Abstract O.71: Thrombosis and Thromboprophylaxis for Patients with Giant Coronary Artery Aneurysms after Kawasaki Disease: A Study from the North American Kawasaki Disease Registry

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Cedric Manlhiot ◽  
William T Mahle ◽  
Kevin D Hill ◽  
Jennifer S Li ◽  
Dawn Tucker ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Acute Phase ◽  
North American ◽  
Event Rate ◽  
Disease Registry ◽  
Coronary Artery Aneurysms ◽  
The North ◽  
Thrombotic Complications

Background: Children with giant coronary artery aneurysms (CAA) after Kawasaki disease (KD) are at substantial risk of thrombosis. There are currently no evidence-based guidelines for optimal thromboprophylactic therapy in these children. Methods: The North American Kawasaki Disease Registry was queried to identify all patients with giant CAA (maximum coronary artery z-score >10) and their antithrombotic therapy. Freedom from thrombosis was modelled using the Kaplan-Meier method; thrombotic complication rate was calculated per patient-year/month of follow-up. Results: n=202 patients with giant CAA were included, of whom 28 (14%) experienced either coronary artery thrombosis with or without myocardial infarction. Freedom from thrombotic complications was 92%, 85% and 79% at 3 months, 5 and 10 years after diagnosis, respectively. Non-pharmacological factors associated with increased risk of thrombotic complications included higher maximum coronary artery z-scores (HR: 1.7/+10 SD, p<0.001), higher number of coronary artery branches with giant CAA (HR: 2.6/branch, p<0.001), higher number of discrete CAA (HR: 1.4/aneurysm, p=0.001) and presence of complex CAA (involving the bifurcation or non-discrete; HR: 3.0, p=0.05). A total of 982 patient-years of follow-up were available for analysis (11% low molecular weight heparin (LMWH), 32% warfarin, 57% antiplatelet alone). All patients were maintained on ASA, with 47 patients (23%) also receiving clopidogrel. Patients while on LMWH had the highest event rate, at 1 event per 13 patient-years, compared to 1 per 39 on warfarin and 1 per 33 on no anticoagulant. However, LMWH was predominantly prescribed immediately after the acute phase, which is also the highest risk phase for thrombosis. When limiting analysis to events within 3 months of the acute phase, patients on LMWH had the lowest event rate at 1 per 46 patient-months, compared to 1 per 27 on warfarin and 1 per 33 on no anticoagulant (p=NS). Conclusions: Current thromboprophylaxis strategies in patients with giant CAA have suboptimal efficacy, and residual thrombosis risk persists. New anticoagulants/antiplatelet agents should be assessed in this population to determine if they provide better, safer and more tolerable thromboprophylaxis.

Abstract 221: Use of Statins in Patients with Coronary Artery Aneurysms: A Pilot Study from the North American Kawasaki Disease Registry

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Michael Khoury ◽  
Michael A Portman ◽  
Cedric Manlhiot ◽  
Anne Fournier ◽  
Rejane F Dillenburg ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Pilot Study ◽  
Kawasaki Disease ◽  
Linear Regression ◽  
North American ◽  
Z Score ◽  
Disease Registry ◽  
Coronary Artery Aneurysms ◽  
The North ◽  
Significant Difference

Background: Statins have been considered as therapy for children with coronary artery aneurysms (CAA) after Kawasaki disease (KD), due to potential beneficial pleiotropic effects which might influence chronic vascular processes and inflammation. Methods: The North American Kawasaki Disease Registry was queried to identify patients who have received statins in the first 6 months following the convalescent phase of KD. Each identified patient was matched by age, gender and CAA z score to 3 patients who were statin-naïve (controls). Linear regression models adjusted for repeated measures and maximum coronary involvement were used to determine an association of statin use with longitudinal changes in coronary artery diameter z-score. Kaplan-Meier analysis was used to compare freedom from angiographically-confirmed stenosis or interventions. Results: Of 29 patients with KD and CAA (maximum coronary artery z-score >10) who received statins at any time (of n=621, 5%), 10 (9 males) patients were started within 6 months of the acute KD episode. The mean age at KD was 6.3±3.4 years (5.4±3.5 for controls, p=0.57). Mean maximum CAA z-score was 36±14 (vs. 29±16, p=0.20); 90% of statin patients and 87% of matched controls had CAAs in 3 or more branches. Linear regression analysis of 442 serial echocardiograms showed that maximum CAA z-score decreased by -1.5 (95%CI: -2.7; -0.4) SD/year (p=0.008) for control patients compared to -2.9 (95%CI: -4.4; -1.4) SD/year (p<0.001) for statin treated patients. The difference between the rate of change of CAA z-score for statin vs. control patients did not reach statistical significance (controls vs. statins: +1.4 SD/year, 95%CI: -0.6; +3.4, p=0.18). n=7 patients (3 on statin, 4 controls) developed stenosis or had revascularization, with no significant difference between groups (HR for statin group: 2.2 (0.4-11.4), p=0.41). Conclusions: This underpowered pilot study suggests that equipoise likely exists with regards to statin therapy in children with KD and CAA, and that a formal registry-nested trial might be considered.

Abstract 225: Variations in Pharmacological Management of Children with Coronary Artery Aneurysms after Kawasaki Disease: A Study from the North American Kawasaki Disease Registry

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Elif Seda Selamet Tierney ◽  
Andrew S Mackie ◽  
Brian W McCrindle ◽  
Mathew Mathew ◽  
Kathryn R Armstrong ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
North American ◽  
Beta Blockers ◽  
Practice Variation ◽  
Z Score ◽  
Disease Registry ◽  
Coronary Artery Aneurysms ◽  
Pharmacological Management ◽  
The North

Background: The pharmacological management of coronary artery aneurysms (CAA) associated with Kawasaki disease (KD) is based on imperfect evidence, which may lead to considerable practice variation. Methods: Pharmacological management of patients included in the North American Kawasaki Disease Registry was reviewed. The Registry included data for 621 patients with CAA after KD (280 patients with maximum CAA z-score between 2.5-5.0, 139 with z-score 5.0-10.0 and 202 with z-score >10.0) followed at 20 medical centers. Practice variation regarding acute treatment, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy and anticoagulation were assessed. Results: Considerable practice variation existed between centers. During the acute phase, 93% of patients received at least one dose of IVIG (range: 80-100%), with 23% (range: 12-50%) receiving additional immunomodulatory treatment (22% additional IVIG, 17% steroids, 4% infliximab). Use of a 3 rd course of IVIG was infrequent (2%). All centers reported using additional IVIG or steroids for IVIG-resistant patients, but only 6 centres reported any experience with infliximab (2 commonly, 4 infrequent). Routine use of non-steroidal anti-inflammatory agents was limited to 2 centres, with 4 additional sites reporting infrequent use (10% of patients). Statins (5%), beta blockers (4%) and abciximab (3%) were mostly used by a single centre and was limited to patients with giant CAAs. Aspirin was the primary antiplatelet modality for 97% of patients, clopidogrel (10% of all patients, 23% in giant CAA) was routinely prescribed to patients with giant CAAs at 6 centres, with 2 more centres reporting infrequent use and the remainder not reporting any use. For patients with giant CAA (z-score>10.0), 46% were maintained on an antiplatelet agent alone, 17% additionally were on low molecular weight heparin(LMWH), 12% on warfarin and 25% had initially received LMWH and were later switched to warfarin. Conclusions: Given the important variations in management between centres and the poor evidence base, randomized controlled trials examining outcomes and nested in a high-quality collaborative registry may be an efficient strategy to address this gap.

Abstract O.58: Medium-term Outcomes of Coronary Artery Aneurysms after Kawasaki Disease: A Study from the North American Kawasaki Disease Registry

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Brian W McCrindle ◽  
Cedric Manlhiot ◽  
Kristen Sexson ◽  
Pei-Ni Jone ◽  
Mathew Mathew ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
North American ◽  
Z Score ◽  
Disease Registry ◽  
Coronary Artery Aneurysms ◽  
Luminal Diameter ◽  
The North ◽  
Increased Risk ◽  
Over Time

Background: One of the main impediments to conceiving and planning studies in children with coronary artery aneurysms (CAA) after Kawasaki disease (KD) is the lack of normative data regarding the prevalence of outcomes over time and risk factors. Methods: The North American Kawasaki Disease Registry was used to determine the prevalence of multiple clinically important outcomes of CAA after KD. All analyses were stratified by severity of CAA (small CAA with z-score = 2.5-5, medium with z-score = 5-10 and giant with z-score >10). All analyses were performed using non-parametric survival analysis. Results: n=621 patients submitted to the Registry had complete follow-up data and were included in the analysis (280 [45%] small CAA, 139 [22%] medium and 202 [33%] giant). Time-related freedom from multiple outcomes stratified by type of CAA are reported in the Table. Reduction in z-scores was strongly associated with the initial size of the lesion, with smaller lesions being more likely to decrease to a normal dimension over time. Thrombosis and stenosis were infrequent in patients without giant CAA. For those patients with giant CAA, the risk of thrombosis, myocardial infarction, angiographically-confirmed stenosis and revascularization was substantial and persisted up to 10 years after diagnosis. In addition to larger luminal diameter, other factors associated with increased risk of adverse outcomes included larger CAA longitudinal area and complex CAA (vs. isolated lesions). Conclusions: Only patients with giant CAA are at substantial risk of adverse clinical outcomes; future trials of pharmacological therapy targeting thrombosis and stenosis risk should focus on these patients.

Atypical coronary artery aneurysms due to Kawasaki disease in Noonan syndrome with a novel PTPN11 mutation

2018 ◽  
Vol 29 (2) ◽  
pp. 228-230
Author(s):  
Shiori Takai ◽  
Kei Takasawa ◽  
Shozaburo Doi
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Acute Phase ◽  
Therapeutic Intervention ◽  
Noonan Syndrome ◽  
Coronary Artery Aneurysms ◽  
Ptpn11 Mutation

AbstractWe report a 3-year-old boy with giant and atypical coronary artery aneurysms in the acute phase of Kawasaki disease, despite appropriate therapeutic intervention, in Noonan syndrome with a novel heterozygous PTPN11 mutation, c. 907 G>A (p.Asp303Asn). We hypothesised that this PTPN11 mutation might affect both hyperinflammation caused by Kawasaki disease and vascular fragility in the coronary artery, resulting in coronary artery aneurysms.

Abstract O.60: Kawasaki Disease Complicated by Coronary Artery Aneurysms: Mortality and 40-year Outcomes

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Cedric Manlhiot ◽  
Andrew M Crean ◽  
Nigel Fernandopulle ◽  
Brendan Lew ◽  
Tanveer H Collins ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
General Population ◽  
Life Expectancy ◽  
Myocardial Infarct ◽  
Coronary Artery Aneurysms ◽  
Cumulative Mortality ◽  
Coronary Artery Involvement ◽  
Coronary Artery Dilatation

Background: Long-term outcomes and life expectancy for children with a previous history of Kawasaki disease (KD), particularly those with coronary artery aneurysms (CAA), remain to be determined. Methods: An inception cohort of all patients with KD assessed at The Hospital for Sick Children in Toronto between 1978 and 2013 was assembled. Patient outcomes were obtained throughout their pediatric and adult clinical follow-up as long as available. Prevalence of outcomes over time was modelled with Kaplan-Meier survival curves. Life tables from Statistics Canada were used to obtain age/gender specific cumulative mortality for the general population. Results: The cohort included 2,623 KD patients, of whom 410 (16%) had coronary artery involvement (215 dilatation, 57 non-giant CAA and 138 giant CAA). Average follow-up for patients with coronary artery involvement was 6.7 years (13.3 years for giant CAA); 57 and 34 patients had at least 15 and 25 years of follow-up, respectively. No patients with coronary artery dilatation or non-giant CAA had revascularization or a myocardial infarct. Freedom from revascularization (14 events) for patients with giant CAA was 90±6%, 87±7% and 80±13% at 10, 20 and 40 years of follow-up. Freedom from myocardial infarct (11 events) was 94±4%, 92±5% and 89±7% at 5, 20 and 40 years. For patients without coronary artery involvement, 3 (0.1%) deaths were recorded, one secondary to complications of macrophage activation syndrome during the acute phase of KD and 2 from cancer. No deaths were noted for patients with coronary artery dilatation or non-giant CAA, although clinical follow-up was more limited. For patients with giant CAA, 3 deaths (2.2%) were noted, 2 related to CAA complications and 1 from non-medical cause. Cumulative mortality for patients with giant CAA was 1.5% at 10 years of age (expected mortality 0.7%, HR: 2.2 (0.3-11.5), p=0.08) and 3.1% at 40 years of age (expected 2.3%, HR: 1.3 (0.4-4.0), p=0.37). Conclusions: Despite risks of myocardial infarction and revascularization, patients with giant CAA had life-expectancy similar to that of the general population up to the fourth decade of life. Additional follow-up will be necessary to determine if these trends continue into later decades.

scholarly journals Medium‐Term Complications Associated With Coronary Artery Aneurysms After Kawasaki Disease: A Study From the International Kawasaki Disease Registry

2020 ◽  
Vol 9 (15) ◽  
Author(s):  
Brian W. McCrindle ◽  
Cedric Manlhiot ◽  
Jane W. Newburger ◽  
Ashraf S. Harahsheh ◽  
Therese M. Giglia ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Medium Term ◽  
Disease Registry ◽  
Coronary Artery Aneurysms

Abstract 222: North American Kawasaki Disease Registry - Advancing Clinical Research Through Collaboration

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Brian W McCrindle ◽  
Keyword(s):  
Kawasaki Disease ◽  
Clinical Research ◽  
North American ◽  
Data Entry ◽  
Practice Variation ◽  
Disease Registry ◽  
Funding Sources ◽  
The North ◽  
Number Of Patients ◽  
Sick Children

Background: Clinical research in children with Kawasaki disease (KD), particularly those with coronary artery aneurysms (CAA), is challenging due to the limited number of patients available at any single institution. This has resulted in imperfect evidence for optimal management and considerable practice variation. Methods: The North American Kawasaki Disease Registry (NAKDR) was started in July 2013 to determine the prevalence, patient-level and pharmacological risk factors for outcomes of CAA after KD. The NAKDR enrolls KD patients diagnosed from 1999-2013 with CAA (defined as any segment with a z-score >2.5). The NAKDR and its internet-based data entry portal are maintained at The Hospital for Sick Children in Toronto. Local ethics approvals and bilateral data sharing agreements are necessary for participation. Participation in the NAKDR is currently unfunded and voluntary. In September 2014, a survey on the future of the NAKDR was sent to all participating centers (response rate: 54%). Results: 45 sites have been invited, of which 37 (82%) agreed to participate. As of September 2014, 20 sites are actively submitting data; 17 are still being initiated; 706 cases have been submitted. The majority (90%) of members indicated that they wished to continue enrolling newly diagnosed patients and continue follow-up on patients already enrolled. Members were split (45% for, 55% against) as to whether the NAKDR should be expanded to include all KD patients, regardless of CAA status. Finally, while most NAKDR members (60%) indicated that site reimbursement was not an absolute condition for future participation, most members suggested that potential funding sources should be sought to expand/facilitate activities. At term, the NAKDR is expected to comprise ~1,400 patients and, if moving forward, add ~120 new KD patients with CAA per year. Conclusions: The NAKDR is an important tool for clinical research in children with CAAs after KD, and its success represents broad support from clinicians. The next step will be to formalize the NAKDR leadership structure, create standard operating procedures, and pursue prospective studies and funding.

Sign in / Sign up

Export Citation Format

Share Document