Follow-Up Defibrillator Testing for Antiarrhythmic Drugs
2006; Lippincott Williams & Wilkins; Volume: 114; Issue: 2 Linguagem: Inglês
10.1161/circulationaha.106.637397
ISSN1524-4539
AutoresMark A. Wood, Kenneth A. Ellenbogen,
Tópico(s)Cardiac Arrhythmias and Treatments
ResumoHomeCirculationVol. 114, No. 2Follow-Up Defibrillator Testing for Antiarrhythmic Drugs Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBFollow-Up Defibrillator Testing for Antiarrhythmic DrugsProbability and Uncertainty Mark A. Wood and Kenneth A. Ellenbogen Mark A. WoodMark A. Wood From the Virginia Commonwealth University Medical Center, Richmond, Va. and Kenneth A. EllenbogenKenneth A. Ellenbogen From the Virginia Commonwealth University Medical Center, Richmond, Va. Originally published11 Jul 2006https://doi.org/10.1161/CIRCULATIONAHA.106.637397Circulation. 2006;114:98–100Probabilism: The doctrine that probability is a sufficient basis for belief or action.Uncertainty: The condition of being in doubt.It has been rigorously demonstrated that implantable cardioverter-defibrillators (ICDs) prolong life as primary and secondary prevention therapies for the management of malignant ventricular tachyarrhythmias. Despite 20 years of clinical use, however, there exist many unresolved issues in ICD therapy.1 Even the most fundamental aspect of ICD implantation, defibrillation threshold (DFT) testing, is not standardized. Determining a DFT is fundamentally different from determining a pacing threshold.1,2 The latter is essentially a fixed value at a given combination of pulse width and voltage. Clinically, there is a sharp demarcation of pacing voltages that capture and those that do not. In contrast, defibrillation is characterized as a probabilistic event based on our current understanding. The dose-response curve for defibrillation is described as sigmoidal in shape with a higher likelihood of success at higher energies.1,2 The possibility of an "outlier" event, defibrillation at low energy, or failure at higher energy remains present. Defining a true defibrillation threshold, ie, that energy above which defibrillation will always succeed and below which it will always fail, is not the goal of defibrillation testing in the clinical setting. Instead, the clinical approach to ICD implantation defines an energy level delivered from a device that has a reasonable likelihood of success. The physician then programs this energy plus an additional safety margin that he or she trusts will compensate for the probabilistic nature of defibrillation. There are many methods to test defibrillation in clinical practice. Methods in clinical use include step down to failure, 2 or 3 successes without failure at a given energy level (DFT+, DFT++), binary search, Bayesian search, 3-reversal method, verification method (single low-energy success), and testing upper limit of vulnerability1,2 These methods may all estimate different positions on the sigmoidal defibrillation dose-response curve, and therefore the method of testing has a bearing on the safety margin. The safety margin is also programmed to allow for uncertainties in the defibrillation energy requirement over time due to progressive cardiac disease, acute ischemia, diurnal changes in autonomic tone, electrolyte or hormonal changes, and the addition of antiarrhythmic drugs. The required magnitude of this energy safety margin is itself debated.2,3 The accepted safety margin for the DFT at implantation is traditionally held to be 10 J below maximal output of the device. Although prospective studies have challenged this fixed margin, the empiric 10-J limit is ingrained from early ICD experience despite an absence of a scientific foundation.3 Some investigators have suggested that with a carefully defined DFT, a position on the DFT curve of at least DFT 80% can be identified and the safety margin may be considerably less than 10 J.2 The methods of DFT testing and determination of the safety margin are in essence exercises in probabilism—the belief that a sufficiently high probability of defibrillation warrants implantation of the device. This view is probably better appreciated by those who remember the vicissitudes of testing early monophasic ICDs.Article p 104Still other uncertainties remain in ICD therapy.1 These unsettled issues include the optimal defibrillation lead configuration, need for waveform optimization at implantation, hemodynamic sequelae of ICD testing, and the need for yearly ICD testing to confirm response to ventricular fibrillation among others. Probably no aspect of ICD therapy is more unsettled than the effects of antiarrhythmics and other drugs on the DFT. Few agents have nonconflicting data presented in the literature. The variable effects reported for these agents can often be attributed to data derived from different animal species, nonuniform methods for determining DFT, and use of different waveforms between studies. Data on antiarrhythmic drugs and DFT in human studies are predominantly retrospective, uncontrolled, or in the form of case reports and anecdotal experiences. From the list of controversial drugs, amiodarone has received the most attention because of its complex electrophysiological effects and its widespread use in the ICD population. Previous reports have suggested that amiodarone can increase, decrease, or affect no change in defibrillation energy requirements in humans.4–8 Fain et al4 reported that intravenous amiodarone reduced DFT, whereas chronic amiodarone therapy increased DFT using a monophasic waveform. Others have reported increased short-term defibrillation energy requirements with intravenous amiodarone.5 Chronic amiodarone use has been reported to increase defibrillation energy requirements by up to 60%.6 Half of the patients evaluated for high DFTs were taking amiodarone in a study by Epstein et al.7 In another study, no change in DFTs in patients taking chronic amiodarone was reported.8 None of these studies, however, have been prospective, randomized trials in patients with modern ICDs.The study by Hohnloser et al,9 which appears in this issue of Circulation, is a welcome addition to the literature. Within the Optimal Pharmacological Therapy in Cardioverter defibrillator patients (OPTIC) study, designed to evaluate the efficacy of amiodarone, sotalol, and β-blockers in the reduction of ICD shocks, these investigators performed serial DFT testing in 94 randomized patients. The investigators demonstrated an average increase in DFT of 1.29 J in 35 patients receiving amiodarone and an average 0.8-J decrease in DFT in 30 patients receiving sotalol. Average DFT decreased by 1.64 J in the control group receiving β-blockers alone. The changes in DFT were statistically significant compared with baseline in the amiodarone and β-blocker groups. The average DFTs for all groups were 10 J had an increase of more than 10 J while receiving amiodarone, although 1 patient with low DFT at baseline (2.5 J) had a 17-J increase of DFT when taking amiodarone. Because drug therapy was initiated at the time of ICD implantation, it is unknown if such individual changes in DFT were due to drug effects, changes in lead positions, or maturation of the ICD system. From the figures, there appears to be at least 1 patient with noticeably increased DFT in the sotalol group. A more detailed characterization of the individual DFT changes in all patients in all 3 groups would have been interesting. Although the authors' intention in describing only those patients with high baseline DFTs is understood, it is not clear from the data whether the magnitude of a DFT increase is proportional to the baseline energy requirements. In fact, the patient with the greatest elevation in DFT had a remarkably low DFT at implantation. In patients with ICDs who had higher average DFTs or a more ill patient population than occurred in the OPTIC trial (patients with New York Heart Association class IV heart failure or ejection fraction 5- or 10-J increase in DFT in response to these agents. In addition, the absence of significant changes in DFT in any of the control patients regardless of DFT would minimize the likelihood that nonpharmacological factors were at play. Nevertheless, all patients in the current study maintained the desired 10-J safety margin for defibrillation. The authors conclude that the DFT is increased by long-term amiodarone therapy but that the magnitude of the increase is unlikely to affect patient outcomes and that routine assessment of DFT after initiation of these drugs may not be required.The authors9 should be congratulated for completing the first randomized controlled evaluation of the effects of these commonly used antiarrhythmics on DFT in humans. The authors made efficient use of a substudy within a larger clinical trial to address an important clinical issue. The evaluation of drug effects as substudies to larger trials may be an attractive means of assessing other controversial agents as well. Otherwise, it is unlikely that specific trials will be undertaken solely to evaluate common drugs such as carvedilol, fentanyl, sildenafil, and calcium channel blockers, which have also been implicated in raising defibrillation energy requirements.10–13Does this study allay all concerns about the effects of amiodarone and DFT? The answer must be "no." There are limitations to any study. First, the number of patients in each arm of the study was relatively small. Individual variations in the response to amiodarone are apparent from the data in this and other studies. The relatively small groups are unlikely to include the full range of responses in clinical practice. Second, some studies have reported a dose-response relationship to the effect of amiodarone on DFT.14 Patients requiring higher doses of amiodarone than tested in this study may have a greater increase in DFT. Third, none of the patients had elevated defibrillation energy requirements at baseline in this study. Given improvements ICD technology, high DFT at implantation is less of a problem now than in the past, but is still encountered. Clearly, the individual increases in DFT seen in the OPTIC substudy could exceed the output of devices in patients with high DFT. Finally, the follow-up DFT testing was performed after a median of 60 days of amiodarone therapy. Long-term exposure to amiodarone may have greater effects. Dispensing with ICD testing after initiation of amiodarone therapy as suggested in this study may be appropriate in the short term and in patients with low baseline DFTs. The potential for problematic DFTs in the long term or in patients with high DFT at baseline are not excluded by this study. In addition, new antiarrhythmic drug therapy can slow the rate of ventricular tachycardias below the detection rate limit and alter the response to antitachycardia pacing. The evaluation of these possibilities and the occasional exposure of otherwise silent system malfunctions remain arguments for follow-up ICD testing independent of the DFT issue.15The study of DFT and individual responses to antiarrhythmic agents deals with probabilities and uncertainties. Physicians establish their faith in the defibrillation capabilities of the ICD at the time of implantation. Yet, uncertainties arise in the individual patient response to the addition of drug therapies. How the physician copes with this uncertainty is a matter of training, personal experience, philosophy, and interpretation of the literature. The findings of this study may be unlikely to persuade a physician to change his or her current practice in regard to follow-up DFT testing. For those who do not routinely perform follow-up testing, the study can be read as a validation. Advocates of follow-up testing may cite the limitations of the study and the unpredictable individual response to amiodarone therapy, especially in the setting of high DFTs. Nevertheless, the study sets a standard for testing unresolved issues surrounding ICD therapy. After 20 years of clinical use and with more than 200 000 ICDs implanted yearly, the time for anecdotal, uncontrolled, and retrospective evaluation of these issues has passed. Defibrillation therapy has largely overcome clinical issues associated with its probabilistic nature. It is now time to systematically and scientifically address its uncertainties.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Sources of FundingDr Ellenbogen has received research grants and Medtronic, Guidant, and St Jude Medical.DisclosuresDr Ellenbogen has honoraria from Medtronic, Guidant, St Jude Medical, and Sorin Biomedical and has served as a consultant on the advisory board of ELA Medical. Dr Wood has no conflicts to disclose.FootnotesCorrespondence to Kenneth A. Ellenbogen, MD, Medical College of Virginia, PO Box 980053, Richmond, VA 23298-0053. E-mail [email protected] or [email protected] References 1 Kroll M, Tchou PJ. Testing and programming of implantable defibrillator functions at implantation. In: Ellenbogen KA, Kay GN, Lau C-P, eds. Clinical Cardiac Pacing and Defibrillation. 3rd ed. Philadelphia, Pa: WB Saunders; In press.Google Scholar2 Singer I, Lang D. The defibrillation threshold. In: Kroll MW, Lehmann HH, eds. Implantable Cardioverter Defibrillator Therapy. Norwell, Mass: Kluwer Academic Publishers; 1996: 89–129.Google Scholar3 Gold MR, Higgins S, Klein R, Gilliam R, Kopelman H, Hessen S, Payne J, Strickberger SA, Breiter D, Hahn S. Efficacy and temporal stability of reduced safety margins for ventricular defibrillation: primary results from the Low Energy Safety Study (LESS). Circulation. 2002; 105: 2043–2048.LinkGoogle Scholar4 Fain ES, Lee JT, Winkle RA. Effects of acute intravenous and chronic oral amiodarone on defibrillation energy requirements. Am Heart J. 1987; 114: 8–17.CrossrefMedlineGoogle Scholar5 Nielson TD, Hamdan MH, Kowal RC, Barbera SJ, Page RL, Joglar JA. Effects of acute amiodarone loading on energy requirements for biphasic ventricular defibrillation. Am J Cardiol. 2001; 88: 446–448.CrossrefMedlineGoogle Scholar6 Pelosi F Jr, Oral H, Kim MH, Sticherling C, Horwood L, Knight BP, Michaud GF, Morady F, Strickberger SA. Effects of chronic amiodarone therapy on defibrillation energy requirements in humans. J Cardiovasc Electrophysiol. 2000; 11: 736–740.CrossrefMedlineGoogle Scholar7 Epstein AE, Ellenbogen KA, Kirk KA, Kay GN, Dailey SM, Plumb VJ. Clinical characteristics and outcome of patients with high defibrillation thresholds: a multicenter study. Circulation. 1992; 86: 1206–1216.CrossrefMedlineGoogle Scholar8 Huang SK, Tan de Guzman WL, Chenarides JG, Okike NO, Vander Salm TJ. Effects of long-term amiodarone therapy on the defibrillation threshold and the rate of shocks of the implantable cardioverter-defibrillator. Am Heart J. 1991; 122: 720–727.CrossrefMedlineGoogle Scholar9 Hohnloser SH, Dorian P, Roberts R, Gent M, Israel CW, Fain E, Champagne J, Connolly SJ. Effect of amiodarone and sotalol on ventricular defibrillation threshold: the Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients (OPTIC) trial. Circulation. 2006; 114: 104–109.LinkGoogle Scholar10 Melichercik J, Goepfrich M, Breidenbach T, Von Hodenberg E. Rise in defibrillation energy requirement under carvedilol therapy. Pacing Clin Electrophysiol. 2001; 24: 1417–1419.CrossrefMedlineGoogle Scholar11 Weinbroum AA, Glick A, Copperman Y, Yashar T, Rudick V, Flaishon R. Halothane, isoflurane, and fentanyl increase the minimally effective defibrillation threshold of an implantable cardioverter defibrillator: first report in humans. Anesth Analg. 2002; 95: 1147–1153.CrossrefMedlineGoogle Scholar12 Shinlapawittayatorn K, Sungoon R, Chattipakorn S, Chittapokorn N. Effects of sildenafil citrate on defibrillation efficacy. J Cardiovasc Electrophysiol. 2006; 17: 292–295.CrossrefMedlineGoogle Scholar13 Jones DL, Klein GJ, Guiraudon GM, Yee R, Brown JE, Sharma AD. Effects of lidocaine and verapamil on defibrillation in humans. J Electrocardiol. 1991; 24: 299–305.CrossrefMedlineGoogle Scholar14 Zhou L, Chen BP, Kluger J, Fan C, Chow MS. Effects of amiodarone and its active metabolite desethylamiodarone on the ventricular defibrillation threshold. J Am Coll Cardiol. 1998; 31: 1672–1678.CrossrefMedlineGoogle Scholar15 Brodsky CM, Chang F, Vlay SC. Multicenter evaluation of implantable cardioverter defibrillator testing after implant: the Post Implant Testing Study (PITS). Pacing Clin. Electrophysiol. 1999; 22: 1769–1776.CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Nof E, Glikson M, Luria D, Gard J and Friedman P (2013) Beyond Sudden Death Prevention: Minimizing ICD Shocks and Morbidity, and Optimizing Efficacy Electrical Diseases of the Heart, 10.1007/978-1-4471-4978-1_40, (621-647), . Schoenhard J and Zei P (2011) Reducing ICD Shocks for Ventricular Arrhythmias, Cardiac Electrophysiology Clinics, 10.1016/j.ccep.2011.05.013, 3:3, (493-502), Online publication date: 1-Sep-2011. Droogan C, Patel C, Yan G and Kowey P (2011) Role of Antiarrhythmic Drugs: Frequent Implantable Cardioverter-Defibrillator Shocks, Risk of Proarrhythmia, and New Drug Therapy, Heart Failure Clinics, 10.1016/j.hfc.2010.12.003, 7:2, (195-205), Online publication date: 1-Apr-2011. Patel C, Yan G, Kocovic D and Kowey P (2009) Should Catheter Ablation be the Preferred Therapy for Reducing ICD Shocks?, Circulation: Arrhythmia and Electrophysiology, 2:6, (705-712), Online publication date: 1-Dec-2009. Álvarez M, Tercedor L, Almansa I and Algarra M (2008) Seguimiento de los pacientes portadores de desfibrilador automático implantable, Revista Española de Cardiología Suplementos, 10.1016/S1131-3587(08)73535-0, 8:1, (22A-30A), Online publication date: 1-Jan-2008. Glikson M, Luria D, Gurevitz O and Friedman P Beyond Sudden Death Prevention: Minimizing Implantable Cardioverter Defibrillator Shocks and Morbidity and Optimizing Efficacy Electrical Diseases of the Heart, 10.1007/978-1-84628-854-8_56, (781-800) SWERDLOW C, RUSSO A and DEGROOT P (2007) The Dilemma of ICD Implant Testing, Pacing and Clinical Electrophysiology, 10.1111/j.1540-8159.2007.00730.x, 30:5, (675-700), Online publication date: 1-May-2007. (2007) Current World Literature, Current Opinion in Cardiology, 10.1097/HCO.0b013e3280126b20, 22:1, (49-53), Online publication date: 1-Jan-2007. July 11, 2006Vol 114, Issue 2 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.106.637397PMID: 16831995 Originally publishedJuly 11, 2006 Keywordstachyarrhythmiastachycardiadeath, suddendefibrillationEditorialsPDF download Advertisement
Referência(s)