Midterm outcomes of coronary artery bypass grafting for Kawasaki disease in children: A multicenter retrospective study in China

To the Editor: Kawasaki disease (KD) is the most common systemic vasculitis in childhood. Coronary artery complications of KD have become a significant cause of acquired heart disease in children.[1,2] Despite the reduction in the overall occurrence rate of coronary artery aneurysms (CAA) due to the administration of intravenous immunoglobulin, the development of giant coronary artery aneurysms (GCAA) is still one of the most severe long-term sequelae of KD, profoundly increasing the risk of myocardial ischemia, myocardial infarction, and sudden death.[3] Current management strategies for coronary lesions in KD, especially in children who are refractory to medical therapy or develop complex GCAA, are controversial. Given that coronary artery bypass grafting (CABG) is an important revascularization technique, its timing, indications, and long-term outcomes, especially the practical experience and results across different populations, require further elucidation. While currently available large-scale clinical evidence regarding CABG in children with KD primarily originates from Japan,[3] comprehensive multicenter summaries of related surgical treatment experience are lacking in China, although China is another region with a high incidence of KD. This gap limits the understanding of the unique clinical characteristics and intervention outcomes in this population. This study aimed to retrospectively analyze the clinical data of children with KD who had undergone CABG at five cardiac surgery centers in China. We specifically focused on the potential impact of GCAA on surgical strategies and prognosis to provide a reference for future clinical decision-making and research design. A retrospective analysis was conducted on patients from five cardiac surgery centers in China from March 2010 to August 2024 [Supplementary Table 1, https://links.lww.com/CM9/C825]. The study was approved by the leading Human Research Ethics Committee of Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine (SCMCIRB-K2024237-1). The requirement for informed consent was waived by the ethics committee due to the retrospective nature of the study. All of the patients had a prior diagnosis of KD-associated coronary artery disease and had undergone CABG. Significant coronary artery stenosis accompanied by clinical signs of myocardial ischemia was the indication for surgical intervention in these cases.[3] Myocardial ischemia was defined as electrocardiographic evidence of abnormal ventricular wall motion, abnormal Q waves, or ST-segment changes, or atrial fibrillation, accompanied by severe valvular regurgitation, and a left-ventricular ejection fraction (LVEF) below 50%. Based on the presence or absence of GCAA, the patients were divided into the GCAA group and the non-GCAA group. The primary outcomes included major adverse cardiovascular events, graft patency, and manifestations of myocardial ischemia during follow-up. Continuous variables were analyzed using Student’s t-test for normally distributed data or the Mann–Whitney U test for non-normally distributed data, with results presented as mean ± standard deviation (SD) or median (interquartile range [IQR]), respectively. Categorical variables were expressed as numbers (percentages) and compared using the chi-squared test or Fisher’s exact test. A Cox regression model was applied to investigate potential influencing factors for myocardial ischemia during the follow-up period. Variables in the model were expressed as hazard ratios (HRs) with their 95% confidence intervals (CIs). All analyses were performed using SPSS Statistics 25.0 (IBM, Chicago, IL, USA), and a two-sided P-value <0.05 was considered statistically significant. The cohort included 45 children who had undergone CABG for KD-related coronary artery lesions, including 38 (84.4%) males and 7 (15.6%) females. The mean age at surgery was 118.7 ± 47.4 months, with a mean interval of 60.4 ± 44.6 months from KD onset to surgical intervention. Preoperative clinical symptoms were present in 25 (55.6%) patients and included chest tightness (n = 6), chest pain (n = 6), syncope (n = 4), and limited exercise tolerance (n = 9). All of the patients had evidence of myocardial ischemia, manifested as abnormal electrocardiographic findings (n = 39; 86.7%), ventricular wall motion abnormalities (n = 31; 68.9%), and severe mitral regurgitation (n = 3; 6.7%). The mean preoperative LVEF was 56.09 ± 8.07% [Supplementary Table 2, https://links.lww.com/CM9/C825]. Single and multiple CAAs were found in 10 (22.2%) and 35 (77.8%) patients, respectively. The CAAs involved the right coronary artery (RCA) in 32 (71.1%) patients, left main coronary artery in 16 (35.6%) patients, left anterior descending artery (LAD) in 29 (64.4%) patients, and left circumflex artery (LCX) in 11 (24.4%) patients. The mean maximum CAA z-score was 15.03 ± 10.70, and the mean diameter was 14.07 ± 8.75 mm. Thirty (66.7%) patients met the criteria for GCAA. Multiple GCAAs were present in 7 (15.6%) patients, and intraluminal thrombus was detected in 41 (91.1%) patients. Preoperative coronary angiography of the patients revealed thrombolysis in myocardial infarction flow grade 0–1 [Supplementary Table 3, https://links.lww.com/CM9/C825]. A total of 85 grafts were performed. Single- and multiple-vessel CABG was performed in 13 (28.9%) and 32 (71.1%) patients, respectively. Graft conduits included the internal thoracic artery (ITA) in 62 (72.9%) grafts, saphenous vein (SV) in 20 (23.5%) grafts, and radial artery (RA) in 1 (1.2%) graft. The target vessels for anastomosis were the RCA (27 grafts, 31.8%), LAD (40 grafts, 47.1%), and LCX (16 grafts, 18.8%). The ITA was used as the primary conduit in all patients [Supplementary Table 4, https://links.lww.com/CM9/C825]. Compared with the non-GCAA group (n = 15), the GCAA group (n = 30) showed a poorer baseline cardiac functional status, including a higher proportion with New York Heart Association (NYHA) functional class II or above (22 [73.3%] vs. 6 [40.0%]; P = 0.030) and a higher incidence of ventricular wall motion abnormalities (24 [80.0%] vs. 7 [46.7%]; P = 0.039). There were no intergroup differences in distribution and degree of stenosis of CAA [Supplementary Tables 2 and 3, https://links.lww.com/CM9/C825]. Eleven (24.4%) patients underwent concomitant procedures during CABG, namely, aneurysm downsizing reconstruction (n = 8) and mitral valvuloplasty (n = 3). Surgery was performed under cardiopulmonary bypass (CPB) in 37 (82.2%) patients. One patient died postoperatively due to refractory low-cardiac-output syndrome. Both CPB time and aortic cross-clamp time among the patients subjected to CPB were longer in the GCAA group than in the non-GCAA group (GCAA group vs. non-GCAA group, 99.56 ± 29.65 minutes vs. 78.08 ± 24.82 minutes, P = 0.037; 64.40 ± 24.36 minutes vs. 48.08 ± 14.20 minutes, P = 0.039) [Supplementary Table 4, https://links.lww.com/CM9/C825]. Mid-term follow-up was completed by 44 (97.8%) patients over a mean duration of 56.52 ± 47.03 months. No deaths or major adverse cardiovascular events occurred during the follow-up. The GCAA group more often received dual anticoagulation therapy (P <0.001). At the most recent follow-up, evidence of persistent myocardial ischemia was present in 12 (27.3%) patients. The incidence of abnormal electrocardiographic findings was higher in the GCAA group (9 [33.3%] vs. 0; P = 0.017). There were no significant inter-group differences in NYHA functional class, LVEF, and incidence of myocardial ischemia [Supplementary Table 5, https://links.lww.com/CM9/C825]. Graft occlusion occurred in 3 (6.8%) patients, all affecting grafts anastomosed to the RCA and all occurring in the non-GCAA group [Supplementary Table 6, https://links.lww.com/CM9/C825]. Eight patients who had undergone concomitant aneurysm downsizing reconstruction (3 in RCA, 2 in LCA, 2 in LAD, and 1 in LCX) were followed for a median of 41.5 months (IQR: 20.0–76.8 months). No graft occlusion was observed in this subgroup. Within this small subgroup, there was a trend toward CAA diameter reduction and LVEF improvement during the follow-up [Supplementary Table 7, https://links.lww.com/CM9/C825]. Notably, at the most recent follow-up, 4 patients within this subgroup remained in NYHA functional class II or above, and 4 patients had evidence of persistent myocardial ischemia. When descriptively compared with the GCAA patients with CAA diameter over 15 mm or z-score over 15 who had not undergone aneurysm downsizing reconstruction, the patients in the reconstruction subgroup exhibited higher mean LVEF values at one and 6 months postoperatively [Supplementary Tables 8 and 9, https://links.lww.com/CM9/C825]. Univariate Cox regression analysis of the outcomes of myocardial ischemia during the follow-up period revealed that preoperative LVEF (P = 0.003; hazard ratio [HR]: 1.078; 95% confidence interval [CI]: 1.026–1.133), the maximum CAA z-score (P = 0.034; HR: 0.934; 95% CI: 0.877–0.995), and the maximum z-score CAA diameter (P = 0.005; HR: 0.908; 95% CI: 0.849–0.971) were associated with the outcomes of myocardial ischemia signs [Supplementary Table 10, https://links.lww.com/CM9/C825]. The clinical characteristics and outcomes of Chinese pediatric patients who had undergone CABG for KD-related coronary artery lesions were summarized. A higher detection rate of GCAA and multi-vessel disease was observed compared with previous studies, while cardiac functional status was poorer.[3,4] Furthermore, we found that more pronounced preoperative manifestations of myocardial ischemia could be associated with worse patient prognosis. Among the 15 patients with concurrent wall motion abnormalities, electrocardiographic abnormalities, and reduced LVEF, nine had persistent myocardial ischemia, including one who died in the early postoperative period. In our cohort, the use of SV graft harvested with a “no-touch” technique was associated with satisfactory midterm patency rates, indicating its potential role as an alternative conduit in complex scenarios where arterial grafts are insufficient. Given the unique aspects of growth and development in children, follow-up for pediatric CABG patients differs from that for adults and should extend into adulthood. It is recommended to evaluate graft patency by computed tomography coronary angiography at 1, 5, and 10 years postoperatively in all patients. Conventional coronary angiography should be performed if imaging is unclear. Additionally, myocardial ischemia should be assessed via echocardiography, cardiac magnetic resonance imaging, and electrocardiography. Attention should also be paid to psychological issues, such as excessive anxiety due to long-term examinations and treatments, as well as uncertainties following CABG, experienced by both the children and their parents. Comprehensive support, including psychological assessment, educational interventions, and communication strategies, should be provided.[5] This study has several limitations. First, it was a retrospective, multicenter study with a long time span, and there were differences among the participating centers (e.g., general hospitals and specialized children’s hospitals) in terms of patient demographic characteristics, treatment strategies, and surgical factors. Second, the vast majority of patients were subjected to SV rather than RA grafting, which is currently the most recommended approach. In the long term, the use of RA grafts may improve graft patency; therefore, further research on RA grafting is warranted. Third, although this study represents a large-scale investigation in the domestic context, the sample size and follow-up duration are limited. Future work should focus on expanding the cohort size and establishing long-term follow-up plans. In summary, CABG is a safe and effective treatment for Chinese pediatric patients with KD-related coronary artery disease, although long-term follow-up of these children remains necessary. GCAAs are associated with poorer preoperative cardiac function and may impede postoperative recovery. Funding Support for this study has been received from the National Clinical Key Specialty Construction Project (No. 10000015Z155080000004) and Shanghai Top Priority Research Center Construction Project (No. 2023ZZ02024). Acknowledgments The authors thank Nianguo Dong (Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China); Zhengxia Pan (Department of Cardiothoracic Surgery, Children’s Hospital of Chongqing Medical University, Chongqing, China); Baoshi Zheng (Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Autonomous Region, China); and all of the unnamed investigators at the participating centers and all patients for their commitment to the study. We thank LetPub (www.letpub.com.cn) for its linguistic assistance during the preparation of this manuscript.