Corrected QT interval in cirrhosis:A systematic review and metaanalysis

BACKGROUND Corrected QT(QTc)interval is prolonged in patients with liver cirrhosis and has been proposed to correlate with the severity of the disease.However,the effects of sex,age,severity,and etiology of cirrhosis on QTc have not been elucidated.At the same time,the role of treatment,acute illness,and liver transplantation(Tx)remains largely unknown.AIM To determine the mean QTc in patients with cirrhosis,assess whether QTc is prolonged in patients with cirrhosis,and investigate whether QTc is affected by factors such as sex,age,severity,etiology,treatment,acute illness,and liver Tx.METHODS In the present systematic review and meta-analysis,the searching protocol“{[QTc]OR[QT interval]OR[QT-interval]OR[Q-T syndrome]}AND{[cirrhosis]OR[Child-Pugh]OR[MELD]}”was applied in PubMed,EMBASE,and Google Scholar databases to identify studies that reported QTc in patients with cirrhosis and published after 1998.Seventy-three studies were considered eligible.Data concerning first author,year of publication,type of study,method used,sample size,mean age,female ratio,alcoholic etiology of cirrhosis ratio,Child-Pugh A/B/C ratio,mean model for end-stage liver disease(MELD)score,treatment withβ-blockers,episode of acute gastrointestinal bleeding,formula for QT correction,mean pulse rate,QTc in patients with cirrhosis and controls,and QTc according to etiology of cirrhosis,sex,Child-Pugh stage,MELD score,and liver Tx status(pre-Tx/post-Tx)were retrieved.The Newcastle-Ottawa quality assessment scale appraised the quality of the eligible studies.Effect estimates,expressed as proportions or standardized mean differences,were combined using the randomeffects,generic inverse variance method of DerSimonian and Laird.Subgroup,sensitivity analysis,and meta-regressions were applied to assess heterogeneity.RESULTS QTc combined mean in patients with cirrhosis was 444.8 ms[95%confidence interval(CI):440.4-449.2;P<0.001 when compared with the upper normal limit of 440 ms],presenting high heterogeneity(I2=97.5%;95%CI:97.2%-97.8%);both Egger’s and Begg’s tests showed non-significance.QTc was elongated in patients with cirrhosis compared with controls(P<0.001).QTc was longer in patients with Child-Pugh C cirrhosis when compared with Child-Pugh B and A(P<0.001);Child-Pugh B patients presented longer QTc when compared with Child-Pugh A patients(P=0.003).The MELD score was higher in patients with cirrhosis with QTc>440 ms when compared with QTc≤440 ms(P<0.001).No correlation of QTc with age(P=0.693),sex(P=0.753),or etiology(P=0.418)was detected.β-blockers shortened QTc(P<0.001).QTc was prolonged during acute gastrointestinal bleeding(P=0.020).Tx tended to improve QTc(P<0.001).No other sources of QTc heterogeneity were revealed.CONCLUSION QTc is prolonged in cirrhosis independently of sex,age,and etiology but is correlated with severity and affected byβ-blockers and acute gastrointestinal bleeding.QTc is improved after liver Tx.

A Case Study of Severe QT Interval Prolongation Caused by Antidepressants

QT interval prolongation can be categorized into primary and secondary types according to its etiology.In this paper,we report a case of severe asymptomatic QT interval prolongation secondary to antidepressants.Regular follow-up and electrocardiogram monitoring is crucial when applying antidepressants,especially for patients without cardiac symptoms.This article presents case studies and examines existing literature on long QT syndrome to enhance the diagnosis and management of QT interval prolongation.This is especially relevant for non-psychiatric healthcare professionals who need to be attentive to the side effects of antidepressants to prevent potential adverse consequences resulting from oversight.

Detailed analysis of the impact of age on the QT interval

Objective To analyze the effect of age on the ECG QT interval, an important predictor of cardiovascular mortality and drug-induced cardiac arrhythmias, and determine whether QT-heart rate correction formulae （QTc） have differential relationships with age and sex. Methods Data were examined from the US National Health and Nutrition Examination Survey （NHANES） II and III, civilian population aged 25 to 90 years. QT weighted means and standard deviations were calculated for all ages. The QTc were evaluated for six QTc： proposed by Bazett （QTcBZT）, Fridericia （QTcFRD）, Hodges （QTcHDG）, Dmitrienko （QTcDMT）, Rautaharju （QTcRTHa） and Framingham （QTcFRM）. Results QTc was strongly related to age and gender, for all formulae except for QTcBZT for women. The relationship between QTc and age was significant regardless of whether the relationship was approximated by a linear or non-linear （quadratic or cubic spline） model. QTc increased more dramatically with age in men. There was a significant （P 〈 0.001） positive relationship between QTc variance and age for each QTc formula for both men and women. There were a greater proportion of individuals with longer QTc with older ages especially age 80 years and above. Conclusion QTc and its variance increase with age. Prolonged QTc is more prevalent in older individuals, especially men.

Aging effects on QT interval： Implications for cardiac safety of antipsychotic drugs

Objectives To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. Methods The Medline databases were searched using the OvidSP platforms with the search strategy： ＂QT interval＂ or ＂QT＂ and ＂age＂ or ＂aging＂. The entry criteria were： over 10,000 apparently healthy individuals with data on both sexes; QT interval corrected for heart rate （QTc） and an expression of its variance for multiple age decades extending into the older ages. Results QTc increased in duration with increasing age. Considering a modest one SD increment in QTc in the normal population, the addition of Chlorpromazine produced a QTc on average greater than 450 ms for ages 70 years and older. Risperidone, that did not on average alter QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70 years under some circumstances. QTc prolongation 〉 500 ms with antipsychotic drugs is more likely for persons with QTc initially at the 99th percentile. It may occur with Haloperidol which does not on average alter QTc. Conclusions The range of values for the QT interval in apparently normal older men or women, when combined with the range of expected QT interval changes induced by antipsychotic drugs, can readily be associated with prolonged QTc. Individuals with QTc at the 99th percentile may have serious QTc prolongation with antipsychotic drugs even those that are not usually associated with QTc prolongation.

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.

Left ventricular hypertrophy amplifies the QT,and Tp-e intervals and the Tp-e/QT ratio of left chest ECG

Objective： To evaluate the changes in Tp-e interval （an interval from the peak to the end of the T wave）, QT interval and Tp-e/QT ratio of the body surface ECG in patients with left ventricular hypertrophy （LVH）. Methods： The Tp-e interval and QT interval were measured on body surface ECGs in 42 patients without either hypertension or LVH （control group）, 41 patients having hypertension but not LVH （non-LVH group）, and 38 patients with both hypertension and LVH （LVH group）. Results： The mean corrected QT （QTc） interval, and mean corrected Tp-e[T（p-e）c] interval were significantly longer in the LVH group （0.430±0.021s vs. 0.409±0.019s, p 〈 0.01; 0.098±0.013s vs. 0.088±0.011s, respectively） than those in the control group. The Tp-e/QT ratio was also amplified in LVH group （0.232± 0.028 vs.0.218± 0.027） （p 〈 0.05）. Conclusion： LVH increased the QT interval, Tp-e interval and Tp-e/QT ratio of the body surface ECG.

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.

Cardiac Electrophysiological Differences Between Kunming and C57BL6/J Mice

Objective To investigate the alterations of cardiac electrophysiological properties and substantial mechanism and find the stable arrhythmia mouse model in Kunming （KM） and C57BL6/J （C57） mice. Methods Electrocardiogram recordings were used to analyze the QT interval in vivo, and mono- phasic action potential of right and left ventricular epicardium was recorded to elicit changes of action potential duration （APD） in conventional and programmed electrical stimulation （PES）. Transient outward potassium current （Its,） was recorded via whole-cell patch-clamp technique in single right and left epicardial myocytes. Results QT interval was prolonged in KM mice relative to C57 mice （62.51±4.47 ms vs. 52.59±4.85 ms, P〈0.05）. The APD at 50% repolarization of the left ventricular epicardium （18.60±0.91 ms vs. 12.90±0.35 ms）, and APDs at 50% （17.31±6.05 ms vs. 12.00±3.24 ms） and 70% repolarization （36.13±5.32 ms vs. 2 1.95±8.06 ms） of the right ventricular epicardium in KM mice were significantly pro- longed compared with C57 mice, respectively （all P〈0.05）. KM mice were more sensitive to PES-induced ventricular tachycardia （25%, 3 of 12 hearts）, and especially to Burst-induced ventricular tachycardia （50%, 6 of 12 hearts） compared with C57 mice, which were 20% （2 of 10 hearts） and 30% （3 of 10 hearts） respec- tively. It,, densities both in the left and right ventricular epicardial myocytes from KM mice were significantly decreased compared with C57 mice, respectively （all P〈0.01）. Conclusion Our data showed that KM mice with tile prolonged QT interval and APD are ruiner- abilities to ventricular arrhythmia, which are attributed to lower Ito densities in ventricular myocytes ob- tained from KM mice than that from C57 mice.

Use of hydroxychloroquine and azithromycin combination to treat the COVID-19 infection

Coronavirus disease 2019(COVID-19)infection is unequivocally the worst crisis in recent decades,which is caused by a severe acute respiratory virus 2.Currently,there is no effective therapy for the COVID-19 infection.Different countries have different guidelines for treating COVID-19 in the absence of an approved therapy for COVID-19.Therefore,there is an imminent need to identify effective treatments,and several clinical trials have been conducted worldwide.Both hydroxychloroquine[HCQS],chloroquine,and azithromycin(AZ)have been widely used for management based on in vitro studies favoring antiviral effects against the COVID-19 virus.However,there is evidence both in favor and against the use of hydroxychloroquine and azithromycin(HCQS+AZ)combination therapy to manage the COVID-19 infection.The combination of hydroxychloroquine and azithromycin was significantly associated with increased adverse events.However,the inference of these findings was from observational studies.Therefore,large randomized trials are imperative to show the future path for the use of HCQS+AZ combination therapy.However,owing to the ban on HCQS use in COVID-19,this may no longer be essential.This review is on the pharmacology,trials,regimens,and side effects of hydroxychloroquine and azithromycin combination therapy.

Electrocardiographic alterations in patients with chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease(COPD)have an increased risk for cardiovascular events,and electrocardiography has an important role in detecting cardiac side effects of COPD-related hypoxia.

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.

Alpha-lipoic Acid:Effects on the Beat-to-Beat Vectorcardiographic Parameters in Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy

Objective:Relevance of cardiac autonomic neuropathy has not been fully recognized and there is no standardized treatment protocol.Aim:To evaluate the effects of alpha-lipoic acid on the beat-to-beat vectorcardiographic parameters,namely spatial QRS-T angle,QT dispersion(QTd)and corrected QT interval(QTc)in type 2 diabetes mellitus persons with cardiac autonomic neuropathy.Research designs and methods:Our study involved 33 persons with definite stage of cardiac autonomic neuropathy and diabetes mellitus type 2,which were assigned to each of two groups:one took standard antihyperglycaemic treatment(n=15,control group)and the other(n=18)in addition to standard therapy-600 mg of alpha-lipoic acid daily for three months.The analysis of vectorcardiographic parameters was performed.Results:It was found out that alpha-lipoic acid contributed to decrease of the vectorcardiographic parameters,namely QRS-T angle,QTd and QTc.Conclusions:The positive influences of alpha-lipoic acid suggest the usefulness of its prescription to type 2 diabetes mellitus persons with definite stage of cardiac autonomic neuropathy.The efficacy of alpha-lipoic acid is the result of its direct effect on the parameters of vectorcardiography.

Changes in Electrocardiogram Findings during Treatment with Gonadotropin-Releasing Hormone Agonist and Surgical Castration for Prostate Carcinoma

Purpose: To investigate electrocardiogram (ECG) changes after complete androgen blockade (CAB) achieved by either surgical or medical castration and compare the outcomes of the groups. Methods: Sixty-three consecutive men (between 58 - 86 years of age) requiring CAB for prostate cancer were enrolled in the study. Patients with diabetes mellitus, an additional malignancy, coronary heart disease, atrial fibrillation, heart failure or a medical history of cardiac event in the last 12 months were excluded from the study. Additionally, those who were taking medicine affecting heart rate were excluded. The participants were divided into two groups according to their modality of castration. The first group consisted of 35 patients who received bilateral orchiectomy plus anti-androgen medication. The second group contained 28 patients who accepted gonadotropin-releasing hormone (GnRH) plus anti-androgen therapy. After complete examinations and biochemical tests, the ECG leads of the patients were obtained conveniently. This was then repeated at three- and six-month visits. ECG findings (including heart rate, PR, QRS, QT, corrected QT (QTc) intervals and QT dispersion (QTd)) were recorded and analysed statistically. The groups were then compared in terms of pre- and post-treatment ECG outcomes. Results: Both groups revealed similarly lower heart rate and prolonged PR, QRS, QT, corrected QTc and QTd by the end of six months. By the end of three months, all variables had changed significantly in the orchiectomy group, whereas in the GnRH group, they had not. Conclusion: CAB may result in lower heart rate and prolonged QT, a condition associated with fatal cardiac arrhythmia and sudden death. Therefore, patients receiving CAB should be monitored closely for cardiac adverse effects.

Sudden Cardiac Death Due to Long QT Syndrome

Identification of sudden cardiac death(SCD)with a structurally normal heart remains an important challenge in forensic pathology.Long QT syndrome(LQTS)is known as an inherited or acquired channelopathy,which is characterized with prolonged QT interval,and is likely to cause SCD in young adults.In this circumstance,no specific pathological change in the heart can be found anatomically or histologically in the LQTS victims.Thus,postmortem LQTS diagnosis is mainly based on clinical manifestations and genetic testing.Here,we reported a 26‑year‑old woman who was found dead at home with a history of unexplained syncope.Her clinical records and an electrocardiograph(ECG)obtained 3 months before her death showed a QTc interval of 539 ms which implicates the diagnosis of LQTS.Although the autopsy and pathological examination findings lacked specificity,we noticed enhanced lipofuscin accumulation in cardiomyocytes,which might be related to LQTS.After excluding potential diseases and injuries,we made the postmortem diagnosis as LQTS according to ECG,clinical history,and forensic postmortem findings.In conclusion,we provided clinical and pathological features of an SCD case due to LQTS,which might enrich the understanding of forensic postmortem SCD diagnosis with nonstructural cardiac diseases.