Background Torsade de pointes (TdP) is a form of polymorphic ventricular tachycardia featuring prolonged QT intervals. Female gender is associated with an increased risk of TdP. However, the causes of the sex differe...Background Torsade de pointes (TdP) is a form of polymorphic ventricular tachycardia featuring prolonged QT intervals. Female gender is associated with an increased risk of TdP. However, the causes of the sex difference in risk are poorly understood. Recently, transmural dispersion of repolarization (TDR) has been implicated in the genesis of TdP. Consequently, we compared TdP incidence and TDR between male and female rabbit hearts in order to investigate the mechanism of sex difference in TdP risk in rabbits in vitro. Methods By means of monophasic action potential recording techniques, the monophasic action potential of the epicardium, midmyocardium, and endocardium were simultaneously recorded using specially designed plunge-needle electrodes placed across the left ventricular free wall of both female (n=8) and male (n=8) rabbit hearts purfused by the Langendorff method. TdP was induced by bradycardia, d-sotalol, and low-K +, Mg 2+ Tyrode solution. Results TDR measurements in all three myocardial layers of male and female rabbit hearts were (18±2) ms and (21±2) ms, respectively (n=8, P>0.05). After perfusion with d-sotalol, the 90% monophasic action potential duration was prolonged in both male and femlae rabbits. TDR in male and female rabbit hearts increased to (29±2) ms and (61±2) ms, respectively, a difference that is significant. Eight female rabbit hearts had early afterdepolarization and 7 of them developed TdP. Seven male rabbit hearts had early after depolarization, but only one of these hearts developed TdP.Conclusion Greater TDR may play an important role in the higher incidence of TdP in female rabbit hearts.展开更多
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...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.展开更多
BACKGROUND Sarcoidosis is a rare multisystem disease characterized histologically by noncaseating granuloma formation in the affected organ.While cardiac sarcoidosis is found on autopsy in up to 25%of sarcoidosis case...BACKGROUND Sarcoidosis is a rare multisystem disease characterized histologically by noncaseating granuloma formation in the affected organ.While cardiac sarcoidosis is found on autopsy in up to 25%of sarcoidosis cases,it is still underdiagnosed and is associated with a poor prognosis.Although the etiology of sarcoidosis remains unclear,an antigen triggered exaggerated immune response has been hypothesized.Early detection and prompt management of cardiac sarcoidosis remains pivotal.CASE SUMMARY A 60-year-old female,with pulmonary sarcoidosis in remission,presented to the cardiology outpatient clinic for evaluation of weeks-long dyspnea on moderate exertion(New York Heart Association class II)that was relieved by rest.Submaximal exercise stress test showed multifocal ventricular extrasystoles,followed by a self-limiting torsades de pointes.Cardiac magnetic resonance imaging showed nondilated and normotrophic left ventricle with basoseptal and mid-septal dyskinesis.The magnetic resonance imaging-derived left ventricular ejection fraction was 45%.Delayed enhancement showed patchy transmural fibrosis of the septum and hyperenhancement of the papillary muscles,all in favor of extensive cardiac involvement of sarcoidosis.A double-chamber implantable cardiac defibrillator was implanted,and methylprednisolone(12 mg/d)and methotrexate(12.5 mg/wk)treatment was initiated.Follow-up and implantable cardiac defibrillator interrogation showed episodes of asymptomatic nonsustained ventricular tachycardia and an asymptomatic episode of nonsustained ventricular tachycardia ending by the first antitachycardia pacing run.CONCLUSION Along an extensive review of the literature,this unusual case report highlights the importance of early detection of cardiac involvement of sarcoidosis,in order to avoid potential complications and increase survival.展开更多
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 hist...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.展开更多
Objective: To study the distribution of I_ Ca,L in endomyocardium(Endo), mid-myocardium(Mid) and epicardium(Epi) in female and male rabbit ventricle and to elucidate the mechanism of sex difference in drug-associated ...Objective: To study the distribution of I_ Ca,L in endomyocardium(Endo), mid-myocardium(Mid) and epicardium(Epi) in female and male rabbit ventricle and to elucidate the mechanism of sex difference in drug-associated torsade de pointes. Methods: Whole-cell patch clamp technique was used to record action potential and I_Ca,L. Results: Action potential duration ofMidinfemale rabbit heart waslonger thanthat in male and transmural dispersion of repolarization in female was largerthan thatinmale. The densities of I_ Ca,L in Endo, Mid and Epi of female rabbits were (7.1±0.6), (10.4±0.9) and (9.6±1.1) pA/pF and they were (9.1±0.9), (10.5±1.0) and (9.8±0.9) pA/pF in male respectively. Transmural heterogeneity of I_ Ca,L in female ventricle was more significant than that in male rabbit.Conclusion:Female rabbitspossessmoresignificant transmural heterogeneityof I_Ca,L,whichmaybe responsiblefor largertransmuraldispersion of repolarization and more drug-associated torsade de pointes in female.展开更多
Summary： Abnormal enhanced transmural dispersion of repolarization （TDR） plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes （TDP） which can be induced in ...Summary： Abnormal enhanced transmural dispersion of repolarization （TDR） plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes （TDP） which can be induced in long-QT （LQT） syndrome. Taking advantage of an in vitro rabbit model of LQT2, we de- tected the effects of KN-93, a CaM-dependent kinase （CaMK） II inhibitor on repolarization heteroge- neity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypo- kalemic, hypomagnesaemic Tyrode＇s solution. At a basic length （BCL） of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave （Tp-e） were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 （0.5μmol/L） could inhibit EAD, R-on-T extrasys- tole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demon- strated KN-93, a CaMK II inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.展开更多
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,bu...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.展开更多
文摘Background Torsade de pointes (TdP) is a form of polymorphic ventricular tachycardia featuring prolonged QT intervals. Female gender is associated with an increased risk of TdP. However, the causes of the sex difference in risk are poorly understood. Recently, transmural dispersion of repolarization (TDR) has been implicated in the genesis of TdP. Consequently, we compared TdP incidence and TDR between male and female rabbit hearts in order to investigate the mechanism of sex difference in TdP risk in rabbits in vitro. Methods By means of monophasic action potential recording techniques, the monophasic action potential of the epicardium, midmyocardium, and endocardium were simultaneously recorded using specially designed plunge-needle electrodes placed across the left ventricular free wall of both female (n=8) and male (n=8) rabbit hearts purfused by the Langendorff method. TdP was induced by bradycardia, d-sotalol, and low-K +, Mg 2+ Tyrode solution. Results TDR measurements in all three myocardial layers of male and female rabbit hearts were (18±2) ms and (21±2) ms, respectively (n=8, P>0.05). After perfusion with d-sotalol, the 90% monophasic action potential duration was prolonged in both male and femlae rabbits. TDR in male and female rabbit hearts increased to (29±2) ms and (61±2) ms, respectively, a difference that is significant. Eight female rabbit hearts had early afterdepolarization and 7 of them developed TdP. Seven male rabbit hearts had early after depolarization, but only one of these hearts developed TdP.Conclusion Greater TDR may play an important role in the higher incidence of TdP in female rabbit hearts.
基金the Beijing Key Clinical Subject Program and Beijing Municipal Administration of Hospitals Incubating Program,No.PX2018002.
文摘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.
文摘BACKGROUND Sarcoidosis is a rare multisystem disease characterized histologically by noncaseating granuloma formation in the affected organ.While cardiac sarcoidosis is found on autopsy in up to 25%of sarcoidosis cases,it is still underdiagnosed and is associated with a poor prognosis.Although the etiology of sarcoidosis remains unclear,an antigen triggered exaggerated immune response has been hypothesized.Early detection and prompt management of cardiac sarcoidosis remains pivotal.CASE SUMMARY A 60-year-old female,with pulmonary sarcoidosis in remission,presented to the cardiology outpatient clinic for evaluation of weeks-long dyspnea on moderate exertion(New York Heart Association class II)that was relieved by rest.Submaximal exercise stress test showed multifocal ventricular extrasystoles,followed by a self-limiting torsades de pointes.Cardiac magnetic resonance imaging showed nondilated and normotrophic left ventricle with basoseptal and mid-septal dyskinesis.The magnetic resonance imaging-derived left ventricular ejection fraction was 45%.Delayed enhancement showed patchy transmural fibrosis of the septum and hyperenhancement of the papillary muscles,all in favor of extensive cardiac involvement of sarcoidosis.A double-chamber implantable cardiac defibrillator was implanted,and methylprednisolone(12 mg/d)and methotrexate(12.5 mg/wk)treatment was initiated.Follow-up and implantable cardiac defibrillator interrogation showed episodes of asymptomatic nonsustained ventricular tachycardia and an asymptomatic episode of nonsustained ventricular tachycardia ending by the first antitachycardia pacing run.CONCLUSION Along an extensive review of the literature,this unusual case report highlights the importance of early detection of cardiac involvement of sarcoidosis,in order to avoid potential complications and increase survival.
文摘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.
文摘Objective: To study the distribution of I_ Ca,L in endomyocardium(Endo), mid-myocardium(Mid) and epicardium(Epi) in female and male rabbit ventricle and to elucidate the mechanism of sex difference in drug-associated torsade de pointes. Methods: Whole-cell patch clamp technique was used to record action potential and I_Ca,L. Results: Action potential duration ofMidinfemale rabbit heart waslonger thanthat in male and transmural dispersion of repolarization in female was largerthan thatinmale. The densities of I_ Ca,L in Endo, Mid and Epi of female rabbits were (7.1±0.6), (10.4±0.9) and (9.6±1.1) pA/pF and they were (9.1±0.9), (10.5±1.0) and (9.8±0.9) pA/pF in male respectively. Transmural heterogeneity of I_ Ca,L in female ventricle was more significant than that in male rabbit.Conclusion:Female rabbitspossessmoresignificant transmural heterogeneityof I_Ca,L,whichmaybe responsiblefor largertransmuraldispersion of repolarization and more drug-associated torsade de pointes in female.
基金supported by Natural Science Foundation of Hubei Province,China(No.2008CDB163)
文摘Summary： Abnormal enhanced transmural dispersion of repolarization （TDR） plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes （TDP） which can be induced in long-QT （LQT） syndrome. Taking advantage of an in vitro rabbit model of LQT2, we de- tected the effects of KN-93, a CaM-dependent kinase （CaMK） II inhibitor on repolarization heteroge- neity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypo- kalemic, hypomagnesaemic Tyrode＇s solution. At a basic length （BCL） of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave （Tp-e） were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 （0.5μmol/L） could inhibit EAD, R-on-T extrasys- tole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demon- strated KN-93, a CaMK II inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.
文摘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.
