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[Treatment of atrial fibrillation in every days practice.]
Internist (Berl). 2008 Nov 21;
Meinertz T, Willems S
Atrial fibrillation is the most common arrhythmia in the adult. During recent years the therapeutic strategy has markedly changed. Some of these changes can be summarized as follows: Basis therapy includes betablockers and - in patients with structural heart disease - ACE-inhibitors and AT(1)-Blockers respectively. Class 1C-antiarrhythmic agents (flecainide or propafenon) should be restricted to patients with no or minimal left ventricular impairment. Amiodaron is the drug of choice in patients refractory to class 1C-agents and in those with already reduced left ventricular function. The "pill-in-the-pocket" regime can be used successfully in patients without structural heart disease and rare episodes of atrial fibrillation.Catheter ablation for paroxysmal and short lasting chronic atrial fibrillation was introduced into the clinical practice in 2006. The European and US-American guidelines recommend this technique for patients with no or minimal structural heart disease who are highly symptomatic and refractory or intolerant to antiarrhythmic agents. Decisions for curative catheter ablation in patients with long standing atrial fibrillation, heart failure or valvular heart disease should be individualized but are to date not generally recommended.
Bullous fixed drug eruption caused by flecainide.
J Am Acad Dermatol. 2008 Nov 13;
Knapp Iii CF, Cooke ER, Sheehan DJ
Heart Rhythm. 2008 Sep 23;
Ripplinger CM, Lou Q, Li W, Hadley J, Efimov IR
BACKGROUND: Sudden cardiac death due to arrhythmia in the settings of chronic myocardial infarction (MI) is an important clinical problem. Arrhythmic risk post-MI continues indefinitely even if heart failure and acute ischemia are not present due to the anatomic substrate of the scar and border zone (BZ) tissue. OBJECTIVE: The purpose of this study was to determine mechanisms of arrhythmia initiation and termination in a rabbit model of chronic MI. METHODS: Ligation of the lateral division of the left circumflex artery was performed 72 +/- 29 days before acute experiments (n = 11). Flecainide (2.13 +/- 0.64 muM) was administered to promote sustained arrhythmias, which were induced with burst pacing or a multiple shock protocol (four pulses, 140-200 ms coupling interval). RESULTS: Panoramic optical mapping with blebbistatin (5 muM) revealed monomorphic ventricular tachycardia (VT) maintained by a single mother rotor (cycle length [CL] = 174.7 +/- 38.4 ms) as the primary mechanism of arrhythmia. Mother rotors were anchored to the scar or BZ for 16 of the 19 rotor locations recorded. Cardioversion thresholds (CVTs) were determined at various phases throughout the VT CL from external shock electrodes. CVTs were found to be phase dependent, and the maximum versus minimum CVT was 7.8 +/- 1.9 vs. 4.1 +/- 1.6 V/cm, respectively (P = .005). Antitachycardia pacing was found to be effective in only 2.7% of cases in this model. CONCLUSIONS: These results indicate that scar and BZ tissue heterogeneity provide the substrate for VT by attracting and stabilizing rotors. Additionally, a significant reduction in CVT may be achieved by appropriately timed shocks in which the shock-induced virtual electrode polarization interacts with the rotor to destabilize VT.
Heart Rhythm. 2008 Oct; 5(10): 1434-40
Benito B, Brugada R, Perich RM, Lizotte E, Cinca J, Mont L, Berruezo A, Tolosana JM, Freixa X, Brugada P, Brugada J
BACKGROUND: Type 3 long-QT syndrome (LQT-3) is caused by gain-of-function mutations in the SCN5A encoding the cardiac sodium channel. Familial atrial fibrillation (AF), previously considered a potassium channelopathy, has recently been related to sodium genetic variants, both in isolated forms and in patients with underlying heart disease. OBJECTIVE: The purpose of this study was to describe the first family associating LQT-3 and AF due to a gain-of-function mutation in SCN5A and assess the usefulness of the sodium blocker flecainide in individuals with both phenotypes. METHODS: Complete family screening was performed after identifying a proband showing paroxysmal AF and a long QT interval suggestive of LQT-3. Secondary causes of AF were ruled out in all individuals. Flecainide was used in two patients for LQT-3 diagnosis and therapeutic treatment of AF. Genetic screening was performed by direct sequencing of the exons and exon-intron boundaries of SCN5A. RESULTS: We identified a three-generation family (eight members), all of them showing long QT intervals. Paroxysmal AF initiated between 20 and 35 years of age in all three adults. The flecainide test led to shortening of the QTc interval. Flecainide was also effective in acutely restoring sinus rhythm. A Y1795C mutation was identified in all members. CONCLUSION: This is the first report showing an association of familial AF and LQT-3 due to a mutation in SCN5A. This finding provides further evidence of the role of SCN5A in AF. We also confirm the usefulness of flecainide in this particular complex phenotype, both as a diagnostic tool for LQT-3 and as an acute treatment for AF.
J Cardiol. 2008 Oct; 52(2): 102-110
Atarashi H, Ogawa S, Inoue H,
BACKGROUND: In patients with paroxysmal atrial fibrillation or flutter (PAF/PAFL), subjective symptoms are not concordant with real arrhythmic events. It is important to elucidate the incidence of asymptomatic PAF/PAFL in symptomatic patients in a clinical setting. METHODS AND RESULTS: To identify a possible relationship with subjective symptoms, we reviewed 6319 trans-telephonic electrocardiographic strips (ECGs) recorded from 123 patients in a double-blind, placebo-controlled trial examining dose-response effects of flecainide. During a 4-week observation, 2848 ECGs, comprising 894 (31.4%) symptomatic and 1954 (68.6%) asymptomatic tracings, and, during 31 days of treatment, 3471 ECGs, comprising 874 (25.2%) symptomatic and 2587 (74.8%) asymptomatic tracings, were transmitted. There were significantly fewer symptomatic ECGs during the treatment period (Fisher's exact test, P
Fetal Diagn Ther. 2008 Oct 6; 24(4): 327-330
Schiermeier S, van Leeuwen P, Reinhard J, Grönemeyer D, Hatzmann W
Background: Magnetocardiography and M-mode fetal echocardiography are non-invasive techniques capable of identifying fetal arrhythmias. The STAN(R)-fetal scalp electrode system can record the fetal echocardiogram in labor. Case: A patient was admitted to hospital with preterm contractions and cervical insufficiency at 28 weeks of gestation. After treatment with a beta-sympathomimetic drug (Partusisten(R)) one fetus developed supraventricular tachycardia. After terminating the Partusisten medication, there was no effect on the fetal arrhythmia and flecainide therapy was initiated. Maintenance dosages controlled the condition thereafter. Cardiac time intervals of a fetus in labor can be presented, which did not change significantly throughout the first stage of labor. Conclusion: Flecainide is an effective therapy for supraventricular tachycardias in a twin pregancy. Analyzing the cardiac time intervals during pregnancy can improve perinatal outcome.
Effect of prenatal antiarrhythmic treatment on cardiac function in a twin pregnancy.
Pacing Clin Electrophysiol. 2008 Sep; 31(9): 1213-7
Van Leeuwen P, Schiermeier S, Hailer B, Lange S, Geue D, Hatzmann W, Grönemeyer D
We present a case of supraventricular tachycardia affecting one fetus in a twin pregnancy. Before and after treatment with flecainide and cardioversion, we examined conduction times and heart rate variability (HRV) in both twins on the basis of magnetocardiography. Cardiac conduction times increased in both fetuses but HRV showed opposing effects with a number of HRV measures. This case demonstrates that magnetocardiography not only enables identification of fetal arrhythmia, but also permits the investigation of the effects of antiarrhythmic treatment on the conductive system as well as on interaction with the autonomic nervous system.
Br J Clin Pharmacol. 2008 Nov; 66(5): 660-6
Lim KS, Cho JY, Jang IJ, Kim BH, Kim J, Jeon JY, Tae YM, Yi S, Eum S, Shin SG, Yu KS
AIMS: The objectives were to evaluate the effect of CYP2D6 genetic polymorphism on the pharmacokinetics of flecainide, and also on the extent of drug interaction with paroxetine as a CYP2D6 inhibitor after a single oral administration in healthy subjects. METHODS: An open-label, two-period, single-sequence, cross-over study was performed in 21 healthy Korean male volunteers (seven for CYP2D6*1/*1 or *1/*2, group 1; seven for CYP2D6*1/*10, group 2; seven for CYP2D6*10/*10 or *10/*36, group 3). Subjects were administered 200 mg of flecainide on day 1. After a 7-day wash-out period, subjects were administered 20 mg of paroxetine from day 8 to 14, and 200 mg of flecainide on day 15. Blood sampling was performed up to 72 h after flecainide administration. RESULTS: Terminal elimination half-life and mean residence time (MRT) were significantly different among three genotype groups after a single oral administration of flecainide (P = 0.021, 0.011, respectively). Area under the concentration-time curve, terminal elimination half-life and MRT increased significantly after paroxetine co-administration only in groups 1 and 2. CONCLUSIONS: This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians.
Postmortem increase of flecainide level in cardiac blood.
J Anal Toxicol. 2008 Jul-Aug; 32(6): 451-3
Yoshitome K, Miyaishi S, Yamamoto Y, Ishizu H
We encountered a case of fatal congestive heart failure that occurred under the influence of flecainide. In this case, an extreme postmortem increase in the flecainide level was identified in cardiac blood. The patient had been administered 400 mg/day of flecainide for seven days before death. Antemortem plasma obtained 13 h before death showed a flecainide concentration of 2.5 mg/L and a pH of 7.4. In comparison, centrifuged supernatants of postmortem right and left cardiac blood contained flecainide concentrations of 13.8 and 44.2 mg/L, respectively, with pH of 5.5 in both samples. This increase in blood flecainide concentration was attributed to postmortem redistribution, as about 18 h had passed between the last intake of flecainide and death.
Is atrial fibrillation with very short cycle length suitable for ablation? A case report.
Europace. 2008 Nov; 10(11): 1336-9
Diemberger I, McCready J, Nunn L, Chow AW
We present a case of a 36-year-old woman with highly symptomatic persistent atrial fibrillation (AF) refractory to sotalol, flecainide, and external direct current (DC) cardioversion. The patient underwent biatrial mapping and ablation procedure for AF. Both atria were characterized by refractory properties which were much shorter than reported previously. Global fibrillatory activity was present with a median cycle length of 120 ms (range: 62-143). Extensive map-guided ablation sets had to be delivered to both left and right sides before effective DC cardioversion enabled sinus rhythm (SR) restoration. The patient remained in SR at 9 months of follow-up.