Prevalence and risk factors for acquired long QT syndrome in the emergency department:a retrospective observational study

BACKGROUND: Long QT syndrome(LQTS) is a heterogeneous syndrome that may be congenital or, more frequently, acquired. The real-world prevalence of acquired LQTS(aLQTS) in the emergency department(ED) remains to be determined. The aim of this study was to determine prevalence of aLQTS and its impact on symptoms on ED admissions.METHODS: Electrocardiograms(ECG) of 5,056 consecutively patients admitted in the ED of a tertiary hospital between January 28th and March 17th of 2020 were reviewed. All patients with aLQTS were included. Clinical data with a focus on QT prolonging drugs and clinical factors were recorded. Statistical comparison was made between the groups with and without corrected QT(QTc) interval greater than 500 ms(value that is considered severely increased).RESULTS: A total of 383 ECGs with prolonged QTc were recognized, corresponding to a prevalence of aLQTS at admission of 7.82%. Patients with aLQTS were more commonly men(53.3%) with an age of(73.49±14.79) years old and QTc interval of(505.3±32.4) ms. Only 20.4% of these patients with aLQTS were symptomatic. No ventricular arrhythmias were recorded. Patients with QT interval greater than 500 ms were more frequently female(59.5%;P<0.001) and were more frequently on QT prolonging drugs(77.3%;P=0.025). Main contributing factor was intake of antibiotics(odds ratio [OR] 4.680) followed by female gender(OR 2.473) and intake of antipsychotics(OR 1.925).CONCLUSION: aLQTS is particularly prevalent in the ED. Female patients on antibiotics and antipsychotics are at particularly high risk. Efforts must be made to avoid, detect and treat aLQTS as early as possible.

Genotypic diagnosis of long QT syndrome by analysis of candidate genes

Objective To diagnose 6 LQTS families by genetic analysis.Methods A total aof 6 LQTS pedigrees with 43 family members were brought together for genetic diagnosis by using short-sequence tandem-repeat(STR)markers or sequencing.Genomic DNA was extracted from blood samples by standard procedure.STR markers or KCNQ1,KCNH2 and SCN5A were amplified.The haplotype analysis for LQTS was performed.If the family got the negative haplotype analysis,the sequencing was performed.Results LQTS patients were always linkaged with the SCN5A gene in family 1.KCNH2 was linkaged with the disease in family 2 to 5.21 gene carriers were identified from these 5 families.A mutation(A561V-KCNH2)was only found in the proband of family 6 and an SNP(G1691A)was found in all the members of the family.Conclusion Genetic diagnosis can not only improve presymptomatic diagnosis,but also provide the basis for personal therapy and research on disease-causing mutations.

A novel mutation—L539fs/47 of hERG in a Chinese long QT syndrome family

Objective To identify the mutation of human ether-a-go-go-related gene(hERG)and analyze the clinical characteristics of a Chinese family with long ST syndrome(LQTS).Methods The electrocardiogram and DNA samples were obtained from a Chinese LQTS family of 26 members.Genotype was performed with polymorphic short tandem repeat(STR)markers at the known LQT1,LQT2,and LQT3 loci.SSCP analysis was used to find aberrant conformers.hERG mutation was confirmed by cloning and sequencing.Results Three gene carriers were linked to chromosome 7q35-36,where the potassium channel gene hERG was encoded.A 19-base pair deletion was identified.The mutation was located at nucleotide position 1 619-1 637 between transmembrane domains S4 and S5.Furthermore,A1692G polymorphism was found both in the normal control and patients.Conclusion A novel 19 bp deletion mutation of hERG is identified in a Chinese family.All gene carriers are demonstrated to be typical LQT2 ECG phenotype.

The Relationship between T-Wave Alternans and Adverse Cardiac Events in Patients with Congenital Long QT Syndrome:A Systematic Review and Meta-Analysis

Background:T-wave alternans(TWA)is a risk factor of ventricular arrhythmias or sudden cardiac death(SCD)in patients with ischemic cardiomyopathy.Nevertheless,the relationship between TWA and adverse cardiac events(ACE)in patients with congenital long QT syndrome(LQT)remains controversial.Methods:A systematic electronic search of PubMed,Embase and the Cochrane Library was conducted from database inception dates to 28 April 2021 and assessed the relationship between TWA and ACE in patients with LQTS.Sub-group analysis evaluated the association between microvolt TWA(MTWA)and ACE in different monitoring models and ECGlead numbers.Results:A pooled analysis of seven studies of 625 patients with LQTS showed that TWA was significantly associated with ACE(OR 3.16,95%CI 1.86–5.37,P<0.001).Advanced analysis showed that macroscopic TWA was significantly related to ACE(OR 6.01,95%CI 2.96–12.21,P<0.001),while MTWA did not(OR 0.92,95%CI 0.37–2.30,P=0.85).Sub-group analysis showed that MTWA recorded in 24 h continuous ECG(OR 6.79,95%CI 0.80–57.75,P=0.08)might have a stronger association with ACE than recorded in stress ECG(OR 0.28,95%CI 0.07–1.10,P=0.07).No difference was observed between MTWA measured in multi-lead ECG and limited ECG leads(P=0.15).Conclusions:Macroscopic TWA was significantly related to ACE in patients with LQTS.In terms of MTWA,MTWA recorded in 24 h continuous ECG might have a stronger association with ACE than stress ECG,but still deserves further evaluation.

Discovery of Digenic Mutation, KCNH2 c.1898A > C and JUP c.916dupA, in a Chinese Family with Long QT Syndrome via Whole-Exome Sequencing

Long QT syndrome(LQTS),which is caused by an ion channel–related gene mutation,is a malignant heart disease with a clinical course of a high incidence of ventricular fi brillation and sudden cardiac death in the young.Mutations in KCNH2(which encodes potassium voltage-gated channel subfamily H member 2)are responsible for LQTS in many patients.Here we report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing.The c.916dupA mutation in JUP(which encodes junction plakoglobin)is also discovered.Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy.The double mutation in the proband may help explain his severe clinical manifestations,such as sudden cardiac death at an early age.Sequencing for the proband’s family members revealed that the KCNH2 mutation descends from his paternal line,while the mutation in JUP came from his maternal line.The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counseling of families affected by malignant arrhythmias.

Mutation analysis of potassium channel genes KCNQ1 and KCNH2 in patients with long QT syndrome

Objective To determine mutations of two common potassium channel subunit genes KCNQ1, KCNH2 causing long QT syndrome (LQTS) in the Chinese.Methods Thirty-one Chinese LQTS pedigrees were characterized for mutations in the two LQTS genes, KCNQ1 and KCNH2, by sequencing.Results Two novel KCNQ1 mutations, S277L in the S5 domain and G306V in the channel pore, and two novel KCNH2 mutations, L413P in the transmembrane domain S1 and L559H in the transmembrane domain S5 were identified. The triggering factors for cardiac events developed in these mutation carriers included physical exercise and excitation. Mutation L413P in KCNH2 was associated with the notched T wave on ECGs. Mutation L559H in KCNH2 was associated with the typical bifid T wave on ECGs. Mutation S277L in KCNQ1 was associated with a high-amplitude T wave and G306V was associated with a low-amplitude T wave. Two likely polymorphisms, IVS11 +18C >T in KCNQ1 and L520V in KCNH2 were also identified in two LQTS patients.Conclusions The mutation rates for both KCNQ1 (6.4%) and KCNH2 (6.4%) are lower in the Chinese population than those from North America or Europe.

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.

A novel deletion-frameshift mutation in the S1 region of HERG gene in a Chinese family with long QT syndrome

Background The congenital Long QT syndrome （LQTS） is a hereditary cardiac channelopathy that is characterized by a prolonged QT interval,syncope,ventricular arrhythmias,and sudden death.The chromosome 7-linked type 2 congenital LQTS （LQT2） is caused by gene mutations in the human ether-a-go-go-related gene （HERG）.Methods A Chinese family diagnosed with LQTS were screened for KCNQ1,HERG and SCN5A,using polymerase chain reaction （PCR）,direct sequencing,and clong sequencing.We also investigated the mRNA expression of the HERG gene.Results We identified a novel i414fs＋98X mutation in the HERG gene.The deletion mutation of 14-bp in the first transmembrane segment （S1） introduced premature termination codons （PTCs） at the end of exon 6.This mutation would result in a serious phenotype if the truncated proteins co-assembled with normal subunit to form the defective channels.But only the proband was symptomatic.Conclusions We found that the mRNA level of the HERG gene was significantly lower in 1414fs＋98X carriers than in noncarriers.We found a novel 1414fs＋98X mutation.The mRNA level supports that NMD mechanism might regulate the novel mutation.

Mutation analysis of KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes in Chinese patients with long QT syndrome

Long QT syndrome(LQTS)is the prototype of the cardiac ion channelopathies,which cause syncope and sudden death.Inherited LQTS is represented by the autosomal dominant Romano-ward syndrome(RWS),which is not accompanied by congenital deafness,and the autosomal recessive Jervell and Lange-Nielsen syndrome(JLNS),which is accompanied by congenital deafness.The LQTS-causing mutations have been reported in patients and families from Europe,North America and Japan.Few genetic studies have been carried out in families with JLNS from China.This study investigates the molecular pathology in four families with LQTS(including a family with JLNS)in the Chinese population.Polymerase chain reaction and DNA sequencing were used to screen for KCNQ1,KCNH2,KCNE1,KCNE2 and SCN5A mutation.A missense mutation G314S in an RWS family was identified,and a single nucleotide polymorphism(SNP)G643S was indentified in the KCNQ1 of the JLNS family.In this JLNS family,another heterozygous novel mutation in exon 2a was found in KCNQ1 of the patients.Our data provide useful information for the identification of polymorphisms and mutations related to LQTS and the Brugada Syndrome(BS)in Chinese populations.

Site-directed mutagenesis of long QT syndrome KCNQ1 gene in vitro

To construct a polymerase chain reaction(PCR)site-directed mutagenesis of the long QT syndrome KCNQ1 gene in vitro,two sets of primers were designed according to the sequence of KCNQ1 cDNA and a mismatch was introduced into primers.Mutagenesis was performed in a two-step PCR.The amplified fragments from the third PCR which contained the mutation site were sub-cloned into the T-vector pCR2.1.Then,the fragments containing the mutation site was obtained from pCR2.1 using restriction enzymes digestion and inserted into the same restriction site of pIRES2-EGFP-KCNQ1.The sequencing analysis shows that the mutation site was correct.Mutation from A to G in site 983 of KCNQ1 cDNA was found.Using the Effectene transfection reagent,pIRES2-EGFP-KCNQ1(G983A)was transfected into HEK cells successfully.These results may shed light on further functional study of KCNQ1 gene.

Clinical Advances in Congenital Long QT Syndrome

Long QT syndrome is an inherited arrhythmia characterized by a prolonged QT interval and increased risk of life-threatening cardiac events, including arrhythmogenic syncope, seizures, and sudden cardiac death with a structurally normal heart. Since its first description in the 1950s, extensive researches allowed a better understanding of the cause and mechanisms of this disease, which improved our ability of early diagnosis, risk stratification, and precise therapy of these patients. This article provides an updated review of the clinical and molecular profiles of this potentially lethal inherited disorder and summarizes current knowledge regarding diagnosis, risk stratification, and therapy.

Case report of antiseizure medicine-induced long QT syndrome and a literature review

Background To realize the clinical characteristics of long QT syndrome(LQTS)caused by antiseizure medicines(ASMs),and to improve the prevention and management of ASM-acquired QT syndrome.Case presentation A case of ASM-acquired QT syndrome was diagnosed and relevant literature was reviewed.The case was a 7-year-old boy who presented with a sudden onset of panic followed by changes in consciousness,with or without convulsions,lasting from tens of seconds to 3 min.The patient then received antiepileptic treatment with valproic acid,levetiracetam and oxcarbazepine and was seizure free for about a year.However,on August 12,2021,his illness flared up again.Electroencephalogram(EEG)showed the background activity was slow,and no obvious epileptic discharge was detected.But electrocardiogram(ECG)showed a surprisingly prolonged QT interval(770 ms).Torsades de Pointes was found during Holter monitoring,while electrolyte levels were normal.The ECG recordings gradually returned to normal after stopping ASMs.For literature search,only 21 related papers were obtained after reading titles and full-texts of 105 English-language papers retrieved using keywords"acquired QT interstitial syndrome/acquired Long QT Syndrome(aLQTS)"and"anti-epileptic seizure drugs/ASMs",in the databases of Wanfang,CNKI,Pubmed,and other databases,from publication year 1965 to October 26,2021.There are 12 types of drug-acquired LQTS caused by ASMs,most of which are Na+blockers,but LQTS caused by oxcarbazepine had not been reported previously.Conclusions ASMs such as oxcarbazepine can cause acquired LQTS.When Na+or K+channel blockers are used clinically,ECG should be reviewed regularly and abnormal ECG should be intervened in time to reduce iatrogenic accidents in patients with epilepsy.

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.

Survey concerning internal medicine physicians and prolonged QT interval:Knowledge and treatment practices

Prolongation of the QT interval is associated with adverse cardiac events specifically Torsades de pointes(TdP).There are multiple mediations that have a known,possible,or conditional risk for prolonged QT interval,but general practitioners’knowledge of these medications is unknown.We conducted a survey to assess internal medicine(IM)providers’knowledge of risk factors and medications associated with prolonged QT as well as provider experience and comfort when treating patients with prolonged QT.A 17-question,anonymous survey was constructed in 2019 and distributed to IM providers and residents at a tertiary care center.Questions included demographic information,6 Likert-scale questions gauging provider experience with prolonged QT,and 10 multiple choice clinical vignettes to assess clinical knowledge.Data was analyzed descriptively.Knowledge was assessed via clinical vignettes and compared by level of training.Forty-one responses were received out of a total of 87 possible respondents(47.1%response rate).About 70%of respondents see patients with acquired prolonged QT once monthly or more.95%rarely see congenital prolonged QT.When presented with QTc drug issues,73%of providers seldom or sometimes consulted pharmacy,but about half used online resources.The average correct score on the clinical vignettes was 5.59/10,with the highest scores seen in attending physicians in their first five years of practice(6.96/10).Our survey suggests that IM providers commonly encounter QT prolonging drugs.Educational efforts to improve knowledge of drug and patient risk factors for TdP may be needed.

The Notched T Waves Associated With HERG Gene Ala561Val Mutation in Congenital LQT Syndrome

Objectives To study the phenotype of a China LQT family and investigate the relationship of phenotype and gene. Methods The clinical materials were analyzed and gene mutations were screened by sequencing. Results A distinctive biphasic T wave pattern was shown in the left precordial leads of all patients. The LQT2 related HERG gene Ala561Val mutation was found. Conclusions A prolonged QT interval accompanied biphasic T wave indicates HERG mutation.

Clinical Characteristics of 5 Chinese LQTS Families and Phenotype-genotype Correlation

Summary: In order to assess the clinical manifestations and electrocardiogram (ECG) characteristics of Chinese long QT syndrome (LQTS) patients and describe the phenotype-genotype correlation, the subjects from 5 congenital LQTS families underwent clinical detailed examination including resting body surface ECG. QT interval and transmural dispersion of repolarization (TDR) were manually measured. Five families were genotyped by linkage analysis (polymerase chain reacting-short tandem repeat, PCR-STR). The phenotype-genotype correlation was analyzed. Four families were LQT2, 1 family was LQT3. Twenty-eight gene carriers were (14 males and 14 females) identified from 5 families. The mean QTc and TDRc were 0.56±0.04 s (range 0.42 to 0.63) and 0.16±0.04 s (range 0.09 to 0.24) respectively. 35.7 % (10/28) had normal to borderline QTc (≤ 0.460 s). There was significant difference in QTc and TDRc between the patients with symptomatic LQTS and those with asymptomatic LQTS, and there was significant difference in TDRc between the asymptomatic patients and normal people also. A history of cardiac events was present in 50 % (14/28), including 9 with syncope, 2 with sudden death (SD) and occurred in the absence of β-blocker. Three SDs occurred prior to the diagnosis of LQTS and had no ECG record. Two out of 5 SDs (40 %) occurred as the first symptom. Typical LQT2 T wave pattern were found in 40 % (6/15) of all affected members. The appearing-normal T wave was found in one LQT3 family. Low penetrance of QTc and symptoms resulted in diagnostic challenge. ECG patterns and repolarization parameters may be used to predict the genotype in most families. Genetic test is very important for identification of gene carriers.

Slow and Steady: The Cautious Use of Neuroleptics in a Patient with Andersen-Tawil Syndrome

Long QT syndrome (LQT) is a disease of cardiac repolarization caused by alterations in the transmembrane potassium and sodium currents. This results in prolongation of the QT interval on electrocardiography (EKG) and can result in torsade de pointes and sudden cardiac death. We present a case of a patient who has Anderson Tawil syndrome;a congenital long QT syndrome, with a history of cardiac arrhythmias who developed acute paranoid schizophrenia that was refractory to treatment with non-QT-prolonging drugs and required institution of neuroleptics to control her psychiatric symptoms.

Electrophysiological Study of V535M hERG Mutation of LQT2

This study examined the current changes of human ether-a-go-go-related gene （hERG） mutation derived from a LQT2 Chinese family with a highly penetrating phenotype. Mutation was identi-fied and site-directed mutagenesis was performed to induce the mutation in wild-type （WT） hERG. WT hERG and mutated V535M were cloned and transiently expressed in HEK293 cells. At the 48th and 72nd h after transfection, membrane currents were recorded using whole cell patch-clamp procedures. An A〉G transition at 1605 resulting in replacement of V535M was identified. Compared to WT, V535M mutation significantly decreased tail currents of hERG. At test potential of-40 mV after depolarizing at ＋50 mV, tail current densities were 83.354-7.06 pA/pF in WT and 50.38-4-7.74 pA/pF in V535M respectively （n=20, P〈0.01）. Gating kinetics of bERG revealed that Vl/2 of steady-state inactivation shifted to negative potential in the mutant （V1/2,v535M： -61.814-1.7 mV vs. V1/2, wx： -43.1q-0.71 mV）. The time constant of recovery from inactivation was markedly prolonged in the mutant compared to WT among test potentials. V535M hERG mutation demonstrated markedly decreased tail current densities, which suggests that V535M is a new loss-of-function mutation of hERG channel responsible for LQT2.

QT hysteresis in long-QT syndrome children with exercise testing

Background Congenital long QT syndrome （LQTS） is an inherited ion channel disorder resulting in abnormal cardiac repolarization that can cause syncope and sudden death associated with a prolonged rate-corrected QT interval and polymorphic ventricular tachycardia. Several studies in adults showed that LQTS patients have altered QT adaptation to heart rate changes compared with normal subjects which forming a ＂hysteresis loop＂ in the QT-circle length plot. This study was to observe the QT interval changing during exercise testing in children long QT syndrome （LQTS） patients, explore the new diagnosis methods of LQTS. Methods The subjects were divided into 3 groups according to 1993 LQTS diagnostic criteria. Group 1： LQTS group （n=17） who scored 〉 or = 4 points indicating definite LQTS. Group 2： Middle group （n=16）, patients who have prolonged QT interval but scored 1.5 to 3.5. Group 3： Normal control group （n=18）. The average age of all study population is （12.3±5.8） years. No case had beta-adrenergic antagonists administration before exercise testing. All subjects were underwent tread mill exercise testing and electrocardiograph in whole exercise testing and recovery were recorded. QT and heart rate changing during whole exercise testing period were recorded. /kQT, the QT interval at 1, 2, 4, 6 minutes into recovery subtract from the QT interval at a similar heart rate during exercise, were calculated. Results In all three groups, QT intervals were shortening with the increasing of heart rate, but QTc had no significant change. ΔQT at 1 minute （（45±11） ms）, 2 minutes （（37±15） ms）, 4 minutes （（23±12） ms） into recovery in LQTS group were significantly greater than that of the other two groups （P〈0.05, P〈0.01, P〈0.01, respectively）. There was no ΔQT significant difference between middle group and normal control group at recovery time. During the recovery phase in LQTS group, the QT interval remained shortened despite a decelerating heart rate, forming a hysteresis ＂loop＂ in the curve relating the QT interval to the cycle length. Conclusions In children LQTS patients, there is significant QT hysteresis loop in the relation of QT interval with heart rate during recovery of exercise testing, which could be useful to the early diagnosis for LQTS.

Torsades de pointes episode in a woman with high-grade fever and inflammatory activation: A case report

BACKGROUND QT interval prolongation can induce torsades de pointes(TdP),a potentially fatal ventricular arrhythmia.Recently,an increasing number of non-cardiac drugs have been found to cause QT prolongation and/or TdP onset.Moreover,recent findings have demonstrated the key roles of systemic inflammatory activation and fever in promoting long-QT syndrome(LQTS)and TdP development.CASE SUMMARY A 30-year-old woman was admitted with a moderate to high-grade episodic fever for two weeks.The patient was administered with multiple antibiotics after hospitalization but still had repeating fever and markedly elevated C-reactive protein.Once after a high fever,the patient suddenly lost consciousness,and electrocardiogram(ECG)showed transient TdP onset after frequent premature ventricular contraction.The patient recovered sinus rhythm and consciousness spontaneously,and post-TdP ECG revealed a prolonged QTc interval of 560 ms.The patient’s clinical manifestations and unresponsiveness to the antibiotics led to the final diagnosis of adult-onset Still’s disease(AOSD).There was no evidence of cardiac involvement.After the AOSD diagnosis,discontinuation of antibiotics and immediate initiation of intravenous dexamethasone administration resulted in the normal temperature and QTc interval.The genetic analysis identified that the patient and her father had heterozygous mutations in KCNH2(c.1370C>T)and AKAP9(c.7725A>C).During the 2-year follow-up period,the patient had no recurrence of any arrhythmia and maintained normal QTc interval.CONCLUSION This case study highlights the risk of systemic inflammatory activation and antibiotic-induced TdP/LQTS onset.Genetic analysis should be considered to identify individuals at high risk of developing TdP.