Implantable cardioverter-defibrillators (ICD), cardiac resynchronization therapy defibrillators (CRT-D), and cardiac resynchronization therapy (CRT-P) are useful tools for improving the prognosis and/or sudden cardiac death event rate in patients with heart failure and/or fatal ventricular arrhythmias [ventricular tachycardia (VT) and ventricular fibrillation (VF)] [1–9]. The ICD implantation rate increased significantly worldwide [10–12] following controlled studies of primary and secondary prevention of cardiac death [13–19]. New guidelines for ICD implantation [12] and the progressive technological advances in implantable devices have also contributed to this ongoing increasing trend.
In Japan, the first guidelines for ICDs were published by the Japanese Circulation Society (JCS) in 2001 [20], a revised version was reported in its website in 2006 [21], and a further revised version was added in 2011 [22]. CRT-Ds were approved in 2006 and the Japan Cardiac Device Therapy Registry (JCDTR) was started in the same year [23]. Interestingly, it has been reported that the actual implantation rates of these devices in Japan may be different from those of western countries [25]. These differences in device utilization rates might be explained by variable factors such as acceptance of published guidelines, differences in clinical presentation of patients, access to electrophysiologists and other implantation specialists, the overall capacity of the workforce to support ICD implantation, acceptance by policymakers, cost-effectiveness, financial constraints, and capitation [23]. However, little is known regarding the recent conditions associated with implantable defibrillators for the treatment of individual underlying heart diseases. Therefore, we investigated the actual conditions associated with implantable defibrillation therapy over a 5-year period in patients from the JCDTR database.
Methods SubjectsA total of 10,884 patients with cardiac implantable devices that had been implanted from 2006 to 2010 were enrolled in the JCDTR database from 283 hospitals or facilities, as previously reported [23]. The JCDTR questionnaires consisted of 3 parts, including implantation information, patient characteristics, and pharmacological treatment at the time of enrollment; the details were described in a previous report [23].
In this study, 10,605 patients, including those with newly implanted ICDs and CRT-Ds and upgraded devices from CRT-Ps to CRT-Ds, were selected. We investigated the clinical aspects of underlying heart disease in primary and secondary prevention of sudden cardiac death, and the number and percentage of implanted ICDs and CRT-Ds, including upgrades from CRT-Ps to CRT-Ds.
Patient diagnoses were determined according to the answers of the JCDTR questionnaire. The underlying heart diseases were divided into 12 categories: ischemic heart disease (IHD), dilated cardiomyopathy (DCM), secondary cardiomyopathy (2nd CM), arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertensive heart disease (HHD), valvular heart disease (VHD), congenital heart disease (CHD), hypertrophic cardiomyopathy (HCM), Brugada syndrome (Brugada), long QT syndrome (LQT), idiopathic VT/VF (IVF group, which excluded Brugada and LQT), and miscellaneous (Mis.).
Furthermore, the 2nd CM patients were divided into 16 underlying disease groups: cardiac sarcoidosis, amyloid cardiomyopathy, muscle dystrophy, (post) myocarditis, collagen disease, left ventricular (LV) aneurysm, dilated-type HCM, LV compaction, drug-induced cardiomyopathy, Takozubo cardiomyopathy, congenital metabolic disease, hemodialysis, complete atrioventricular (AV) block, tachycardia-induced cardiomyopathy, cardiac tumor, and Mis.
In addition, the IVF group consisted of 8 categories: IVF, catecholaminergic polymorphic VT, short-coupled polymorphic VT, vasospastic angina, early repolarization syndrome, idiopathic VT, familial IVF, and syncope of unknown etiology.
Regarding the clinical aspects, we studied the gender ratio (male/female), left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) classification, type of defibrillator and mode (ICD or CRT-D and single chamber or dual chamber), and the incidence of atrial fibrillation (AF), in all patients. Furthermore, we investigated the number of therapeutic interventions for the primary and secondary prevention of underlying heart disease, distribution of underlying heart diseases, changes in the number of ICDs and CRT-Ds and the trends in the percentage of primary prevention (% primary) from 2006 to 2010.
Statistical analysisThe values for the continuous variables are presented as the mean±the standard deviation. The differences in the clinical characteristics were tested by the chi-square test. Informed consent for each examination was obtained at the individual hospitals and facilities.
ResultsA total of 10,605 patients were included in our study, with 7016 ICDs (66.2%), 3518 CRT-Ds (33.2%), and 71 upgrade devices from CRT-Ps to CRT-Ds (0.7%).
Age and gender (Table 1)
Age and gender distribution of patients with underlying heart disease.Primary Secondary Total n Mean±sd M/F n Mean±sd M/F n Mean±sd (min.−max.) p. vs. s. M/F pri. vs. sec. IHD 1196 68.8±9.9 7.4 2468 66.9±10.5 5.8 3664 67.6±10.3 16–95 0.0001 6.3 0.0213 DCM 1524 64.8±12.5 2.7 1147 63.4±12.5 2.9 2671 64.2±12.5 14–93 0.0193 2.8 0.3886 2nd CM 354 61.5±13.4 1.3 441 60.0±13.2 1.3 795 60.7±13.3 12–89 0.2616 1.3 0.9029 ARVC 36 53.6±16.5 1.1 160 57.4±14.9 2.5 196 56.7±15.3 16–87 0.1578 2.1 0.0320 HHD 44 71.3±8.4 7.8 105 67.5±10.5 3.4 149 68.6±10.0 38–88 0.0982 4.1 0.106 VHD 132 69.4±8.6 4.1 202 66.9±12.0 2.1 334 67.9±10.8 18–90 0.0291 2.7 0.0123 CHD 34 55.7±18.7 2.1 81 52.6±19.3 1.5 115 53.5±19.1 12–87 0.5089 1.7 0.4694 HCM 299 61.8±12.8 1.9 596 61.1±15.1 2.7 895 61.3±14.4 11–91 0.4453 2.4 0.0219 Brugada 403 50.3±13.8 20.2 457 47.4±14.1 23.1 860 48.8±14.1 15–83 0.0025 21.6 0.6916 IVF 42 53.8±20.2 3.7 608 51.6±16.3 3.4 650 51.8±16.6 12–92 0.5449 3.5 0.8683 LQT 12 45.2±23.6 0.5 149 48.3±21.8 0.4 161 48.1±21.9 10–87 0.6869 0.4 0.6658 Mis. 28 63.7±16.9 6.0 87 61.8±14.0 2.5 115 62.2±14.7 13–92 0.7687 3.0 0.1257 0.5 Total 4104 63.9±13.4 3.5 6501 61.6±14.6 3.4 10605 62.5±14.2 10–95 0.0001 3.4 0.6981 M/F: the ratio of male to female, AF: atrial fibrillation, IHD: ischemic heart disease, DCM: dilated cardiomyopathy, 2nd CM: secondary cardiomyopathy, ARVC: arrhythmogenic right ventricular cardiomyopathy, HHD: hypertensive heart disease, VHD: valvular heart disease, CHD: congenital heart disease, HCM: hypertrophic cardiomyopathy, Brugada: Brugada syndrome, LQT: long QT syndrome, IVF: idiopathic ventricular fibrillation (excluding Brugada and LQT), Mis.: miscellaneous, Primary/pri.: primary prevention, Secondary/sec.: secondary prevention, sd: standard deviation, min.: minimum, max.: maximum.
In general, the gender ratio (male/female) was greater than 1 for all underlying diseases, except LQT (0.4). A remarkable difference in gender ratio was observed in patients with Brugada (21.6) and IHD (6.3). The gender ratios for IHD and VHD were significantly higher in the primary prevention group than in secondary prevention group, and vice versa for ARVC and HCM. In the IHD primary prevention group, the NYHA classification was significantly lower in males (2.3±0.9) than in females (2.4±0.9), but the LVEF was not significantly different between males (36.5±18.2%) and females (35.7±17.4%). In the IHD secondary prevention group, there were significant gender differences in both the NYHA classifications (males 1.8±0.9 vs. females 1.9±0.9; p<0.0001) and LVEF (males 45.6±17.8% vs. females 47.0±18.1%; p<0.0001).
The mean age of the patients was 62.5±14.2 years, and ranged from 10 to 95 years of age. Overall, the patients in the primary prevention group were significantly older (63.9±13.4 years of age; p<0.0001) than the patients in the secondary prevention group (61.6±14.6 years of age). Patients with HHD, VHD, and IHD were relatively older (mean age>76 years of age), and patients with LQT, Brugada, and IVF were relatively younger (mean age<52 years of age) relative to patients with the other underlying diseases in this study.
LVEF and NYHA classification of patients with underlying heart disease (Table 2)
LVEF and NYHA classification of patients with underlying heart disease.[Table omitted. See PDF]
See Table 1 for abbreviation definitions.
In general, the LVEF of the primary prevention group (36.3±18.0%) was significantly lower (p<0.0001) than that of secondary prevention group (45.9±17.9%), and the incidence of NYHA class III and IV was higher in the primary prevention group (53.4 and 8.2%, respectively) than those of the secondary prevention group (23.3 and 5.7%, respectively). The LVEF values of patients treated for the primary prevention of DCM, IHD, 2nd CM, VHD, and HHD were significantly lower than those of the secondary prevention group. However, the mean LVEF of patients with HCM, Brugada, IVF, and LQT was higher than 63%. The mean LVEF of patients with DCM, IHD, 2nd CM, and VHD was lower than 40%. Interestingly, the DCM group had the worst LVEF and contained the largest number of NYHA class III and IV patients.
Incidence of AF (Table 3)
Incidence of atrial fibrillationn AF % IHD 3664 363 9.9 DCM 2671 353 13.2 2nd CM 795 62 7.8 ARVC 196 5 2.6 HHD 149 30 20.1 VHD 334 93 27.8 CHD 115 18 15.7 HCM 895 133 14.9 Brugada 860 21 2.4 IVF 650 31 4.8 LQT 161 4 2.5 Mis. 115 63 54.8 Total 10605 1176 11.1 See Table 1 for abbreviation definitions.
The highest incidence of AF occurred in the VHD group (27.8%). The Brugada,
LQT, IVF, and ARCV groups had relatively lower incidences, which were less than 5%.
Distribution of underlying heart disease (overall, primary, and secondary prevention)
The major underlying diseases in this patient cohort included IHD (35%), DCM (25%), 2nd CM (8%) and Brugada (8%). IHD and DCM occurred in 60% of patients, and occurred in 66% of the primary prevention group and 56% of the secondary prevention group (Fig. 1). Note that the incidence of IHD (29%) was lower than that of DCM (37%) in the primary prevention group, but the opposite occurred in the secondary prevention group (IHD: 38%, DCM: 18%).
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Fig. 1. Distribution of the underlying heart diseases (among all patients, patients that underwent primary prevention therapy, and patients that underwent secondary prevention therapy).See Table 1 for abbreviation definitions.
Type of defibrillator and mode (Table 4)
Type and mode of defibrillation device in patients with underlying heart disease by year2006 2007 2008 2009 2010 2006–2010 Pri. Sec. Pri. Sec. Pri. Sec. Pri. Sec. Pri. Sec. Pri. % Sec. % Total % A. ICD+CRT-D IHD 137 405 223 488 275 557 304 560 257 458 1196 32.6 2468 67.4 3664 100.0 DCM 122 209 321 259 362 252 348 235 371 192 1524 57.1 1147 42.9 2671 100.0 2nd CM 46 86 72 96 70 82 80 108 86 69 354 44.5 441 55.5 795 100.0 ARVC 9 33 6 35 6 38 8 24 7 30 36 18.4 160 81.6 196 100.0 HHD 8 15 4 22 4 21 11 19 17 28 44 29.5 105 70.5 149 100.0 VHD 14 34 31 40 31 45 25 52 31 31 132 39.5 202 60.5 334 100.0 CHD 4 12 4 11 7 25 10 15 9 18 34 29.6 81 70.4 115 100.0 HCM 44 102 65 151 65 123 73 126 52 94 299 33.4 596 66.6 895 100.0 Brugada 72 79 103 104 89 89 71 88 68 97 403 46.9 457 53.1 860 100.0 IVF 12 85 7 115 13 131 7 146 3 131 42 6.5 608 93.5 650 100.0 LQT 0 20 5 31 4 32 1 39 2 27 12 7.5 149 92.5 161 100.0 Mis. 0 12 6 20 7 23 7 19 8 13 28 24.3 87 75.7 115 100.0 Total 468 1092 847 1372 933 1418 945 1431 911 1188 4104 38.7 6501 61.3 10605 100.0 B. ICD IHD 85 367 79 387 100 458 126 449 105 376 495 19.5 2037 80.5 2532 100.0 DCM 49 126 55 131 68 121 71 117 55 76 298 34.3 571 65.7 869 100.0 2nd CM 20 70 28 59 36 49 28 85 35 48 147 32.1 311 67.9 458 100.0 ARVC 9 31 4 33 6 36 8 20 7 29 34 18.6 149 81.4 183 100.0 HHD 6 12 3 18 2 15 3 13 6 27 20 19.0 85 81.0 105 100.0 VHD 6 24 7 29 6 32 3 33 4 25 26 15.4 143 84.6 169 100.0 CHD 4 11 4 11 2 14 7 11 6 13 23 27.7 60 72.3 83 100.0 HCM 44 98 60 147 62 118 68 123 51 90 285 33.1 576 66.9 861 100.0 Brugada 72 79 102 104 89 89 71 87 68 97 402 46.9 456 53.1 858 100.0 IVF 12 85 7 115 13 131 7 144 3 129 42 6.5 604 93.5 646 100.0 LQT 0 20 5 29 4 32 1 38 2 26 12 7.6 145 92.4 157 100.0 Mis. 0 11 2 20 5 17 5 18 5 12 17 17.9 78 82.1 95 100.0 Total 307 934 356 1083 393 1112 398 1138 347 948 1801 25.7 5215 74.3 7016 100.0 C. CRT-D IHD 52 38 144 101 175 99 178 111 152 82 701 61.9 431 38.1 1132 100.0 DCM 73 83 266 128 294 131 277 118 316 116 1226 68.0 576 32.0 1802 100.0 2nd CM 26 16 44 37 34 33 52 23 51 21 207 61.4 130 38.6 337 100.0 ARVC 0 2 2 2 0 2 0 4 0 1 2 15.4 11 84.6 13 100.0 HHD 2 3 1 4 2 6 8 6 11 1 24 54.5 20 45.5 44 100.0 VHD 8 10 24 11 25 13 22 19 27 6 106 64.2 59 35.8 165 100.0 CHD 0 1 0 0 5 11 3 4 3 5 11 34.4 21 65.6 32 100.0 HCM 0 4 5 4 3 5 5 3 1 4 14 41.2 20 58.8 34 100.0 Brugada 0 1 1 0 0 0 0 1 0 0 1 50.0 1 50.0 2 100.0 IVF 0 0 0 0 0 0 0 2 0 2 0 0.0 4 100.0 4 100.0 LQT 0 0 0 2 0 0 0 1 0 1 0 0.0 4 100.0 4 100.0 Mis. 0 0 4 0 2 6 2 1 3 1 11 55.0 9 45.0 20 100.0 Total 161 158 491 289 540 306 547 293 564 240 2303 64.2 1286 35.8 3589 100.0 In patients with ICDs, IHD was the most prevalent underlying disease (36%), followed by DCM (12%), HCM (12%), Brugada (12%), and IVF (9%) [Table 4, Fig. 2]. On the other hand, 50% of CRT-Ds were implanted for the treatment of DCM, and 32% were implanted for IHD treatment. Including patients with a 2nd DCM increased the incidence of DCM to 70% in patients with CRT-Ds (Table 4C, Fig. 2).
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Fig. 2. Distribution of the underlying heart diseases (according to the type of defibrillator).See Table 1 for abbreviation definitions.
In all patients (Table 3D), dual chamber devices were used in 80.1% and single chamber devices were used in 19.9%. The underlying disease in which single chamber ICDs were most frequently used was VHD (36.5%), followed by Brugada (34.8%) and IVF (27.7%).
Subclassification of the underlying heart diseases
Subclassification of the 2nd CM and IVF groups (Table 5): in the 2nd CM group, cardiac sarcoidosis had the highest incidence, and occurred in 45% of all patients, in 43.5% of the primary prevention group, and in 46.3% of the secondary prevention group (Table 5A). The second most prevalent condition was DCM, with 22.5% incidence among all patients, 26.8% incidence in the primary prevention group, and 19.0% occurrence in the secondary prevention group.
Mode of defibrillation device in patients with underlying heart disease by year2006 2007 2008 2009 2010 2006–2010 Dual Single Dual Single Dual Single Dual Single Dual Single Dual % Single % Total % IHD 458 84 534 177 699 133 789 75 632 83 3112 84.9 552 15.1 3664 100.0 DCM 220 111 347 233 462 152 509 74 497 66 2035 76.2 636 23.8 2671 100.0 2nd CM 108 24 127 41 130 22 177 11 138 17 680 85.5 115 14.5 795 100.0 ARVC 36 6 35 6 40 4 29 3 32 5 172 87.8 24 12.2 196 100.0 HHD 19 4 18 8 23 2 26 4 40 5 126 84.6 23 15.4 149 100.0 VHD 27 21 38 33 57 19 50 27 40 22 212 63.5 122 36.5 334 100.0 CHD 14 2 14 1 26 6 19 6 21 6 94 81.7 21 18.3 115 100.0 HCM 136 10 191 25 171 17 180 19 130 16 808 90.3 87 9.7 895 100.0 Brugada 109 42 127 80 118 60 107 52 100 65 561 65.2 299 34.8 860 100.0 IVF 77 20 75 47 104 40 118 35 96 38 470 72.3 180 27.7 650 100.0 LQT 19 1 29 7 26 10 35 5 26 3 135 83.9 26 16.1 161 100.0 Mis. 11 1 16 10 21 9 23 3 17 4 88 76.5 27 23.5 115 100.0 Total 1234 326 1551 668 1877 474 2062 314 1769 330 8493 80.1 2112 19.9 10605 100.0 See Table 1 for abbreviation definitions.
In the IVF group (Table 5B), IVF was the most prevalent condition (n=480; 73.8%), with a substantially higher incidence in the secondary prevention group (n=608; 93.5%) than in the primary prevention group (n=42; 6.5%). The second most prevalent condition was idiopathic VT (n=86; 13.2%), and the third most prevalent condition was vasospastic angina (n=66; 10.2%).
Changes in the rates of ICD and CRT-D utilization (Fig. 3)
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Fig. 3. Changes in the rates of ICD and CRT-D utilization for primary and secondary prevention.See Table 1 for abbreviation definitions.
The percentage of CRT-Ds used for primary prevention dramatically increased from 2006 (10.3%) to 2007 (22.1%) and then gradually increased from 2007 to 2010; the opposite occurred in the percentage of ICDs used for secondary prevention. The percentage of CRT-Ds for secondary prevention and ICDs for primary prevention did not change significantly during this time period.
Trends in the % primary: Among the 4 major diseases, the DCM group had the largest number of patients (n=1524) and the highest % primary (57.1%; Table 4). The second highest % primary (46.9%) occurred in the Brugada group. The IHD group had the fourth highest % primary (32.6%), but had the second highest number of patients (n=1196). Over the 5-year period, the % primary values of the DCM and HCM group gradually increased (Fig. 4, Table 4). The % primary of the IHD group also gradually increased, but the ratio of this increase was smaller compared with the DCM group. Conversely, the % primary of the Brugada group gradually increased since 2006, and then gradually decreased from 2008 to 2010 (Fig. 4). The % primary for patients with DCM and implanted CRT-Ds dramatically increased from 2006 (46.8%) to 2007 (67.5%), and then gradually increased until 2010 (73.1%). For patients with IHD and implanted CRT-Ds, the % primary gradually increased from 2006 (57.8%) to 2010 (65.0%)
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Fig. 4. Trends in the percentage of primary prevention (% primary) in patients with IHD, DCM, HCM, and Brugada.See Table 1 for abbreviation definitions.
The purpose of this study was to determine the current status of defibrillation therapy (ICD/CRT-D) in Japan by using the JCDTR database administrated by the device enrollment and assessment committee of the Japanese Heart Rhythm Society. Specifically, the clinical aspects and trends in the % primary for sudden cardiac death were emphasized, because the effectiveness of defibrillation therapy for secondary prevention has been assessed and confirmed throughout the world [5,9]
Gender and ageIn an analysis of a national sample of Medicare inpatient, outpatient, and carrier standard analytical files and the corresponding denominator files, women were found to be significantly less likely than men to receive ICD therapy for the primary or secondary prevention of sudden cardiac death [26], which was similar to the findings of this study.
In LQT, the gender ratio varies by age and abnormal gene type. Women have slightly longer QT intervals than men do, and this difference is more pronounced at slower heart rates [12]. In an international study of 287 child patients, the gender ratio was 0.8 [27]. In a prospective longitudinal study of 328 families who were mostly adults, the gender ratio of the probands was 3.8 [28]. In this study, the gender ratio of LQT was 0.4 in patients who underwent secondary prevention therapy in Japan.
A remarkable difference in the gender ratios was observed in the Brugada group, with a ratio of 21.6 in all patients, and 23.1 in the secondary prevention group. These results are not inconsistent with previous reports [16–19,29]; however, these reports also revealed that the gender ratio in all patients ranges from 2.5 [19] to 3.2 [16] in western countries and is 21.0 in Japan [18]. Of note, the gender ratio in symptomatic patients ranges from 5.0 [16] to 11.0 [17] in western countries and is 23.6 in Japan [18]. In this study, the gender ratio was 23.1 in secondary prevention patients and 20.2 in primary prevention patients; therefore, our data were not inconsistent with previous Japanese data [18].
There were significant differences in the gender ratios of patients with IHD, ARVC, VHD, and HCM between the primary and secondary prevention groups (Table 1). Those of the IHD and VHD groups were significantly higher in the primary prevention group than in the secondary prevention group, and vice versa for patients with ARVC and HCM. The clinical significance of these results remains unclear.
The mean age was 62.5±14.2 years among all of the patients, and ranged from 10 to 95 years of age. The patients with HHD, VHD, and IHD were relatively older, and those with LQT, Brugada, and IVF were relatively younger compared with patients with the other underlying diseases in this study. These results were not inconsistent with general concepts. Patients with IHD, DCM, and Brugada that underwent primary prevention therapy were significantly older than those in the secondary prevention group. These findings might be explained by the fact that defibrillation therapy was performed in spite of their age when patients had lethal ventricular arrhythmias.
Distribution of underlying diseases (Figs. 1 and 2)The major underlying diseases in patients with implanted ICDs included IHD (36%), cardiomyopathy (19%; 12% with DCM plus 7% with 2nd CM), HCM (12%), ARVC (3%) and the IVF group (21%; 12% with Brugada plus 9% with IVF). A study published in 1998 regarding ICDs in Japan [25] included a patient cohort with IHD (34%), DCM (16%), HCM (12%), ARVC (3%), an IVF group (19%), and other underlying diseases (12%). Thus, the distribution of the underlying heart diseases in this study was similar to the previous report [25]. However, among all of the patients in the current study, we found that the major underlying diseases included IHD (35%), cardiomyopathy (33%; 25% with DCM plus 8% with 2nd CM), HCM (8%), ARVC (2%) and the IVF group (14%; 8% with Brugada plus 6% with IVF). Of note, the percentage of patients with DCM in the current study was higher than that of the study published in 1998 [25]. This difference may be explained by the increase in prophylactic therapy, especially the utilization of CRT-Ds in patients with cardiomyopathy.
This distribution of the underlying heart diseases in Japan was absolutely different compared with that of western countries. In the USA, IHD was reported in 80% of registry patients, cardiomyopathy in 10%, and IVF in 3% [25]. Another registry report from Italy [10] during the period from 2001 to 2004 revealed that the 68.1% of patients had IHD. Over the same period, DCM was reported in 23.2% of all cases, HCM in 3.3%, ARVC in 1.5%, VHD in 1.7%, LQT in 0.7%, and IVF in 1.5% of patients [10].
Primary and secondary preventionThere were 82% primary and 18% secondary prevention indications in the ICD therapy registry collected from December 2004 to April 2005 in the United States, compared with 42% primary and 58% secondary prevention indications in the Italian ICD registry collected from January to December 2005 (p<0.0001) [11]. In a comparison of the 2006–2010 data for ICD and CRT-D use in this study, there was a significantly (p<0.0001) lower primary prevention rate (38.7%) in Japan than that in Italy in 2005 [11].
In western countries, the distribution of underlying heart diseases in patients treated with ICDs for primary prevention is very similar to that of all ICD recipients [10], indicating that there is not much difference in the distribution of underlying heart diseases between primary and secondary prevention patients. However, differences in the distribution of diseases between primary and secondary prevention patients were observed in the current study, especially in patients with DCM and IVF (Fig. 1). In the DCM group, the percentage changed from 18% in the secondary prevention group to 37% in the primary prevention group, and the opposite trend was observed in patients with IVF (9–1%). The DCM group had the largest number of patients and the highest % primary (57.1%), and no other disease was associated with a % primary greater than 50%. The % primary in IHD (32.6%) was not particularly high, and was the fourth highest among the individual underlying diseases; however, this group had the second highest number of patients in the primary prevention category, since the IHD group included the highest number of patients with defibrillation therapy.
The reason for the relatively lower % primary in patients with IHD compared with those of western countries is unclear, although these differences are likely due to the population differences in the IHD. Furthermore, Japanese physicians tend to believe that Japanese patients have a lower risk of IHD and decreased LVEF than those of western countries [24]. Indeed, Japanese patients who had received intracoronary thrombosis or an emergent and/or elective percutaneous transluminal coronary angioplasty, had a favorable prognosis [30]. Furthermore, the presence of non-sustained VT was a significant predictor of death (p=0.036) only in the patients who did not receive acute reperfusion, and the percentage of patients with LVEF<35% was only 5.7% at 13±8 days after myocardial infarction [31]. There is a low incidence of sudden cardiac death in survivors of myocardial infarction in the primary percutaneous coronary intervention era, although LVEF is a predictor of increased risk for SCD [32]. Tanno et al. [33] suggested that it might be inappropriate to apply Multicenter Automatic Defibrillator Implantation Trial II [2] (MADIT II) criteria to Japanese patients, because the survival rate in their study was comparable with that in the MADIT II [2] defibrillator group. They also stated that a significantly greater percentage of the recently studied patients were found to be in NYHA class I and that they had undergone more percutaneous coronary intervention procedures than those enrolled in MADIT II [2].
The evaluation of defibrillation therapy strategies becomes difficult when the primary prevention rate is much smaller in patients with structural heart disease. In western countries, the number of implanted devices for primary prevention has already been reported to be larger than that for secondary prevention of sudden cardiac death [11].
Single chamber vs. dual chamber devicesAmong all of the defibrillator devices in this study, single chamber devices comprised 19.9%, which was significantly smaller compared with that of western countries, with 45.9% in the USA and 50.7% in Italy [11]. The diseases that were more commonly treated with single chamber devices were VHD (36.5%), Brugada (34.8%), and IVF (27.7%). An explanation for the relatively higher incidence of VHD that was treated with single chamber devices might be a high incidence of AF, as the highest percentage of AF was observed in patients with VHD in this study. With regard to the number of single chamber ICDs that were used in Brugada, single chamber ICDs are preferred for primary prevention in western countries [11,17,19]. The rationale for this preference is that minimizing the exposure to lead will result in fewer lead-associated problems.
Distribution of 2nd CMIn patients with 2nd CM, cardiac sarcoidosis was the most commonly associated disease in this study. This disease was invasive in only 2% of hearts; [34] although this is rare in systemic sarcoidosis, it can occur suddenly. Furthermore, the initial phase of sarcoidosis had a relatively high incidence of sudden cardiac death. Therefore, the defibrillation devices in patients with sarcoidosis had a tendency to be implanted in the early phase of this disease [34]. The second most commonly associated disease in patients with 2nd CM was dilated-type HCM in this study, which is associated with a poor prognosis and a tendency to cause lethal congestive heart failure and/or lethal ventricular arrhythmia [35].
Distribution of the IVF groupPatients in the IVF group had no apparent heart disease, and IVF was the most common diagnosis (73.8%) in the IVF group. The purpose of ICD implantation in these patients was almost entirely secondary prevention (95%), which can be expected due to the clinical characteristics of IVF.
The second most common underlying disease in patients with IVF in this study was idiopathic VT (13.2%), which was a bit surprising since this disease is classified as indication class III, according to the 2006 JCS guidelines [21]. However, VT is capable of inducing syncope, dizziness, or heart failure, and the final decision regarding device implantation depends on discussions between the doctors and patients. The third most common underlying disease in the IVF group was vasospastic angina (n=66; 10.2%), for which the indication of defibrillation therapy was classified as indication III according to the 2006 JCS guidelines [21]. However, the indication class of this disease is still controversial [36]. The newest 2011 JCS guidelines [22] suggest that this disease should be moved to class IIb from class III. However, further studies are necessary to determine the appropriate patients in which implanted device therapy should be performed.
Changes in the rates of ICD and CRT-D utilizationThe percentage of CRT-Ds that were used for primary prevention increased gradually according to this study, which is not inconsistent with the data reported by the Japanese device association [22]. Furthermore, similar phenomena have occurred in western countries [10]. There are several possible explanations as to why the percentage of CRT-D implantation for primary prevention increased rapidly, with the first being that CRT-Ds were approved by the Japanese Ministry of Health, Labor, and Welfare in August 2006. Other possible explanations are the new guidelines for ICD implantation, the favorable results of mega-trials [7,8,37,38], the progressive technological advances in devices, and the cooperation between cardiologists in the heart failure clinics and electrophysiology laboratories of Japanese hospitals.
Though non-sustained VT and inducible VT/VF are major risk factors for patients with severe LV function [1], ICDs reduce the number of sudden cardiac deaths in patients with or without non-sustained VT and/or inducible VT/VF [2]. Also, the 2006 JCS guidelines [21] state that the indication of device implantation in patients with severe LV dysfunction (LVEF≤35%) is classified as class IIa, regardless of the presence of ventricular arrhythmia. In the patients with a LVEF≤35%, drug resistant congestive heart failure (NYHA class III/IV), intraventricular conduction disturbance (a QRS complex with a width of 130 ms or more), and with or without a history of fatal ventricular arrhythmias, the implantation of CRT-P or CRT-D were classified as a class I indication. After these guidelines were published, prophylactic defibrillation therapy, especially CRT-D, dramatically increased.
Trends in the % primaryDuring the 5-year period in the current study, the JCDTR has demonstrated a significant increase in the utilization of prophylactic defibrillation devices (ICD/CRT-D). Interestingly, the % primary values in patients with DCM and HCM gradually increased from 2006 to 2010. The % primary in patients with IHD also gradually increased, but the ratio of this increase was smaller compared to that of the DCM group (Fig. 4). These findings reflect the rapid clinical implementation of the results of randomized studies [3,4,7].
With regard to patients with HCM, appropriate ICD interventions were analyzed with respect to previously identified HCM risk factors [13–15]. The 5 primary prevention risk factors were: (1) history of premature HCM-related sudden death in 1 or more first-degree or other relatives that were younger than 50 years of age, (2) massive LV hypertrophy (a maximum wall thickness of 30 mm or more), (3) 1 or more runs of non-sustained VT at heart rates of 120 beats/min or greater while under 24-h ambulatory Holter electrocardiographic monitoring, (4) prior unexplained syncope judged to be inconsistent with a neurocardiogenic origin, and (5) hypotensive blood pressure response to exercise [15]. In most reliable data registry of 506 HCM patients from 42 centers [13], discharge rates were 5.5%/year overall, 11%/year for secondary prevention (after cardiac arrest or sustained VT), and 4%/year for primary prevention (with 1 or more risk factors). Therefore, a single marker of high risk for sudden death may be sufficient to justify prophylactic defibrillator implantation in selected patients with HCM [13]. These statements most likely increased the prophylactic ICD implantation rates in patients with HCM in Japan. Furthermore, a new 2011 JCS guideline [22] is associated with this statement.
Conversely, the % primary in patients with Brugada gradually increased at first, then gradually decreased from 2008 to 2010 in this study. This phenomenon might be explained as follows. In 2003, Brugada et al. [16] indicated that patients with induced VF during the electrophysiologic stimulation test (EPS) had a moderately high risk even if they were asymptomatic. However, the mega-trial conducted by Ecardt in 2005 [17], which was opened to Japanese patients in 2009 [18], and results from the France, Italy, Netherlands, Germany (FINGER) registry [19] reported in 2010, stated that clinicians should be prudent in implanting ICDs in patients with asymptomatic Brugada, even if VF was induced during electrophysiologic stimulation test. According to the 2007 JCS guidelines for Brugada and LQT syndrome [39], the history of syncope due to an undetermined cause, family history of sudden cardiac death, and inducible VF are risk factors for sudden cardiac death in asymptomatic Brugada. The indication of device implantation is class IIa when patients have 2 or more risk factors, and it is a class IIb indication when patients have only 1 risk factor. We have no data as to whether this statement is accurate; however, a 2011 report from Italy [40] supported the 2007 JCS Brugada guidelines [39]. The authors of the Italian study selected the 3 risk factors (syncope, family history of sudden cardiac death, and positive EPS) in patients with asymptomatic type 1 Brugada, which were the same as those described in the 2007 JCS guidelines. The follow-up data from this study indicated that subjects with the highest risk of sudden cardiac death have at least 2 risk factors, and that the remaining subjects have a low risk [40]. The annual event rate in patients with asymptomatic Brugada was 0.5% [18], and the indication for device implantation was carefully considered because of the relatively low risk, the poor cost-effectiveness, and the reduction of quality of life (QOL). This evidence seemed to influence the physician's decision regarding the indication of ICD use in patients with Brugada.
Study limitationsThe JCDTR database collects clinical and technical data of patients treated with ICDs and CRT-Ds. It is the largest such database, consisting of more than 10,000 patients with implanted defibrillation devices in Japan. Since the final diagnoses were made in each hospital or by faculty in this study, the details of the diagnoses were not organized. Although the number of registries did not run parallel to the real number of implanted devices, the changes observed in the percentage of ICD or CRT-D use over the 5-year period was similar to the previous report on this matter. Therefore, we believe that the data in the present study reflects the real world scenario of implantation defibrillation devices.
ConclusionsThe JCDTR database revealed that the major underlying diseases in patients that underwent defibrillator therapy were ICD, DCM, HCM, and Brugada in Japan. The distribution of diseases that were treated with ICDs in this study was similar to that reported in a study in 1998 [25]. The % primary was relatively higher in patients with DCM and Brugada. Recent evidence (mega-trial reports) and guidelines have influenced the indication of primary prevention for sudden cardiac death in patients, especially those with DCM in Japan. Such evidence has also influenced this indication in patients with IHD, but this group had a relatively lower % primary, despite its large number of patients.
Decisions regarding defibrillation therapy become difficult when the primary prevention rate is much smaller in patients with structural heart disease. Importantly, a long-term observation study is needed to determine whether the current status of defibrillation therapy in Japan is heading in the right direction for patients (Table 6).
Distribution of 2nd CM and idiopathic ventriculartachycardia/fibrillation with the exception of Brugada syndrome| Primary | Secondary | Total | ||||
| n | % | n | % | n | % | |
| A. 2nd CM | ||||||
| Cardiac sarcoidosis | 154 | 43.5 | 204 | 46.3 | 358 | 45.0 |
| Amyloid cardiomyopathy | 31 | 8.8 | 15 | 3.4 | 46 | 5.8 |
| Muscular dystrophy | 18 | 5.1 | 18 | 4.1 | 36 | 4.5 |
| (Post) myocarditis | 11 | 3.1 | 34 | 7.7 | 45 | 5.7 |
| Collagen disease | 2 | 0.6 | 9 | 2.0 | 11 | 1.4 |
| Left ventricular aneurysm | 5 | 1.4 | 17 | 3.9 | 22 | 2.8 |
| Dilated-type HCM | 95 | 26.8 | 84 | 19.0 | 179 | 22.5 |
| Left ventricular compaction | 10 | 2.8 | 13 | 2.9 | 23 | 2.9 |
| Drug-induced | 6 | 1.7 | 6 | 1.4 | 12 | 1.5 |
| Takozubo cardiomyopathy | 1 | 0.3 | 7 | 1.6 | 8 | 1.0 |
| Congenital metabolic disease | 3 | 0.8 | 6 | 1.4 | 9 | 1.1 |
| Hemodialysis | 2 | 0.6 | 5 | 1.1 | 7 | 0.9 |
| Complete AV block | 3 | 0.8 | 13 | 2.9 | 16 | 2.0 |
| Tachycardia-induced | 7 | 2.0 | 0 | 0.0 | 7 | 0.9 |
| Cardiac tumor | 1 | 0.3 | 4 | 0.9 | 5 | 0.6 |
| Mis. | 5 | 1.4 | 6 | 1.4 | 11 | 1.4 |
| Total | 354 | 100.0 | 441 | 100.0 | 795 | 100.0 |
| B. Distribution of idiopathic ventricular tachycardia/fibrillation with the exception of Brugada syndrome and long QT syndrome | ||||||
| Idiopathic ventricular fibrillation | 24 | 57.1 | 456 | 75.0 | 480 | 73.8 |
| Catecholaminergic polymorphic ventricular tachycardia | 1 | 2.4 | 4 | 0.7 | 5 | 0.8 |
| Short-coupled polymorphic ventricular tachycardia | 0 | 0.0 | 2 | 0.3 | 2 | 0.3 |
| Vasospastic angina | 4 | 9.5 | 62 | 10.2 | 66 | 10.2 |
| Early repolarization syndrome | 1 | 2.4 | 1 | 0.2 | 2 | 0.3 |
| Idiopathic ventricular tachycardia | 11 | 26.2 | 75 | 12.3 | 86 | 13.2 |
| Family of idiopathic ventricular fibrillation | 1 | 2.4 | 0 | 0.0 | 1 | 0.2 |
| Syncope of unknown etiology | 0 | 0.0 | 8 | 1.3 | 8 | 1.2 |
| Total | 42 | 100.0 | 608 | 100.0 | 650 | 100.0 |
See Table 1 for abbreviation definitions.
We sincerely thank the following facilities for their participation in the Japanese Cardiac Defibrillation Therapy Registry.
Facilities that enrolled more than 40 patients (98 facilities in alphabetical order)
Aichi Cardiovascular and Respiratory Center, Aichi Medical University, Akita Medical Center, Anjo Kosei Hospital, Bell Land General Hospital, Dokkyo Medical University, Edogawa Hospital, Ehime Prefectural Central Hospital, Ehime University, Fukushima Medical University, Fukuyama City Hospital, Gifu Prefectural General Medical Center, Gifu University, Gunma University, Hirosaki University, Hokkaido Social Institute Hospital, Hokkaido University Hospital, Hokko Memorial Hospital, Hyogo College of Medicine, IMS Katsushika Heart Center, Japanese Red Cross Ishinomaki Hospital, Japanese Red Cross Kumamoto Hospital, Japanese Red Cross Kyoto Daini Hospital, Japanese Red Cross Maebashi Hospital, Japanese Red Cross Matsue Hospital, Japanese Red Cross Osaka Hospital, Japanese Red Cross Wakayama Medical Center, Jichi Medical University, Juntendo University, Juntendo University Urayasu Hospital, Kagoshima University, Kakogawa East City Hospital, Kameda Medical Center, Keio University, Kitasato University, Kobe City Medical Center General Hospital, Kobe University, Kochi Health Sciences Center, Kokura Memorial Hospital, Koseikai Takeda Hospital, Kurashiki Central Hospital, Kyoto Prefectural University of Medicine, Kyoto-Katsura Hospital, Kyushu Medical Center, Matsumoto Kyoritsu Hospital, Mie University, Minami Tohoku Hospital, Mito Saiseikai General Hospital, Nagasaki University, Nagoya University, Nara Medical University, National Hospital Organization Kagoshima Medical Center, National Hospital Organization Osaka National Hospital, National Hospital Organization Shizuoka Medical Center, New Tokyo Hospital, Nihon University, Nippon Medical School, Odawara Municipal Hospital, Okayama University, Okinawa Prefectural Chubu Hospital, Osaka City General Hospital, Osaka City University, Osaka Medical College, Osaka Police Hospital, Saiseikai Central Hospital, Saiseikai Kumamoto Hospital, Saiseikai Yokohamashi Tobu Hospital, Saitama Red Cross Hospital, Sakakibara Heart Institute of Okayama, Sakurabashi Watanabe Hospital, Seirei Hamamatsu General Hospital, Sendai Kosei Hospital, Shiga University of Medical Science, Shinshu University, Shizuoka Hospital, Showa General Hospital, St. Luke's International Hospital, St. Marianna University School of Medicine, Tenri Hospital, The University of Tokyo, Toho University, Tokai University, Tokyo Medical and Dental University, Tokyo Medical University, Tokyo Metropolitan Hiroo Hospital, Tokyo Metropolitan Tama Medical Center, Tokyo Women's Medical University, Tottori University, Toyohashi Heart Center, Tsuchiura Kyodo General Hospital, University of Fukui, University of Occupational and Environmental Health Japan, University of Tsukuba, Yamagata University, Yamaguchi University, Yamanashi Prefectural Central Hospital, Yokohama City University, and Yokohama Rosai Hospital.
Facilities that enrolled less than 40 patients (185 facilities).
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