Devices
Validation of the Implantable Cardioverter-Defibrillators Indication Criteria for Nonischemic Cardiomyopathy ― Why? When? How? ―
2023 年 87 巻 1 号 p. 101-102
詳細
2023 年 87 巻 1 号 p. 101-102
The utility of implantable cardioverter-defibrillators (ICDs) for secondary prevention (SP) in resuscitated cases of fatal ventricular tachyarrhythmias due to irreversible causes is clear and is essentially a Class I indication in the guidelines. Contrarily, the indication for primary prevention (PP) with ICDs in patients with organic heart disease with reduced left ventricular ejection fraction (LVEF) is less robust. In particular, evidence of ICDs for PP significantly differs between patients with ischemic cardiomyopathy (ICM) and those with nonischemic cardiomyopathy (NICM).
Article p 92
For ICM, the PP efficacy of ICDs has long been demonstrated in many large clinical trials. Classically, in 1996, the MADIT study1 compared ICDs with drug therapy in patients with myocardial infarction and nonsustained ventricular tachycardia (NSVT) with an LVEF ≤35% and electrophysiologic testing of ventricular tachyarrhythmia, and found a 54% reduction in mortality over 2 years. The later MADIT-II trial2 showed that ICDs significantly reduced mortality in patients with LVEF <30% due to ICM, regardless of whether it was NSVT or inducible ventricular tachyarrythmia. Subsequent European and US clinical trials also provided the evidence base for guideline recommendation.3
In contrast, most clinical trials conducted on NICM patients with reduced LVEF have failed to demonstrate a statistically significant prognostic benefit of ICDs. First, the DEFINITE trial published in 2004,4 a large clinical trial limited to patients with NICM, randomized 458 heart failure patients with LVEF <35% with frequent ventricular extrasystoles or NSVT into ICDs or medical therapy. The trial failed to demonstrate statistical significance in the primary endpoint of all-cause death at a 2-year follow-up. Furthermore, the DANISH trial5 published in 2016 randomized 1,106 NICM patients with symptomatic heart failure and LVEF <35% into ICD or drug therapy; the patients were followed up for 67.6 months, and no significant difference in all-cause death was observed. However, a subsequent meta-analysis revealed the utility of ICDs,6 and the guidelines recommend Class I for patients with NYHA class II or higher, LVEF ≤35%, and NSVT as well as Class IIa for patients without NSVT, even with adequate medical therapy.3
In Japan, unlike the USA and Europe, the underlying diseases are more common among patients with NICM than among those with ICM. In this issue of the Journal, Sasaki et al7 analyze data obtained from the NIPPON Storm Study and report a comparison using propensity scores of the outcomes of NICM patients with ICD implantation for PP and SP. The NIPPON Storm Study was conducted by the Japanese Heart Rhythm Society to investigate electrical storms, a frequent shock deriver of ICDs, and was a registry study that included 1,570 patients with ICD implantation between 2010 and 2012. They analyzed 126 NICM patients in each of the PP and SP groups via propensity score matching. During a mean follow-up of 775 days, among patients with LVEF ≤35%, the incidence of appropriate ICD therapy in the SP group was significantly higher than that in the PP group (21.0% in the PP group vs. 34.5% in the SP group, P=0.026).
In ICM patients, Kondo et al similarly conducted a subanalysis of the NIPPON Storm Study via propensity score matching and reported no significant difference in the incidence of appropriate treatment in the 2 groups (15.3% in the PP group vs. 23.9% in the SP group, P=0.114).8 It is noteworthy that the difference in the results of these studies does not imply that the indication criteria for the PP implantation of ICD in NICM are inappropriate.
It is important to recognize that ICDs are “underused” in Asia, including Japan, compared with Europe and the USA.9 The reasons for this seem to include physique, cultural resistance to device implantation, and the hypothesis that the prognosis of Japanese patients is better than that of Western patients. In actuality, the prognosis of Japanese patients who meet the criteria for primary ICD prophylaxis is poor,10 and it has been recently reported that ICDs are fully effective in patients with adequate risk levels.11 Therefore, ICD implantation in accordance with the guidelines is appropriate under the current circumstances.
In contrast, it is also important to note that significant progress has been made in other treatments of NICM. First, in addition to the standard medical treatments for heart failure with reduced LVEF, such as β-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and mineralocorticoid receptor antagonists, sodium-glucose cotransporter-2 inhibitor, and angiotensin receptor-neprilysin inhibitors (ARNI) have been shown to improve prognosis.12,13 Furthermore, the incidence of sudden cardiac death (SCD) has decreased over time even in patients without ICD implantation.14 Moreover, ARNI has demonstrated significant SCD risk reduction with and without ICD, especially in patients with NICM.9
The present report included a large number of cases of cardiac resynchronization (CRT) with defibrillator (64%).7 According to the 2011 nonpharmacologic guideline for arrhythmia, the QRS width for CRT indication was ≥120 ms, but later it was found that the response rate of CRT was low in non-left bundle branch block. However, in the 2018 guideline the recommendation for CRT in non-left bundle branch block cases was changed to be limited to cases with wider QRS width.3 Moreover, advances such as multipoint pacing and automated optimization algorithms have reduced the incidence of nonresponders. Recently, a meta-analysis of CRT with and without defibrillator in NICM reported no significant difference between both of the devices in terms of life expectancy.15
Evidence for ICDs should be further updated, considering the aforementioned changes. In practice, however, it is difficult to conduct randomized controlled trials in Japan. Thus, we need to continue putting our efforts towards updating the Japanese evidence with well-designed, bias-controlled registry studies, such as that conducted by Sasaki et al.7
