Prevalence and Characteristics of Acquired Coronary Fistulas After Successful Revascularization of Chronic Total Occlusion

Background and Objectives: Acquired coronary fistulas (ACFs) are rare coronary artery abnormalities in patients with chronic total occlusion (CTO). It has been found after revascularization, and it may cause fluster during the CTO percutaneous coronary intervention (CTO PCI). How to distinguish between ACFs and coronary perforation (CP) is very important for CTO operators. Chronic total occlusion reopening may reveal the microchannel of the adventitial vascular layers. Some of ACFs have been seen after revascularization. This study aimed to investigate the characteristics of ACFs after successful CTO PCI.Methods: The clinical and procedural characteristics, medical history, and findings in electrocardiography (ECG), echocardiography, and coronary angiography were collected from 2,169 consecutive patients undergoing CTO PCI between January 2018 and December 2019 and analyzed retrospectively.Results: About 1,844 (85.02%) underwent successful CTO PCI with complete revascularization. Acquired coronary fistulas were found in 49 patients (2.66%): the majority of patients with ACFs were men (81.63 vs. 60.78%; p = 0.016) and younger (62.8 vs. 66.69 years; p = 0.003), and had a history of myocardial infarction (MI) or Q-wave (69.39 vs. 54.21%; p = 0.035); 38 (77.55%) patients had multiple fistulas (≥3), and ACFs affected multiple branches of the CTO vessel (≥3) in 29 (59.18%) patients. None had pericardial effusion, tamponade, and hemodynamic abnormality before or after PCI.Conclusion: Acquired coronary fistulas after successful CTO PCI are mainly present in young and male patients with a history of MI, and they often involve multiple fistulas and distal CTO vessels.

The impact of the American Heart Association guidelines on patients treated for incomplete Kawasaki disease

Objectives: To compare patients treated for incomplete Kawasaki disease whose practitioners followed versus did not follow American Heart Association criteria and to evaluate the association of cardiology consultation with adherence to these guidelines. Study design: Single centre retrospective cohort study of patients <18 years old who received ≥1 dose of intravenous immunoglobulin for Kawasaki disease between 01/2006 and 01/2018. We collected demographics, clinical and laboratory data, coronary artery abnormalities, and cardiology consultation status. Patients treated for incomplete Kawasaki disease were divided into two groups based on adherence versus nonadherence to American Heart Association guidelines and compared by Wilcoxon rank sum test and chi-squared or Fisher’s exact test. Results: Of the 357 patients treated for Kawasaki disease, 109 (31%) were classified as incomplete Kawasaki disease. The American Heart Association algorithm for identifying patients with incomplete Kawasaki disease was followed in 81/109 (74%). Coronary artery abnormalities were present in 46/109 (42%) of the patients who were treated for incomplete Kawasaki disease. Cardiology consultation was more frequent in those fulfilling American Heart Association criteria for the diagnosis of incomplete Kawasaki disease versus those who did not fulfill criteria (76% versus 48%, p = 0.005). Conclusions: Over 25% of patients treated for incomplete Kawasaki disease did not meet American Heart Association guidelines. Guidelines were more frequently followed when the paediatric cardiology team was consulted. Consulting physicians with experience and expertise in the evaluation and management of incomplete KD should be strongly considered in the care of these patients.

Abnormal Differentiation and Proliferation of Coronary Arterial Endothelium in Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a severe form of single ventricle congenital heart disease characterized by an underdevelopment of the left ventricle. Early serial postmortem examinations revealed high rate of coronary artery abnormalities in HLHS fetal hearts, which may impact ventricular development and intra-cardiac hemodynamics, leading to a poor prognosis after surgical palliations. Previous study reported that endothelial cells (ECs) lining the coronary vessels showed DNA damage in the left ventricle of human fetal heart with HLHS, indicating that EC dysfunction may contribute to the coronary abnormalities in HLHS. To investigate the underlying mechanism of HLHS coronary artery abnormalities, we profiled both human fetal heart with an underdeveloped left ventricle (ULV) and ECs differentiated from induced pluripotent stem cells (iPSCs) derived from HLHS patients at single cell resolution. CD144+/NPR3- vascular ECs were selected and further classified as venous EC (NR2F2high), arterial EC (EFNB2high) and late arterial EC (GJA5high) subclusters based on previously reported marker genes. To study the arterial phenotype, we specifically generated iPSC-arterial ECs (AECs, CD34+CDH5+CXCR4+NT5E-/low) derived from three HLHS patients and three age-matched healthy controls to further dissect the phenotype of HLHS-AECs. As compared to normal human heart and control iPSC-ECs respectively, ULV late arterial EC subcluster and HLHS iPSC-EC arterial clusters showed significantly reduced expression of arterial genes GJA5, DLL4, and HEY1. Pathway enrichment analysis based on differentially expressed genes revealed several defects in late AEC cluster from ULV compared to normal human heart, such as impaired endothelial proliferation, development and Notch signaling. HLHS iPSCs exhibited impaired AEC differentiation as evidenced by the significantly reduced CXCR4+NT5E-/low AEC progenitor population. Consistent with human heart transcriptomic data, matured HLHS iPSC-AECs also showed a lower expression of the arterial genes such as GJA5, DLL4, HEY1 compared with control. Additionally, matured HLHS iPSC-AECs showed significantly decreased expression of cell proliferation marker Ki67 and G1/S transition genes (CCND1, CCND2) compared with control, indicating that HLHS iPSC-AECs largely resided in the G0/G1 phase and failed to enter the cell cycle normally. In summary, we found that coronary AECs from HLHS showed impaired arterial development and proliferation. These functional defects in HLHS coronary AECs could contribute to the vascular structure malformation and impaired ventricular development.

Cardiac echocardiogram findings of severe acute respiratory syndrome coronavirus-2-associated multi-system inflammatory syndrome in children

Background: A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic. Objectives: To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children. Methods: Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum. Results: Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04). Conclusion: Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

A Retrospective Cohort Study of Intravenous Immunoglobulin Therapy in the Acute Phase of Kawasaki Disease: The Earlier, the Better?

Background. Although intravenous immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities of Kawasaki disease (KD) in the acute phase, the timing and effectiveness of IVIG remain to be determined. The association of timing of IVIG administration in KD patients with coronary artery abnormalities is evaluated in this cohort study. Methods. We systematically studied KD patients from two participating institutions between 2015 and 2017. To reveal the effectiveness of IVIG treatment, these patients were classified into four groups regarding the time of IVIG treatment. Primary outcome was coronary artery abnormalities by echo at diagnosis and 12 months follow-up; secondary outcomes included inflammatory markers. Results. A total of 1281 patients were included in this study. The best time of IVIG treatment cut-off values in 12 months follow-up for predicting coronary artery abnormalities was days 7.5 of illness onset. According to the best time of IVIG treatment cut-off values, all patients were classified into 4 groups. Group 1 was defined as earlier IVIG treatment administration on days ≤4 of the illness ( n = 77 ). Group 2 was defined with days 5-7 ( n = 817 ), group 3 with days 8-10 ( n = 249 ), group 4 with days >10 ( n = 138 ). A greater proportion of IVIG-resistant KD patients were group 4 than the other three groups, and there were significant differences ( p < 0.05 ). The incidence of coronary artery lesions (CALs) and coronary artery aneurysms (CAAs) in group 3 and group 4 was higher than that in group 1 ( p < 0.05 ) and group 2 ( p < 0.05 ) during a 12-month follow-up. Additionally, the incidence of CALs in group 1 was higher than that in group 2 but without statistical significance ( p > 0.05 ). The OR was significantly higher for those who started IVIG administration more than 7 days from the onset was positively associated with the occurrence of CALs (OR, 5.3; 95% CI, 2.0-13.9) and CAAs (OR, 13.5; 95% CI, 2.9-14.1) 12 months after initial onset. Multivariate regression revealed that the timing of IVIG treatment and IVIG-resistance was independent risk factors of CALs. Conclusions. IVIG treatment less than 7 days after illness onset are found to be sufficient for preventing developing coronary artery abnormalities in KD patients. Earlier IVIG treatment administration within 4 days may not increase the higher incidence of coronary artery abnormalities and IVIG resistance (Chinese Clinical Trial Registry:ChiCTR1800015800).

GIANT CORONARY ANEURYSM IN A 6 WEEK OLD INFANT, AN UNUSUAL FINDING?

Kawasaki disease (KD) is a self-limited vasculitis with significant morbidity and even mortality if not treated early. The diagnosis and timely treatment in children younger than 3 months is challenging, most of them have an incomplete or atypical presentation. Coronary artery abnormalities are frequent in this type of patients. We present a 6-week-old female infant with Kawasaki disease who developed a giant coronary aneurysm. The timely diagnosis and promptly treatment as well as the echocardiographic and multimodality follow-up allowed us to improve our clinical approach and management.

Desquamation in Kawasaki Disease

(1) Background: Desquamation is a common characteristic of Kawasaki disease (KD). In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship. (2) Methods: We retrospectively reviewed children with KD. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet. We classified the desquamation level from 0 to 3 and defined high-grade desquamation as grade 2 and 3. (3) Results: We enrolled a total 112 patients in the study. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p = 0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p = 0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell counts (p = 0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p = 0.016). (4) Conclusions: This report is the first to demonstrate that the desquamation level of hands or feet in KD is associated with different coronary artery abnormalities and laboratory findings.