Role of Implantable Cardioverter Defibrillators in Patients With Heart Failure and Nonischemic Cardiomyopathy in Japan ― Analysis From the Nippon Storm Study ―
論文ID: CJ-23-0783
詳細
論文ID: CJ-23-0783
An implantable cardioverter defibrillator (ICD) is an effective treatment for sudden cardiac death (SCD), with demonstrated usefulness in ischemic cardiomyopathy.1 However, whether ICDs confer a significant prognostic benefit in nonischemic cardiomyopathy (NICM) is controversial.
Article p ????
The main trials of primary prevention with ICDs are as follows. The Cardiomyopathy Trial (CAT) investigated the prognosis of 104 patients with dilated cardiomyopathy, and found no significant differences in cumulative survival between the ICD and medication groups over a 4-year observation period.2 The Defibrillators In Non-Ischemic Cardiomyopathy Treatment (DEFINITE) trial3 compared medication with and without an ICD in patients with NICM and premature ventricular contractions or nonsustained ventricular tachycardia. Although the incidence of SCD was lower in the ICD group, there were no significant differences in mortality rates. The Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial compared cardiac resynchronization–pacemaker (CRT-P) and CRT with defibrillator (CRT-D) therapy, finding that that CRT-D significantly reduced the mortality rate.4 However, in a subsequent meta-analysis by Long et al, CRT-D was non-superior to CRT-P in terms of overall deaths in NICM.5 Thus, despite the many clinical trials that have been conducted, no reliable evidence has been obtained.
The Japanese Circulation Society (JCS) guidelines recommend ICDs as primary or secondary prevention.6 As primary prevention an ICD is indicated for patients with heart failure (HF), mainly based on left ventricular ejection fraction (LVEF) ≤35% in both ICM and NICM. In the new European Society of Cardiology (ESC) guidelines, the recommendation for ICD implantation as primary prophylaxis in patients with NICM has been downgraded from Class I to Class IIa,7 a modification based on a finding from the Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure (DANISH) study that ICD use was not associated with reduction of long-term death in NICM.8
Many parts of the JCS guidelines have been developed and revised following the ESC guidelines, but while it is possible to change the JCS guidelines on ICD as primary prevention for NICM, it is important to confirm that Japanese patients have the same clinical course as patients in other countries, because the etiology of HF varies. To determine whether the results of the DANISH study are applicable to Japanese patients, the Nippon Storm study was conducted.9,10 In this issue of the Journal, Kondo et al11 investigate the efficacy of ICD therapy in patients with NICM or ICM in the Nippon Storm study.11 They found that the risks associated with appropriate ICD therapy were higher in the NICM group, from which they concluded that careful consideration is needed before revising the JCS guidelines for prophylactic ICD use in patients with HF. Looking at the patients’ characteristics, there are some differences between the study conducted by Dr. Kondo and colleagues as a subanalysis of the Nippon Storm Study and DANISH study (Table). The Nippon Storm Study included more patients with more severe HF (New York Heart Association classes III and IV) than in the DANISH study. Moreover, use of angiotensin-converting enzyme inhibitors/angiotensin II receptors and β-blockers was more common in the DANISH study. These factors might improve the outcomes not only in terms of reductions in ventricular arrhythmias, but also in clinical outcomes of NICM. However, ICDs were somewhat useful in Japanese patients with NICM in the Nippon Storm study.
Patients’ Characteristics in the Nippon Storm and DANISH Studies
| Characteristics | Nippon Storm study (n=132)* |
DANISH study (n=556) |
|---|---|---|
| Age, years | 67.9 (mean) | 64 (median) |
| BNP or NT-proBNP, pg/mL | 714.3 (mean BNP) | 1,244 (median NT-proBNP) |
| NHYA III or IV disease, n (%) | 75 (56.8) | 259 (46) |
| CRT-D, n (%) | 92 (69.7) | 322 (58) |
| Comorbidity | ||
| Diabetes mellitus, n (%) | 37 (28) | 99 (18) |
| Hypertension, n (%) | 52 (39.4) | 181 (33) |
| Medications | ||
| β-blocker, n (%) | 98 (74.8) | 509 (92) |
| ACEI or ARB, n (%) | 93 (72.1) | 544 (97) |
| Amiodarone or class III AAD, n (%) | 35 (26.7) | 34 (6) |
*Guideline-directed medical therapy was insufficiently used in patients recruited for the Nippon Storm study compared with patients in the DANISH study. AAD, antiarrhythmic drug; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor; BNP, B-type natriuretic peptide; CRT-D, cardiac resynchronization therapy with a defibrillator; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association.
Sasaki et al conducted subanalyses of the Nippon Storm study to investigate the usefulness of prophylactic ICD therapy as primary vs. secondary prevention in NICM.12 Although appropriate therapy occurred more frequently in the secondary prevention group, the primary prevention group had appropriate ICD therapy. The authors emphasized the considerable risk of developing fatal ventricular arrhythmias in patients with ICDs for primary prophylaxis.
Like the previous DEFINITE and COMPANION clinical trials, the study by Kondo et al also revealed that ICD use is associated with a reduction of SCD in NICM, even though the DANISH study did not show that ICD use is associated with benefits in long-term outcomes in NICM. That result confirmed the efficacy of ICDs in life-threatening ventricular arrhythmia. However, the long-term mortality rate did not decrease. Thus, another message from the DANISH study is that SCD is not the main cause of death in patients with HF. In most patients, the cause of death is progression of HF. Thus, it is difficult to assess the efficacy of ICD, because NICM and the clinical status of patients with HF are heterogenous. Previously, we found that SCD was not a common cause of death in patients who receive CRT; the most frequent cause of death was HF (Figure).13 Patients with HF often have complications such as frailty, kidney disease, and lung disease caused by their general condition, making it difficult to predict the effectiveness of ICDs.
Causes of death in patients with heart failure who received cardiac resynchronization therapy. Heart failure was the most frequent cause of death. Sudden cardiac death was relatively rare. (Reproduced from reference 13 with permission.)
ICDs definitely reduce the risk of SCD. Some patients with HF might be candidates for prophylactic ICD therapy. However, previous studies have shown that HF or other diseases are the causes of death, not SCD, especially in patients with severe HF. The decision for ICD therapy should take into consideration each patient’s comorbidities and social background.
Unfortunately, there have not been any large-scale studies of the usefulness of prophylactic ICD therapy in Japan. Further information is needed to develop or revise JCS guidelines for appropriate ICD use. Studies such as the one by Kondo et al are important because they provide information about the real-world situation of Japanese patients that is useful for decision-making about ICD therapy.
T.N. belongs to an endowed department established by contributions from Abbott Medical Japan, Biotronik Japan, Medtronic Japan, and Japan Lifeline, and has received lecture fees from Abbott Medical Japan and Medtronic Japan.
N/A.
