Quantitative Assessment of Myocardial Edema by MR T2 Mapping in Children With Kawasaki Disease.

BACKGROUND: Few studies assessed myocardial inflammation using Cardiovascular Magnetic Resonance Imaging in Kawasaki disease (KD) patients. PURPOSE: To quantify myocardial edema in KD patients using T2 mapping and explore the independent predictors of T2 values. STUDY TYPE: Prospective. SUBJECTS: Ninety KD patients including 40 in acute phase (26 males, 65.0%) and 50 in chronic phase (34 males, 68.0%). Thirty-one healthy volunteers (21 males, 70.0%). FIELD STRENGTH/SEQUENCE: 3.0 T T2-weighted Turbo Spin Echo-Short Time of Inversion Recovery sequence, True fast imaging with steady precession flash sequence and fast low-angle shot 3D spoiled gradient echo sequence. ASSESSMENT: T2 values were compared among KD groups and controls. STATISTICAL TEST: Student's t test and Fisher's exact test; One-way analysis of variance; Pearson correlation analysis; Receiver operating curve analysis; Multivariable linear regression. RESULTS: Global T2 value of KD patients in acute phase was the highest, followed by those of chronic-phase patients and controls (38.83 ± 2.41 msec vs. 37.55 ± 2.28 msec vs. 36.05 ± 1.64 msec). Regional T2 values showed a same trend. There were no significant differences in global and regional T2 values between KD patients with and without coronary artery (CA) dilation, no matter in acute or chronic phase (all KD patients: P = 0.51, 0.51, 0.53, 0.72; acute KD: P = 0.61, 0.37, 0.33, 0.83; chronic KD: P = 0.65, 0.79, 0.62, 0.79). No significant difference was observed in global T2 values between KD patients with Z score > 5.0 and 2.0 < Z score ≤ 5.0 (P = 0.65). Multivariate analysis demonstrated that stage of disease (ß = -0.123) and heart rate (ß = 0.280) were independently associated with global T2 values. DATA CONCLUSION: The degree of myocardial edema was more severe in acute-phase than in chronic-phase KD patients. Myocardial edema persists in patients regardless of the existence or degree of CA dilation. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Evaluation of left ventricular stiffness with echocardiography.

Half of patients with heart failure are presented with preserved ejection fraction (HFpEF). The pathophysiology of these patients is complex, but increased left ventricular (LV) stiffness has been proven to play a key role. However, the application of this parameter is limited due to the requirement for invasive catheterization for its measurement. With advances in ultrasound technology, significant progress has been made in the noninvasive assessment of LV chamber or myocardial stiffness using echocardiography. Therefore, this review aims to summarize the pathophysiological mechanisms, correlations with invasive LV stiffness constants, applications in different populations, as well as the limitations of echocardiography-derived indices for the assessment of both LV chamber and myocardial stiffness. Indices of LV chamber stiffness, such as the ratio of E/e' divided by left ventricular end-diastolic volume (E/e'/LVEDV), the ratio of E/SRe (early diastolic strain rates)/LVEDV, and diastolic pressure-volume quotient (DPVQ), are derived from the relationship between echocardiographic parameters of LV filling pressure (LVFP) and LV size. However, these methods are surrogate and lumped measurements, relying on E/e' or E/SRe for evaluating LVFP. The limitations of E/e' or E/SRe in the assessment of LVFP may contribute to the moderate correlation between E/e'/LVEDV or E/SRe/LVEDV and LV stiffness constants. Even the most validated measurement (DPVQ) is considered unreliable in individual patients. In comparison to E/e'/LVEDV and E/SRe/LVEDV, indices like time-velocity integral (TVI) measurements of pulmonary venous and transmitral flows may demonstrate better performance in assessing LV chamber stiffness, as evidenced by their higher correlation with LV stiffness constants. However, only one study has been conducted on the exploration and application of TVI in the literature, and the accuracy of assessing LV chamber stiffness remains to be confirmed. Regarding echocardiographic indices for LV myocardial stiffness evaluation, parameters such as epicardial movement index (EMI)/ diastolic wall strain (DWS), intrinsic velocity propagation of myocardial stretch (iVP), and shear wave imaging (SWI) have been proposed. While the alteration of DWS and its predictive value for adverse outcomes in various populations have been widely validated, it has been found that DWS may be better considered as an overall marker of cardiac function performance rather than pure myocardial stiffness. Although the effectiveness of iVP and SWI in assessing left ventricular myocardial stiffness has been demonstrated in animal models and clinical studies, both indices have their limitations. Overall, it seems that currently no echocardiography-derived indices can reliably and accurately assess LV stiffness, despite the development of several parameters. Therefore, a comprehensive evaluation of LV stiffness using all available parameters may be more accurate and enable earlier detection of alterations in LV stiffness.

Using nomogram scores to predict the early regression of coronary artery aneurysms of Kawasaki disease.

BACKGROUND: Coronary artery aneurysms have been considered the most serious complication of Kawasaki disease. However, some coronary artery aneurysms do regress. Therefore, the ability to predict the expected time of coronary artery aneurysm regression is critical. Herein, we have created a nomogram prediction system to determine the early regression (<1 month) among patients with small to medium coronary artery aneurysms. METHODS: Seventy-six Kawasaki disease patients identified with coronary artery aneurysms during the acute or subacute phase were included. All the patients who met inclusion criteria demonstrated regression of coronary artery aneurysms within the first-year post Kawasaki disease diagnosis. The clinical and laboratory parameters were compared between the groups of coronary artery aneurysms regression duration within and beyond 1 month. Multivariate logistic regression analysis was used to identify the independent parameters for early regression based on the results from the univariable analysis. Then nomogram prediction systems were established with associated receiver operating characteristic curves. RESULTS: Among the 76 included patients, 40 cases recovered within 1 month. Haemoglobin, globulin, activated partial thromboplastin time, the number of lesions, location of the aneurysm, and coronary artery aneurysm size were identified as independent factors for early regression of coronary artery aneurysms in Kawasaki disease patients. The predictive nomogram models revealed a high efficacy in predicting early regression of coronary artery aneurysms. CONCLUSION: The size of coronary artery aneurysms, the number of lesions, and the location of aneurysms presented better predictive value for predicting coronary artery aneurysms regression. The nomogram system created from the identified risk factors successfully predicted early coronary artery aneurysm regression.

Myocardial perfusion impairment in children with Kawasaki disease: assessment with cardiac magnetic resonance first-pass perfusion.

Background: Kawasaki disease (KD) potentially increases the risk of myocardial ischemia. This study aimed to semi-quantitatively evaluate myocardial perfusion impairment using cardiac magnetic resonance (CMR) first-pass perfusion in children with KD and explore the association between coronary artery (CA) dilation and myocardial perfusion. Methods: From December 2018 to July 2021, 77 patients with KD (48 male, 5.71±2.80 years) and 37 age- and sex-matched normal controls (20 male, 6.19±3.32 years) who underwent CMR in West China Second University Hospital were enrolled in this cross-sectional study with prospective data collection. A total of 30 of these patients completed the follow-up CMR, with a median interval of 13 months. Myocardial perfusion parameters including perfusion index (PI) and maximum signal intensity (Max SI) were obtained through rest first-pass perfusion. The internal diameter of the CA was assessed via coronary magnetic resonance angiography (CMRA) to calculate the coronary Z score. The global and regional myocardial parameters among the subgroups were compared. Statistical analysis included one-way analysis of variance (ANOVA), Pearson's correlation, and multivariate linear regression. Results: The global Max SI and regional Max SI of all segments in patients with and without CA dilation decreased compared with those in controls (P=0.19 and P<0.001, respectively). The global PI of patients with CA dilation and regional PI in segments subtended by dilated CA were lower than that of controls (P=0.002 and P<0.001, respectively) and were negatively correlated with the Z score (global: r=-0.576; regional: r=-0.351, both P<0.001). Multivariate analysis revealed that the Z score was negatively associated with global PI in KD (ß=-0.409, P=0.02, model R2=0.170). The global Max SI of patients with and without CA dilation during the follow-up CMR decreased compared with that of the first CMR (42.18±9.84 vs. 34.48±8.24, P=0.02; 44.82±7.13 vs. 36.61±7.67, P=0.03, respectively). Conclusions: CMR myocardial first-pass perfusion imaging can semi-quantitatively evaluate impaired myocardial perfusion in KD patients. Not only patients with CA dilation and segments subtended by dilated CA but also those without CA dilation and segments subtended by non-dilated CA developed myocardial perfusion impairment, the severity of myocardial perfusion impairment is associated with the degree of CA dilation.

Di-(2-ethylhexyl) Phthalate Exposure Induces Developmental Toxicity in the Mouse Fetal Heart via Mitochondrial Dysfunction.

Congenital heart disease (CHD) is a major cause of infant mortality and morbidity, with growing interest in the role of environmental factors in its etiology. Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, has been implicated in the development of CHD. This study aimed to investigate the effects of DEHP exposure on fetal heart development in mice. Pregnant mice exposed to DEHP exhibited increased fetal malformations, decreased fetal weight, and reduced crown-rump length.f Transcriptomic analysis revealed the downregulation of genes involved in aerobic respiration and mitochondrial ATP synthesis. Functional assays demonstrated reduced mitochondrial respiration, decreased ATP production, elevated reactive oxygen species levels, and lowered mitochondrial membrane potential in DEHP-exposed fetal cardiomyocytes. These findings underscore the detrimental effects of DEHP on fetal cardiac health and provide insights into the molecular mechanisms underlying DEHP-induced CHD. Understanding these mechanisms is crucial for developing preventive strategies against environmental toxicants that affect fetal cardiac development.

Coronary artery dilation in children with febrile illnesses other than Kawasaki disease: A case report and literature review.

Background: Coronary artery dilation (CAD) had rarely been described as a cardiac complication of febrile disease other than Kawasaki disease (KD). There are rare cases complicated by CAD reported in patients with Mycoplasma pneumoniae (MP) infection. Case presentation: A 6-year-old boy with severe Mycoplasma pneumoniae pneumonia (MPP) was transferred to our hospital due to significant respiratory distress on the 11th day from disease onset. Nadroparin, levofloxacin, and methylprednisolone followed by oral prednisone were aggressively prescribed. His clinical condition gradually achieved remission, and the drugs were withdrawn on the 27th day. Regrettably, the recurrent fever attacked him again in the absence of infection-toxic manifestations. Necrotizing pneumonia (NP) was found on chest CT. And echocardiography revealed right CAD (diameter, 3.40mm; z-score, 3.8), however, his clinical and laboratory findings did not meet the diagnostic criteria of KD. CAD was proposed to result from MP infection, and aspirin was prescribed. Encouragingly, the CAD regressed one week later (diameter, 2.50mm; z-score, 1.4). Additionally, the child defervesced seven days after the initiation of prednisone and Nadroparin treatment. The patient was ultimately discharged home on the 50th day. During follow-up, the child was uneventful with normal echocardiography and fully resolved chest CT lung lesions. Conclusions: CAD can develop in patients with severe MP infection. Pediatricians should be alert to the possibility of CAD in patients with severe MP infection and recognize that CAD might also develop in febrile disease rather than KD.

Kawasaki disease complicated by peripheral artery thrombosis: a case report and literature review.

BACKGROUND: Peripheral gangrene is rarely documented as a possible complication of Kawasaki disease (KD). There are many causes of peripheral gangrene, and the common cause is in situ thrombosis or embolism. Most cases are reported to have regrettable outcomes (amputation or necrotic shedding). Herein, we report the successful management of KD complicated by peripheral artery thrombosis in an older Chinese boy, and a review of all cases of peripheral gangrene in KD in the literature. CASE PRESENTATION: We found that most of the children with this complication were under 1 year old, had a heavy inflammatory response combined with the use of cortisol and immunoglobulin, and most children had coronary artery lesions. In addition, Peripheral gangrene mainly occurred in the subacute or chronic stage, and the prognosis is poor. CONCLUSIONS: In the presence of high risk factors, we consider it is necessary to monitor coagulation function and administer prophylactic anticoagulation therapy. When peripheral artery thrombosis or embolism occur, heparin and prostaglandins can be used for treatment.

Predictive role of sampling-time specific prognostic nutritional index cut-off values for intravenous immunoglobulin resistance and cardiovascular complications in Kawasaki disease.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance and cardiovascular complications prediction are pivotal topic of interests in Kawasaki disease (KD). The prognostic nutritional index (PNI) has been proposed to be valuable in predicting the severity of inflammatory status and prognosis in clinical circumstances, with limited data in KD. Therefore, we prospectively investigated the role of sampling-time specific PNI cut-off values in predicting initial IVIG resistance as well as cardiovascular complications in patients with KD for the first time. METHODS: A total of 755 patients with KD were prospectively recruited between January 2015 and December 2019. Patients with KD were subgrouped based on the presence of IVIG resistance or cardiovascular complications. The clinical and laboratory parameters were compared. Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance and cardiovascular complications. The receiver operating characteristic (ROC) curve was further applied to assess the predictive values of PNI in IVIG resistance and cardiovascular complications. RESULTS: The lower level of PNI was identified as independent risk factors for initial IVIG resistance and cardiovascular complications. The discriminating cut-off values of the PNI for IVIG resistance, all cardiovascular complications, CALs, KDSS and myocarditis were 47.8, 52.2, 38.6, 48.2 and 52.0, with the corresponding sensitivities of 0.573, 0.679, 0.174, 0.750, 0.851, and specificities of 0.753, 0.549, 0.957, 0.679 and 0.576, respectively. After sampling time stratification, the sensitivities and specificities of the PNI obtained at the sixth day from fever onset for prediction of both IVIG resistance (0.778, 0.787) and all cardiovascular complications (0.667, 0.753) remarkably improved. CONCLUSION: PNI may serve as a promising predictor for KDSS in patients with KD. PNI obtained at sixth day from fever onset possess good predictive power for both IVIG resistance and all cardiovascular complications in KD.

Sterile Pyuria in Kawasaki Disease: A Large Prospective Cohort Study.

Background: Kawasaki disease (KD) is an acute systemic vasculitis and is becoming the leading cause of acquired cardiac disease in Children. Sterile pyuria is a known complication of KD. However, its associations with the inflammatory reaction severity, IVIG resistance as well as coronary artery lesions (CALs) in KD remain elusive. Aims: We aimed to analyze the clinical profiles of sterile pyuria in KD, to determine whether sterile pyuria is an indicator of the disease severity in patients with KD, and to assess the associations between sterile pyuria and IVIG resistance as well as CALs. Methods: We prospectively collected data from 702 patients with KD between January 2015 and June 2020. Profiles of patients with sterile pyuria (group A, n = 63) were compared to those of patients without sterile pyuria (group B, n = 639). The associations between sterile pyuria and IVIG resistance as well as CALs in KD were further determined by univariate and/or multivariate logistic regression analysis. Results: Sterile pyuria was observed in 9.0% of patients with KD, without predominance in age spectrum and gender. The levels of neutrophil percentages, alanine transaminase, total bilirubin, blood urea nitrogen, creatinine, the incidence of initial IVIG resistance, and rate of moderate/giant coronary artery aneurysms (CAAs) were significantly higher in group A than that in group B. Sterile pyuria was identified as an independent risk factor for initial IVIG resistance, yielding high specificity (92.7%) and low sensitivity (18.5%). However, sterile pyuria was not associated with repeated IVIG resistance and persistence of CALs in KD. Conclusion: The incidence of sterile pyuria is relatively low in KD patients. Patients with sterile pyuria in KD exhibited a more severe inflammatory burden and were more likely to develop the initial IVIG resistance and moderate/giant CAAs. The overall prognosis of KD patients with sterile pyuria was satisfactory.

Case Report: Hypothyroidism Misdiagnosed as Fulminant Myocarditis in a Child.

Background: Hypothyroidism can lead to bradycardia, reduced cardiac output, cardiac enlargement, and abnormal electrocardiogram. However, hemodynamic instability and malignant arrhythmias due to hypothyroidism is rarely reported in children. Patient Findings: We report the case of a child with third-degree atrioventricular block, cardiogenic shock, and Adams Stokes Syndrome, who was initially misdiagnosed with fulminant myocarditis and was later found to have hypothyroidism during treatment. Summary: The child's condition did not improve after the administration of gamma globulin, methylprednisolone, and isoproterenol. Even after the placement of temporary pacemakers, the therapeutic effect was still not ideal. Upon reviewing the medical history, the child's condition improved rapidly after levothyroxine supplementation. Conclusions: Hypothyroidism is a common disease, but secondary severe cardiovascular lesions are particularly rare in children. Therefore, the delay in diagnosis can lead to serious cardiovascular manifestations. When pediatric patients develop severe AVB and bradycardia, hypothyroidism should be considered as a possible cause.

Predictive value of Albumin-Bilirubin grade for intravenous immunoglobulin resistance in a large cohort of patients with Kawasaki disease: a prospective study.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance prediction is one of the primary clinical issues and study hotspots in KD. This study aimed to prospectively investigate the value of albumin-bilirubin grade (ALBI) in predicting IVIG resistance in KD and to assess whether ALBI has more predictive value or accuracy than either ALB or TBil alone in predicting IVIG resistance. METHODS: A total of 823 patients with KD were prospectively enrolled. The clinical and laboratory data were compared between the IVIG-response group (n = 708) and the IVIG-resistance group (n = 115). Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of ALBI, ALB, and TBil in predicting IVIG resistance. RESULTS: ALBI was significantly higher in patients with IVIG resistance and was identified as an independent risk factor for IVIG resistance in KD. The parameter of ALBI ≥ - 2.57 (AUC: 0.705, 95 %CI: 0.672-0.736), ALB ≤ 33.0 g/L (AUC: 0.659, 95 %CI: 0.626-0.692), and TBil ≥ 16.0µmol/L (AUC: 0.626, 95 %CI: 0.592-0.659), produced a sensitivity, specificity, PPV, and NPV of 0.617, 0.657, 0.226 and 0.914; 0.374, 0.850, 0.289 and 0.893; 0.269, 0.941, 0.425 and 0.888, respectively. CONCLUSIONS: A higher ALBI was an independent risk factor for IVIG resistance in KD. It yielded better predictive ability than ALB and TBil alone for initial IVIG resistance.

Predictive Value of the Systemic Immune-Inflammation Index for Intravenous Immunoglobulin Resistance and Cardiovascular Complications in Kawasaki Disease.

Background: The prediction of intravenous immunoglobulin (IVIG) resistance and cardiovascular complications are critically clinical issues in Kawasaki disease (KD). This prospective study firstly aimed to determine the predictive ability of the systemic immune inflammation index (SII) for IVIG resistance and cardiovascular complications and compare the prognostic accuracy of SII with that of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). Methods: Patients with KD were divided into different groups according to the presence of IVIG resistance or cardiovascular complications (coronary artery lesions, valve regurgitation, myocarditis, pericardial effusion, and Kawasaki disease shock syndrome [KDSS]). The clinical and laboratory parameters were compared. Further analysis stratified by platelet level was performed. Multivariate logistic regression analysis was used to identify predictors for IVIG resistance and cardiovascular complications. The receiver operating characteristic (ROC) curve was applied to assess and compare the ability of SII, NLR, and PLR for predicting IVIG resistance and cardiovascular complications. Results: SII was significantly higher in KD patients with IVIG-resistance, myocarditis, valve regurgitation, and KDSS. It was identified as an independent risk factor for IVIG resistance, myocarditis, and valve regurgitation. For KD patients with thrombocytopenia, there were no significant differences in SII between KD patients with IVIG resistance/cardiovascular complications and those without. The best cutoff values of SII for IVIG resistance, myocarditis, valve regurgitation, and KDSS prediction in the whole cohort were 1331.4 × 109, 1368.6 × 109, 1002.4 × 109, and 1485.4 × 109, with a corresponding sensitivity of 0.525, 0.614, 0.754, and 0.670, a specificity of 0.711, 0.723, 0.584, and 0.730, respectively. The predictive value of SII for both IVIG resistance and cardiovascular complications were not superior to that of NLR. Conclusion: Although the parameter of SII may predict IVIG resistance, myocarditis, valve regurgitation, and KDSS in KD as a single parameter, its predictive ability was not good enough and not superior to NLR. SII might not be applicable in patients with KD having thrombocytopenia.