QT prolongation is associated with increased mortality in end stage liver disease

AIM To determine the prevalence of QT prolongation in a large series of end stage liver disease(ESLD) patients and its association to clinical variables and mortality.METHODS The QT interval was measured and corrected for heart rate for each patient,with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females.Multiple clinical variables were evaluated including sex,age,serum sodium,international normalized ratio,creatinine,total bilirubin,beta-blocker use,Model for EndStage Liver Disease(MELD),MELD-Na,and etiology of liver disease. RESULTS Among 406 ESLD patients analyzed,207(51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender(OR = 3.04,95%CI:2.01-4.60,P < 0.001). During the study period,187patients(46.1%) died. QT prolongation was a significant independent predictor of mortality(OR = 1.69,95%CI:1.03-2.77,P = 0.039). In addition,mortality was also associated with viral etiology of ESLD,elevated MELD score and its components(P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation. CONCLUSION QT prolongation was commonly encountered in an ESLD population,especially in males,and served as a strong independent marker for increased mortality in ESLD patients.

Comparison of QT Correction Methods in the Pediatric Population of a Community Hospital: A Retrospective Study

Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formula has yet to be determined in the pediatric population,although it has intrinsically greater extremes in heart rate(HR)and is more susceptible to errors in measurement.The authors of this study compare six dif-ferent QTc methods(Bazett,Fridericia,Framingham,Hodges,Rautaharju,and a computer algorithm utilizing the Bazett formula)for consistency against variations in HR and RR interval.Methods:Descriptive Retrospective Study.We included participants from a pediatric cardiology practice of a community hospital who had an ECG performed in 2017.All participants were healthy patients with no past medical history and no regular med-ications.Results:ECGs from 95 participants from one month to 21 years of age(mean 9.7 years)were included with a mean HR of 91 beats per minute(bpm).The two-sample paired t-test or Wilcoxon signed-rank test assessed for any difference between QTc methods.A statistically significant difference was observed between every combination of two QTc formulae.The Spearman’s rank correlation analysis explored the QTc/HR and QTc/RR relationships for each formula.Fridericia method was most independent of HR and RR with the lowest absolute value of correlation coefficients.Bazett and Computer had moderate correlations,while Framingham and Rautaharju exhibited strong correlations.Correlations were positive for Bazett and Computer,reflecting results from prior studies demonstrating an over-correction of Bazett at higher HRs.In the linear QTc/HR regression analysis,Bazett had the slope closest to zero,although Computer,Hodges,and Fridericia had comparable values.Alternatively,Fridericia had the linear QTc/RR regression coefficient closest to zero.The Bland-Altman method assessed for bias and the limits of agreement between correction formulae.Bazett and Computer exhibited good agreement with minimal bias along with Framingham and Rautaharju.To account for a possible skewed distri-bution of QT,all the above analyses were also performed excluding the top and bottom 2%of data as sorted by heart rate ranges(N=90).Results from this data set were consistent with those derived from all participants(N=95).Conclusions:Overall,the Fridericia correction method provided the best rate correction in our pedia-tric study cohort.

The ionic mechanisms of long QT interval in diabetic rabbits

Objective Abnormal QT prolongation associated with arrhythmias is considered the major cardiac electrical disorder and a significant predictor of mortality in diabetic patients. The precise ionic mechanisms for diabetic QT prolongation remained unclear. The present study was designed to analyze the changes of ventricular repolarization and the underlying ionic mechanisms in diabetic rabbit hearts. Methods Diabetes was induced by a single injection ofalloxan （145mg/kg, Lv. ）. After the development of diabetes （10 weeks）, ECG was measured. Whole-cell patch-clamp technique was applied to record the action potential duration （APD50, APD90）, slowly activating outward rectifying potassium current （IKs）, L-type calcium current （ICa-L） and inward rectifying potassium current （IK1）. Results The action potential duration （APD50 and APD90） of ventricular myocytes was obviously prolonged from 271.5＋32.3 ms and 347.8＋36.3 ms to 556.6~72.5 ms and 647.9~72.2 ms respectively （P〈 0.05）. Meanwhile the normalized peak current densities of IKs in ventricular myocytes investigated by whole-cell patch clamp was smaller in diabetic rabbits than that in control group at test potential of＋50mV （1.27~0.20 pA/pF vs 3.08~0.67 pA/pF, P〈0.05）. And the density of the ICa-L was increased apparently at the test potential of 10 mV （-2.67~0.41 pA/pF vs -5.404-1.08 pA/pF, P〈0.05）. Conclusion Ventricular repolarization was prolonged in diabetic rabbits, it may be partly due to the increased L-type calcium current and reduced slow delayed rectifier K＋ current （IKs） （J Geriatr Cardio12010; 7：25-29）.

Ondansetron and Hypothermia Induced Cardiac Arrest in a 97-Year-Old Woman: A Case Report

Background:Ondansetron and hypothermia are both known to induce bradycardia or QT interval prolongation,thus placing affected patients at risk of cardiac arrest.Case Report:Herein,we report the case of a 97-year-old woman who initially presented with confusion and hypothermia,and experienced severe bradycardia and asystolic cardiac arrest after a 4 mg intravenous ondansetron bolus injection.Conclusion:Ondansetron is associated with bradycardia and QTc prolongation,both of which might be further exacerbated by hypothermia.Clinicians should be aware that administering ondansetron in patients with hypothermia might further increase the risk of adverse cardiac events and eventual cardiac arrest.

Torsades de Pointes Secondary to Excessive Loperamide Use

Abstract： Loperamide is a common, over-the-counter, antidiarrheal medication that has been implicated in cases of ventricular tachycardia. A 32 year-old female patient with a history of opioid abuse and no prior history of cardiovascular disease experienced Torsades de pointes. An electrocardiogram at the time of hospital presentation revealed a prolonged QT interval at 636 msec. Diagnostic evaluation was unremarkable for any underlying cardiovascular pathology. Further investigation revealed the patient had been taking 30-40 loperamide 2 mg tablets oral daily for 2 weeks prior to the onset of Torsades de pointes. At high doses, loperamide may prolong the QT interval through antagonism of the human ether-a-go-go potassium current, thus increasing the risk of ventricular arrhythmias. Clinicians should be cautious with administration of high doses of loperamide to all patients, especially patients at high risk for QT interval prolongation.

Cirrhotic cardiomyopathy:Isn't stress evaluation alwaysrequired for the diagnosis?

AIM:To describe the proportion of patients with cirrhotic cardiomyopathy(CCM) evaluated by stress echocardiography and investigating its association with the severity of liver disease.METHODS:A cross-sectional study was conducted.Cirrhotic patients without risk factors for cardiovascular disease were included.Data regarding etiology and severity of liver disease(Child-Pugh score and model for end-stage liver disease),presence of ascites and gastroesophageal varices,pro-brain natriuretic peptide(proBNP) and corrected QT(QTc) interval were collected.Dobutamine stress echocardiography(conventional and tissue Doppler imaging) was performed.CCM was considered present when diastolic and/or systolic dysfunction was diagnosed at rest or after pharmacological stress.Therapy interfering with cardiovascular system was suspended 24 h before the examination.RESULTS:Twenty-six patients were analyzed,17(65.4%) Child-Pugh A,mean model for end-stage liver disease(MELD) score of 8.7.The global proportion of patients with CCM was 61.5%.At rest,only 2(7.7%)patients had diastolic dysfunction and none of the patients had systolic dysfunction.Dobutamine stress echocardiography revealed the presence of diastolic dysfunction in more 6(23.1%) patients and of systolic dysfunction in 10(38.5%) patients.QTc interval prolongation was observed in 68.8%of the patients and increased pro-BNP levels in 31.2%of them.There was no association between the presence of CCM and liver impairment assessed by Child-Pugh score or MELD(P= 0.775,P= 0.532,respectively).Patients with QTc interval prolongation had a significant higher rate of gastroesophageal varices comparing with those without QTc interval prolongation(95.0%vs 50.0%,P= 0.028).CONCLUSION:CCM is a frequent complication of cirrhosis that is independent of liver impairment.Stress evaluation should always be performed,otherwise it will remain an underdiagnosed condition.

Possible convulsion and electroencephalographic abnormality in a patient taking long-term oral clarithromycin:A case report

BACKGROUND Clarithromycin is a macrolide antibiotic commonly prescribed to patients with upper respiratory and otolaryngological infections.Neuropsychiatric adverse effects of clarithromycin include agitation,insomnia,delirium,psychosis,and seizure.CASE SUMMARY A 52-year-old man was admitted to our hospital with a convulsion.He had>10-year history of clarithromycin intake for chronic sinusitis.One week before admission,he started to take diltiazem for angina pectoris.On admission,his convulsion subsided.His electroencephalography showed frontal intermittent rhythmic delta activity.One week after he ceased clarithromycin,his electroencephalographic abnormalities disappeared.We suggested that the patient developed convulsions due to increased blood levels of clarithromycin caused by oral administration of diltiazem,which is involved in CYP3A metabolism.CONCLUSION Clarithromycin has a relatively high safety profile and is a frequently prescribed drug.However,there are a few previous reports of clarithromycin-related convulsive disorders.Clinicians should be aware of the drug interaction and rare side effects of seizures.

Repolarization reserve, arrhythmia and new drug development

Repolarization-related lethal arrhythmias have led to the concept of“repolarization reserve”,which may help elucidate the relationship between K^(+) currents and other components of repolarization.Pharmacological manipulation as well as congenital and cardiac disease may affect repolarization and alter the repolarization reserve,leading to the development of arrhythmias.Pharmacological enhancement of outward currents or suppression of inward currents has been shown to be of therapeutic value.A number of newly found selective ion channel inhibitors or agonists have been investigated for their ability to enhance repolarization reserve and decrease the incidence of arrhythmia.In this paper we review the development,potential mechanisms,clinical application,and pharmacological significance of repolarization reserve in order to better understand,predict and prevent unexplained adverse cardiac events.