(SC-ICDs) in secondary sudden cardiac death (SCD) prevention.

Transcription

1 Heart, Lung and Circulation (216) 25, /4/$36. ORIGINAL ARTICLE Efficiencies and Complications of Dual Chamber versus Single Chamber Implantable Cardioverter Defibrillators in Secondary Sudden Cardiac Death Prevention: A Meta-analysis Zuo-Ying Hu, MD PhD 1, Juan Zhang, MD 1, Zhou-Tao Xu, MD 1, Xiao-Fei Gao, MD, Hang Zhang, MD, Chang Pan, MD, Shao-Liang Chen, MD PhD FACC * Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, China Received 29 November 214; received in revised form 12 May 215; accepted 19 July 215; online published-ahead-of-print 1 August 215 Background Dual chamber implantable cardioverter defibrillators (ICDs) are considered to have better clinical outcomes than single chamber ICDs, however, an individual trial may not have sufficient power to prove it. This metaanalysis aimed to compare clinical outcomes of dual chamber ICDs (s) with single chamber ICDs (s) in secondary sudden cardiac death (SCD) prevention. Methods We searched Medline, the Cochrane Library, and other internet sources, without language or date restrictions for articles comparing clinical outcomes between s and s. Studies were selected for inclusion based on the following criteria: Randomised controlled trial.; Controlled design was used to compare s and s; Retrospective study if the survival analysis was performed. Efficacy endpoints were mortality, appropriate therapy, inappropriate detection of SVT, inappropriate therapy. Safety endpoints were lead-related complication and all complications. Relative risk (RR) or odds ratios (ORs) with 95% confidence intervals (CI) were calculated, and a x2-based test of homogeneity was performed. Results We identified nine trials (n=2594) with a weighted mean follow-up of 18.9 months. Compared with DC- ICDs, s were associated with a significant reduction in lead complications (RR:3.3; 95% CI: ; p=.2). However, both groups had similar rates of mortality (OR:.91; 95%CI: ; p=.73), appropriate therapy (RR:.9; 95%CI: ; p=.32), inappropriate detection of SVT (RR: 1.82; 95%CI: ; p=.21), inappropriate therapy (RR: 2.8; 95%CI: ; p=.86) and all complications (OR: 1.27; 95%CI: ; p=.81). Conclusions Besides more lead-related complications, s had similar efficacy and all complications as s in secondary sudden cardiac death prevention. Keywords Implantable cardioverter-defibrillator Dual chamber Single chamber Secondary prevention Meta-analysis *Corresponding author at: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, No.68 Changle Road, 216, Nanjing City, Jiangsu Province. Tel.: ; fax: , chennfh@163.com 1 These authors equally contributed to this work. 215 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.

2 ICD in secondary prevention 149 Introduction Implantable cardioverter defibrillators (ICDs) have been shown to reduce mortality and the risk of SCD due to ventricular tachycardia or ventricular fibrillation in patients with cardiomyopathy and other cardiac disease in the last two decades [1 3]. Dan D. Matlock, et al. reported that the variation in use of s depended on the hospital and doctors instead of the patients conditions, in 212. More than 6% of patients with ICDs in America had received s by discretionary decision-making because of little definitive and inconclusive evidence [4]. But in China, the majority of patients had received s due to cheaper prices. In theory, s could provide more benefits including enhanced device arrhythmia discrimination algorithms, possible reductions in inappropriate therapies and the potential for a reduced risk of death [5 7]. In reality, s were reported not superior to s in some research [8,9]. Otherwise, s may have some risks of device-related complications [1]. Therefore, current American College of Cardiology/American Heart Association/Heart Rhythm Society practice guidelines do not specify s or SD- ICDs for patients who need it in primary or secondary prevention. Secondary prevention refers to prevention of SCD in those patients who have survived a prior sudden cardiac arrest or sustained ventricular tachyarrhythmia, according to 212 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 28 guidelines for device-based therapy of cardiac rhythm abnormalities [11]. Evidence from multiple randomised controlled trials supports the use of ICDs for secondary prevention of sudden cardiac arrest regardless of the type of underlying structural heart disease [1 3]. It is also uncertain when and whether to select either a or SC- ICD. Given the increase in patients with ICDs, and the paucity of data regarding the outcome and safety of s or SD- ICDs, further investigation is warranted. The objective of this study was to perform a meta-analysis to compare outcomes of s with SD-ICDs in secondary sudden cardiac death prevention. Methods Data Sources and Search Strategy We performed a computerised search of Medline, the Cochrane Library, and internet sources for clinical RCTs from January 1998 to July 214 using the medical subject heading terms implantable cardioverter-defibrillator, dual chamber, and single chamber. We used the Science Citation Index as a cross reference to identify trials that met the search criteria. Medline was searched using the method described by Biondi-Zoccal et al [25]. An additional search for potential trials included the references for previous metaanalysis, review articles, and the scientific sessions of the American College of Cardiology, American Heart Association. Study Identification Studies were selected for analysis based on the following inclusion criteria: Randomised controlled trial. Controlled design was used to compare s and s. Retrospective study if the survival analysis was performed. One of the following outcomes was reported: mortality, rate of patients with inappropriate therapy, appropriate therapy, inappropriate detection of SVT, ICD leadrelated complications and ICD-related complications. Exclusion criteria for this analysis were as follows: Studies only focussed on paediatric or younger patients. Studies were not designed for secondary sudden cardiac death prevention. Data Extraction Studies were identified by two independent reviewers (Yu ZT, Hu ZY) using the aforementioned search strategy. A third reviewer (Gao XF) was consulted when there was uncertainty regarding eligibility. The data being extracted from studies included name of the first author, year of publication, study design, participants age and gender, sample size, duration, follow-up duration, baseline characteristics, and clinical results of s and s. Clinical Endpoints Efficacy endpoints were mortality, appropriate therapy, inappropriate detection of SVT, inappropriate therapy. Safety endpoints were lead-related complication and all complications. Statistical Analysis We calculated RR and 95% CI from the extracted data. The fixed-effects model (based on the Mantel-Haenszel method) and the random-effects model (DerSimonian and Laird method) were used for the meta-analyses. A x 2 -based test of homogeneity was performed, and the inconsistency index (I 2 ) statistic was determined. If I 2 was >5% or <75%, the trials were considered to be heterogeneous or highly heterogeneous, respectively. An I 2 <25% indicated homogeneity among the studies. When heterogeneity existed between studies (I 2 >5%) a random-effects model was calculated. Otherwise, fixed-effects models were calculated. Sensitivity analysis was performed based on the leave-one-out approach. Publication bias analysis was not performed because the number of studies was not enough to detect an asymmetric funnel. All analyses were performed using Review Manager (RevMan) [Computer program] Version 5.2. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 212. A value of P<.5 was considered to indicate statistical significance. Results Eligible Trials and Baseline Characteristics A total of nine studies were included in this meta-analysis after applying the inclusion and exclusion criteria [8]. A

3 15 Z.-Y. Hu et al. Records iden fied through database searching (n=198) Records a er duplicates removed (n=144) Records screened (n=78) Full-text ar cles assessed for eligibility (n=38) Studies included in quan ta ve synthesis (meta-analysis) (n=9) flowchart of the study selection is shown in Figure 1. The characteristics of included trials are showed in Table 1. Data were analysed from 114 patients who underwent s and 14 patients with implantation. All-cause Mortality The ORs for the all causes mortality of these studies ranged from.55 to 1.51 (Fig. 2). There was homogeneity in the combined OR among these studies (Chi 2 =.57, I 2 =61%, D=.11), therefore a fixed effects model of analysis was used. Examination of the combined OR revealed a significant difference between s and s therapy. The combined OR was.91 (95% CI.55 to 1.51, D=.73), indicating that patients with s had no significant difference from those with s. Appropriate Therapy No difference of appropriate therapy was observed between s and s recipients after pooling the results from these studies (RR,.9; 95%CI, ; D=.32; Fig. 3). Inappropriate Detection of SVT The RR for inappropriate detection of SVT of these studies ranged from.71 to 4.64 (Fig. 4). There was heterogeneity in the combined RR among these studies (Chi 2 =24.35, I 2 =61%, D=.11), therefore a random effects model of analysis was used. The combined RR was 1.82 (95% CI,.71 to 4.64; D=.21), indicating that patients with s had no significant difference from those with s. Inappropriate Therapy Records iden fied through database searching (n=18) Records excluded (n=4) Full-text ar cles excluded with reasons (n=27) Figure 1 Flow chart of meta-analysis. According to the PRISMA statement, 9 trials were identified from literature search, internet sources and conference proceedings. The RR for inappropriate therapy of these studies is shown in Figure 5. There was heterogeneity in the combined RR among Table 1 Characteristics of included trials. DM EF% Hypertension DCM CHD Male Age (years) Sample Size Cohort s s FLU (months) Authors Year Published Deisenhofer et al /61 89/91 68/66 21/9 Wilkoff et al. 22 DAVID /64 77/74 83/84 15/16 61/64 34/28 26/28 Theuns et al. 24 PINAPP /57 74/82 84/72 1/21 31/29 Kolb et al /6 87/92 71/67 19/1 Olshansky et al /63 79/78 67/68 71/71 53/5 27/ /64 74/94 67/64 38/34 Takahashi /62 58/86 51/67 39/17 29/35 Soundarraj /68 78/77 75/83 43/39 26/26 Jodko

4 ICD in secondary prevention 151 Deisenhofer 21 Jodko 29 Kolb 26 Olshansky 27 Soundarraj 26 Takahashi 22 Theuns 24 Wilkoff 22 Events Total Events 1 25 Total % 77.3% 1.69 [.68, 4.2].69 [.37, 1.27] Heterogeneity: Chi² = 2.57, df = 1 (P =.11); I² = 61% Test for overall effect: Z =.35 (P =.73) 1.%.91 [.55, 1.51] Figure 2 Forest plot for the all-cause mortality. Year Deisenhofer 21 Takahashi 22 Wilkoff 22 Theuns 24 Soundarraj 26 Kolb 26 Olshansky 27 Jodko % 67.2% 17.4%.94 [.58, 1.5].81 [.62, 1.5] 1.23 [.77, 1.97] Heterogeneity: Chi² = 2.41, df = 2 (P =.3); I² = 17% Test for overall effect: Z = 1. (P =.32) 1.%.9 [.73, 1.11] Figure 3 Forest plot for appropriate therapy. M-H, Random, 95% CI Year M-H, Random, 95% CI Deisenhofer 21 Takahashi 22 Wilkoff 22 Theuns 24 Kolb 26 Soundarraj 26 Olshansky 27 Jodko % 2.9% 28.8% 26.3%.76 [.33, 1.73] 2.15 [.71, 6.5] 1.14 [.87, 1.48] 5.88 [3.23, 1.69] % 12 8 Heterogeneity: Tau² =.78; Chi² = 27.74, df = 3 (P <.1); I² = 89% Test for overall effect: Z = 1.25 (P =.21) 1.82 [.71, 4.64] Figure 4 Forest plot for Inappropriate detection of SVT. these studies (Chi 2 =14.83, I 2 =87%, D=.6), therefore a random effects model of analysis was used. The combined RR was 2.8 (95% CI, -.22 to.19; D=.86), indicating that patients with s had no significant difference from those with s. Lead-related Complication and all Complications The ORs for lead-related complication in these studies ranged from 1.17 to 9.3 (Fig. 6). There was homogeneity

5 152 Z.-Y. Hu et al. Risk Difference M-H, Random, 95% CI Year Risk Difference M-H, Random, 95% CI Deisenhofer 21 Wilkoff 22 Takahashi 22 Theuns 24 Kolb 26 Soundarraj 26 Olshansky 27 Jodko % 3.2% 37.7%.8 [-.7,.23].7 [-.11,.25] -.17 [-.24, -.1] % 1 Heterogeneity: Tau² =.3; Chi² = 14.83, df = 2 (P =.6); I² = 87% Test for overall effect: Z =.17 (P =.86) -.2 [-.22,.19] Figure 5 Forest plot for inappropriate therapy. Year Deisenhofer 21 Wilkoff 22 Takahashi 22 Theuns 24 Kolb 26 Soundarraj 26 Olshansky 27 Jodko % 33.4%.95 [.18, 5.] 7.97 [1.69, 37.55] Heterogeneity: Chi² = 3.4, df = 1 (P =.7); I² = 71% Test for overall effect: Z = 2.25 (P =.2) 1.% 3.3 [1.17, 9.3] Figure 6 Forest plot for lead related complication. in the combined OR among these studies (Chi 2 =3.4, I 2 =71%, D=.7), therefore a fixed effects model of analysis was used. Examination of the combined OR discovered no significant difference between s and s therapy. The combined OR was 3.3 (D=.2), indicating that patients with Ss had significantly less lead-related complications than those with s. The ORs for complication of these studies is shown in Figure 7. There was heterogeneity in the combined RR among these studies (Chi 2 =14.83, I 2 =87%, D=.3), therefore a M-H, Random, 95% CI Year M-H, Random, 95% CI Deisenhofer 21 Takahashi 22 Wilkoff 22 Theuns 24 Kolb 26 Soundarraj 26 Olshansky 27 Jodko % 53.5%.44 [.1, 1.89] 3.16 [1.13, 8.86] % Heterogeneity: Tau² = 1.52; Chi² = 4.69, df = 1 (P =.3); I² = 79% Test for overall effect: Z =.24 (P =.81) 1.27 [.19, 8.67] Figure 7 Forest plot for all complications.

6 ICD in secondary prevention 153 random effects model of analysis was used. The combined RR was 1.27 (95% CI,.19 to 8.67; D=.81), indicating that patients with s had no significant difference from those with s. Discussion The purpose of this study was to compare mortality, appropriate therapy, inappropriate detection of SVT, inappropriate therapy and complications among patients who received dual or single-chamber ICDs for secondary prevention of sudden cardiac death. The results of this meta-analysis indicated no significant difference in mortality, appropriate therapy, inappropriate detection of SVT, inappropriate therapy and all complications, and a higher risk of lead-related complications in s arms. There is a great deal of evidence supporting the use of ICDs for both primary and secondary prevention of SCD regardless of the use of s or s [19 22]. Several studies have reported that patients with s had received clear benefits over the patients with s in some fields [19], while other studies do not agree [2]. Dr. Theuns demonstrated in a meta-analysis that s were associated with a reduction in the number of inappropriate treated episodes without reduction in the number of patients who experience inappropriate therapy [23]. Dr. Francia argued in his clinical review that ICD arrhythmia discrimination tools were improved and s were superior to s in preventing inappropriate therapies [24]. Dr. Chen recently revealed in a systematic review and meta-analysis that s showed no conclusive superiority over s and suggested that s might be the preferred selection without indications for antibradycardia therapy [21]. However, patients who have survived a prior sudden cardiac arrest or sustained VT especially need appropriate and optimising ICDs for secondary pretention from SCD. Hence, we performed this meta-analysis to compare DC- ICDs to s in such patients for secondary sudden cardiac death pretention. Although randomised trials were limited, there were still sufficient retrospective studies and randomised trials for analysis. Kuhlcamp et al. found that inappropriate therapies for atrial fibrillation in s arms were not decreased compared with s [13]. Deisenhofer et al. concluded in their prospective study that the implanted s had similar safe and effective results for SCD, further, the applied detection algorithms in s did not offer benefits in avoiding inappropriate therapies during supraventricular tachyarrhythmia [12]. Bruce I. Wilkoff and the DAVID trial investigators analysed the randomised trial results and suggested that s were not associated with improved quality of life or decreased frequency of hospitalisation, inappropriate shocks from the defibrillator or atrial fibrillation [16]. In the other randomised trial aimed to investigate the performance of single and dual chamber tachyarrhythmia detection algorithms, Theuns et al. discovered that the applied detection criteria in s did not offer benefits in the rejection of atrial tachyarrhythmia [15]. Kolb et al. further performed a prospective randomised study in patients with preserved sinus and atrioventricular nodal function and found that s had no advantage over SC- ICDs with respect to mortality and arrhythmogenic morbidity in a long-term follow-up[14]. More importantly, s were associated with similar outcomes including all-cause mortality as with s in the randomised INTRINSIC RV trial [17]. Nevertheless, Soundarraj et al. considered that patients with s were less likely to receive inappropriate therapy as compared to patients with s [18]. Moreover, Takahashi et al. found in 178 consecutive patients with either a or from July 1997 to April that the may have a higher frequency of device- and lead-related major complications including atrial lead dislodgment, ventricular lead malfunction and pocket haematoma [1]. The limitations of our study include the lack of randomised trials comparing s with s. Device programming was discretely decided by the individual investigator including brady and tachy parameters and detection enhancement algorithms. Successive generations of ICD devices have offered different advanced algorithms to identify and treat ventricular arrhythmias in these trials. A prospective and randomised trial is expected to be proposed to compare s to s on a large scale. Conclusions Besides more lead-related complications, s had similar efficacy and all complications as s in secondary sudden cardiac death prevention. Acknowledgments There was no financial assistance with the project. 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