Use of Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death in Asia

The effectiveness of primary prevention implantable cardioverter-defibrillators (ICDs) is well established. However, there are several unsolved problems related to ICD use for primary prevention in Asia, including ICD underuse, population differences in underlying heart disease, and the rate of appropriate ICD therapy compared with Western countries. Although the prevalence of ischemic cardiomyopathy in Asia is lower than in Europe and the United States, the mortality rate of Asian patients with ischemic heart disease has been increasing recently. As for the use of ICDs for primary prevention, there have been no randomized clinical trials, and limited data are available in Asia. This review focuses on the unmet needs related to ICD use for primary prevention in Asia.

inability to pay for the device (53.8%), followed by not believing in the benefits of the ICD (19.4%) in the Improve SCA (Improve Sudden Cardiac Arrest) study, which included Asia. 9 Hence, there were 3 barriers to ICD for primary prevention, including government level, health care provider level, and patient level. At the government level, rapid socioeconomic and epidemiologic transitions have occurred in Asia. Patients in low-and middle-income countries receive minimal to no reimbursement for ICD therapy, and reimbursement is restricted to secondary prevention implantations. 10 In addition, out-of-pocket expenses tend to be higher in low-income regions such as Indonesia (46.9%), the Philippines (53.7%), and India (62.4%), 11,12 where ICD use was low, contributing to the disparity in ICD use in Asia. At the health care provider level, physician unawareness 13,14 was the contributing factor to underuse in Asia. Previous studies have revealed that physician awareness of the indications for ICD therapy is low, 13,14 which leads to low referral rates and underuse of ICD insertion. 5,14,15 As Asian patients tend to rely on their physicians for health information and are more accepting of ICD therapy if their physicians strongly recommend it, 16 physicians should recommend ICD insertion for patients with heart failure (HF) with optimal ICD eligibility. At the patient level, a lack of knowledge about the preventive role of ICD was a main reply among patient responses to the questionnaire. As one-third of ICD nonrecipients (32.6%) were uncertain if devices could improve their quality of life and survival in a previous study, and knowledge of the role of ICDs for primary prevention was the most important factor influencing patient decisions, better patient education and physician recommendation could improve access. 16 Physicians and government officials in Asia should address these fundamental issues.

ICDs FOR PRIMARY PREVENTION
The use of ICDs is effective in reducing lifethreatening ventricular arrhythmia and preventing sudden cardiac death (SCD) for patients with structural heart disease, and their efficacy has been demonstrated not only for secondary prevention [17][18][19] but also for primary prevention patients. In MADIT-II  LVEF #35% to conventional therapy plus placebo, conventional therapy plus amiodarone, or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD, which excluded NSVT as an inclusion criterion, and ICD therapy was associated with a 23% decreased risk for death compared with the placebo and amiodarone groups after trial included 458 patients with nonischemic dilated cardiomyopathy, LVEF <36%, and premature ventricular complexes or NSVT, and ICD insertion was associated with a nonsignificant reduction in death of any cause (35%; P ¼ 0.08). 22 SCD-HeFT showed that ICD therapy reduced the risk for death among all cohorts, but the total mortality of NICM was less than that of ICM (NICM, 27% at 5 years; ICM, 43% at 5 years). Moreover, although the ICD group had 27% reduced total mortality compared with the placebo group, the difference was not significant (P ¼ 0.06).
The DANISH (Danish Study to Assess the Efficacy of

ICDs in Patients with Non-Ischemic Systolic
Heart Failure on Mortality) included 556 patients with LVEF #35% not caused by CAD that were randomly assigned to ICD vs non-ICD and revealed that the overall mortality rate was reduced by 13% but was not significantly different between the 2 groups (P ¼ 0.28) during a median follow-up period of 68 months. 23 Meanwhile, a meta-analysis of the effects of ICD    patients with SCD in Asia is lower than in Western countries. 46 The Hisayama study, a prospective population-based study of cardiovascular disease that has been under way since 1961 in Japan, revealed that ischemic heart disease was the most common cause of SCD according to autopsy data, but the rate was 28.9% among sudden death victims. 47 In Hong Kong, 289 SCD victims were evaluated, and the major cause of death was CAD (35%). 48 The rates of CAD among SCD victims were lower than in the United States (62%). 45  This ischemic HF prevalence was considerably low compared with that reported in Western studies. 54 In the primary percutaneous coronary intervention era, there remains a low incidence of SCD in Asians, 55 but the prophylactic use of ICD remains effective for primary prevention patients with LV dysfunction.
The JID-CAD (Japan Implantable Devices in Coronary Artery Disease) study, which included CAD and ICD or cardiac resynchronization therapy device patients in Japan, revealed that the rates of appropriate ICD therapy in the primary (n ¼ 165) and secondary (n ¼ 227) groups were similar during the follow-up period. 51 The presence of appropriate ICD therapy was 37% at 3 years in the Japanese cohort using MADIT-II criteria for patients with ICM with primary prevention ICDs. 56 A subanalysis of the Nippon Storm Study demonstrated that the incidence of ICD therapy in patients with CAD for primary and secondary prophylaxis was not significantly different. 57 Even though the incidence of SCD due to CAD is low in Asians, the efficacy of prophylactic ICD is comparable with secondary prevention ICD.
In contrast, the Hisayama study showed that the prevalence of ischemic heart disease among the causes of SCD increased significantly with time. 47  China. 60 Thus, rigorous consideration of primary prevention ICD indications for patients with ICM with LV dysfunction will become much more important in the future, as SCD is expected to occur more frequently as the rate of ICM increases.

NONISCHEMIC CARDIOMYOPATHY
The DANISH study questioned the efficacy of pro-  The incidence of death of ischemic heart disease per 100,000 people per year on the basis of World Health Organization data on the leading causes of death. The incidence of death of ischemic heart disease was more than 2-to 3-fold in Western countries compared with Asian countries in 2000, but recent data showed that the gaps are closing between Western and Asian countries.
Australia) who did not receive ICDs, though there was a lower rate of appropriate ICD therapy at U.S. sites. 70 The data showing that primary prevention ICD use was higher and that there were higher rates of lower risk populations in the United States than elsewhere were associated with a lower rate of appropriate ICD therapy. In addition, there is no significant difference in the rate of ICD-appropriate therapy among Asia This illustration shows the unmet needs for primary prevention implantable cardioverter-defibrillator (ICD) therapy in Asia, namely, ICD underuse, a lower rate of ischemic cardiomyopathy, limited data on the optimal cutoff age for ICD indication in nonischemic cardiomyopathy, and the necessity of nonsustained ventricular tachycardia (NSVT) and electrophysiological study (EPS) for an ICD indication for cardiac sarcoidosis. ACC ¼ American College of Cardiology; AHA ¼ American Heart Association; HF ¼ heart failure; JCS ¼ Japanese Circulation Society; LVEF ¼ left ventricular ejection fraction; PM ¼ pacemaker; SCD ¼ sudden cardiac death.
prophylactic ICD therapy for HCM. 78 Prophylactic ICD indications for HCM should be considered prudently, taking this background into account.

CARDIAC SARCOIDOSIS
There has been a marked increase over time

HIGHLIGHTS
ICD is the standard care for primary prevention in patients with structural heart disease and high risk of SCD.
There are unmet needs in Asia, including ICD underutilization, the lower prevalence of ICM and SCD compared to Western countries.
This review also focused on the lack of data about the risk stratification of non-ICM, HCM, and CS in Asia.
Large scale cohort studies or RCTs tackled with these issues in Asian patients are required in the future.