. We converted antipsychotics dosage to chlorpromazine equivalents and defined daily doses. We analysed the effects of the minor (i. e. rs12143842-CT/TT and rs10494366-GT/GG) and major (i. e. rs12143842-CC and rs10494366-TT) allele genotypes to QTc interval for female and male participants separately. As expected, rs12143842 and rs10494366 exhibit strong linkage disequilibrium. Both polymorphisms had no direct effect on antipsychotic use or QTc interval. However, there was a continuous increase in QTc interval with increasing antipsychotic dosage in males. For both variants, positive correlation of QTc length with antipsychotic dosage was found in homozygous male carriers of the major alleles (i. e. rs12143842-CC and rs10494366-TT), but not in minor allele carriers. There was no significant interaction between antipsychotic dosage and QTc interval for either genotype in female patients. In this study, a significant interaction was found between both NOS1AP variants, rs12143842 and rs10494366, and antipsychotic treatment on the QTc interval in a sex-dependent manner. Our findings might be relevant for adequate antipsychotic treatment in rs12143842 and rs10494366 major allele carriers.

QTc Prolongation with the Use of Hydroxychloroquine and Concomitant Arrhythmogenic Medications: A Retrospective Study Using Electronic Health Records Data.

IntroductionHydroxychloroquine can induce QT/QTc interval prolongation for some patients; however, little is known about its interactions with other QT-prolonging drugs.ObjectiveThe purpose of this retrospective electronic health records study was to evaluate changes in the QTc interval in patients taking hydroxychloroquine with or without concomitant QT-prolonging medications.MethodsDe-identified health records were obtained from the Cerner Health Facts® database. Variables of interest included demographics, diagnoses, clinical procedures, laboratory tests, and medications. Patients were categorized into six cohorts based on exposure to hydroxychloroquine, methotrexate, or sulfasalazine alone, or the combination of any those drugs with any concomitant drug known to prolong the QT interval. Tisdale QTc risk score was calculated for each patient cohort. Two-sample paired t-tests were used to test differences between the mean before and after QTc measurements within each group and ANOVA was used to test for significant differences across the cohort means.ResultsA statistically significant increase in QTc interval from the last measurement prior to concomitant exposure of 18.0 ms (95% CI 3.5–32.5; p < 0.05) was found in the hydroxychloroquine monotherapy cohort. QTc changes varied considerably across cohorts, with standard deviations ranging from 40.9 (hydroxychloroquine monotherapy) to 57.8 (hydroxychloroquine + sulfasalazine). There was no difference in QTc measurements among cohorts. The hydroxychloroquine + QTc-prolonging agent cohort had the highest average Tisdale Risk Score compared with those without concomitant exposure (p < 0.05).ConclusionOur analysis of retrospective electronic health records found hydroxychloroquine to be associated with a moderate increase in the QTc interval compared with sulfasalazine or methotrexate. However, the QTc was not significantly increased with concomitant exposure to other drugs known to increase QTc interval.

EFFECTS OF ACUTE NORMOBARIC HYPOXIA-INDUCED PULMONARY HYPERTENSION ON ELECTROCARDIGRAPHIC MEASURES IN POST-MYOCARDIAL INFARCTION PATIENTS

Objective: Normobaric hypoxia induces pulmonary hypertension (PH) in healthy individuals and post-myocardial infarction (P-MI) patients. Depending on the size of the myocardial scar and the remaining left ventricular ejection fraction, P-MI patients are potentially more vulnerable to cardiac rhythm disorders than healthy individuals. Albeit of utmost importance for P-MI patients planning high altitude sojourn, data regarding effects of hypoxia on cardiac rhythm remain contradictory. The objective was to evaluate if normobaric hypoxia-induced PH triggers electrocardiographic changes at rest and under exertion in P-MI patients. Design and method: At the German Aerospace Center:envihab facility, 4 non-professional male athletes (57.8 ± 3.3years) in clinically stable condition after left ventricular ST-elevation MI (3 type I and 1 type II MI, all&gt; 1 year since event) and subsequent drug-eluting stent implantation for single-vessel coronary artery disease were exposed to normobaric hypoxia achieved by nitrogen dilution. Starting at 20.9%, oxygen content was gradually decreased to a minimum of 11.5% over a period of 19 days. Within the following 3 days hypoxia was stepwise reduced back to 20.9% oxygen. Standard 12-lead resting electrocardiogram (ECG) and transthoracic echocardiography (TTE) were performed daily. For echocardiographic detection of PH, systolic pulmonary arterial pressure (sPAP) was measured. Exercise ECG was performed under normoxia and under 17.5% oxygen. Results: Normobaric hypoxia with a minimum of 11.5% O2 led to elevated sPAP in TTE. Echocardiographic signs of PH were closely linked to significantly increased QTc interval using Bazett’s (from 402 ± 13 to 417 ± 25ms) and Holzmann’s (103 ± 4 to 107 ± 6%) formula compared to normoxia (all p &lt; 0.01). In exercise ECG under hypoxia, an increased number of ventricular and supraventricular extrasystoles could be detected compared to normoxia. Conclusions: In clinically stable P-MI patients, exposure to normobaric hypoxia leading to PH significantly prolongs corrected QT interval and potentially triggers cardiac arrhythmias like premature beats under exertion. P-MI patients should undergo echocardiography and exercise electrocardiography in suitable facilities under hypoxic conditions prior to planned high altitude sojourn. Particularly P-MI patients with prolonged QTc interval under normoxia appear susceptible to cardiac arrhythmias due to the additional QTc interval-prolonging effect under hypoxia. Further studies are pending in this context.

Investigation of the Severity of Increased QT Interval Incidence in Young Patients with COVID-19

Introduction: ECG abnormality is a major problem in COVID-19 patients, especially in the elderly, which can result in fatal dysrhythmias. In this article, QT interval prolongation was investigated in admitted Covid-19 patients of 20-50 years of age without any history of cardiac problems. Methods: This study is a descriptive and analytical study. All consenting patients admitted to the hospital for Covid-19 infection aged 20-50 years old entered the study. Patients with underlying heart and kidney disease, history of taking any medication or cardiac dysrhythmias were excluded. An electrocardiogram was performed on admission and the third day of hospitalization. Results: The average length of hospital stay was 7.9±3.68 days, and all patients had QT interval prolongation after 3 days, but no cardiac dysrhythmia occurred. There was no statistically significant increase in QTc interval for each drug used alone, but the use of various drugs that affect the electrical conduction of the heart and also the presence of underlying inflammation, especially in patient’s heart cells can be the underlying cause of QTc interval prolongation. Many Covid-19 patients have QT interval prolongation. It can be due the infection itself, the drugs used for treatment or viral myocarditis. The results of the present study showed that taking drugs such as kaletra even for 3 days can significantly increase the QTc interval in patients, so care should be taken in the use of these drugs to avoid iatrogenic cardiac disease in patients, although in most cases the increase was mild and didn’t cause mortality in patients.

QTc Interval Prolongation with Therapies Used to Treat Patients with Parkinson's Disease Psychosis: A Narrative Review.

In addition to the classic motor symptoms of Parkinson’s disease (PD), people with PD frequently experience nonmotor symptoms that can include autonomic dysfunction and neuropsychiatric symptoms such as PD psychosis (PDP). Common patient characteristics, including older age, use of multiple medications, and arrhythmias, are associated with increased risk of corrected QT interval (QTc) prolongation, and treatments for PDP (antipsychotics, dementia medications) may further increase this risk. This review evaluates how medications used to treat PDP affect QTc interval from literature indexed in the PubMed and Embase databases. Although not indicated for the treatment of psychosis, dementia therapies such as donepezil, rivastigmine, memantine, and galantamine are often used with or without antipsychotics and have minimal effects on QTc interval. Among the antipsychotics, data suggesting clinically meaningful QTc interval prolongation are limited. However, many antipsychotics have other safety concerns. Aripiprazole, olanzapine, and risperidone negatively affect motor function and are not recommended for PDP. Quetiapine is often sedating, can exacerbate underlying neurogenic orthostatic hypotension, and may prolong the QTc interval. Pimavanserin was approved by the US Food and Drug Administration (FDA) in 2016 and remains the only FDA-approved medication available to treat hallucinations and delusions associated with PDP. However, pimavanserin can increase QTc interval by approximately 5–8 ms. The potential for QTc prolongation should be considered in patients with symptomatic cardiac arrhythmias and those receiving QT-prolonging medications. In choosing a medication to treat PDP, expected efficacy must be balanced with potential safety concerns for individual patients.

Prolongation of QTc interval at the beginning and during dialysis is associated with hypervolemia and calcium and magnesium change in the first 2h.

High rates of sudden cardiac death are mostly attributed to ventricular arrhythmias including QTc prolongation in hemodialysis patients. We aimed to investigate the correlation of electrolyte and volume changes with QTc interval prolongation in hemodialysis patients. The present study is designed as a cross-sectional study. The study was conducted at the hemodialysis unit of a training and research hospital and its' satellite dialysis unit. Patients were divided into three groups. Group-1: with normal QTc interval both at the beginning and during dialysis session; group-2: with prolonged QTc interval at the beginning and remained prolonged during dialysis session; group-3: with normal QTc interval at the beginning but prolonged during the dialysis session. In addition, patients were evaluated in terms of QTc change between the beginning and 2nd hour (delta-QTc-1) and between 2nd hour and 4th hour (delta-QTc-2), respectively, and defined as 'patients with increased QTc interval' and 'patients without increased QTc interval'. A total of 45 prevalent hemodialysis patients were enrolled in the study. 14 patients (31.1%) had normal QTc interval (group-1), 13 patients (28.9%) had prolonged QTc interval at the beginning and remained prolonged during dialysis session (group-2) and 18 patients (40%) had normal QTc interval at the beginning but prolonged during dialysis session (group-3). There was no statistically significant difference between groups in terms of baseline electrolyte levels. Calcium change in the first 2h was lower in patients with QTc prolongation from the start or during the dialysis session (group-2 and group-3). In addition, systolic blood pressure (SBP) levels at the beginning of the session (118 ± 15mmHg vs 124 ± 28mmHg vs138 ± 24mmHg; p = 0.04) and intradialytic ultrafiltration (UF) rate were higher (1.96 ± 0.6 L/4h vs 2.6 ± 1.0 L/4h vs 2.8 ± 0.9 L/4h; p = 0.03) in group-2 and group-3 compared to patients in group-1. Increase in QTc interval was found higher in patients with less calcium increase (Rho: -0.36; p = 0.01) and with greater magnesium decrease in the first 2h (Rho: 0.31; p = 0.04). QTc interval prolongation is common among hemodialysis patients. High intradialytic UF rates, change in serum magnesium and calcium levels in the first 2h were found associated with QTc prolongation. However, QTc prolongation was found independently associated only with UF volume and calcium change in the first 2h.

Ventricular arrhythmia susceptibility in a new porcine model of heart failure (HF) with reduced ejection fraction

Abstract Introduction Sudden death secondary to ventricular arrhythmias is common in HF patients, with no effective treatment available outside of implantable cardiac defibrillators. While animal models are essential for the discovery of anti-arrhythmic drugs, no reliable large animal HF models with associated ventricular arrhythmias have been described so far. Objectives We aimed at evaluating ventricular remodeling and arrhythmia susceptibility in an HF pig model with reduced ejection fraction (EF) following myocardial infarction (MI). Methods MI was induced in 53 male Göttingen minipigs (12–15 months, 20–25 kg) by coronary embolization in mid-left anterior descending and mid-left circumflex coronary arteries using endovascular coils. Seven other pigs underwent sham operation and were used as control. Two weeks after surgery, cardiac function was assessed by echocardiography, and animals were included based on EF&amp;lt;50% (n=15/53), assigned either to 12 weeks of vehicle (n=9) or perindopril (n=6, 1 mg/kg/d, per os) group. At the end of the study, their left ventricular (LV) electrical remodeling was studied by echocardiography/electrocardiography and a programmed-electrical stimulation protocol was performed to evaluate the susceptibility to develop ventricular arrhythmias. Results At the end of the study, animals in the vehicle group had a significant LV remodeling associated with a reduced EF (p&amp;lt;0.05 vs. sham, see table). This remodeling was associated with cardio-pulmonary congestion, significant increases in LV end-diastolic pressure, left atrial volume, and lung mass (all p&amp;lt;0.05 vs. sham, see table), fully prevented by perindopril treatment. They had also an electrical remodeling as evidenced by an increase in PR, QRS, and QTc intervals, as well as LV effective refractory period (+18%, 14%, 33%, and 13%, respectively, p&amp;lt;0.05, compared to sham animals). Electrical changes were mitigated by perindopril treatment (p=NS vs. sham). LV mechanical dispersion measured with speckle-tracking echocardiography was significantly increased in vehicle group (58±5 vs. 22±1 ms in sham group, respectively) as well as in perindopril group. Programmed-electrical stimulations induced in 6/8 vehicle animals either non-sustained (n=3) or sustained (n=2) ventricular tachycardia, or ventricular fibrillation (n=1). In sham group only 1/7 animal had a ventricular fibrillation. No inducible ventricular arrhythmia was observed in animals treated with Perindopril. Conclusion In this new pig model of congestive HF with reduced EF, LV remodeling was associated with electrical remodeling and susceptibility to develop arrhythmias. Chronic angiotensin-converting enzyme inhibitor treatment prevented congestion, mitigated electrical remodeling, and suppressed arrhythmia susceptibility. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Servier Research Institute - CardioVascular &amp; Metabolic Diseases Center for Therapeutic Innovation Table 1

Impact of Hydroxychloroquine Treatment of COVID-19 on Cardiac Conduction: The Beat Goes On

Objectives: Our study aimed to investigate the frequency of malignant cardiac arrhythmias in hospitalized patients receiving hydroxychloroquine alone and those receiving a combination of hydroxychloroquine with azithromycin, as well as the quantitative extent of QT prolongation within Tisdale Risk Score (TRS) categories. Background: There have been over 33 million cases of SARS-CoV-2 (COVID-19) resulting in over 600,000 deaths in the United States. As the current COVID-19 pandemic continues, numerous medications have been administered to attempt to treat patients afflicted by the disease. While hydroxychloroquine has been in use for decades for rheumatologic and infectious disease processes, it does have potential cardiotoxicity related to drug-induced QT prolongation. Drug-induced QT prolongation has an increased risk of arrhythmogenicity, potentially progressing into torsades de pointes (TdP) and increased patient mortality. The relationship between QT prolongation and TdP is complex and inexact, but there remains optimism regarding the use of these medications in the treatment of COVID-19 despite limited data on their true efficacy. Methods: We retrospectively identified 75 patients who were admitted with COVID-19 and underwent treatment with hydroxychloroquine for 5 days. The hydroxychloroquine protocol was defined as an initial dose of 400 mg BID for the first day, followed by 400 mg daily for the next 4 days. Baseline demographics, medications, medical histories, lab values, ECG QT intervals, and Tisdale Risk Categories were collected for all patients. Results: Seventy-four (98.7%) patients completed the full course of hydroxychloroquine. There were 41 males (54.7%) and 34 females (45.3%). Average length of stay was 8.9 days (95% CI: 7.5, 10.2). One patient who could not complete the course due to inability to swallow medication tablets. There were no reports of new arrythmias or incidence of torsades de pointes during the study. Seventy-two patients (96%) were taking at least 2 QT prolonging medications. The average corrected QT intervals were as follows: day 1 of admission was 421.62 milliseconds (n = 66, 95% CI: 412.19, 431.05), day 2 was 431.50 ms (n = 30, 95% CI: 416.34, 446.66), day 3 was 433.48 ms (n = 23, 95% CI: 413.34, 453.61), day 4 was 427.59 ms (n = 17, 95% CI: 400.83, 454.35), and day 5 was 444.28 ms (n = 18, 95% CI: 428.43, 460.12). The corrected QT interval prolonged by 22.66 ms from day 1 to day 5 (p = 0.03) in the overall population. Conclusion: There were no patients who experienced arrhythmogenicity or Torsades de Pointes despite a statistically significant increase in QTc intervals after patients received the 5-day course of hydroxychloroquine for treatment of COVID-19.

The Adverse Cardiovascular Effects and Cardiotoxicity of Kratom (Mitragyna speciosa Korth.): A Comprehensive Review.

Background: Kratom or Mitragyna speciosa (Korth.) has received overwhelming attention recently due to its alleged pain-relieving effects. Despite its potential therapeutic value, kratom use has been linked to many occurrences of multiorgan toxicity and cardiotoxicity. Accordingly, the current narrative review aimed to provide a detailed account of kratom’s adverse cardiovascular effects and cardiotoxicity risk, based on in vitro studies, poison center reports, coroner and autopsy reports, clinical case reports, and clinical studies. Methods: An electronic search was conducted to identify all research articles published in English from 1950 to 2021 using the major research databases, such as Google Scholar, Web of Science, PubMed, Scopus, Mendeley, EMBASE, Cochrane Library, and Medline. We then analyzed the literature’s discussion of adverse cardiovascular effects, toxicity, and mortality related to kratom use. Results: Our findings revealed that, although in vitro studies have found kratom preparations’ most abundant alkaloid—mitragynine—to cause a prolonged QTc interval and an increased risk of torsades de pointes, a clinical study examining humans’ regular consumption of kratom did not report such a risk. However, this latter study did show that regular kratom use could induce an increased QTc interval in a dose-dependent manner. A few case reports also highlighted that kratom consumption is associated with ventricular arrhythmia and cardiopulmonary arrest, but this association could have ensued when kratom was co-administered with another substance. Similarly, analyses of national poison data showed that kratom’s most common adverse acute cardiovascular effects include tachycardia and hypertension. Meanwhile, coroner and autopsy reports indicated that kratom’s cardiovascular sequelae encompass coronary atherosclerosis, myocardial infarction, hypertensive cardiovascular disease, left ventricular hypertrophy, cardiac arrhythmia, cardiomegaly, cardiomyopathy, focal band necrosis in the myocardium, and myocarditis. Given the available data, we deduced that all cardiac eventualities reported in the literature could have been compounded by polysubstance use and unresolved underlying medical illnesses. Conclusion: Although kratom use has been associated with death and cardiotoxicity, especially at higher doses and when associated with other psychoactive drugs, the dearth of data and methodological limitations reported in existing studies do not allow a definitive conclusion, and further studies are still necessary to address this issue.

Evaluating the risk of QTc prolongation associated with hydroxychloroquine use with antidepressants in lupus patients with fibromyalgia.

Hydroxychloroquine (HCQ) is widely used in patients with systemic lupus erythematosus (SLE) due to its immunomodulatory properties. Antidepressants are commonly used in patients with fibromyalgia syndrome (FMS). Both HCQ and antidepressants are reported to cause QTc prolongation, which potentially increases the risk for a lethal ventricular arrhythmia that can result in sudden death. The objective of the study is to investigate the risk of QTc prolongation associated with HCQ use concomitantly with antidepressants in lupus patients with FMS. Outpatient 12-lead electrocardiograms (ECGs) were extracted from an electronic medical record and QTc intervals were calculated using the Bazett's formula. QTc intervals in 135 lupus patients treated with HCQ with or without antidepressants were analyzed. We found taking HCQ was associated with mild QTc prolongation, and the prolongation was not affected by the length of time of HCQ use or the accumulated dose of HCQ. Concurrent use of HCQ and antidepressants had not further increased QTc intervals in this cohort. However, four patients on HCQ alone and three patients on HCQ and antidepressants were found QTc interval more than 500 milliseconds and most of these patients had underlying cardiological conditions. It is important to evaluate lupus patient with ECG before and after starting HCQ, though our study suggests that while HCQ use did prolong the QTc in some, but the overall prolongation was subclinical, with or without antidepressants. ECG monitoring therefore is essential to identify new changes potentially related to drug use.