Introduction. CLINICAL RESEARCH Sudden Death and ICDs
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1 Europace (2011) 13, doi: /europace/eur066 CLINICAL RESEARCH Sudden Death and ICDs Determinants of geographic variations in implantation of cardiac defibrillators in the European Society of Cardiology member countries data from the European Heart Rhythm Association White Book Andrzej Lubinski 1, Andrzej Bissinger 1 *, Lucas Boersma 2, Antoine Leenhardt 3, Bela Merkely 4, Ali Oto 5, Alessandro Proclemer 6, Josep Brugada 7, Panos E. Vardas 8, and Christian Wolpert 9 1 Department of Interventional Cardiology, Medical University of Lodz, Poland; 2 Cardiology Department, St. Antonius Hospital, Heart Lung Center Utrecht, Utrecht, The Netherlands; 3 Cardiology Department, Lariboisiere University Hospital, Paris, France; 4 Semmelweis University, Heart Center, Budapest, Hungary; 5 Hacettepe University Departments of Cardiology, Ankara, Turkey; 6 Division of Cardiology, Department of Cardiovascular Sciences, S. Maria della Misericordia, Hospital, Udine, Italy; 7 Thorax Institute, Hospital Clínic, University of Barcelona, Institut d Investigació Biomèdica August Pi i Sunyer, Barcelona, Catalonia, Spain; 8 Department of Cardiology, Heraklion University Hospital, Heraklion, Crete, Greece; and 9 Department of Medicine-Cardiology, Nephrology and Internal Intensive Care Medicine, Ludwigsburg, Klinikum Ludwigsburg, Germany Received 8 May 2010; accepted after revision 16 February 2011; online publish-ahead-of-print 31 March 2011 Aims Sudden cardiac death (SCD) is a major health concern in developed countries. Many studies have demonstrated the efficacy of implantable cardioverter defibrillator (ICD) therapy in the prevention of SCD and total mortality reduction. However, the high individual costs and the reimbursement policy may limit widespread ICD utilization.... Methods This study analyzed the temporal and the geographical trends of the ICD implantation rate. Data were gathered from and results two editions of the European Heart Rhythm Association (EHRA) White Books published in 2008 and The analysis revealed significant differences in the rates of ICD implantation per million capita between the countries, but the median implantations was constantly increasing. The number of ICD implantations correlated with gross domestic product (GDP), GDP per capita, expenditure on health, life expectancy, and the number of implanting centres.... Conclusion There are great number of differences in the ICD-implanting rates between EHRA member countries, consequent to the increase in the number of ICD implantations. The ICD implantation rates are related to national economic status and healthcare expenses Keywords Implantable cardioverter defibrillator Geographic variations Implantation rate Europe Reimbursement Healthcare expenses Introduction Sudden cardiac death (SCD) claims victims annually in the USA. 1 While no official statistics are reported in Europe, the very similar cardiovascular risk profile of Western Europeans implies that the SCD number must be similar. Thus, SCD is responsible for more deaths than cancers, stroke, and AIDS combined. 1,2 Many studies have demonstrated the efficacy of implantable cardioverter defibrillator (ICD) therapy in the prevention of SCD and total mortality reduction. 3 7 The European guidelines published in 2006 are intended to assist healthcare providers by describing a range of acceptable approaches for utilization of ICD therapy in selected patients for primary and secondary prevention of SCD. 8 However, despite the established European guidelines for the implantation of ICDs, the rate of implantation varies * Corresponding author. Tel: ; fax: , abissinger@gmail.com Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oup.com.
2 Determinants of geographic variations in implantation of cardiac defibrillators 655 between countries. Therefore, the European Heart Rhythm Association (EHRA) launched a project to assess the treatment of arrhythmias in all European Society of Cardiology (ESC) member countries, thereby creating a platform for a progressive harmonization of arrhythmia treatment. As a result, two EHRA White Books were published in 2008 and ,10 The White Book provides information about the status of cardiac electrophysiology, demographic, economic, and healthcare data. The study analysed temporal and geographical trends of the ICD implantation rate in the years in the European Society of Cardiology member countries and identified the determinants for geographical variations. Methods Data were gathered from the EHRA White Book publications. 9,10 A total of 41 countries members of the ESC provided comprehensive Table 1 Demographic, economic, and insurance data Population, GDP, Health expenditure, Government health Public ICD million 2008 Euro/capita Euro/capita expenditure (%) insurance (%) reimbursement... Armenia Yes Austria Yes Belarus Yes Belgium Yes Bulgaria No Croatia No Cyprus No Czech Republic Yes Denmark No Egypt No Estonia Yes Finland Yes France Yes Georgia Yes Germany Yes Greece Yes Hungary Yes Iceland No Ireland Yes Israel Yes Italy Yes Latvia Yes Lebanon Yes Lithuania Yes Luxembourg Yes FYROM No Netherlands Yes Norway Yes Poland Yes Portugal Yes Romania Yes Russia Yes Serbia Yes Slovakia Yes Slovenia Yes Spain Yes Sweden Yes Switzerland Yes Tunisia Yes Turkey Yes UK Yes
3 656 A. Lubinski et al. Italy Germany Denmark Czech Republic Netherlands Finland Switzerland Belgium Iceland Austria France 2008 Israel Slovakia Greece 2007 Poland Spain Luxembourg 2006 Sweden United Kingdom Portugal Hungary Slovenia Cyprus Armenia Serbia Lebanon Croatia Latvia Lithuania Estonia Tunisia Romania Belarus Georgia Macedonia Missing or partial data for 2008 Bulgaria Egypt Norway Ireland Turkey Russian Federation Figure 1 Number of implantable cardioverter defibrillator implantations per million inhabitants in the years The data sorted according to implantations in the year data and were included in the analysis. The list of participating countries is presented in Table 1. It should be noted that demographic or economic data were dated a few years earlier in some cases, but did not exceed 3 years. Implantation data from the years 2006, 2007, and 2008 have been analysed. To gather data on specific items, a questionnaire was constructed. Each chairperson of the societies and/or working groups was asked to provide data for each item. Many of the countries used their national registry as the data source. In other countries, the presidents of the societies conducted a national survey or used national health institutions data or other available sources. To validate the gathered data, presidents of the different working groups and national societies were contacted and asked to verify and authorize all the information that became available through these various sources. In cases where valid data were not available, the data were not presented. The detailed process of collecting data to the White Book was presented by Merkely et al. 11 The analysed variables included: (1) ICD implantations per million of the population in the years 2006, 2007, and (2) Single- vs. dual-chamber ICDs implantations (in several countries these data were not available). (3) Number of implanting centres per 1 million population. (4) Number of ICD implantations per centre annually. (5) Correlations between ICD implantations per million and: (a) National gross domestic product (GDP) or expenditure on health. (b) Number of implanting centres per 1 million inhabitants. (c) Density of physicians. (d) Number of hospitals or beds. (e) Life expectancy at birth. Statistical analysis For comparison, data are shown as mean and median. Shapiro Wilk W test was used to test for a normal distribution. Correlations were performed using Spearman s correlation tests. A P value of,0.05 was considered significant. Results The analysis revealed significant differences in the rates of ICD implantations per million capita between the countries (Figure 1). Highest numbers of implants per million annually in 2008 was in Italy, Germany, and Denmark. In almost all countries, increasing numbers of ICD implantations from the years 2006 to 2008 were observed (Figure 2). The median implantations per million was constantly increasing from 39 in the year 2006 to 75 in the year Table 2 presents percentiles of the implantation rate. The mean growth of implantations per million between 2006 and 2008 was (87%) from 22.5 to implantations per million. Some countries, such as Switzerland, Slovakia, and Poland, had increased their implantation rate by 1.5 times. The utility of single- vs. dual-chamber ICDs varied considerably from country to country. The distribution of single- and dual-
4 Determinants of geographic variations in implantation of cardiac defibrillators 657 Denmark Switzerland Finland Netherlands Italy Czech Republic Germany Slovakia France Poland Greece Spain Sweden Belgium Austria Portugal Israel Armenia Luxembourg Hungary Serbia United Kingdom Lithuania Latvia Slovenia Croatia Belarus Estonia Tunisia Romania Georgia Egypt Russian Macedonia Lebanon >75 percentile percentile <25 percentile Figure 2 Changes in the implantable cardioverter defibrillator implantation in per million inhabitants. Percentiles of implantation rate in the year 2006 marked with different colours. Table 2 The distribution of the ICD implantation rates in the years 2006 and 2008 Number ICDs/ Percentiles million chamber device utilization in the mentioned countries is presented in Figure 3. The analysis revealed that the number of ICD implanting centres also significantly varies between countries, from 0.1 to 6.88 per million populations. The mean number of implantations per centre varies from 2 to 251, and the median is 43. The data are presented in Table 3. The analysis of the relationship between ICD implantations per million population in 2008 with economic data revealed significant correlations between the number of ICD implantations and the GDP (r ¼ 0.68, P, ), the GDP per capita (r ¼ 0.79, P, ), and the expenditure on health (r ¼ 0.69, P, ). The type of implanted ICD single or dual chamber did not correlate with GDP and expenditure on health. Of interest, is that a significant correlation was found between life expectancy and implantation rates (r ¼ 0.71, P, ). A weak correlation was observed between density of physicians and ICD implant rates (r ¼ 0.35, P ¼ 0.04). Also, strong positive correlation between the number of implanting centres per million and the ICD implantations per million population was observed (r ¼ 0.68, P, ). No correlation was found between healthcare indices like: number of hospitals or beds, and ICD implantation rates. In addition, the presence of a subspecialty in cardiac electrophysiology had no influence on implantation rates (Table 4). Discussion Implantable cardioverter defibrillator utilization The ESC guidelines for the use of ICDs 8 were published and accepted in numerous European countries, long before the beginning of the data collection in the White Book. Despite these acknowledged guidelines, ICD implantation rates remain significantly different among the ESC member countries. Not only economic factors affect these differences. There is an open space for activity of scientific organizations, such as, EHRA to foster discussion and offer education to increase awareness of the risk of SCD and appropriate ways of its prevention. There are a limited number of world surveys of ICD practices, and most are based on information from national registers or questionnaires sent to selected hospitals or industry data. One of these surveys is a worldwide quadrennial survey of cardiac pacing and ICD practices conducted by the International Cardiac Pacing and Electrophysiology Society. Implantable cardioverter defibrillators were included in this survey in 1993 and it covered 43 countries in All countries surveyed showed a significant rise in the use of ICDs. 12 The authors analysis
5 658 A. Lubinski et al. Single-chamber ICD Dual-chamber ICD 0% 20% 40% 60% 80% 100% Armenia Greece Israel Sweden Belarus Estonia Latvia Switzerland United Kingdom Austria Denmark Iceland Belgium Egypt Germany Finland Slovakia Lithuania Czech Republic Hungary Spain Poland Serbia Slovenia Luxembourg Portugal Lebanon Bulgaria Georgia Macedonia Figure 3 Percentage of implanted single- and dual-chamber implantable cardioverter defibrillators in the year Average 60% were singlechamber implantable cardioverter defibrillators. based on the White Book showed that the number of implantations increased significantly from the year 2006 to Almost all countries noted an increase in ICD utilization. It is interesting that countries with a higher number of implants in the year 2006 (upper quartile) showed a higher increase in implantation from 2006 to 2008 (Figure 2). It is possible that one of the factors influencing a higher number of implantations is that countries implanting more ICD for several years have a higher replacement rate. Analysed data contain primary implants and replacements together. Higher rate of replacement in some years may be also connected with advisory of manufacturers due to problems with various parts of ICD. 13 Other explanation is that, leading ICD implantation countries have a healthcare system favourable for SCD prevention. In spite of the increasing number of implantations, there are great discrepancies between the analysed countries. A high implantation rate may be provided also in countries with modest economic resources (e.g. Czech Republic). On the basis of the White Book, in most countries (60%) physicians preferred utilization of single-chamber ICDs. The decision about selecting single- or dual-chamber ICD is a still matter of debate. The clinical advantages of dual-chamber over singlechamber ICD has not been confirmed in large clinical studies. 14 Even though the results of the recently published DATAS trial 15 suggest potential benefits of dual-chamber devices, the optimal approach remains unsettled. The authors did not reveal the relationship between implantation rates of dual- or single-chamber ICDs and health expenditure or GDP. It seems that the factors determining the selection of double- or single-chamber ICD are not dependent on economics. It was observed (Figure 3) that more expensive dual-chamber ICDs were implanted by countries with low GDP and health expenditure as well as by countries with high GDP and health expenditure. The specific reasons for differences in ICD implantation patterns between countries could not be explained on the basis of the analysed data. Economic factors The analysis demonstrated that economic status presented as the total GDP and GDP per capita directly correlated with ICD implants. Furthermore, a higher expenditure on health positively correlated with implantation rates. This observation was also confirmed by Ovsyshcher and Furman 16 who also found a modest correlation between GDP per capita and annual health expenditures with the European first-time ICD implantation rates (r ¼ 0.66, P, 0.01). Besides GDP and health expenditure, the implantation
6 Determinants of geographic variations in implantation of cardiac defibrillators 659 Table 3 ICD implantation data ICD/million Change 2006 %of ICD implanting Number of ICD EP National population 2008, ICD/ single-chamber centres/million implantation per subspecialty ICD 2008 million ICDs 2008 population centre guidelines population... Armenia No No Austria No No Belarus Yes Yes Belgium No Yes Bulgaria 1.2 n.a No No Croatia n.a No No Cyprus 44.2 n.a. n.a No No Czech Yes Yes Republic Denmark No Yes Egypt 0.2 n.a Yes Yes Estonia No No Finland No Yes France n.a No Yes Georgia No No Germany No Yes Greece No No Hungary Yes Yes Iceland n.a No No Ireland 79.2* n.a. n.a n.a. No Yes Israel No No Italy n.a No Yes Latvia Yes Yes Lebanon No No Lithuania No No Luxembourg No No FYROM No No Netherlands n.a Yes Yes Norway 126.8* n.a. n.a n.a. No No Poland Yes No Portugal Yes No Romania n.a No No Russia 2.3* n.a. n.a n.a. Yes Yes Serbia No No Slovakia Yes Yes Slovenia No No Spain Yes Yes Sweden No Yes Switzerland No Yes Tunisia n.a Yes No Turkey 12.5* n.a. n.a n.a. n.a. No No United No Yes Kingdom n.a., no data available. *Data from rate may be influenced by other economic factors like procedural reimbursement to physicians and hospitals. Even though almost all countries have reimbursement for ICD devices (exceptions being Bulgaria, Cyprus, Croatia, Egypt, and Former Yugoslav Republic of Macedonia FYROM), the forms of reimbursement are complex and heterogeneous in different countries (Table 5).
7 660 A. Lubinski et al. Table 4 Analysis of correlations between ICD implantations and economic and healthcare data X ICD implantations per million in the year GDP r ¼ 0.68 P, GDP per capita r ¼ 0.79 P, Total expenditure on health r ¼ 0.69 P, Life expectancy at birth r ¼ 0.71 P, Number of implanting centres r ¼ 0.68 P, per million inhabitants Density of physicians r ¼ 0.35 P ¼ 0.04 Hospitals ns Beds ns Population over 65 years old ns (r), correlation coefficient; ns, non-significant. Table 5 Examples of reimbursement schemes of cardiac devices in selected countries Case or DRGs Hospital global budgets Positive list... Germany Spain Belgium UK Italy France France Switzerland Portugal Austria Netherlands Denmark Finland Norway Sweden Reimbursement refers to the coverage of medical costs by the public authorities (healthcare funds, regional or central government agencies). Reasonable reimbursement should be based on the basis of a cost-effectiveness data. Cost effectiveness of ICD was confirmed in many studies, especially in the US population. 17,18 Cowie et al. 19 presented a modelling study in which the cost effectiveness of primary prophylactic ICD implantation according to the current European guidelines was analysed in the European population. Cowie et al. 19 found that under most assumptions in a European healthcare setting, the prophylactic implantation of an ICD has a cost-effectiveness ratio below EUR per QALY (quality-adjusted life years) in patients with an increased risk of SCD due to low left ventricular ejection fraction (,35%). Although full implementation of this therapy, according to the guidelines has potentially high costs and organizational implications for European healthcare systems, this analysis however indicates that such expenditure represents good value for money. The authors have no data to analyse other important economic factors such as procedural costs that include cost of the device, implantation, and hospitalization. It is particularly interesting to note how implant reimbursement costs vary significantly between countries. For example, the reimbursement costs for the single-chamber ICD implantation in Belgium are EUR, whereas in the Netherlands this is EUR. The latter value is thrice higher than that in Germany ( EUR), depending on the calculation in the diagnosis-related groups Diagnostic-Related Group (DRG). 20 In some countries such as Poland, despite the use of the same expense calculation based on DRG, reimbursement costs are only 8500 EUR, including other costs such as device and hospitalization. Although economic indices seem to be very important factors influencing the implantation rate, some other factors may also be of significance. There are several countries with a lower economic status but with a higher implantation rate than more wealthy countries (e.g. Czech Republic, Israel, or Slovakia). Conversely, some countries with a similar economic status have significantly different ICD implantation rates. For example, the UK has much lower implant rates than Italy or France. The data from international ICD registries reported not only differences between various countries but also regional differences within the same country. For example, the report from the UK National Survey 2008 presents significant regional differences in the ICD implantation rates. 21 Similar situations are observed in other European countries. 22,23 Therefore, it is seen that besides economics, there are other factors responsible for differences in implantation rates. Healthcare factors The present analysis revealed a significant positive correlation between life expectancy and ICD implantation rates. There are variations in life expectancy between different countries, mostly caused by differences in public health, medical care, and access to healthcare. Improvements in healthcare and welfare increase life expectancy. 24 The observation that in countries with longer life expectancy implantable devices were more frequently used suggests that in countries with well-developed healthcare access to ICD implantations is easier. Only borderline correlation between the number of physicians per population and the implantation rate indicates that the number of physicians is not the predominant factor in determining adherence to the guidelines. It would be of interest to calculate the correlation between the number of implanting physicians and the implantation rate. A high number of ICD implants in countries with a high density of implantation centres may favour such a hypothesis. Although most of the countries have at least one centre per million inhabitants, the relatively low number of procedures per centre is surprising. According to the Core curriculum for the hearth rhythm specialist published on behalf of the Accreditation Committee of the European Heart Rhythm Association, the training centre should perform at least 50 ICD implantations/replacements per year. 25 A mean implantation rate over 50 per centre yearly was reported in Armenia, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, the Netherlands, Poland, Slovakia, and the UK. The World Survey published by Mond et al. 12 revealed that countries with predominantly government-funded services, such as Denmark and the United Kingdom, generally have fewer
8 Determinants of geographic variations in implantation of cardiac defibrillators 661 implanting hospitals and hence higher implant numbers per centre. Interestingly enough, there is no influence of cardiac electrophysiology subspecialty on ICD implantation. Camm et al. 23 suggest that more of the electrophysiologists workload is spent on ablation procedures and this effort competes with the time of the electrophysiologist and the electrophysiology laboratory that can be made available for ICD implantation. This may be another important contributor to the underutilization of ICDs in Europe. On the other hand, there are some data that physicians are not always aware of, such as the effectiveness of ICD treatment in those at risk of SCD. 26 Therefore, organizations such as EHRA should educate doctors, and also nurses, physiologists, technicians, patients, caregivers, support groups, healthcare payers, healthcare managers, and government officials in terms of the improvement of the care of patients with cardiac arrhythmias. Potential implantable cardioverter defibrillator recipients Another factor affecting ICD implantation could be the target population. In some countries, the population for ICDs consists mainly of cardiac arrest survivors (secondary prevention), while in other countries, mainly primary prevention patients receive a device. The data in national ICD registries indicate that the number of patients treated with an ICD for primary prevention is rapidly increasing. For example, in Italy, prophylactic ICD implantation was 44.2% of the total implants in 2005 and 55.7% in 2007, 27 and it is noteworthy that in the USA 80% of ICD recipients have primary prevention implants. 14,28 Information about primary vs. secondary prevention implants will be available in the next edition of the White Book. One of the factors for determining the disparities in ICD implants rate can be different adherence to guidelines. Unfortunately, in the 2008 and 2009 editions of the White Book, no data about indications for ICD implantations are provided. Practical implications Such data as presented in the White Book can provide the opportunity to share and exchange information from ESC member countries on specific needs for improvements, reimbursement policy, and training issues. The data can also be used for creating standards for education and training and offer assistance necessary to harmonize treatment of arrhythmias. Limitations The White Book contains only selective information about economies and healthcare systems. The limited data published in the EHRA White Book do not allow for a thorough analysis of all factors that could have an influence on the selection of patients for the ICD implantation. Information about indications for ICD implantations is missing. Also, the White Book did not provide information about first-time implantation and device replacement. The data represent a reasonable percentage of the actual procedures but not the absolute reality. However, it is possible to make approximation of replacements rates and indications for ICD on the basis of previous studies and according to information from manufacturers and European Confederation of Medical Devices Association (EUCOMED). In the White Book data from EUCOMED were only used if the national chairman authorized the correctness of data for his country and only served as an additional source. Conclusions (1) There are great differences in the ICD-implanting rates between EHRA member countries. (2) The number of ICD implantations is increasing in almost all countries. (3) There are discrepancies in the number of implanting centres per million inhabitants between countries. The number of centres correlate with implantation rates. (4) The factors affecting the number of ICD implantations are national economic status and healthcare expenses. Conflict of interest: none declared. Funding The EHRA White Book project was made possible by an unrestricted educational grant from BIOTRONIK SE & Co. KG, Germany. References 1. Centers for Disease Control and Prevention. State-specific mortality from sudden cardiac death-united States, Morb Mortal Wkly Rep (MMWR) 2002;51: American Heart Association Heart and Stroke Statistical. Dallas, TX: Amercian Heart Association; Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999;341: Kuck KH, Cappato R, Siebels J, Ruppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation 2000;102: Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346: Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004;350: Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study Hamburg. Canadian Implantable Defibrillator Study. Eur Heart J 2000;21: Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M et al. ACC/ AHA/ESC 2006 Guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114:e The EHRA White Book. July publications/documents/ehra-white-book-2008.pdf The EHRA White Book. July publications/documents/ehra-white-book-2009.pdf Merkely B, Roka A, Kutyifa V, Boersma L, Leenhardt A, Lubinski A et al. 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9 662 A. Lubinski et al. 12. Mond HG, Irwin M, Ector H, Proclemer A. The world survey of cardiac pacing and cardioverter-defibrillators: calendar year 2005 an International Cardiac Pacing and Electrophysiology Society (ICPES) project. Pacing Clin Electrophysiol 2008;31: Maisel WH. Pacemaker and ICD generator reliability: meta-analysis of device registries. JAMA 2006;295: Brown DW, Croft JB, Greenlund KJ, Mensah GA, Giles WH. Trends in hospitalization for the implantation of cardioverter-defibrillators in the United States, Am J Cardiol 2008;101: Almendral J, Arribas F, Wolpert C, Ricci R, Adragao P, Cobo E et al. Dualchamber defibrillators reduce clinically significant adverse events compared with single-chamber devices: results from the DATAS (Dual chamber and Atrial Tachyarrhythmias Adverse events Study) trial. Europace 2008;10: Ovsyshcher IE, Furman S. Determinants of geographic variations in pacemakers and implantable cardioverter defibrillators implantation rates. Pacing Clin Electrophysiol 2003;26: Mark DB, Nelson CL, Anstrom KJ, Al Khatib SM, Tsiatis AA, Cowper PA et al. Cost-effectiveness of defibrillator therapy or amiodarone in chronic stable heart failure: results from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Circulation 2006;114: Sanders GD, Hlatky MA, Owens DK. Cost-effectiveness of implantable cardioverter-defibrillators. N Engl J Med 2005;353: Cowie MR, Marshall D, Drummond M, Ferko N, Maschio M, Ekman M et al. Lifetime cost-effectiveness of prophylactic implantation of a cardioverter defibrillator in patients with reduced left ventricular systolic function: results of Markov modelling in a European population. Europace 2009;11: Meine M, Smith T, Hauer RN. The economical challenge in the treatment of chronic heart failure: is primary prophylactic ICD therapy cost-effective in Europe? Europace 2009;11: Heart Rhythm Devices: UK National Survey nsf Danish Pacemaker and ICD Register Camm JA, Nisam S. European utilization of the implantable defibrillator: has 10 years changed the enigma? Europace 2010;12: Sullivan A, Sheffrin SM. Economics: Principles in action. Upper Saddle River, New Jersey: Pearson Prentice Hall; Merino JL, Arribas F, Botto GL, Huikuri H, Kraemer LI, Linde C et al. Core curriculum for the heart rhythm specialist. Europace 2009;11(Suppl. 3): iii EUCOMED. Awareness of Device Therapy Survey, Brussels, December Proclemer A, Ghidina M, Gregori D, Facchin D, Rebellato L, Fioretti P et al. Impact of the main implantable cardioverter-defibrillator trials in clinical practice: data from the Italian ICD Registry for the years Europace 2009;11: Greenberg SM, Epstein AE, Deering T, Goldman DS, Ghidina M, Neason C et al. A Comparison of ICD implantations in the United States versus Italy. Pacing Clin Electrophysiol 2007;30(Suppl. 1):S143 6.
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