Prolonged QT interval in acute psychotic patients

QT interval prolongation of the electrocardiogram has been associated with the occurrence of life-threatening fatal ventricular arrhythmias. To understand the relationship between preclinical cardiac conduction assessment to clinical outcome, comparisons of free (unbound)-plasma drug concentrations and their associated effects in the conscious mongrel dog were made to the free plasma concentrations in humans reported to produce QT prolongation. E-4031 (an experimental class III antiarrhythmic), cisapride, terfenadine, terodiline, and verapamil all affect cardiac repolarization and can produce QT prolongation in humans. In the conscious dog, the QT interval was assessed on a beat-to-beat basis in relation to each preceding RR interval at concentrations approximating the same unbound human concentrations. E-4031, cisapride and terodiline statistically increased the QT(RR1000) interval [the QT interval at a 60 beats/min (bpm) heart rate] 23, 8, and 9 ms, respectively, at concentrations 0.3 to 15.8 times their relevant clinical level. Increases were not observed for terfenadine or verapamil (p > 0.05 at all doses). Inspection of individual dog QT versus RR interval relationships showed clear QT interval responses specific to each treatment but not readily apparent when data are averaged at a heart rate of 60 bpm. For specific rectifier K(+) current (IKr) blockers, robust effects on mean QT prolongation can be detected. However, for drugs that affect repolarization through multiple channels, the effect on the mean QT interval may be more difficult to detect. Inspection of the beat-to-beat QT-RR interval relationship in an individual animal can increase the sensitivity for more accurate clinical prediction.

Drug-induced QT interval prolongation has been reported to be related to life-threatening polymorphic ventricular tachycardia (torsade de pointes). Proton pump inhibitors (PPIs) are prescribed widely for hospitalized patients; the QT interval prolongation and torsade de pointes caused by PPIs were reported. We conducted a study to determine the association between PPI treatment and QT interval prolongation in critically ill patients. This study included patients with electrocardiography (ECG) reports from the Medical Information Mart for Intensive Care III database (MIMIC-III). Patients younger than 18years, missing baseline laboratories and with QT interval prolongation before intensive care unit (ICU) admission were excluded. The end point was the diagnosis of QT interval prolongation reported by ECG. This study included 24,512 ICU patients. Of them, 11,327 patients were treated with PPIs, 4181 with histamine 2 receptor antagonists (H2RAs) and 6351 without acid suppression therapy (non-AST); the incidence of QT interval prolongation were 8.5%, 3.3% and 3.4% respectively. After adjustment for demographics, electrolytes, comorbidities and medications, PPIs were associated a higher risk of QT interval prolongation compared with H2RAs (OR 1.66, 95% CI 1.36 - 2.03) and non-AST (OR 1.54, 95% CI 1.31 - 1.82), while there was not significant difference between H2RAs and non-AST (OR 0.93, 95% CI 0.73 - 1.17). In the propensity score matching population, the results were consistent. Pantoprazole (OR 2.14, 95% CI 1.52 - 3.03) and lansoprazole (OR 1.80, 95% CI: 1.18 - 2.76) showed a higher QT prolongation risk than omeprazole. Several drugs caused higher QT prolongation risk when used in combination with PPIs. In ICU patients, the association between PPI prescription and increased risk of QT interval prolongation was independent of known QT-prolonging factors; pantoprazole and lansoprazole had a higher risk compared with omeprazole. The combination of PPIs and other QT-prolonging drugs should be avoided.

Purpose: QT prolongation can occur with both first- (FGA) and second-generation antipsychotics (SGA). QT prolongation was identified in an adult patient who presented to the emergency room with schizophrenia, fluid and electrolyte imbalances, and pneumonia. Quetiapine, an SGA, was a component of the pharmacotherapy regimen. Based on the Naranjo adverse drug reaction probability scale rating criteria, a probable causal association was made. Methods: PubMed and Ovid were searched using the terms antipsychotic, psychotropic, QT interval, corrected QT interval (QTc) prolongation, and quetiapine. References were examined for additional articles related to antipsychotic drugs and the QT interval. Discussion: In this patient, the use of quetiapine was identified as a contributing factor in QT prolongation. Prior QT prolongation was experienced with ziprasidone, another SGA. The antidepressant and dose remained consistent throughout the inpatient course of treatment. Other risk factors in this patient included hypokalemia, dehydration, pneumonia, age, gender, and concurrent usage of an antidepressant. Dual psychiatric diagnoses, preexisting cardiovascular disease, and electrolyte disturbances may increase this risk potential. Conclusion: Psychiatric patients may be more at risk of cardiovascular complications, such as QT interval prolongation. The pharmacist can help evaluate risk factors and provide input into the care of all patients, particularly those identified as at risk.

Effects of β-adrenergic blockade on dispersion of ventricular repolarization in newborn infants with prolonged QT interval

To evaluate the literature on protease inhibitor (PI)-associated QT interval prolongation and risk for torsade de pointes in patients infected by HIV. Primary literature was identified through MEDLINE (1950-August 2011) and EMBASE (1980-August 2011), using the following search terms: antiretroviral agents, HIV, protease inhibitors, QTc, QT prolongation, and torsade de pointes. English-language case reports of antiretroviral therapy-associated QT interval prolongation, studies of healthy volunteers, or studies that evaluated the impact of PIs on QT interval in patients infected with HIV were reviewed and selected. Article bibliographies and conference abstracts were also reviewed. Several case reports, as well as in vitro data, have implicated PIs as a potential cause of QT interval prolongation and/or torsade de pointes. Saquinavir, therapeutically boosted with the potent CYP3A4 inhibitor ritonavir, was the only PI shown to be associated with significant QT interval prolongation in studies with healthy volunteers. While 1 case control study in HIV-infected patients found that nelfinavir or efavirenz, a nonnucleoside reverse transcriptase inhibitor, increased the risk of QT interval prolongation, larger prospective studies have not demonstrated any significant increase in QT interval following exposure to PIs. Similar risk factors for QT interval prolongation seen in non-HIV-infected patients, such as older age, female sex, ethnicity, cardiac conditions, diabetes mellitus, and concomitant use of other QT interval-prolonging medications, especially methadone, were risk factors identified in studies of HIV-infected patients. PIs do not appear to independently predispose patients to QT interval prolongation. However, other risk factors (both HIV-related and non-HIV-related) may increase the risk of QT interval prolongation. Available data suggest that baseline and follow-up electrocardiogram monitoring are unnecessary precautions, but may be considered in patients who are initiating PI therapy and are on multiple medications with proarrhythmic potential and/or have multiple comorbidities, increasing the risk.

Plasma leptin in treated patients with schizophrenia

BackgroundChronic arsenic exposure is associated with cardiovascular abnormalities. Prolongation of the QT (time between initial deflection of QRS complex to the end of T wave) interval and profound repolarization changes on electrocardiogram (ECG) have been reported in patients with acute promyelocytic leukemia treated with arsenic trioxide. This acquired form of long QT syndrome can result in life-threatening arrhythmias.ObjectiveThe objective of this study was to assess the cardiac effects of arsenic by investigating QT interval alterations in a human population chronically exposed to arsenic.MethodsResidents in Ba Men, Inner Mongolia, have been chronically exposed to arsenic via consumption of water from artesian wells. A total of 313 Ba Men residents with the mean arsenic exposure of 15 years were divided into three arsenic exposure groups: low (≤ 21 μg/L), medium (100–300 μg/L), and high (430–690 μg/L). ECGs were obtained on all study subjects. The normal range for QTc (corrected QT) interval is 0.33–0.44 sec, and QTc ≥ 0.45 sec was considered to be prolonged.ResultsThe prevalence rates of QT prolongation and water arsenic concentrations showed a dose-dependent relationship (p = 0.001). The prevalence rates of QTc prolongation were 3.9, 11.1, 20.6% for low, medium, and high arsenic exposure, respectively. QTc prolongation was also associated with sex (p < 0.0001) but not age (p = 0.486) or smoking (p = 0.1018). Females were more susceptible to QT prolongation than males.ConclusionsWe found significant association between chronic arsenic exposure and QT interval prolongation in a human population. QT interval may potentially be useful in the detection of early cardiac arsenic toxicity.

THU0307 Qt interval and its correlations with traditional risk factors of development of cardiovascular diseases in patients with active early psoriatic arthritis

To investigate the relation between QT and RR intervals in the sick sinus syndrome or high degree atrioventricular block. 32 patients with episodes of prolonged RR intervals (> or = 2.6 s) on Holter electrocardiographic recordings. QT and RR intervals were measured manually every 100 to 150 beats on electrocardiographic strips reprinted from the Holter tape over 24 hours. The slope of the QT/RR relation was determined by the linear regression equation for RR intervals < or = 1.4 s (slope 1) and > 1.4 s (slope 2). Slope 2 (0.0068 (0.0030)) was significantly lower than slope 1 (0.0824 (0.0059), P < 0.0001) in the overall patient population. Slopes 1 and 2 were significantly lower (P < 0.001) in the 23 patients with QT intervals at the preceding RR interval of 1 s (QT1s) of < 0.44 s (0.0692 (0.0053) and 0.0019 (0.0030), respectively) than in the nine patients with QT1s intervals > or = 0.44 s (0.1159 (0.0091) and 0.0194 (0.0055), respectively). Slopes 1 and 2 correlated positively with QT1s interval in all patients. The QT/RR relation was comparatively flat when the RR interval was prolonged. Patients with prolonged QT intervals showed exaggerated prolongation of the QT interval with prolonged cycle lengths when compared with patients with normal QT intervals.

Low-circulating levels of adiponectin (ADPN) are associated with obesity, diabetes mellitus, and coronary artery disease. On the contrary, some studies have demonstrated a link between relatively high levels of plasma ADPN and heart failure, atrial fibrillation, and adverse outcome. However, little is known about the relationship between ADPN level and prolonged QT interval. The aim of this study was to investigate the association between plasma ADPN levels and prolonged QT interval in patients with stable angina.In this retrospective study, because the diverse disease severity and condition of the study population may have affected the results, we chose individuals with stable angina. Plasma ADPN concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient.We enrolled 479 stable-angina patients. Patients with an abnormal corrected QT (QTc) interval had higher median plasma ADPN levels than those with normal QTc intervals. Age- and sex-adjusted ADPN levels were positively associated with heart rate, QTc interval, left ventricular mass index, and creatinine but negatively associated with left ventricular ejection fraction, waist circumference, current smoking, total cholesterol, triglycerides, low-density lipoprotein cholesterol, albumin, and estimated glomerular filtration rate. A multiple logistic regression analysis revealed ADPN as an independent association factor for abnormal QTc interval. Increasing concentrations of sex-specific ADPN were independently and significantly associated with abnormal QTc interval, even after full adjustment of known biomarkers.Our results indicate that ADPN may play a role in the pathogenesis of abnormal QTc interval in patients with stable angina.

Severe chronotropic insufficiency, while uncommon in psychiatric populations, presents unique challenges in patients with psychotic disorders because many antipsychotics can adversely affect cardiac rhythm by exacerbating bradycardia or prolonging the QT interval. This case report describes a young male with a complex psychiatric history, severe substance use disorder, and coexisting cardiac abnormalities, who presented with profound sinus bradycardia and a prolonged QT interval. The patient's psychiatric symptoms were compounded by medication nonadherence and illicit drug use. The patient had a history of profound sinus bradycardia (heart rates in the 20s to 30s) with a mean heart rate of 41 beats/min (SD = 4), yet remained asymptomatic from a cardiovascular perspective. Despite the presence of bradycardia and a prolonged QT interval (mean QT = 495 ms (66), QTcB = 427 (30) (Bazett), and QTcF = 448 (32) (Fridericia)), he was treated with oral olanzapine and valproate. His psychiatric symptoms improved significantly, with no exacerbation of bradycardia or QTc prolongation noted during treatment.This is a rare case of a hemodynamically stable young man treated with second-generation antipsychotics, without any notable effect on the length of the QT interval. QT prolongation is a side effect of many antipsychotics, and bradycardia tends to further prolong the QT interval, increasing the risk of adverse cardiac outcomes, such as torsades de pointes or sudden cardiac death, for patients taking antipsychotics. An interprofessional, interdisciplinary, and cohesive team can reduce the cardiac risk to the patient while effectively treating the underlying psychiatric disorders. Nonetheless, it is essential for psychiatrists to have a solid understanding of psychotropic medications and cardiac rhythms, particularly because many free-standing psychiatric facilities do not have direct access to a cardiology consult team. In this report, the authors will attempt to provide a structured framework for psychiatrists managing patients with bradycardia who require antipsychotic therapy.

Dear Editor, Macrolides, a class of antibiotics produced by strains of streptomyces have a complex chemical structure being linked to one or more sugars (cladinasone and desosamine) and act by inhibiting protein synthesis [1]. Most commonly used macrolides are azithromycin, erythromycin, clarithromycin, and roxithromycin. The most common adverse effects of macrolides are diarrhea, abdominal pain, vomiting, severe skin reactions and other gastrointestinal problems [2]. Previously, azithromycin has been reported to be a broad spectrum macrolide antibiotic free from cardiac toxicity [3]. It is the first macrolide antibiotic belonging to the azalide group derived from erythromycin by adding a nitrogen atom to the lactone ring [4]. Azithromycin differs from other antibiotics in its unusual pharmacokinetic properties. It is rapidly accumulated in cells and tissues, particularly in blood leucocytes and is slowly released from the sites with a half life of 40h [5]. In the recent past azithromycin has been shown to possess proarrhythmic effects [6]. There are seven reports of QT interval prolongation in patients with normal QT intervals prescribed a five day course of azithromycin [5]. A recent article mentions that compared to other antibiotics like amoxicillin, ciprofloxacin and levofloxacin, the risk of cardiovascular death is more with azithromycin [7]. The United States Food and Drug Administration (US FDA) warns that azithromycin may cause abnormal changes in the heart’s electrical activity leading to fatal arrhythmias [8]. This communication is based on the findings of a study [7] by medical researchers as well as another study reported by one of the manufacturers of azithromycin that assessed the arrhythmogenic potential for the drug [8]. This applies only to patients with prolonged QT intervals, low levels of blood potassium or magnesium, and a slower heart rate than normal. The possible mechanism of macrolide induced QT prolongation is inhibition of repolarization of cardiac cells through potassium channels [9,10]. The macrolide antibiotics erythromycin, clarithromycin and azithromycin show similar QT prolongation but have divergent proarrhythmic potential [11]. Administration of azithromycin to healthy human subjects resulted in acute stimulation of neutrophil degranulation and phagocytosis associated respiratory burst [12]. Patients with prolonged QT intervals need to obtain advice from their healthcare professional before starting treatment with azithromycin. Health care professionals need to have information about their patient’s family history, QT intervals, abnormal heart beat, and bradyarrhythmias before starting treatment with azithromycin The evidence shows that azithromycin not only produces cardiac arrest in patients with prolonged QT interval, but also affects healthy human subjects when azithromycin is taken for more than 4 days. If treatment is required for a longer duration, it is better to use other antibiotics like amoxicillin or ciprofloxacin. Azithromycin should be a priority candidate for pharmacovigilance and adverse drug reaction monitoring. In addition, large scale studies (if possible multicentric) covering large populations are needed to evaluate the exact clinical impact of these preliminary findings considering the large scale use of azithromycin and other macrolides.

QT interval prolongation is one of the most important causes of withdrawal of drugs from the market, due to its association with Torsades de Pointes (TdP), a potentially fatal arrhythmia. Although many antimicrobial drugs are capable of inducing this type of arrhythmia, the importance of this effect is usually underestimated. Macrolides, quinolones, azoles, pentamidine, protease inhibitors, antimalarial drugs and cotrimoxazole are the anti-infective agents more frequently associated with this adverse effect. Despite the fact that the risk of QT prolongation and TdP under single antimicrobial therapy is low, these drugs are so extensively used that sporadic cases of this arrhythmia are reported. Moreover, antimicrobial drugs are susceptible to pharmacokinetic and pharmacodynamic interactions with other drugs, which may increase the risk of this arrhythmia. Therefore, physicians must be familiar with not only the antimicrobial drugs capable of producing QT interval prolongation, but also their potential interactions. In addition, patient's specific risk factors of prolonging QT interval or producing TdP must be taken into account. This article reviews the role of anti-infective drugs in QT prolongation, focusing on QT prolongation mechanisms, potential drug interactions, and patients' predisposing factors to this arrhythmia.

Jervell and Lange-Nielsen syndrome: neurologic and cardiologic evaluation

This editorial refers to ‘The genetics underlying acquired long QT syndrome: impact for genetic screening’[†][1], by H. Itoh et al ., on page 1456. The QT interval on the electrocardiogram reflects the duration of ventricular repolarization which results from the concerted opening and closing of ion channels in the cell membrane of ventricular myocytes. The long QT syndrome (LQTS) is a potential lethal entity because a prolonged QT interval is associated with the development of a polymorphic ventricular tachycardia, termed Torsades de Pointes (TdP), which can degenerate to ventricular fibrillation and sudden death.1 Several clinically easily identifiable factors are recognized to prolong the QT interval, including bradycardia, hypokalaemia, hypomagnesaemia, and particularly a large variety of drugs such as antiarrhythmics, antibiotics, antihistamines, and antidepressants. A prolonged QT interval in the presence of such risk factors is called acquired LQTS (aLQTS), and the principal underlying mechanism is believed to be mediated by a reduction of IKr, one the most essential potassium currents in the heart.2 Unfortunately, the response of the QT interval to acquired risk factors is often unpredictable, even in individuals with similar clinical characteristics, ranging from no or minimal change in QT interval to severe QT prolongation and TdP.3 In clinical practice, this has led to the unforeseen death of subjects using therapeutic dosages of a certain drug, and, as a result, withdrawal of some promising drugs from the market. Therefore, although difficult, it is of utmost clinical importance to identify those subjects at risk of developing aLQTS. In the mid-1990s, the discovery that mutations in genes coding for cardiac ion channels and their regulatory proteins can cause … [1]: #fn-2