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Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis

  • Antonio Salsano EMAIL logo , Jingda Liao , Ambra Miette , Massimo Capoccia , Giovanni Mariscalco , Francesco Santini and Antonio F. Corno
Published/Copyright: March 9, 2021

Abstract

Background

Kawasaki disease (KD) is a systemic inflammatory condition occurring predominantly in children. Coronary artery bypass grafting (CABG) is performed in the presence of inflammation and aneurysms of the coronary arteries. The objectives of our study were to assess which CABG strategy provides better graft patency and early and long-term outcomes.

Methods

A systematic review using Medline, Cochrane, and Scopus databases was performed in February 2020, incorporating a network meta-analysis, performed by random-effect model within a Bayesian framework, and pooled prevalence of adverse outcomes. Hazard ratios (HR) and corresponding 95% credible intervals (CI) were calculated by Markov chain Monte Carlo methods.

Results

Among 581 published reports, 32 studies were selected, including 1,191 patients undergoing CABG for KD. Graft patency of internal thoracic arteries (ITAs), saphenous veins (SV), and other arteries (gastroepiploic artery and radial artery) was compared. ITAs demonstrated the best patency rates at long-term follow-up (HR 0.33, 95% CI: 0.17–0.66). Pooled prevalence of early mortality after CABG was 0.28% (95% CI: 0.00–0.73%, I 2 = 0%, tau2 = 0), with 63/1,108 and 56/1,108 patients, undergoing interventional procedures and surgical re-interventions during follow-up, respectively. Pooled prevalence was 3.97% (95% CI: 1.91–6.02%, I 2 = 60%, tau2 = 0.0008) for interventional procedures and 3.47% (95% CI: 2.26–4.68%, I 2 = 5%, tau2 <0.0001) for surgical re-interventions. Patients treated with arterial, venous, and mixed (arterial plus second venous graft) CABG were compared to assess long-term mortality. Mixed CABG (HR 0.03, 95% CI: 0.00–0.30) and arterial CABG (HR 0.13, 95% CI: 0.00–1.78) showed reduced long-term mortality compared with venous CABG.

Conclusions

CABG in KD is a safe procedure. The use of arterial conduits provides better patency rates and lower mortality at long-term follow-up.

1 Introduction

Kawasaki disease (KD) is a systemic inflammatory condition occurring predominantly in children (80% of patients are younger than 5 years of age), first reported in 1974 as an acute febrile illness with mucocutaneous lesions and lymphadenopathy [1,2]. The incidence of KD varies across the world from 19 to 265 cases per 1,00,000 in children less than 5 years of age [2]. It can be complicated by a systemic vasculitis with particular involvement of the coronary arteries; if left untreated, 20% of children could develop coronary artery aneurysm [2]. In the acute phase of the disease, inflammatory formation of coronary aneurysms can occur, eventually associated with rupture of the latter, while thrombosis or narrowing of the affected coronary arteries can complicate the late phases [2,3,4,5,6]. In high income countries, KD remains the leading cause of acquired heart disease in children, with complication such as acute myocardial infarction [2,7,8,9]. Despite extraordinary results due to early recognition of the disease and treatment with intravenous administration of immunoglobulins [2,10], long-term studies showed that complications secondary to inflammation and aneurysmatic dilatation of the coronary arteries can still occur, with subsequent impairment of the left ventricular function [2,8,9,11,12,13,14]. Selective coronary angiography is indispensable in those situations to provide essential information for the decision making, before percutaneous or surgical myocardial revascularization [2,14,15,16,17]. Coronary artery bypass grafting (CABG) is performed in the presence of inflammation and aneurysms of the coronary arteries, using both arterial and/or venous grafts [17,18]. In the literature, only retrospective studies about CABG after KD are found and no meta-analysis has been published until now; grafts’ patency and long-term outcomes such as survival rates appear uncertain. Since the risk of progression of the systemic arteritis with formation of aneurysms in other arterial districts [19], such as internal thoracic artery (ITA) [20], the choice of the best type of surgical revascularization is still a matter of discussions [18].

The objectives of our study were to assess which surgical strategy of CABG provides better graft patency and early and long-term outcomes, through a literature systematic review and a Bayesian network meta-analysis.

2 Materials and methods

No ethical approval or review protocol was applicable for this study, since it was a review of existing literature. This work was in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (see Supplementary Materials – Appendix 1).

Primary endpoint is graft patency for ITAs, saphenous veins (SV), and other conduits (gastroepiploic [GEA] and radial [RA] arteries). Patency assessment at follow-up was performed using either invasive angiography or noninvasive computed tomographic angiography, and significative coronary stenosis (>70%) or occlusions were considered non-patent grafts [8].

Secondary endpoints were early mortality (in-hospital or 30-days mortality), need for interventional procedures and surgical re-interventions, and long-term mortality for arterial, venous, or mixed (arterial plus second venous graft) types of revascularization.

2.1 Search strategy

A systematic review using Medline, Cochrane, and Scopus databases has been performed in March 2020, incorporating a Bayesian network meta-analysis. A search strategy with a time interval from 1980 to 2020 was performed using the following search string for Medline (remaining strings have been reported in Supplementary Material): (cabg [Title/Abstract]) OR bypass [Title/Abstract] OR cardiac surgery [Title/Abstract] OR revascularisation [Title/Abstract] OR revascularization [Title/Abstract])) AND Kawasaki [Title/Abstract]. The articles were screened by three investigators (A. S., J. L., A. M.) initially by title and abstract, irrelevant articles were excluded, and subsequently full texts were evaluated for eligibility.

2.2 Inclusion and exclusion criteria

Inclusion criteria for the study were: (1) subjects involved in the study were patients with KD who underwent surgical revascularization; (2) comparison between different surgical strategies of myocardial revascularization; (3) at least one of the endpoints has to be included, such as graft patency, early and long-term mortality, and need of interventional procedures and/or surgical re-interventions; (4) sufficient quality data should have been provided in the original studies. Exclusion criteria for the study: (1) case reports, conference proceedings or reviews; (2) duplicates studies; (3) publications with full text in languages other than English. PICOS study design was used for inclusion/exclusion criteria (Table S1).

2.3 Data extraction

Three investigators (A. S., J. L., A. M.) independently identified and extracted all relevant data of eligible studies from original articles: first author’s name, year of publication, numbers of patients, mean age at surgery, gender, surgical strategy of myocardial revascularization, number of grafts, and endpoints such as graft patency, early and long-term mortality, and need of interventional procedures and/or surgical re-interventions. Data were retrieved only from the articles, and no attempt was made to get missing data from the authors. Any disagreement was solved by consensus.

2.4 Quality assessment

Study quality was assessed using the Newcastle-Ottawa Scale, a scale to evaluate the quality of non-randomized studies [21], and the US Preventive Services Task Force [22]. The Cochrane Risk of Bias tool was also used to evaluate the methodological quality of all included studies [23]. Quality assessment of each study is presented in Tables S2–S5.

2.5 Statistical analysis

Baseline and early mortality data were pooled using meta-analysis of means or proportions, with individual study effect size accounted for using inverse variance methods. Results were displayed as values and percentages with 95% confidence intervals (CI) or 95% credible intervals (CrI). Graft patency and long-term mortality for arterial, venous, or mixed CABG were analyzed across all arm-level studies, with direct and indirect comparisons using a mixed-treatment comparison based on a Bayesian hierarchical model. HRs and corresponding 95% credible intervals were calculated by Markov chain Monte Carlo methods using the “BUGSnet” package of R software (version 3.6.3; R Foundation, Vienna, Austria) [24]. Brooks–Gelman–Rubin plots method, trace plot, and density plot were used to assess the model convergence [25]. Besides, rank probabilities were calculated to obtain the hierarchical amount effects of multiple treatments. Given the graft type, CABG modalities, and time period over which included studies were conducted, a random-effect model was used. For the purposes of the mixed-treatment comparison, consistency in direct and indirect effects was assumed [26]. Heterogeneity between comparisons within the network was analyzed by examining I values for the random-effect model. Inconsistency was graphically examined using the BUGSnet nma.compare function to plot the individual data points’ posterior mean deviance contributions for the consistency model versus the inconsistency model [27]. For early mortality, need of interventional procedures, and surgical re-interventions, a frequentist approach (meta-analysis of proportions) has been applied. Pooled prevalence of adverse outcome has been calculated using the package “meta” of R software [28].

3 Results

3.1 Search results and study characteristics

The systematic literature review from 1981 to 2019 provided the following results: 581 reports and, after duplicates removal, 261 were screened. After screening of titles and abstract, 92 papers were excluded. The full texts of the remaining 169 articles were evaluated, and 137 studies were excluded with reasons. A total of 32 articles (observational studies and case series, no randomized controlled trial), including 1,191 patients, were selected [29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60].

Patients were mostly male with a mean age of 12.17 years and received CABG using 1.79 grafts per patient on average (Table 1).

Table 1

Pooled patients baseline data

Variables Pooled data
Patients, n 1,191
Males, n (%) 718/965 (74.40%)
Age, mean (95% CI) 12.17 (10.67–13.88) years
Grafts 2,043
Grafts per patient, mean (95% CI) 1.79 (1.55–2.00)
Redo surgery, n (%) 56/1,114 (5.02%)
Off-pump surgery, n (%) 60/871 (6.89%)

A PRISMA flow diagram of the study selection process can be found in Figure 1. The quality assessment of the included studies is reported in Tables S2–S5. Detailed pooled patients’ data are presented in Table 1. For all studies, patients’ characteristics, main surgical strategies, and early outcome results are summarized in Table 2.

Figure 1 
                  Flow diagram of the literature selection process.
Figure 1

Flow diagram of the literature selection process.

Table 2

Studies, patients’ characteristics, main surgical strategies, and extracted outcomes

Study Year Patients Age (years) Male sex N. Graft ITA LITA RITA RA or GEA SV N. CABG Arterial CABG Venous CABG Mixed CABG Off-pump On pump Early patients mortality
Matsumoto et al. [29] 2019 3 21 ± 7.8 2 (67%) 3 3 (100%) 3 (100%) 0 0 0 3 3 (100%) 0 0 3 (100%) 0 0
Tadokoro et al. [30] 2019 92 14.9 ± 10.4 75 (82%) 175 125 (71%) NA NA 36 (21%) 14 (8%) 102 82 (80%) 8 (8%) 2 (2%) 17 (17%) 85 (83%) 0
Jeong et al. [31] 2018 20 20.15 ± 11.73 4 (20%) 44 40 (91%) 27 (61%) 13 (30%) 3 (7%) 1 (2%) 20 19 (95%) 0 1 (5%) 16 (80%) 4 (20%) 0
Beckmann et al. [32] 2017 2 27 ± 6 1 (50%) 6 4 (67%) 2 (33%) 2 (33%) 2 (33%) 0 2 2 (100%) 0 0 1 (50%) 1 (50%) 0
Ramírez-Marroquín et al. [33] 2017 7 6.14 ± 3.71 4 (57%) 13 12 (92%) 5 (38%) 7 (54%) 1 (8%) 0 7 7 (100%) 0 0 0 7 (100%) 0
Dionne et al. [34] 2017 11 8.3 ± 3.9 NA NA NA NA NA NA NA 11 7 (64%) 0 4 (36%) NA NA 0
Jang et al. [35] 2015 14 NA NA NA 11 NA NA 2 1 14 12 (86%) 0 1 (7%) NA NA 1 (7%)
Tsuda et al. [36] 2014 90 NA NA 155 NA NA NA NA NA 90 NA NA NA NA NA 0
Guo et al. [37] 2010 8 21.25 ± 13.57 5 (63%) 20 8 (40%) 6 (30%) 2 (10%) 1 (5%) 11 (55%) 8 3 (37.5%) 2 (25%) 3 (37.5%) 2 (25%) 6 (75%) 1 (13%)
Muta et al. [38] 2010 81 13 ± 9 60 (74%) 131 99 (76%) NA NA 20 (15%) 12 (9%) 81 69 (85%) 2 (4%) 9 (11%) 10 (12%) 71 (88%) 1 (1%)
Viola et al. [39] 2010 5 8.8 ± 3.63 NA 11 9 (82%) 5 (45.5%) 4 (36.5%) 0 2 (18%) 5 4 (80%) 0 1 (20%) 0 5 (100%) 0
Legendre et al. [40] 2010 2 0.94 ± 1.04 NA 4 4 (100%) 2 (50%) 2 (50%) 0 0 2 2 (100%) 0 0 NA NA 0
Kitamura et al. [41] 2009 114 NA 86 (75%) 198 154 (78%) 111 (56%) 43 (22%) 14 (7%) 30 (15%) 114 90 (79%) 3 (3%) 21 (18%) 0 114 (100%) 0
Mueller et al. [42] 2009 2 NA NA 5 3 (60%) 2 (40%) 1 (20%) 0 2 (40%) 2 1 (50%) 0 1 (50%) NA NA 0
Wakisaka et al. [43] 2009 13 10.38 ± 5.78 11 (85%) 32 11 (34%) 10 (31%) 1 (3%) 1 (3%) 20 (63%) 13 0 3 (23%) 10 (77%) NA NA 0
Kitamura et al. [44] 2008 2 25 ± 7 2 (100%) 4 3 (75%) 2 (50%) 1 (25%) 1 (25%) 0 2 2 (100%) 0 0 0 2 (100%) 0
Tsuda et al. [45] 2008 2 7.5 ± 3.53 0 2 2 (100%) 2 (100%) 0 0 0 2 2 (100%) 0 0 NA NA 0
Tsuda et al. [46] 2007 67 NA 48 (72%) 125 95 (76%) 0 0 13 (10%) 17 (14%) 71 54 (76%) 0 17 (24%) 7 (10%) 64 (90%) 0
Tsuda et al. [47] 2004 244 13 ± 8 188 (77%) 435 310 (70%) NA NA 40 (10%) 85 (20%) 244 NA NA NA 4 (2%) 240 (98%) 1 (0%)
Yamauchi et al. [48] 2004 21 11.86 ± 7.42 17 (81%) 32 29 (91%) 26 (81%) 3 (9%) 3 (9%) 0 21 21 (100%) 0 0 0 21 (100%) 0
Inoue et al. [49] 2001 6 9.3 ± 2.25 5 (83%) 8 5 (62.5%) 4 (50%) 1 (12.5%) 0 3 (37.5) 6 3 (50%) 2 (33%) 1 (17%) NA NA 0
Suda et al. [50] 2000 2 8 ± 1.41 2 (100%) 2 0 0 0 0 2 (100%) 2 0 2 (100%) 0 0 2 (100%) 0
Yoshikawa et al. [51] 2000 100 10 ± 5 72 (72%) 168 138 (82%) 99 (59%) 39 (23%) 9 (5%) 21 (13%) 100 79 (79%) 2 (2%) 19 (19%) NA NA 0
Mavroudis et al. [52] 1999 4 6.12 ± 4.8 NA 5 5 (100%) 3 (60%) 2 (40%) 0 0 4 4 (100%) 0 0 0 4 (100%) 0
Kitamura et al. [53] 1994 168 10.6 ± 8.1 127 (76%) 288 143 (50%) NA NA 12 (4%) 133 (46%) 168 114 (68%) 0 54 (32%) 0 168 (100%) 1 (0%)
Suzuki et al. [54] 1990 26 NA NA 37 28 (76%) 24 (65%) 4 (11%) 0 9 (24%) 26 NA NA 6 (23%) 0 26 (100%) 1 (4%)
Kitamura et al. [55] 1983 5 12.2 ± 9.4 4 (80%) 9 0 0 0 0 9 (100%) 5 0 5 (100%) 0 0 5 (100%) 0
Suma et al. [56] 1981 8 7.75 ± 2.55 5 (63%) 13 0 0 0 0 13 (100%) 8 0 8 (100%) 0 NA NA 0
Hirose et al. [57] 1986 5 NA NA 10 2 (20%) NA NA 0 8 (80%) 5 NA NA NA NA NA 0
Torii et al. [58] 1996 9 NA NA 18 9 (50%) NA NA 9 (50%) 0 9 9 (100%) 0 0 NA NA 0
Ohara et al. [59] 1989 22 NA NA 28 20 (71%) NA NA 0 8 (29%) 22 15 (68%) 2 (9%) 5 (23%) NA NA 0
Takeuchi et al. [60] 1992 36 NA NA 62 27 (43.5%) 22 (35.5%) 5 (8%) 8 (13%) 27 (43.5%) 36 NA NA NA NA NA 0

N, number; CABG, coronary artery bypass graft; ITA, internal thoracic artery; LITA, left internal thoracic artery; NA, not applicable; RITA, right internal thoracic artery; RA, radial artery; GEA, gastroepiploic artery; SV, saphenous vein; PCI, percutaneous coronary intervention.

Categorical data were presented as frequencies and percentages, continuous variables as means, and standard deviation (if reported in the included studies).

3.2 Results from network meta-analysis

3.2.1 Primary outcome: graft patency

Overall, 1,191 patients were included in the present meta-analysis, with an average of 1.79 (95% CI: 1.55–2.00) grafts per patient. ITA, RA or GEA, and SV conduits were used; however, the exact numbers of each graft type and graft target vessels were incompletely reported. Of the 32 studies, 15 arm-level papers were included to perform the Bayesian network meta-analysis, with a total of 1,441 grafts with 324 significative stenosis/occlusions [30,31,32,33,39,41,42,43,44,47,49,53,54,57,59]. Mean follow-up for coronary angiography across studies was 92.19 months (follow-up: min 3–max 264 months). For the primary outcome, we compared patency of ITAs, SV, and other arteries (GEA and RA) at follow-up. Patency rates at follow-up for ITAs, SV, and other arteries are 87.82 ± 12.41%, 65.98 ± 27.84%, and 77.63 ± 22.75%, respectively. The network model, trace plot, and density plot for graft patency are shown in Figures S1 and S2.

Summary results for all grafts patency at follow-up are shown in Figure 2a, with SV used as reference. These pooled results show that ITAs and other arteries (GEA and RA) are superior to SV. Rank probability analysis for graft patency at follow-up demonstrates that ITA had higher probabilities of being the first most effective treatment (Figure 2b).

Figure 2 
                     (a) Forest plot for graft patency. (b) Sucra plot for graft patency showing rank probability analysis.
Figure 2

(a) Forest plot for graft patency. (b) Sucra plot for graft patency showing rank probability analysis.

The efficacy of different treatments in terms of graft patency at follow-up using HR and corresponding 95% CrI is displayed in Figure 3. Pairwise comparisons for graft patency at follow-up are shown in Figures S3a–c. I 2 demonstrated that heterogeneity was low for SV versus ITAs comparison and was moderate for SV and ITAs versus other arteries (GEA and RA). After comparison of consistency and inconsistency models through individual data points’ posterior mean deviance contributions, we conclude that there is a lack of evidence to suggest inconsistency within the network (Figure S4).

Figure 3 
                     League table for graft patency.
Figure 3

League table for graft patency.

3.2.2 Secondary outcomes: early and long-term mortality, need of interventional procedures, and surgical re-interventions

In all 32 studies included in the meta-analysis, only 6 early deaths were reported among 1,191 patients. Pooled prevalence of early mortality after CABG was 0.28% (95% CI: 0.00–0.73%, I 2 = 0%, tau2 = 0, Figure S5).

Twenty six studies reported interventional procedures and surgical re-interventions rates: 63/1,108 and 56/1,108 patients underwent interventional procedures and surgical re-interventions at follow-up (mean 110.35 months, 95% CI: 28.50–264.00 months), respectively.

Pooled prevalence of interventional procedures was 3.97% (95% CI: 1.91–6.02%, I 2 = 60%, tau2 = 0.0008, Figure S6). Across the studies that reported interventional procedures, high heterogeneity demonstrated elevated variability across the included studies.

Among the interventional procedures, percutaneous transluminal balloon angioplasty was performed only for graft stenosis, while percutaneous transluminal rotational ablation was done for coronary artery lesions. 7 DES stents were implanted for conduit stenoses (5 SVG graft, 1 ITA graft, and 1 RA graft). Pooled prevalence of surgical re-interventions was 3.47% (95% CI: 2.26–4.68%, I 2 = 5%, tau2 <0.0001, Figure S7).

Patients treated with arterial, venous, and mixed (arterial plus second venous graft) CABG were compared to assess long-term mortality. Eight arm-level papers out of 32 studies were included to perform the network meta-analysis [31,34,39,41,42,43,49,53]. Mean follow-up across studies for long-term mortality was 142.56 months (follow-up: min 48–max 264 months). Survival at follow-up after arterial, venous, and mixed CABG is 99.07 ± 2.27%, 83.33 ± 28.87%, and 99.87 ± 0.33%, respectively. The network model, trace plot, and density plot for long-term mortality are shown in Figures S8 and S9. Summary results are shown in Figure 4a, while rank probability analysis is shown in Figure 4b.

Figure 4 
                     (a) Forest plot for long-term mortality compared to SV. (b) Sucra plot for long-term mortality showing rank probability analysis.
Figure 4

(a) Forest plot for long-term mortality compared to SV. (b) Sucra plot for long-term mortality showing rank probability analysis.

The efficacy of different treatments using HR and corresponding 95% CrI is displayed in Figure S10. Pairwise comparisons at follow-up are shown in Figure S11a–c. There is a lack of evidence to suggest inconsistency within the network model (Figure S12). Briefly, mixed CABG (HR 0.03, 95% CrI: 0.00–0.30) and arterial CABG (HR 0.13, 95% CrI: 0.00–1.78) showed reduced long-term mortality compared with venous CABG.

More in deep, focusing on the comparison between long-term mortality for arterial CABG vs. mixed CABG, we are facing with 58 single CABG out of a total of 133 cases (43.6%) in which at least one arterial conduit has been employed (Figure S11c) [34,39,41,42,49]. It appears that the use of arterial conduit, even better if applied in a multiple CABG setting, provides benefits on long-term mortality. Although the low number of deaths at follow-up is a positive finding, caution is required in interpreting these results and it needs to be confirmed in future studies.

4 Conclusions

This network meta-analysis aimed to assess which CABG strategy provides better graft patency and long-term outcomes. Results from 32 studies with a total of 1,191 cases demonstrated that CABG for KD is a safe procedure with satisfying long-term outcomes.

Our systematic review and meta-analysis showed a low early mortality after CABG in KD, ranging between 0 and 1%. The excellent efficacy of surgical revascularization was also demonstrated by 10-year survival rates above 90%, with a 3.5–4% rate of interventional procedures or surgical re-interventions during the follow-up.

The choice of conduits in coronary artery surgery remains a debated and controversial issue, and the following points should be considered before CABG: the expected long-term patency of the graft, considering that the factors that may influence long-term patency are the presence of competitive flow from the native vessel or collaterals, further development of atherosclerosis, and abnormal coronary artery structure and function at the site of the anastomosis. The choice between arterial revascularization with ITA, free gastroepiploic artery, or free radial artery versus venous CABG with saphenous vein has to be well-discussed prior to surgery. The growth potential of the graft relative to the somatic growth of the patient, particularly in the pediatric age, has to be taken into account: ITA in situ appears to grow with the patient, but there are doubts on the growth of free grafts conduits. However, the risk of progression of the systemic arteritis with formation of aneurysms in other arterial districts, such as ITAs [19,20], has to be considered too.

Recently published guidelines recommended a tailored approach to individual practice [61,62]. The standard surgical strategy of myocardial revascularization used in adult patients was not been adequately studied in patients with KD, giving rise to numerous speculations. The use of bilateral thoracic artery was appealing in younger patients, although diabetes, obesity, chronic obstructive disease, and female sex remained adverse factors and should be taken into serious consideration even in adult patients. The radial artery represented a valid alternative to the saphenous vein with encouraging medium to long-term results. The right gastroepiploic and inferior epigastric arteries remain of limited application with less supporting evidence for their usage in the adults. Allografts and artificial grafts are very rarely, if ever, used. The choice of conduit should be addressed for each patient or group of patients and balanced on anatomical criteria, patient background, conduit availability, and surgical expertise [18,61,62].

In the future, we could assist in a rising number of KD cases due to the potential association with pediatric COVID-19 [63], for which it is even more actual and important to know the better strategy of treatment for coronary complications after KD.

To assess the latter, in this study we compared graft patency of ITA, SV, and other arteries (gastroepiploic artery and radial artery); and patients treated with arterial, venous, and mixed (arterial plus second venous graft) CABG to assess long-term mortality.

Our meta-analysis demonstrated that arterial conduits provided better patency rates at 10 years follow-up, with ITAs as the first most effective surgical option, when compared to SV. No progression of the systemic arteritis in other arterial districts was detected in the included studies.

Arterial or mixed (arterial plus a second venous graft) CABG, seen as a surrogate for the use of arterial conduits for revascularization, has been shown to be associated with higher patients’ survival rates. This result complies with the superiority of the arterial grafts when used for surgical myocardial revascularization for KD patients.

4.1 Limits of the study

We have identified the following limits. Network meta-analyses for early mortality, need of interventional procedures, and surgical re-interventions were not conducted. Randomized clinical trial evidences for graft patency following CABG after KD were not published. We pooled observational studies results on the topic, including not adjusted comparative studies. This is a potential source of underpowering that increases heterogeneity where there is variability between patency results. Moreover, a low-moderate risk of bias for the included studies should be taken into account in the interpretation of the results. Nevertheless, this systematic review and meta-analysis represents an overview of the surgical myocardial revascularization in KD and may represent a starting point for further studies and refinement of the technique.

Meta-regression has not been applied. It is unlikely that this represents a source of bias since young patients with few comorbidities have been included in this review. Given that, it cannot certainly be excluded since <5% of patients develop obstructive lesions resulting in ischemic coronary disease regardless of the administration of gamma-globulins [8]. Graft patency was compared regardless of the territory of revascularization. “Grey literature” was not investigated. Furthermore, as the included studies were published between 1981 and 2019, improvements in patency outcomes or long-term mortality could be expected to vary over time due to operative and therapeutic improvements.

In conclusion, our results demonstrate that CABG in KD is a safe procedure, with an overall early mortality rate of 0.28% and rates of surgical re-interventions and interventional procedures at follow-up of 3.47% and 3.97%, respectively. The use of arterial conduits was associated with better patency rates and lower mortality at follow-up.


Equal contributors.

tel: +39-328-708-3993

  1. Contribution of coauthors: A. S., J. L., A. M.: conceptual design, data collecting, statistical analysis, writing, language editing, revision. M. C., G. M., F. S., A. F. C.: conceptual design, data collecting, writing, revision.

  2. Conflict of interest: Antonio Salsano declares to be Section Editor in Open Medicine, but this fact hasn't affected the peer-review process. The other coauthors state no conflict of interest.

  3. Data availability statement: All data generated or analysed during this study are included in this published article (and its supplementary information files).

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Received: 2020-11-06
Revised: 2021-01-05
Accepted: 2021-02-03
Published Online: 2021-03-09

© 2021 Antonio Salsano et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
  200. Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
  201. Pulmonary parenchymal involvement caused by Tropheryma whipplei
  202. Mediastinal mixed germ cell tumor: A case report and literature review
  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
  204. Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
  205. Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
  206. Primary orbital ganglioneuroblastoma: A case report
  207. Primary aortic intimal sarcoma masquerading as intramural hematoma
  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
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