Figure 3. Example of a Poincar plot showing the calculation of SD1 and SD2 from an ellipse fitted to the plot. with its length. The non-linear index SD12 quantifies the shape of the Poincar plot. SD12 is the ratio of the lengths of the axes of an imaginary ellipse which has its center at the average RR or NN ; interval of the time series and is fitted to the Poincar plot. As shown in Figure 3, the longitudinal axis of this ellipse is along a line beginning at the origin and with a slope of 1 and has a length called SD2. SD2 reflects intermediate-term variability. The length of the transverse axis of the ellipse is SD1 and reflects short-term variability. SD12 is the ratio of these measures. In our lab, HRV from 740 tapes recorded before antiarrhythmic therapy in the Cardiac Arrhythmia Suppression Trial was studied15. CAST was an historic post MI study with impaired left ventricular ejection fraction and high grade ventricular arrhythmias that were suppressed with one of three antiarrhythmic therapies encainide, flecainide or moricizine ; 16. Holter recordings were obtained at a large range of times post MI. Subjects in the HRV substudy were patients with ventricular premature contractions VPCs ; suppressed on the first randomised antiarrhythmic treatment. They were 70121 post MI and follow up was 362241days 70 deaths ; . Traditional time and frequency domain HRV were determined from the qualifying, prerandomization Holter recording. Non-linear HRV measures included short-term fractal scaling exponent and SD12, each calculated from an average of 1000 normal-to-normal interbeat intervals and power law slope calculated from the entire recording. As mentioned, this group of patients was at a broad range of times post-MI whereas in the studies discussed earlier HRV was measured shortly after MI. As a result, some patients had undergone CABG surgery between their MI and their first Holter recordings. Decreased HRV among post-CABG patients is caused by the surgery itself and has been shown to be of prognostic value. Therefore, post-CABG patients were excluded from the analysis17. Similarly, in the CAST population, the decreased HRV associated with diabetes was not prognostic. Thus, when the analysis was limited to those without CABG surgery post-MI or diabetes, power law slope had no association with mortality. Indian Pacing and Electrophysiology Journal ISSN 0972-6292 ; , 5 3 ; : 210-220 2005
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Implications for Patient Therapy Based on our study results, in a patient population without substantial structural heart disease, yet with significant prior exposure to agents such as digoxin, calcium channel antagonists, and , 8-blockers, flecainide appears safe and clearly efficacious for the prevention of symptomatic electrocardiographically documented PSVT. Flecainide should be considered an important therapeutic alternative for patients having PSVT. Acknowledgments We appreciate the secretarial support of Monica D. Roby and Susan E. Lockshine in preparation of this manuscript.
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Flecainide, propafenone, and sotalol are recommended as initial antiarrhythmic therapy because they are generally well tolerated and are essentially devoid of extracardiac organ toxicity. When one or another of these drugs is ineffective or is associated with side effects, then second or third-line choices include amiodarone, dofetilide, disopyramide, procainamide, and quinidine, which have greater potential for adverse reactions. For patients with CHF, safety data support the selection of amiodarone or dofetilide to maintain sinus rhythm. Patients with ischemic heart disease often require beta-blocker medication, and sotalol, a drug with both beta-blocking activity and primary antiarrhythmic efficacy, is considered first, unless the patient has HF. Amiodarone and dofetilide are considered secondary agents. In patients with hypertension without LV hypertrophy, drugs such as flecainide and propafenone, which do not prolong repolarization and the QT interval, may offer a safety advantage and are recommended first. If these agents either prove ineffective or produce side effects, then amiodarone, dofetilide, or sotalol represent appropriate secondary choices. Disopyramide, procainamide, and quinidine are considered third-line agents in this situation. Hypertrophied myocardium may be prone to proarrhythmic toxicity and development of the torsade de pointes type of ventricular tachycardia. Amiodarone is suggested as first-line therapy in patients with LV hypertrophy wall thickness greater than or equal to 1.4 cm ; because of its relative safety compared with several other agents. 3. Recurrent Persistent AF. Patients with minimal or no symptoms referable to AF who have undergone at least 1 attempt to restore sinus rhythm may remain in AF after its second occurrence, with therapy for rate control and prevention of thromboembolism as needed. Alternatively, those with symptoms favoring sinus rhythm should be treated with an antiarrhythmic agent in addition to medications for rate control and anticoagulation ; before cardioversion. The selection of an antiarrhythmic drug should be based on the same algorithm used for patients with recurrent paroxysmal AF. 4. Permanent AF. Permanent AF is the designation given to cases in which sinus rhythm cannot be sustained after cardioversion of AF or when the patient and physician have decided to allow AF to continue without further efforts to restore sinus rhythm. It is important to maintain control of the ventricular rate and to use anti-thrombotic therapy. modified from JACC 2001; 38: 1266i-lxx.
Amellem O and Pettersen EO 1997 ; Cell inactivation and cell cycle inhibition as induced by extreme hypoxia: the possible role of cell cycle arrest as a protection against hypoxia-induced lethal damage. Cell Prolif 24: 127141. Bachelerie F, Alcami J, Avenzana-Seisdedos F and Virelizier JL 1991 ; HIV enhancer activity perpetuated by NF- B induction of infection on monocytes. Nature Lond ; 350: 709 712. Batra RK, Guttridge DC, Brenner DA, Dubinett SM, Baldwin AS and Boucher RC 1999 ; IkappaBalpha gene transfer is cytotoxic to squamous-cell lung cancer cells and sensitizes them to tumor necrosis factor-alpha-mediated cell death. J Respir Cell Mol Biol 21: 238 245. Bush RS, Jenkin RD, Allt WE, Beale FA, Bean H, Dembo AJ and Pringle JF 1978 ; Definitive evidence for hypoxic cells influencing cure in cancer therapy. Br J Cancer Suppl 37: 302306. Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, et al. 1998 ; Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature Lond ; 394: 485 490. Chen CL and Uckun FM 2000 ; Highly sensitive liquid chromatography-electrospray mass spectrometry LC-MS ; method for the determination of etoposide levels in human serum and plasma. J Chromatogr B Biomed Sci Appl 744: 9198.
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Of all the other living species on earth, humans are most closely related to three of the great apes: gorillas, chimpanzees and their close cousins, bonobos. 92- 98.5% of their DNA is identical with ours; we share the same ABO blood groups with them; they have 48 chromosomes, we have 46. Apes and humans belong to the large mammalian `Order of Primates' which also includes lemurs and monkeys. Within that Order, humans belong to the Family of Hominids which includes all two-legged, man-like species, extinct or living. Within the Hominid family are a number of extinct erectwalking apes, our immediate ancestors, and ourselves. We are members of the Genus Homo "Man" ; . Our species name is and flolan
Krishnan SC, Antzelevitch C: Flecainide-induced arrhythmia in canine ventricular epicardium. Phase 2 reentry? Circulation 1993, 87 2 ; : 562-572. Miller JM, Zipes DP: Management of the patient with cardiac arrhythmias. In Heart Disease Edited by: Braunwald E, Zipes DP, Libby P. WB Saunders Company; 2001: 700-774. Corkeron MA, van Heerden PV, Newman SM, Dusci L: Extracorporeal circulatory support in near-fatal flecainide overdose. Anaesth Intensive Care 1999, 27 4 ; : 405-408. Auzinger GM, Scheinkestel CD: Successful extracorporeal life support in a case of severe flecainide intoxication. Crit Care Med 2001, 29 4 ; : 887-890. Flecainide in Toxbase [ : spib.axl toxbase poi sons%20Information F Flecainide ] Goldman MJ, Mowry JB, Kirk MA: Sodium bicarbonate to correct widened QRS in a case of flecainide overdose. J Emerg Med 1997, 15 2 ; : 183-186. Siegers A, Board PN: Amiodarone used in successful resuscitation after near-fatal flecainide overdose. Resuscitation 2002, 53 1 ; : 105-8.
Department of Pharmacy, Christie Hospital National Health Service Trust, Wilmslow Road, Manchester M20 9BX, UK. Email: helen.flint christie-tr.nwest.nhs ; fax: + 44 0 ; 161 446 3437 and flu.
Tambocor 3m pharmaceuticals ; composition: flecainide acetate.
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Arr's presence in the cardiovascular category, particularly through our generic Warfarin Sodium product, continued to grow during fiscal 2001. We launched Warfarin in 1997, the first generic equivalent of Coumadin, an anticoagulant given to patients with heart disease and or high risk of stroke. Since then, our product has been dispensed more than 16 million times. During fiscal 2001, the percentage of Coumadin prescriptions filled with a generic version has increased steadily to approximately 42%. Total U.S. generic and brand sales of Warfarin Sodium were approximately 5 million last year. In addition to our continued support of legislative initiatives to remove barriers to Warfarin substitution, we continued our commitment to educating physicians, pharmacists and patients about the benefits of generic Warfarin. Our Warfarin web site warfarininfo ; , which was launched a year ago, has logged nearly 1 million visits. During fiscal 2001, we also added another cardiovascular therapy to the products that we currently market. In January 2001, we received approval for Amiodarone Hydrochloride, the generic equivalent of Wyeth Ayerst Laboratories, Inc.'s Cordarone. Cordarone is indicated for the treatment of life threatening recurrent ventricular arrhythmias, recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia. Current annual sales are approximately 5 million. In May 2000, we filed an application with the FDA initiating a patent challenge on Flecainide Acetate tablets, which are sold under the brand name, Tambocor. This case involves an alleged infringement of raw material patents and is not a challenge to the validity of patents protecting the product. Flecainide has current annual sales of approximately million and fludarabine.
43. Sicouri S, Quist M, Antzelevitch C. Evidence for the presence of M cells in the guinea pig ventricle. J Cardiovasc Electrophysiol 7: 503511, 1996. Slawsky MT, Castle NA. K channel blocking actions of flecainide compared with those of propafenone and quinidine in adult rat ventricular myocytes. J Pharmacol Exp Ther 269: 66 74, ten Tusscher KHWJ, Noble D, Noble PJ, Panfilov AV. A model for human ventricular tissue. J Physiol Heart Circ Physiol 286: H1573 H1589, 2004. 46. Tian XL, Yong SL, Wan X, Wu L, Chung MK, Tchou PJ, Rosenbaum DS, Van Wagoner DR, Kirsch GE, Wang Q. Mechanisms by which SCN5A mutation N1325S causes cardiac arrhythmias and sudden death in vivo. Cardiovasc Res 61: 256 267, Vecchietti S, Rivolta I, Severi S, Napolitano C, Priori S, Cavalcanti S. Computer simulation of wild-type and mutant human cardiac Na current. Med Biol Eng Comput 44: 35 44, Viswanathan PC, Rudy Y. Pause induced early afterdepolarizations in the long QT syndrome: a simulation study. Cardiovasc Res 42: 530 542, Wang DW, Kiyosue T, Sato T, Arita M. Comparison of the effects of class I anti-arrhythmic drugs, cibenzoline, mexiletine and flecainide, on the delayed rectifier K current of guinea-pig ventricular myocytes. J Mol Cell Cardiol 28: 893903, 1996. Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 100: 1660 1666.
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The improved efficacy of flecainide as compared to digoxin alone in conversion of fetal svt was statistically significant with a p value conclusions : digoxin remains a safe and effective first line therapy in the treatment of fetal svt and flecainide.
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