Intimal thickening and disruption of the media occur in the arterial walls of coronary arteries not associated with coronary arterial aneurysms in patients with Kawasaki disease

Abstract Background Coronary artery aneurysm (CAA) is an important complication of Kawasaki disease (KD) that is associated with arterial structure damage. However, few studies have examined structural changes in coronary arteries that are not associated with CAA. Methods We examined coronary arteries in KD patients with CAAs who underwent follow-up coronary angiography (CAG) and optical coherence tomography (OCT). Coronary arterial branches with no abnormal findings during the most recent CAG were classified into two groups. Arteries with an acute-phase CAA that later regressed were classified as group R; arteries with no abnormal findings on either acute or convalescent phase CAG were classified as group N. Coronary arterial wall structural changes were compared between groups using OCT. Results Fifty-seven coronary arterial branches in 23 patients were evaluated by OCT. Thirty-six branches showed no abnormality during the most recent CAG. Both groups R and N comprised 18 branches. Maximum intimal thicknesses in groups R and N were 475 and 355 µm, respectively (p = 0.007). The incidences of media disruption were 100% and 67%, respectively (p = 0.02). Calcification, macrophage accumulation, and thrombus were not found in either group. Conclusions Intimal thickening and disruption of the media occur in coronary arteries with acute phase CAAs that later regress in the convalescent phase, as well as in arteries with normal CAG findings in the acute and convalescent phases.

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Intimal Thickening and Disruption of The Media Occur in The Arterial Walls of Coronary Arteries Not Associated With Coronary Arterial Aneurysms in Patients With Kawasaki Disease

10.21203/rs.3.rs-145808/v1 ◽

2021 ◽

Author(s):

Tomoya Tsuchihashi ◽

Nobuyuki Kakimoto ◽

Takashi Takeuchi ◽

Tomohiro Suenaga ◽

Takayuki Suzuki ◽

...

Keyword(s):

Kawasaki Disease ◽

Acute Phase ◽

Coronary Arteries ◽

Structural Changes ◽

Artery Aneurysm ◽

Intimal Thickening ◽

Structure Damage ◽

Convalescent Phase ◽

Arterial Structure ◽

The Media

Abstract Background Coronary artery aneurysm (CAA) is an important complication of Kawasaki disease (KD) that is associated with arterial structure damage. However, few studies have examined structural changes in coronary arteries not associated with CAA.Methods We examined coronary arteries in KD patients with CAAs who underwent follow-up coronary angiography (CAG) and optical coherence tomography (OCT). Coronary arterial branches with no abnormal findings on most recent CAG were classified into two groups. Arteries with an acute-phase CAA that later regressed were classified as group R and arteries with no abnormal findings on either acute or convalescent phase CAG were classified as group N. Coronary arterial wall structural changes were compared between groups using OCT.ResultsFifty-seven coronary arterial branches in 23 patients were evaluated by OCT. Thirty-six branches showed no abnormality on most recent CAG. Both groups R and N comprised 18 branches. Maximum intimal thickness in groups R and N was 475 and 355 µm, respectively (p = 0.007). The incidence of disruption of the media was 100% and 67%, respectively (p = 0.02). Calcification, macrophage accumulation, and thrombus were not found in either group.ConclusionsIntimal thickening and disruption of the media occur not only in coronary arteries with acute phase CAAs that later regress in the convalescent phase, but also in arteries with normal CAG findings in the acute and convalescent phases.

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Brain natriuretic peptide can be a useful biochemical marker for myocarditis in patients with Kawasaki disease

Cardiology in the Young ◽

10.1017/s1047951102000318 ◽

2002 ◽

Vol 12 (2) ◽

pp. 153-158 ◽

Cited By ~ 25

Author(s):

Takashi Kawamura ◽

Masakuni Wago

Keyword(s):

Kawasaki Disease ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Acute Phase ◽

Biochemical Marker ◽

Cross Sectional ◽

T Wave ◽

Convalescent Phase ◽

The Mean ◽

St Segments

So as to determine the value of brain natriuretic peptide in the plasma as a biochemical marker for myocarditis of Kawasaki disease, we studied 69 patients. The blood samples, electrocardiograms and cross-sectional echocardiograms were obtained before the commencement of treatment and in the convalescent phase. Results: The mean concentration of brain natriuretic peptide in the plasma was 73.2 ± 107.7 (mean ± SD) pg/ml in the acute phase, and 7.9 ± 7.5 pg/ml in the convalescent phase. We checked the electrocardiograms to find abnormal Q waves, elevation or depression of the ST segments, change in the pattern of the QRS complexes, and flattening or inversion of the T wave, all believed to be markers of myocarditis in Kawasaki disease. Those in whom the concentrations were greater than 50 pg/ml in the acute phase showed abnormal electrocardiograms more frequently than did those in whom the values were less than 50 pg/ml (21/29 vs 3/40, p < 0.0001 odds ratio 32.4). Amplitudes of the T wave in standard limb leads were measured both in the acute and convalescent phases, and the differences calculated. We regarded the sum total of these differences as representing “flattening T wave”, and we named this variable as the total suppressed T wave voltage. We examined the correlation between the variable and the levels of brain natriuretic peptide in the plasma during the acute phase, demonstrating a significant correlation (r = 0.500, p < 0.0001). We conclude, therefore, that the concentration of brain natriuretic peptide measured in the plasma can be a useful biochemical marker for the myocarditis of Kawasaki disease. When the titer is over 50 pg/ml, the patient probably has an abnormal electrocardiogram and is most likely to have myocarditis.

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Usefulness and safety of anakinra in refractory Kawasaki disease complicated by coronary artery aneurysm

Cardiology in the Young ◽

10.1017/s1047951117002864 ◽

2018 ◽

Vol 28 (5) ◽

pp. 739-742 ◽

Cited By ~ 18

Author(s):

Marie-Paule Guillaume ◽

Héloïse Reumaux ◽

François Dubos

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Coronary Arteries ◽

Coronary Artery Aneurysm ◽

Artery Aneurysm ◽

Intravenous Immunoglobulins ◽

Unknown Aetiology ◽

Partial Regression ◽

Coronary Aneurysms

AbstractKawasaki disease is an acute self-limited vasculitis of unknown aetiology. The prognosis depends mainly on coronary damage. There is no consensus regarding optimal adjunctive therapeutics for refractory forms to treatment by intravenous immunoglobulins and corticosteroids. We report the case of an 18-month-old infant with refractory Kawasaki disease complicated by diffuse aneurysms of coronary arteries and successfully treated by anakinra with partial regression of coronary aneurysms

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3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) Intoxication in a Young Adult with Giant Coronary Aneurysms from Kawasaki Disease

Academic Forensic Pathology ◽

10.1177/1925362118797751 ◽

2018 ◽

Vol 8 (3) ◽

pp. 752-762 ◽

Cited By ~ 1

Author(s):

Renee Eigsti ◽

Dennis J. Firchau ◽

Marcus B. Nashelsky

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Left Ventricle ◽

Coronary Arteries ◽

Coronary Artery Spasm ◽

Artery Aneurysm ◽

Unknown Etiology ◽

Stress Tests ◽

Coronary Aneurysms ◽

Increased Risk

Kawasaki disease is an acute vasculitis of unknown etiology that usually occurs in children less than five years old. Coronary artery aneurysm due to arteritis is the most common cardiac complication. Chronic aneurysms are associated with an increased risk of developing luminal thrombosis and ischemic myocardial injury. We present a case of an 18-year-old male with a history of Kawasaki disease complicated by chronic giant aneurysms of the right and left coronary arteries. Serial echocardiographic studies and treadmill electrocardiogram stress tests as recent as 1.5 years before death revealed excellent cardiac function by clinical criteria. The decedent sustained a witnessed collapse after ingesting 3,4-methylenedioxymethamphetamine (MDMA) and ethanol. He was pronounced dead in the emergency department after unsuccessful resuscitative efforts. Autopsy revealed large aneurysms of the three main epicardial coronary arteries with extensive foci of severe stenosis by intimal fibrosis and organizing thrombus. Microscopic examination revealed multifocal severe myocyte hypertrophy. There were remote microinfarcts in the anterior and posterior aspects of the left ventricle and a recent, healing microinfarct in the posterior aspect of the left ventricle. Toxicology examination of postmortem femoral blood revealed MDMA, ethanol, and amiodarone. This case illustrates the residual, lasting effects of cardiac disease due to Kawasaki disease and a potential complication in the setting of use of an illicit stimulant, MDMA, an amphetamine derivative that produces sympathetic activation and cardiovascular effects including tachycardia, vasoconstriction, dysrhythmias, and coronary artery spasm. Kawasaki disease-related abnormalities of the heart likely resulted in a lower threshold for developing a fatal cardiac dysrhythmia under the circumstance of stimulant use.

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Abstract 190: Continuous Vascular Remodeling Related To Development Of Arteriosclerosis Or Atherosclerosis In Kawasaki Disease ~ Immunohistochemical Study using an Animal Model ~

Circulation ◽

10.1161/circ.131.suppl_2.190 ◽

2015 ◽

Vol 131 (suppl_2) ◽

Author(s):

Kenji Hamaoka ◽

Maiko Fujii ◽

Yuki Kuchitsu ◽

Ayako Yoshioka ◽

Akiko Okamoto ◽

...

Keyword(s):

Smooth Muscle ◽

Kawasaki Disease ◽

Smooth Muscle Cells ◽

Coronary Arteries ◽

Chronic Phase ◽

Muscle Cells ◽

Histopathological Analysis ◽

Intimal Thickening ◽

Clinical Issue ◽

Thickened Intima

Background: Atherosclerotic coronary heart disease has recently emerged as a clinical issue among young individuals with a history of Kawasaki disease (KD), which is a systemic vasculitis unique to children. However, whether or not and how KD promotes atherosclerosis remains unclear. We hypothesized that, analogous to the pathogenesis of arteriosclerosis or atherosclerosis, endothelial injury and the resultant intimal thickening are induced in coronary arteries after attenuation of vasculitis. Methods: We used a rabbit model of KD developed by Onouchi et al. and performed histopathological analysis of the coronary arteries at acute (1, 3, 5, and 7 days) and chronic (3 months) phases of the disease. Results: In these rabbit models, a pan-arteritis with significant intimal cellular hypertrophy was histologically detected in the acute phase, and arterial intimal thickening was observed during the chronic phase. Immunohistochemical analysis of the coronary arteries revealed that the thickened intimal lesions observed during the chronic phase comprised abundant α-smooth muscle actin (α-SMA)-positive cells, most of which concomitantly expressed vascular cell adhesion molecule-1 and nuclear factor-κB. Although macrophages positive for RAM11 were barely detected, macrophage colony stimulating factor was strongly expressed in migrating smooth muscle cells in the intimal layer. In addition, the accumulation of proteoglycan as extracellular matrix was distinctly visible in the thickened intima, indicating progressive accumulation of lipids and proliferation of smooth muscle cells within the lesion. Conclusions: These findings suggest that, in KD-associated vasculitis, the migration of α-SMA-positive cells into the thickened intima might induce continuous vascular inflammation and remodeling, which might progress to coronary arteriosclerosis or atherosclerosis.

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Determination of layer-specific mechanical properties of human coronary arteries with nonatherosclerotic intimal thickening and related constitutive modeling

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00934.2004 ◽

2005 ◽

Vol 289 (5) ◽

pp. H2048-H2058 ◽

Cited By ~ 535

Author(s):

Gerhard A. Holzapfel ◽

Gerhard Sommer ◽

Christian T. Gasser ◽

Peter Regitnig

Keyword(s):

Mechanical Properties ◽

Coronary Arteries ◽

Wall Thickness ◽

Tissue Type ◽

Outer Diameter ◽

Intimal Thickening ◽

Mechanical Heterogeneity ◽

Tensile Stresses ◽

The Media ◽

The Individual

At autopsy, 13 nonstenotic human left anterior descending coronary arteries [71.5 ± 7.3 (mean ± SD) yr old] were harvested, and related anamnesis was documented. Preconditioned prepared strips ( n = 78) of segments from the midregion of the left anterior descending coronary artery from the individual layers in axial and circumferential directions were subjected to cyclic quasi-static uniaxial tension tests, and ultimate tensile stresses and stretches were documented. The ratio of outer diameter to total wall thickness was 0.189 ± 0.014; ratios of adventitia, media, and intima thickness to total wall thickness were 0.4 ± 0.03, 0.36 ± 0.03, and 0.27 ± 0.02, respectively; axial in situ stretch of 1.044 ± 0.06 decreased with age. Stress-stretch responses for the individual tissues showed pronounced mechanical heterogeneity. The intima is the stiffest layer over the whole deformation domain, whereas the media in the longitudinal direction is the softest. All specimens exhibited small hysteresis and anisotropic and strong nonlinear behavior in both loading directions. The media and intima showed similar ultimate tensile stresses, which are on average three times smaller than ultimate tensile stresses in the adventitia (1,430 ± 604 kPa circumferential and 1,300 ± 692 kPa longitudinal). The ultimate tensile stretches are similar for all tissue layers. A recently proposed constitutive model was extended and used to represent the deformation behavior for each tissue type over the entire loading range. The study showed the need to model nonstenotic human coronary arteries with nonatherosclerotic intimal thickening as a composite structure composed of three solid mechanically relevant layers with different mechanical properties. The intima showed significant thickness, load-bearing capacity, and mechanical strength compared with the media and adventitia.

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Atypical Kawasaki disease

Medicinski pregled ◽

10.2298/mpns1602053r ◽

2016 ◽

Vol 69 (1-2) ◽

pp. 53-57 ◽

Cited By ~ 1

Author(s):

Ljiljana Ristovski ◽

Olgica Milankov ◽

Melanija Vislavski ◽

Radojica Savic ◽

Milena Bjelica

Keyword(s):

Kawasaki Disease ◽

Coronary Arteries ◽

Clinical Signs ◽

Artery Aneurysm ◽

Cardiac Complications ◽

Incomplete Kawasaki Disease ◽

Coronary Abnormalities ◽

Unexplained Fever ◽

Atypical Kawasaki Disease ◽

Echocardiographic Findings

Introduction. Kawasaki disease is an acute vasculitis which occurs primarily in children under the age of 5. The etiology of the disease is still unknown. Diagnostic criteria for Kawasaki disease are fever and at least four of the five additional clinical signs. Incomplete Kawasaki disease should be taken into consideration in case of all children with unexplained fever for more than 5 days, associated with 2 or 3 of the main clinical findings of Kawasaki disease. The diagnosis of incomplete Kawasaki disease is based on echocardiographic findings indicating the involvement of the coronary arteries. Cardiac complications, mostly coronary artery aneurysm, can occur in 20% to 25% of untreated patients and in 4% of treated patients. Case Report. In this report we present a case of atypical Kawasaki disease in a 3.5-month-old infant. As soon as the diagnosis was made, the patient received high doses of intravenous immunoglobulin, with the initial introduction of ibuprofen, then aspirin with a good clinical response. Due to the presence of aneurysm of coronary arteries, further therapy involved aspirin and clopidogrel over the following 3 months, and then only aspirin for 2 years. There was a gradual regression of the changes in the coronary blood vessels to the normalization of the echocardiographic findings after 2 years. Conclusion. Kawasaki disease is the second most common vasculitis of childhood, so it should be included in the differential diagnosis for any child with a prolonged unexplained fever. Atypical Kawasaki disease should be taken into consideration in cases when not all clinical criteria are present but coronary abnormalities are documented.

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Blood routine risk factors for coronary artery aneurysm in infants younger than 8 months with Kawasaki disease

BMC Pediatrics ◽

10.1186/s12887-021-03083-3 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Ge Haiyan ◽

Lai Jianming ◽

Tong Suqian ◽

Qu Dong ◽

Liu Shuang ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Regression Analysis ◽

Platelet Count ◽

Coronary Artery ◽

Kawasaki Disease ◽

Acute Phase ◽

Logistic Regression Analysis ◽

Coronary Artery Aneurysm ◽

Artery Aneurysm

Abstract Objective The aims of this study were to characterize the evolution of routine blood values within the first 10 days of illness and coronary artery outcome in infants < 8 months with Kawasaki disease (KD) and to identify risk factors for coronary artery aneurysm (CAA). Methods Laboratory data, clinical features and coronary artery outcomes from 78 infants < 8 months old and 86 patients between 8 months and 7 years old were retrospectively analyzed. Logistic regression analysis was conducted to evaluate the potential risk factors for CAA. Results Infants < 8 months old were more likely to present with incomplete KD (37.2% vs 4.7%, P < 0.001), erythema and induration at the BCG inoculation site (24.4% vs 3.5%, P < 0.001) and CAA (47.4% vs 15.1%, P < 0.001) even with timely diagnosis and treatment with intravenous immunoglobulin (IVIG) compared with patients ≥8 months old. Clinical feature related to diagnostic criteria for KD including bilateral conjunctival injection, oral changes, unilateral cervical lymphadenopathy and extremity changes were less common in the younger group. During the acute phase, the percentage neutrophils and neutrophil to lymphocyte ratio [NLR] peaked on median illness day 3, followed by white blood cell (WBC) and CRP on median illness day 4, hemoglobin on median illness day 7 and platelet count on median illness day 9. CAA occurred on median illness day 6 and regressed on median illness day 28. Multivariate logistic regression analysis revealed that the peak percentage neutrophils (odds ratio [OR] per 0.1: 1.597, 95% confidence interval [CI]: 1.041–2.452, P = 0.032) and the peak platelet count (OR per 10 × 109/L: 1.029, 95% CI: 1.004–1.055, P = 0.024) were independent risk factors for CAA. Hemoglobin on the 5th day was associated with persistent CAA at 1 year after KD onset. Conclusion Factors associated with CAA include a high peak percentage neutrophils, increased peak platelet count, and reduced hemoglobin within 4–6 days during the acute phase of KD. Therefore, this population should receive primary therapy with IVIG and adjunctive anti-inflammatory medications.

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Abstract 169: Impact of Resistance to Intravenous Immune Globulin on Changes of Left Ventricular Myocardial Deformation Over Time in Children with Kawasaki Disease

Circulation ◽

10.1161/circ.131.suppl_2.169 ◽

2015 ◽

Vol 131 (suppl_2) ◽

Author(s):

Soo Jung Kang ◽

Dong Keon Yon

Keyword(s):

Kawasaki Disease ◽

Immune Globulin ◽

Acute Phase ◽

Left Ventricular ◽

Myocardial Deformation ◽

Intravenous Immune Globulin ◽

Myocardial Mechanics ◽

Convalescent Phase ◽

The Impact ◽

Over Time

Introduction: This study aimed to assess the impact of resistance to intravenous immune globulin(IVIG) on left ventricular(LV) myocardial deformation in children with Kawasaki disease(KD) during the acute and convalescent phases of illness. Few studies have elucidated the impact of resistance to IVIG on the progressive changes of myocardial mechanics over time in patients with KD. Methods: We studied 26 patients with KD and 8 normal control subjects. Of the 26 patients, 16 were IVIG non-responders. Echocardiograms were obtained during the acute and convalescent phases of KD. Standard echocardiographic data and peak systolic global LV longitudinal strain[strain(ε)] were obtained using vector velocity imaging. Results: During the acute phase of KD, peak systolic global LV longitudinal ε decreased significantly in both IVIG non-responders(-21.18 % ± 3.97) and responders(-20.94 % ± 3.15) compared to controls(-24.99 % ± 2.23). Although in the acute phase, LV ejection fraction(EF) was significantly higher in the IVIG non-responders(55.38 % ± 5.14) compared to the responders(50.2 % ± 6.53), peak systolic global LV longitudinal ε was not significantly higher in the IVIG non-responders compared to the responders. During the convalescent phase, peak systolic global LV longitudinal ε tended to increase in non-responders(-21.62% ± 3.98) and responders(-21.83% ± 2.61) compared to the acute phase, but remained significantly decreased in both groups compared to controls. The increment of peak systolic global LV longitudinal ε from acute to convalescent phase tended to be smaller in the IVIG non-responders compared to the responders. The proportion of patients with coronary dilatations in both IVIG non-responders(4 of 16) and IVIG responders(2 of 10) did not differ significantly. Conclusions: The increment of peak systolic global LV longitudinal ε over time tended to be smaller in the IVIG non-responders compared to the IVIG responders. Resistance to IVIG may delay normalization of myocardial mechanics in IVIG non-responders. Further studies with larger number of patients, as well as long-term follow-up of myocardial deformation in KD are necessary.

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Kawasaki disease with giant aneurysm of left coronary artery and complete occlusion of right coronary artery

Cardiology in the Young ◽

10.1017/s1047951120000426 ◽

2020 ◽

Vol 30 (4) ◽

pp. 580-581

Author(s):

Kader Muneer ◽

Santhosh Narayanan

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Coronary Arteries ◽

Left Coronary Artery ◽

Coronary Artery Aneurysm ◽

Artery Aneurysm ◽

Giant Aneurysm ◽

Common Complication ◽

Complete Occlusion ◽

Stenosis And Occlusion

AbstractKawasaki disease is an acute febrile medium-vessel vasculitis affecting children. Though coronary artery aneurysm is a common complication, stenosis and occlusion are rare. Here, we report a case of Kawasaki disease with concomitant aneurysm and complete occlusion of different coronary arteries in the same patient.

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