QTc Prolongation In Patients Research Articles

QT interval in patients receiving HCQ in SARS-CoV-2- A study on risk factors and correlation of baseline QTc with delta QTc in Pakistani population

Funding AcknowledgementsType of funding sources: None.IntroductionHydroxychloroquine(HCQ) use alone or in combination with Azithromycin (AZM) in SARS-CoV-2 infection is associated with QTc prolongation and risk of arrhythmias.ObjectivesTo determine changes in QTc interval and factors predictive of extreme QTc prolongation in patients receiving HCQ alone or in azithromycin combination in Pakistani patients.MethodologyRetrospective review of records of hospitalized patients with SARS-Cov2 RT-PCR positive result who received HCQ or HCQ/Azithromycin in combination from March-May 2020. Baseline ECGs as well as post drug use ECGs data was recorded. Tisdale score was calculated for predicting risk of QTc prolongation,QTc interval was calculated using Bazett formula. Data entry and analysis was done in SPSS version 23. ResultsA total of 134 patients were included in the study. 82.1%(110) were males and 17.9%(24) were females, mean age was 54.9 ± 13.7 years. 61.2% (82) had severe disease and 38.8 %(52) had non-severe disease. 14.2%(19) had history of cardiac disease, 35.8%(48) had hypertension and 35.1%(47) had diabetes mellitus. 70.1% (94) patients had received HCQ, AZM, or HCQ/AZM in combination. 40(29.9%) patients had not received any drug. Median baseline QTc among controls and non-control group was 383.5 (IQR 342.25-413.75)msec and 379(IQR 358-402)msec respectively. HCQ alone was administered to 26.9%(36) and HCQ/AZM to 33.6%(45) patients. 55.6% (45/81) developed QTc prolongation(QTc> 480 msec) or delta QTc increase > 60 msec. 6.2%(5/81) had absolute QTc > 500 msec post-drug administration. 55.6%(25/45) and 30.6%(11/36) (p-value 0.024) developed QTc prolongation in combination and HCQ alone groups respectively. Delta QTc increased to >60msec in 42.0% (34/81); 53.3%(24/45) in combination group and in 27.8%(10/36) of those receiving HCQ alone( p-value 0.021). Median delta change was 63( IQR 25-81) and 48.5(IQR 26.25-66.75) msec; Median Day 2 QTc was 413.5 msec (IQR 377.5-436) and 413 msec (IQR361-447); and median maximum QTc was 447(IQR391-471) and 429.8(IQR401.5-45.75) msec in those receiving HCQ/AZM combination and HCQ alone respectively. 9%(12/134) had arrhythmias during hospital stay, in 8.9% (4) and 5.6%(2) patients of those receiving HCQ/AZM combination and HCQ alone respectively, no patient developed torsade de pointes, one patient had non-sustained VT. There was no statistically significant association of QTc prolongation with mortality, acute kidney injury, myocardial injury or severity of disease. Diuretic use was found to be statistically significant association with QTc prolongation(p-value 0.038). There was a weak correlation of baseline QTc with Δ QTc(r = 0.207 and p-value 0.017)ConclusionQTc prolongation was observed in a significant population of patients receiving HCQ and HCQ/AZM combination, however, no significant life threating arrhythmias occurred.

Dorsal vagal nucleus involvement relates to QTc-prolongation after acute medullary infarction.

Infarction of the medulla has been associated with prolongation of the QTc, severe arrhythmia, and sudden cardiac death, yet the precise anatomical substrate remains uncertain. We sought to determine the possible anatomical structures relating to QTc-prolongation in patients with acute medullary infarction. We included 12 subjects with acute ischemic medullary infarction on brain MRI, who presented within 4.5h from the last known well time, with a 90-day follow-up. For an unbiased lesion analysis, medullary infarcts were manually outlined on diffusion weighted MRI and co-registered with an anatomical atlas. Nine out of 12 had QTc-prolongation. Qualitative and semi-quantitative comparisons were made between infarct location and QTc-prolongation. Among patients with QTc-prolongation, the greatest degree of congruence of the infarct location was over the dorsal vagal nucleus (DVN, 8 out of 9). There was a significant correlation between the number of sections showing infarction of the DVN and presence of QTc-prolongation (r=.582, p=.047). Among patients without QTc-prolongation, the maximum lesion overlap included the medial aspect of the gigantocelluar reticular nucleus of the reticular formation. We found that the DVN is a key anatomical substrate related to QTc-prolongation. Further studies with more patients and high-resolution, volumetric MRI are needed to confirm our findings.

Prevalence of QTc Prolongation in Patients with Parkinson's Disease. Assessment of the Effects of Drugs, Clinical Risk Factors and Used Correction Formula.

Background: Parkinson’s disease (PD) is a possible risk factor for corrected QT interval (QTc) prolongation. PD patients frequently take QTc-prolonging drugs. The aim of the study was to assess the prevalence of QTc prolongation in PD and the influence of drugs and other potential risk factors on the QTc length in PD. Methods: 101 patients with PD and a good quality ECG were included in the study. The prolonged QTc was defined as ≥450 ms for men and ≥460 ms for women. Bazett’s (QTcB) and Framingham (QTcF) formulas were utilized to calculate QTc. Data about sex, age, PD duration, disease’s severity, comorbidities and QTc-prolonging drugs were collected. Multiple linear regressions with backward elimination were used to assess factors influencing the QTc. Results: A long QTc was presented in 13 patients (12.9%) for QTcB and 4 patients (4%) for QTcF. Longer QTc in PD patients was associated with older age, male sex and QTc-prolonging drugs regardless of the used formula. The QTcB was also significantly affected by the heart rate (HR). Conclusion: QTc prolongation is common in PD. Age, drugs and male gender are potential risk factors for QTc prolongation in PD.

Abstract P130: QTc Prolongation in Acute Medullary Infarction Maps to the Dorsal Vagal Nucleus

Objective: To determine the spatial relationship between acute medullary infarction and QTc prolongation. Background: Ischemic stroke has been associated with QTc-prolongation which increases the risk of cardiac arrhythmia and sudden cardiac death. In particular, pathological arrhythmia and unexpected sudden cardiac death has been described after acute medullary infarction (AMI). Nevertheless, it is not well understood why only as subset of patients with AMI develop significant cardiac arrhythmia. To gain insight into this issue, we sought to determine the possible anatomical structures relating to QTc-prolongation in patients. Methods: We retrospectively reviewed 1072 consecutive adult patients admitted for an acute ischemic stroke or a transient ischemic attack, who presented within 4.5 hours from the last known well time and had an admission ECG available. 724 patients had brain MRIs and among these, 13 (1.8 %) patients had an AMI and were included. For an unbiased lesion analyses, medullary infarcts were manually outlined on diffusion weighted MRI and manually co-registered with an anatomical atlas. Infarct lesions were then superimposed on each other as stratified by normal versus prolonged (men > 430 ms, women > 450 ms) QTc to determine the area of greatest degree of congruence. Results: 76.9 % of patients (10 out of 13, 9 men and 1 woman) had a prolonged QTc (476.9 ± 43.3 ms for men, 515 ms for women). There was no significant difference in electrolyte levels and preexisting comorbidities between subjects with normal and prolonged QTc. Among patients with QTc prolongation, the greatest degree of congruence of the infarct location was the dorsal vagal nucleus (DVN, 7 out of 10 patients). Conclusions: Our unbiased lesion segmentation approach identified the DVN a key anatomical substrate related to QTc-prolongation. Biological plausibility of our data and the presence of a causal link between the DVN and cardiac arrhythmia stems from the prior animal experimental data showing that selectively silencing the DVN via a pharmacogenetic approach caused QTc-prolongation in the rat. Further studies with more patients and high-resolution, volumetric MRI are needed to confirm our findings.

Bedaquiline for multidrug-resistant tuberculosis and QTc prolongation in California

BackgroundBedaquiline (BDQ) is recommended for the treatment of multidrug-resistant tuberculosis (MDR TB), however, it has the potential to prolong QTc interval. We assessed the frequency and severity of QTc prolongation in patients receiving BDQ in California. MethodsBased on chart review for patients receiving BDQ as part of MDR TB therapy from January 2013–May 2019, we analyzed QTc values at six pre-specified time points during BDQ therapy (baseline, 2, 4, 8, 12, and 24 weeks), as well as peak QTc, time to peak QTc, and the clinical characteristics of patients who had QTc elevation >500 milliseconds (ms) during therapy. ResultsA total of 37 patients were treated with BDQ during the analysis period, with a total of 449 QTc measurements available for analysis. Most patients (89%) received at least one QTc-prolonging drug in addition to BDQ. Median QTc values at all pre-specified time points were <450 ms. Median peak QTc was 455 ms (interquartile range [IQR]: 437–486) and median time to peak was 57 days (IQR: 19–156). Four patients (11%) had a non-transient elevation in QTc to >500 ms, including one patient with profound hypokalemia and one receiving concurrent chemotherapy, but none had cardiac arrhythmia. Less than 10% of patient in our cohort had ECGs performed at all six pre-specified time points. DiscussionBDQ was generally well-tolerated in a cohort of patients treated for MDR TB in California, with 11% of patients experiencing a non-transient QTc elevation >500 ms, and no episodes of arrhythmia. Frequent ECG monitoring during BDQ therapy presents a challenge for TB clinicians, even in well-resourced countries.

A Systematic Approach to Evaluating and Managing QTc Prolongation in Patients Undergoing Methadone Agonist Treatment for Opioid Use Disorder

A Systematic Approach to Evaluating and Managing QTc Prolongation in Patients Undergoing Methadone Agonist Treatment for Opioid Use Disorder

QTc prolongation in patients with COVID-19: a retrospective chart review.

Drug-induced corrected QT (QTc) prolongation can cause Torsade de Pointes (TdP) which leads to severe arrhythmia or sudden cardiac death. However, information on the prevalence of QTc prolongation in coronavirus disease 2019 (COVID-19) patients and risk factors is limited. A retrospective chart review was conducted in COVID-19 patients admitted to Chonburi Hospital from April to October 2020. The outcomes were the incidence of QTc prolongation and prevalence of risk factor QTc prolongation. We included 29 COVID-19 patients. After treatments were initiated, QTc prolongation occurred in 17 patients (58.62%). QT prolongation could be found as early as two days after the treatment initiation (median = 6 days interquartile range [IQR], 4–7). The median QTc interval in those 17 patients increased from 410 (IQR, 399.5–425.0) ms to 460 (453.50–466.50) ms, with the maximum QTc interval of 488 ms. They were treated with multiple drugs that were reported as a cause of QTc prolongation. 64.71% (n = 11) of them were treated with chloroquine. The median TdP risk score in patients with and without QTc prolongation was 3 (IQR, 2–3) and 2 (IQR, 1–2), respectively. The percentage of patients with comorbidities including atrial fibrillation, bradycardia, concomitant use of diuretics, diabetes, electrolyte imbalance was higher in patients with QTc prolongation. COVID-19 patients were treated with multiple drugs that were reported as a cause of QTc prolongation. COVID-19 patients with QTc prolongation had more comorbidities that are risk factors for QTc prolongation.

The QT Interval in Patients With the Turner Syndrome

Patients with the Turner syndrome (TS) often have longer QT intervals compared with age-matched peers although the significance of this remains unknown. We sought to determine the degree, frequency and impact of QTc prolongation in patients with TS. A chart review of all patients with an electrocardiogram (ECG) and genetically proven TS was performed. Medications at the time of the ECG were reviewed and QTc calculated. Medications were classified according to QTc risk using www.crediblemeds.com. ECG parameters were compared with an age, gender, and cardiac lesion-matched control group. Over the 10-year period of review, 112 TS patients with a mean age of 34 ± 25 years underwent 226 ECGs. At least 1 QTc prolonging medication was prescribed in 81 (74%) patients. Longer QTc interval correlated with absence of y chromosomal material (p = 0.01), older age (p <0.0001), increased number of QTc prolonging and nonprolonging medications (p <0.0001 each). During the 7.0 ± 5.1 years of follow-up, no patient had ventricular arrhythmia or unexplained sudden death. QTc was significantly shorter in matched controls using either Bazett or Hodges formula (424 ± 16 ms vs 448 ± 28 ms, p <0.0001; and 414.8 ± 16 ms vs 424.2 ± 20 ms; p = 0.0002, respectively). However, there was no difference in the frequency of QTc prolongation >460 msec (2.8% vs 2.6%, p = 0.9). In conclusion, despite frequent use of QT-prolonging medications, ventricular arrhythmias are rare in TS.

Clinical characterization and outcome of prolonged heart rate-corrected QT interval among children with syndactyly.

Prolonged heart rate-corrected QT (QTc) interval is an independent risk factor for sudden cardiac death, which is the hallmark of Timothy syndrome (TS). There are little data on children with syndactyly and QTc prolongation.To evaluate the characteristics and long-term outcomes in children with syndactyly, and to attempt to identify TS in patients with syndactyly and QTc prolongation.This is a retrospective case-control study of children with syndactyly who visited Beijing Jishuitan Hospital between July 2003 and February 2013. The patients with prolonged QTc intervals are matched 1:4 with patients without prolongation. Genetic testing of the CACNA1C gene is routinely performed in patients with QTc prolongation.The mean age at admission is 3.4 ± 2.3 years. Compared with the normal QTc group, those with QTc prolongation showed higher frequencies of congenital heart disease (11.8% vs 1.5%, P = .042), mental retardation and facial dysmorphia (11.8% vs 0, P = .004), and T wave alternans (23.5% vs 4.4%, P = .01). In the multivariable analysis, only T wave alternans (OR = 10.61, 95%CI: 1.39–81.16, P = .023) is independently associated with QTc prolongation in patients with syndactyly. One child with QTc prolongation had a mutation in the CACNA1C gene. No patients with prolonged QTs interval met the threshold for TS.Children with syndactyly and prolonged QTc interval had more multisystem diseases and electrocardiography abnormalities. T wave alternans is independently associated with QTc prolongation in patients with syndactyly.

No QTc Prolongation in Girls and Women with Turner Syndrome.

ContextTurner syndrome (TS) is a genetic condition that is reported to be associated with a prolonged rate-corrected QT (QTc) interval.ObjectivesTo evaluate the prevalence of QTc prolongation in patients with TS, to compare their QTc intervals with healthy controls, and to investigate whether QTc prolongation is associated with a monosomy 45,X karyotype.MethodGirls (n = 101) and women (n = 251) with TS visiting our center from 2004–2018 were included in this cross-sectional study. QT intervals of 12-leaded electrocardiograms were measured manually, using Bazett’s and Hodges formulas to correct for heart rate. A QTc interval of >450 ms for girls and >460 ms for women was considered prolonged. Corrected QT (QTc) intervals of patients with TS were compared to the QTc intervals of healthy girls and women from the same age groups derived from the literature.ResultsIn total, 5% of the population with TS had a prolonged QTc interval using Bazett’s formula and 0% using Hodges formula. Mean QTc intervals of these patients were not prolonged compared with the QTc interval of healthy individuals from the literature. Girls showed shorter mean QTc intervals compared with women. We found no association between monosomy 45,X and prolongation of the QTc interval.ConclusionsThis study shows that the QTc interval in girls and women with TS is not prolonged compared with the general population derived from the literature, using both Bazett’s and Hodges formulas. Furthermore, girls show shorter QTc intervals compared with women, and a monosomy 45,X karyotype is not associated with QTc prolongation.

Abstract 338: Qtc Prolongation in Patients With Left Ventricular Heart Failure and Its Relation to Increased Mortality and Hospitalizations

Background: Cardiovascular disease (CVD) is the second leading cause of death among Canadians for decades. It is also no surprise that heart failure rates are on the rise. 600,000 cases of heart failure are diagnosed yearly in Canada. The aim of our investigation was to conduct a retrospective observational study to investigate if prolonged QTc intervals lead to increased re-hospitalization and mortality in patients suffering from Left Ventricular Failure. Methods: We performed an observational case series with a retrospective chart review of 356 CHARM clinic patients who have been diagnosed with Left Ventricular Heart Failure from August 2017 till June 2019. The primary endpoint was to look at patients with left ventricular Heart failure, QTc interval recorded and their files where verified from Alberta’s health care portal to see if re-hospitalizations increased and/or mortality happened. Pre-cautions taken not to include patients with Cardiac re-synchronization therapy and congenital prolonged QTc interval in the study. Patients in Group A were HF patients who had prolonged QTc interval and Group B HF patients with Normal QTc interval. Bazett formula was applied to the QT and correct to Heart rate accordingly. Results: The data from 356 patients with heart failure revealed the following Patients with Heart failure and prolonged QTc interval- 35% had re-hospitalizations while heart failure patients with normal QTc interval had a re-hospitalization rate of 13%. Mortality was also seen higher in Group A versus Group B. It must be noted that Medications that prolonged QT interval was also accounted for and notifications were made as to the presence of arrythmia in patients with increased QT intervals. Presence or increased incidence of arrhythmia there by leads to increased chances of mortality and re-admission. Group 1 had the consumption of medications that increased QT interval more prevalent that Group 2. Conclusion: Prolongation of QTc interval should be noted as an important prognostic factor into the re-admission and mortality rate of patients with heart failure as subtracting various flawing factors. Further resources and investigation should be conducted to truly figure out if QTc prolongation leads to mortality.

QTc prolongation in patients of cirrhosis and its relation with disease severity: An observational study from a rural teaching hospital.

Introduction:Cirrhotic cardiomyopathy is characterised by increased baseline cardiac output, systolic and diastolic dysfunction, diminished cardiovascular response to stressful stimuli and electrophysiological abnormalities in patients of cirrhosis in the absence of any underlying cardiac disease. QTc prolongation has been described as a common electrocardiographic abnormality in cirrhosis patients.Aims and Objectives:This study was done to evaluate the prevalence of QTc changes in patients of cirrhosis coming to a rural tertiary care centre and to analyse its correlation with disease severity.Materials and Methods:The present study was conducted on 100 patients suffering from cirrhosis of liver presented to the department of medicine. Around 100 age and sex-matched individuals were recruited as controls. The Child-Pugh score was used to determine the disease severity in cirrhosis patients. Standard 12-lead ECG was recorded in all cases and controls.Results:Prolongation of QTc interval on ECG was observed in the majority (80%) of cirrhosis patients and it was significantly higher as compared to the healthy controls (P <0.01). The prolongation of QTc was significantly associated with the duration of disease (P <0.05) and disease severity as measured by the Child-Pugh score (P <0.01).Conclusion:QTc prolongation on ECG may be an early marker of cardiac involvement in patients of cirrhosis and is significantly associated with disease severity.

Prevalence of QTc Prolongation in Patients With Advanced Cancer Receiving Palliative Care—A Cause for Concern?

ContextMedications commonly used for symptom control along with other known risk factors have the potential to prolong ventricular repolarization as measured by the QT interval (the time from the start of the Q wave to the end of the T wave) on a standard electrocardiogram (ECG). ObjectivesTo document the prevalence of a prolonged QT interval corrected for heart rate (QTc) interval in the palliative/oncology setting, compare automatic ECG QTc measurements with manual readings and identify any correlation between QTc prolongation and the use of drugs or other risk factors. MethodsA convenience sample of consecutive patients with cancer, admitted under or known to the palliative/supportive care teams in two metropolitan hospitals, and willing to provide an ECG recording and basic demographic information including QTc risk factors were included. Both automated and manually calculated QTc intervals were recorded. Multivariable analysis was used to determine risk factors independently associated with prolonged QTc intervals. ResultsOf the 389 participants, there was a significant difference in mean QTc between sites using automated but not manual calculations. Manual readings were therefore used with predetermined cutoffs of 0.44 seconds (males) and 0.46 seconds (females). Seventy-two (18.5%) of the participants had a prolonged QTc with six (1.5%) having a prolongation of >0.50 seconds. At-risk drugs were being taken by 218 participants (56.0% of total cohort). Factors shown to be associated with QTc prolongation included age, gender, performance status, and hypocalcemia. No specific medication was associated with increased risk. ConclusionAlthough almost 20% of patients receiving palliative care had prolongation of QTc, the possibility of serious consequences appeared to be low despite the frequent occurrence of risk factors.

Drug interactions and creatinine levels are associated with QTc prolongation in intensive care units: a prospective, observational study.

Background Prolongation of the QTc interval may lead to life threatening arrhythmias. QTc prolongation is common in intensive care unit (ICU) patients. The objectives of this study were to identify the role of drug-drug interactions (DDIs) and other predictors (age, sex, cardiovascular diseases, and electrolyte abnormalities) in life threatening QTc prolongation in patients admitted to medical (M), surgical (S) and emergency (E) ICUs. Methods This prospective, observational study included patients above the age of 18 years who were admitted to SICU, EICU, and MICU at a tertiary respiratory referral center. Electrocardiogram (ECG) monitoring was performed during the first 5 days of ICU admission. Risk factors and DDIs which were anticipated to be associated with the prolongation of the QTc interval were assessed for all patients. Results Two hundred patients were included in the study. QTc prolongation occurred in 10.7% of patients and the majority of patients presenting with QTc prolongation had creatinine levels above 1.3 mg/dL during their 5 days of ICU admission. Incidence of pharmacodynamic (PD) DDIs was significantly higher in patients with QTc prolongation vs. other patients. Creatinine levels above 1.3 mg/dL and PD DDIs were associated with QTc prolongation during 5 days of ICU admission. Conclusions High serum creatinine and PD DDIs can increase the risk of QTc prolongation in patients admitted to the ICU. QTc interval measurements should be performed prior to initiation or after starting any drug that is associated with QT prolongation, specifically in patients with the known risk factors.

QTc Prolongation in Patients with Dementia and Mild Cognitive Impairment: Neuropsychological and Brain Imaging Correlations.

The QTc interval is the electrocardiographic manifestation of ventricular depolarization and repolarization. This marker is often prolonged in acute and chronic neurological conditions. The cause of the cerebrogenic QT prolongation remains unclear. The aim of the study was to analyze the relation between QTc interval and the degree of cognitive impairment and structural brain imaging changes in patients with dementia and mild cognitive impairment (MCI). To this aim, 269 patients were screened, of whom 61 met one or more exclusion criteria. The remaining 208 patients (56 control subjects, 44 patients with MCI, and 108 with dementia) were recruited. Eighty-five patients using drugs causing prolongation of QT interval were further excluded. The QT interval was measured manually in all 12 leads by a single blinded observer, assuming the longest QT value adjusted for heart rate by using the Bazett's formula. All patients underwent a structural brain imaging and the following measures were obtained: the bicaudate ratio and the periventricular hyperintensity and deep white matter hyperintensity using the modified Fazekas scale. Prolonged QTc interval was prevalent in 1) patients with dementia, especially in those with moderate-severe degree; 2) subjects with impairment of praxis and attention, low functional status, and behavioral symptoms; 3) patients with global and temporal atrophy and with higher scores on the Fazekas or leukoaraiosis scales. Degenerative and vascular processes might play a main role in QTc interval prolongation because of the damage to brain areas involved in the control of the autonomic cardiac nervous system.

Plasma fatty acid-binding protein 4 (FABP4) level is associated with abnormal QTc interval in patients with stable angina and chronic kidney disease

BackgroundFatty acid-binding protein 4 (FABP4) (also known as adipocyte FABP or adipocyte P2) is expressed in adipocytes, macrophages, and capillary endothelial cells. Previous studies have shown associations among plasma FABP4, insulin resistance, metabolic syndrome, diabetes mellitus, greater coronary plaque burden, coronary artery disease, heart failure, and mortality. However, little is known about the relationship between FABP4 level and prolonged QT interval. The aim of this study was to investigate whether plasma FABP4 level is associated with a prolonged QT interval by analyzing 12-lead electrocardiograms (ECGs) in patients with stable angina and chronic kidney disease (CKD).MethodsThis study included 397 consecutive patients with stable angina and CKD who were enrolled in a disease management program. Plasma FABP4 concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient. We assessed the relationships between FABP4 levels (both as a continuous variable and stratified by tertile) at admission and corrected QT (QTc) prolongation.ResultsPatients with an abnormal QTc interval had higher median plasma FABP4 levels than those with borderline and normal QTc intervals (15.9 ng/mL vs. 10.2 ng/mL vs. 8.5 ng/mL, respectively, P < 0.0001). Statistically significant associations were observed between plasma FABP4 levels and QTc interval (β = 0.267, P < 0.0001). Using multivariate and trend analyses, a higher concentration of plasma FABP4 level was independently associated with QTc prolongation in patients with stable angina and CKD.ConclusionIn this study, plasma FABP4 levels were significantly higher in the patients with an abnormal QTc interval and were correlated with QTc prolongation. Further studies are required to elucidate whether plasma FABP4 plays a role in the pathogenesis of QTc prolongation.

Cardiovascular Safety of Gabapentinoids

The objective of this manuscript is to describe the cardiovascular effects of the gabapentinoids gabapentin and pregabalin. The most frequent adverse effects of gabapentin and pregabalin affect the central nervous system, such as somnolence and fatigue. Additionally, pregabalin, and a much lesser extent, gabapentin, may adversely affect the cardiovascular system. Pregabalin induces peripheral edema and may cause or exacerbate heart failure. Pregabalin use has been associated with QTc prolongation in patients taking other QTc–prolonging agents, although the relative contributions of pregabalin to QTc prolongation may be minimal. Pregabalin and gabapentin have been associated with a dose-related increased risk of atrial fibrillation. Most evidence for adverse cardiovascular effects of gabapentinoids derives from case reports and observational studies. Clinicians should be aware of the potential for pregabalin and possibly gabapentin to contribute to cardiovascular dysfunction.

Evaluation of QTc Interval Prolongation Among Patients With Cancer Using Enteral Methadone.

The effect of methadone on corrected QT interval (QTc) in patients with cancer pain is not well-known. To describe and characterize the effect of low-, moderate-, and high-dose enteral methadone on QTc interval in patients with cancer. Retrospective cohort study including patients prescribed enteral methadone during the 27-month study period. Participants were divided into 3 methadone daily dose groups: <30 (low dose), 30 to 59 (moderate dose), ≥60 (high dose) mg. The primary outcome was the incidence of QTc prolongation (>450 ms for females and >430 ms for males). Secondary outcomes included the magnitude of change in QTc after starting methadone, the incidence of clinically significant QTc prolongation (>500 ms) and the prevalence of torsades de pointes and syncope. Two hundred three patients met study inclusion criteria: 91 (45%) low dose, 52 (26%) moderate dose, and 60 (29%) high dose. Incidence of QTc prolongation for low-, moderate-, and high-dose groups was 50 (55%), 37 (71%), and 43 (72%), respectively ( P = .039, low vs high dose). Incidence of clinically significant QTc prolongation was 10 (11%), 4 (8%), and 7 (12%) for low-, moderate-, and high-dose groups. For patients without QTc prolongation prior to initiating methadone, 62% of moderate-dose patients and 67% of high-dose patients had QTc prolongation, while taking methadone. This study found a notably high incidence of QTc prolongation in patients with cancer using enteral methadone. Future studies should aim to determine the risk of adverse cardiac effects in the cancer population and determine appropriate monitoring of methadone for pain management.

QTc prolongation during ciprofloxacin and fluconazole combination therapy: prevalence and associated risk factors.

Ciprofloxacin and fluconazole combination therapy is frequently used as prophylaxis for, and treatment of, infections in patients with haematological malignancies. However, both drugs are known to prolong the heart rate-corrected QT (QTc) interval, which is a serious risk factor for torsade de pointes (TdP). Therefore, the aim of the current study was to assess the prevalence of QTc prolongation during ciprofloxacin and fluconazole use. The secondary objective was to determine associated risk factors of QTc prolongation in these patients. A prospective observational study was performed in patients admitted to the Erasmus University Medical Centre and treated with ciprofloxacin and fluconazole. A 12-lead electrocardiogram (ECG) was recorded at the estimated time to peak concentration (Tmax ) for the last added drug. The main outcome was the proportion of patients with QTc prolongation during treatment. Data on the following potential risk factors were collected: patient characteristics, serum electrolyte levels, dosage of ciprofloxacin and fluconazole, renal and liver function and concomitant use of other QTc-prolonging drugs and cytochrome P450 3A4 inhibitors. A total of 170 patients were included, of whom 149 (87.6%) were treated for haematological malignancies. The prevalence of QTc prolongation was 4.7%. No risk factors were found to be associated with QTc prolongation. The QTc interval increased by 10.7ms [95% confidence interval (CI) 7.2, 14.1ms] during ciprofloxacin and fluconazole combination therapy. The prevalence of QTc prolongation in patients using ciprofloxacin and fluconazole is low compared with the prevalence in the general population, which varies from 5% to 11%. In addition, no risk factors were found. Given the low prevalence, routine ECG monitoring in patients on this therapy should be reconsidered.

QTc Prolongation in Patients Receiving Triazoles and Amiodarone

Background Prolonged QT interval may lead to ventricular arrhythmias, torsade de pointes and sudden death. Triazole antifungals are often administered to inpatients with cardiac disease and with other QT prolonging drugs. Amiodarone is a commonly used antiarrhythmic that can prolong QT and be proarrhythmic but safety of co-administering these agents in the clinical setting is not known.Methods We conducted a retrospective, observational cohort study of adult inpatients at Duke University Medical Center who received concomitant systemic azoles and amiodarone from 2007 to 2013. Included subjects had ≥1 electrocardiogram (EKG) performed while receiving either agent alone within 1 month of starting concomitant therapy (baseline, BL) and ≥1 follow-up (FU) EKG after ≥2 days of concomitant therapy. A paired t-test was used to assess the maximum change in corrected QT interval (QTc, Bazett’s correction) from BL to FU. Logistic regression was used to evaluate predictors of FU QTc ≥500 ms (age, race, gender, and BL QTc ≥500 ms). Patient discharge diagnoses of ventricular arrhythmias or other cardiac events were reviewed to assess clinical outcome.ResultsOf 816 subjects identified, 252 had EKG results eligible for analysis. Azoles received were fluconazole (86.5%), voriconazole (11.5%), posaconazole (1.6%) or itraconazole (0.4%). Subjects were a median of 65 (IQR 25–88) years of age, 64.3% male and 78.6% Caucasian. Median duration of concomitant therapy was 7 days (IQR 4–11 days). Mean maximal change in QTc was +32 ms from BL (95% CI 26.2–38.6, P < 0.0001). 25.4 and 48.8% of subjects had a BL and FU QTc ≥500 ms, respectively. BL QTc ≥500 ms but not age, race, or gender was associated with FU QTc ≥500 ms (OR 6.32 95% CI 3.21–12.43). Thirty-day all-cause mortality was 26.2%. No cardiac events were apparent in relation to concomitant azole-amiodarone therapy.Conclusion Prolongation of the QTc interval was frequently observed in this cohort of patients receiving azoles and amiodarone. Clinical impact is challenging to assess in this critically ill, complex patient population but appears to be limited. Additional analyses are needed to further evaluate safety of azoles in the setting of other QTc prolonging agents.Disclosures All authors: No reported disclosures.