Flecainide acetate is a class IC antiarrhythmic agent and its clinical efficacy has been confirmed by the results of several clinical trials. Nowadays, flecainide is recommended as one of the first line therapies for ...Flecainide acetate is a class IC antiarrhythmic agent and its clinical efficacy has been confirmed by the results of several clinical trials. Nowadays, flecainide is recommended as one of the first line therapies for pharmacological conversion as well as maintenance of sinus rhythm in patients with atrial fibrillation and/or supraventricular tachycardias. Based on the Cardiac Arrhythmia Suppression Trial study results, flecainide is not recommended in patients with structural heart disease due to high proarrhythmic risk. Recent data support the role of flecainide in preventing ventricular tachyarrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia associated both with ryanodine receptor and calsequestrin mutations. We herein review the current clinical data related to flecainide use in clinical practice and some concerns about its role in the management of patients with coronary artery disease.展开更多
AIM: To examine the effect of ibutilide on novel indexes of repolarization in patients with persistent atrial fibrillation (AF). METHODS: We studied consecutive patients scheduled for elective electrical cardioversion...AIM: To examine the effect of ibutilide on novel indexes of repolarization in patients with persistent atrial fibrillation (AF). METHODS: We studied consecutive patients scheduled for elective electrical cardioversion. Intravenous ibutilide (1+1mg) was administered before the electrical cardioversion while close electrocardiographic (ECG) monitoring was performed. ECG indexes such as corrected QT interval (QTc), the interval from the peak until the end of T wave (Tpe), and the Tpe/QT ratio were measured before ibutilide infusion and 10 min after the end of infusion. RESULTS: The final study population consisted of 20 patients (mean age: 67.1±9.9 years, 10 men). Six patients were cardioverted pharmacologically and did not proceed to electrical cardioversion. Two patientsdeveloped short non-sustained episodes of torsades de pointes ventricular tachycardia. All but one of the aforementioned ECG indexes increased significantly after ibutilide administration. In specific, the QTc interval increased from 442 ± 29 to 471 ± 37 ms (P=0.037), the Tpe interval in precordial leads from 96 ms (range 80-108 ms) to 101 ms (range 91-119 ms) (P=0.021), the Tpe interval in lead Ⅱ from 79 ms (range 70-88 ms) to 100 ms (range 87-104 ms) (P<0.001), the Tpe/QT ratio in precordial leads from 0.23 ms (range 0.18-0.26 ms) to 0.26 ms (range 0.23-0.28 ms) (P=0.028), and the Tpe interval dispersion from 25 ms (range 23-30 ms) to 35 ms (range 27-39 ms) (P=0.012). However, the Tpe/QT ratio in lead II did not change significantly. CONCLUSION: Ibutilide increases the duration and dispersion of ventricular repolarization. The prognostic value of Tpe and Tpe/QT in the setting of drug-induced proarrhythmia needs further study.展开更多
Cytochrome P4502J2(CYP2J2)metabolizes arachidonic acid(AA)to cardioprotective epoxyeicosatrienoic acids(EETs).Dronedarone,an antiarrhythmic drug prescribed for treatment of atrial fibrillation(AF)induces cardiac adver...Cytochrome P4502J2(CYP2J2)metabolizes arachidonic acid(AA)to cardioprotective epoxyeicosatrienoic acids(EETs).Dronedarone,an antiarrhythmic drug prescribed for treatment of atrial fibrillation(AF)induces cardiac adverse effects(AEs)with poorly understood mechanisms.We previously demonstrated that dronedarone inactivates CYP2J2 potently and irreversibly,disrupts AA-EET pathway leading to cardiac mitochondrial toxicity rescuable via EET enrichment.In this study,we investigated if mitigation of CYP2J2 inhibition prevents dronedarone-induced cardiac AEs.We first synthesized a deuterated analogue of dronedarone(termed poyendarone)and demonstrated that it neither inactivates CYP2J2,disrupts AA-EETs metabolism nor causes cardiac mitochondrial toxicity in vitro.Our patch-clamp experiments demonstrated that pharmacoelectrophysiology of dronedarone is unaffected by deuteration.Next,we show that dronedarone treatment or CYP2J2 knockdown in spontaneously beating cardiomyocytes indicative of depleted CYP2J2 activity exacerbates beat-to-beat(BTB)variability reflective of proarrhythmic phenotype.In contrast,poyendarone treatment yields significantly lower BTB variability compared to dronedarone in cardiomyocytes indicative of preserved CYP2J2 activity.Importantly,poyendarone and dronedarone display similar antiarrhythmic properties in the canine model of persistent AF,while poyendarone substantially reduces beat-to-beat variability of repolarization duration suggestive of diminished proarrhythmic risk.Our findings prove that deuteration of dronedarone prevents CYP2J2 inactivation and mitigates dronedarone-induced cardiac AEs.展开更多
Background Cardiac resynchronization therapy （CRT） could improve heart function, symptom status, quality of life and reduce hospitalization and mortality in patients with severe heart failure （HF） with optimal med...Background Cardiac resynchronization therapy （CRT） could improve heart function, symptom status, quality of life and reduce hospitalization and mortality in patients with severe heart failure （HF） with optimal medical management. However,the possible adverse effects of CRT are often ignored by clinicians.Method A retrospective analysis of CRT over a 6-year period was made in a single cardiac center.Results Fifty-four patients were treated with CRT（D） device, aged （57±11） years, with left ventricular ejection fraction of （32.1±9.8）%, of which 4 （7%） developed ventricular tachycardia/ventricular fibrillation （VT/VF） or junctional tachycardia after operation. Except for one with frequent ventricular premature beat before operation, the others had no previous history of ventricular arrhythmia. Of the 4 patients, 3 had dilated cardiomyopathy and 1 had ischemic cardiomyopathy,and tachycardia occurred within 3 days after operation. Sustained, refractory VT and subsequent VF occurred in one patient, frequent nonsustained VT in two patients and nonparoxysmal atrioventricular junctional tachycardia in one patient. VT was managed by amiodarone in two patients, amiodarone together with beta-blocker in one patient, and junctional tachycardia was terminated by overdrive pacing. During over 12-month follow-up, except for one patient＇s death due to refractory heart and respiratory failure in hospital, the others remain alive and arrhythmia-free.Conclusions New-onset VT/VF or junctional tachycardia may occur in a minority of patients with or without prior history of tachycardia after biventricular pacing. Arrhythmia can be managed by conventional therapy, but may require temporary discontinuation of pacing. More observational studies should be performed to determine the potential proarrhythmic effect of CRT.展开更多
文摘Flecainide acetate is a class IC antiarrhythmic agent and its clinical efficacy has been confirmed by the results of several clinical trials. Nowadays, flecainide is recommended as one of the first line therapies for pharmacological conversion as well as maintenance of sinus rhythm in patients with atrial fibrillation and/or supraventricular tachycardias. Based on the Cardiac Arrhythmia Suppression Trial study results, flecainide is not recommended in patients with structural heart disease due to high proarrhythmic risk. Recent data support the role of flecainide in preventing ventricular tachyarrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia associated both with ryanodine receptor and calsequestrin mutations. We herein review the current clinical data related to flecainide use in clinical practice and some concerns about its role in the management of patients with coronary artery disease.
文摘AIM: To examine the effect of ibutilide on novel indexes of repolarization in patients with persistent atrial fibrillation (AF). METHODS: We studied consecutive patients scheduled for elective electrical cardioversion. Intravenous ibutilide (1+1mg) was administered before the electrical cardioversion while close electrocardiographic (ECG) monitoring was performed. ECG indexes such as corrected QT interval (QTc), the interval from the peak until the end of T wave (Tpe), and the Tpe/QT ratio were measured before ibutilide infusion and 10 min after the end of infusion. RESULTS: The final study population consisted of 20 patients (mean age: 67.1±9.9 years, 10 men). Six patients were cardioverted pharmacologically and did not proceed to electrical cardioversion. Two patientsdeveloped short non-sustained episodes of torsades de pointes ventricular tachycardia. All but one of the aforementioned ECG indexes increased significantly after ibutilide administration. In specific, the QTc interval increased from 442 ± 29 to 471 ± 37 ms (P=0.037), the Tpe interval in precordial leads from 96 ms (range 80-108 ms) to 101 ms (range 91-119 ms) (P=0.021), the Tpe interval in lead Ⅱ from 79 ms (range 70-88 ms) to 100 ms (range 87-104 ms) (P<0.001), the Tpe/QT ratio in precordial leads from 0.23 ms (range 0.18-0.26 ms) to 0.26 ms (range 0.23-0.28 ms) (P=0.028), and the Tpe interval dispersion from 25 ms (range 23-30 ms) to 35 ms (range 27-39 ms) (P=0.012). However, the Tpe/QT ratio in lead II did not change significantly. CONCLUSION: Ibutilide increases the duration and dispersion of ventricular repolarization. The prognostic value of Tpe and Tpe/QT in the setting of drug-induced proarrhythmia needs further study.
基金supported by the National University Heart Centre Singapore (NUHCS) Cardiovascular Research Institute (CVRI)Core Fund [Grant NUHSRO/2019/082/Core]SCEPTRE CG Seed Grant [Grant NMRC/CG/M008/2017, Singapore]+2 种基金Singapore Ministry of Education Tier 1 Academic Research Funding [Grant R-148-000-193-112]the National University of Singapore, Department of Pharmacy, Final Year Project Funding [Grant C148-000-003-001] provided to Eric Chun Yong Chanfrom Japan Society for the Promotion of Science (JSPS) KAKENHI [grant number 20K16136] provided to Ryuichi Kambayashi
文摘Cytochrome P4502J2(CYP2J2)metabolizes arachidonic acid(AA)to cardioprotective epoxyeicosatrienoic acids(EETs).Dronedarone,an antiarrhythmic drug prescribed for treatment of atrial fibrillation(AF)induces cardiac adverse effects(AEs)with poorly understood mechanisms.We previously demonstrated that dronedarone inactivates CYP2J2 potently and irreversibly,disrupts AA-EET pathway leading to cardiac mitochondrial toxicity rescuable via EET enrichment.In this study,we investigated if mitigation of CYP2J2 inhibition prevents dronedarone-induced cardiac AEs.We first synthesized a deuterated analogue of dronedarone(termed poyendarone)and demonstrated that it neither inactivates CYP2J2,disrupts AA-EETs metabolism nor causes cardiac mitochondrial toxicity in vitro.Our patch-clamp experiments demonstrated that pharmacoelectrophysiology of dronedarone is unaffected by deuteration.Next,we show that dronedarone treatment or CYP2J2 knockdown in spontaneously beating cardiomyocytes indicative of depleted CYP2J2 activity exacerbates beat-to-beat(BTB)variability reflective of proarrhythmic phenotype.In contrast,poyendarone treatment yields significantly lower BTB variability compared to dronedarone in cardiomyocytes indicative of preserved CYP2J2 activity.Importantly,poyendarone and dronedarone display similar antiarrhythmic properties in the canine model of persistent AF,while poyendarone substantially reduces beat-to-beat variability of repolarization duration suggestive of diminished proarrhythmic risk.Our findings prove that deuteration of dronedarone prevents CYP2J2 inactivation and mitigates dronedarone-induced cardiac AEs.
文摘Background Cardiac resynchronization therapy （CRT） could improve heart function, symptom status, quality of life and reduce hospitalization and mortality in patients with severe heart failure （HF） with optimal medical management. However,the possible adverse effects of CRT are often ignored by clinicians.Method A retrospective analysis of CRT over a 6-year period was made in a single cardiac center.Results Fifty-four patients were treated with CRT（D） device, aged （57±11） years, with left ventricular ejection fraction of （32.1±9.8）%, of which 4 （7%） developed ventricular tachycardia/ventricular fibrillation （VT/VF） or junctional tachycardia after operation. Except for one with frequent ventricular premature beat before operation, the others had no previous history of ventricular arrhythmia. Of the 4 patients, 3 had dilated cardiomyopathy and 1 had ischemic cardiomyopathy,and tachycardia occurred within 3 days after operation. Sustained, refractory VT and subsequent VF occurred in one patient, frequent nonsustained VT in two patients and nonparoxysmal atrioventricular junctional tachycardia in one patient. VT was managed by amiodarone in two patients, amiodarone together with beta-blocker in one patient, and junctional tachycardia was terminated by overdrive pacing. During over 12-month follow-up, except for one patient＇s death due to refractory heart and respiratory failure in hospital, the others remain alive and arrhythmia-free.Conclusions New-onset VT/VF or junctional tachycardia may occur in a minority of patients with or without prior history of tachycardia after biventricular pacing. Arrhythmia can be managed by conventional therapy, but may require temporary discontinuation of pacing. More observational studies should be performed to determine the potential proarrhythmic effect of CRT.
