Myocardial contractile reserve impairment in patients with Kawasaki disease during convalescent phase: a study based on two-dimensional speckle-tracking stress echocardiography

Myocardial contractile reserve impairment in patients with Kawasaki disease during convalescent phase: a study based on two-dimensional speckle-tracking stress echocardiography | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Myocardial contractile reserve impairment in patients with Kawasaki disease during convalescent phase: a study based on two-dimensional speckle-tracking stress echocardiography Haiyong Wang, Xiaoli Long, Zhiming Han, Xin Dong, Ruiling Yan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5433121/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Dec, 2024 Read the published version in Pediatric Cardiology → Version 1 posted 9 You are reading this latest preprint version Abstract Background Persistent myocardial impairment proved by histopathologic studies universally existed in patients with Kawasaki disease (KD), however, the long-term effects on myocardial contractile reserve in KD patients, especially on patients without coronary artery lesions (CALs), is still unknown. The aim of this study was to investigate myocardial contractile reserve in KD patients during late convalescent stage by speckle-tracking adenosine triphosphate (AT) echocardiography. Methods A total of 63 antecedent KD patients at least 4 years after the disease onset and 40 age- and gender-matched normal controls were prospectively enrolled. Based on coronary artery status, patients were further divided into CALs group and non-CALs (NCALs) group. Left ventricular ejection fraction (LVEF), speckle-tracking derived-global longitudinal strain (GLS) and global circumferential strain (GCS) were evaluated at rest and during AT peak stress. Myocardial contractile reserve parameters including ΔLVEF, ΔGLS and ΔGCS were defined as the absolute increases in LVEF, GLS and GCS from rest to peak stress. Results KD patients regardless of CALs had lower GLS and GCS than normal controls at resting condition. Significant decreases in ΔGLS and ΔGCS were observed in patients with CALs compared to normal controls under peak stress. While ΔGLS and ΔGCS increased in patients without CALs following stress, improvements were significantly weaker than those in normal controls. However, no significant differences in LVEF at rest and ΔLVEF under peak stress between KD patients irrespective of CALs and normal controls were found. In additional, when comparing with patients with NCALs, patients with CALs had lower GLS and GCS at rest, lower ΔGLS and ΔGCS in response to stress. Conclusions Subclinical abnormality of myocardial contractile reserve existed in KD patients during late convalescent phase. Even patients without CALs need an additional surveillance on myocardial contractile reserve in the long-term follow-up. These novel findings by speckle-tracking stress echocardiographic analysis may provide more valuable clinical implications for better understanding and long-term management of such patients. myocardial contractile reserve two-dimensional speckle-tracking echocardiography late convalescent stage Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Kawasaki disease (KD) characterized by acute systemic vasculitis as the main pathological feature is the leading cause of acquired coronary artery disease in children in developed countries [ 1 ]. However, the etiology and pathogenesis of KD is still unclear until now. Coronary artery lesions (CALs) including coronary artery aneurysm, coronary artery stenosis and coronary thrombosis occurred in 20–25% in patients untreated with intravenous immunoglobulin (IVIG), and the occurrence of CALs can be decreased to 5% in patients timely treated with IVIG [ 2 ]. Nevertheless, 20–25% of patients are still resistant to IVIG treatment, and the occurrence risk of CALs in these patients is up to 9 times higher than that in IVIG responsive patients [ 3 ]. Although the development of CALs during acute phase received intensive attentions, KD-induced myocarditis in acute phase is more prevalent than CALs which can persist into adulthood [ 4 – 6 ]. Myocardial contractile reserve as the principal part of cardiac reserve is an important prognostic indicator for many cardiovascular diseases, early detection of myocardial contractile reserve abnormality is crucial for clinicians to make optimal treatments and improve the prognosis of patients [ 7 – 9 ]. However, whether the progression of chronic myocardial injury over time in KD patients will lead to myocardial contractile reserve dysfunction during late convalescent phase is not fully delineated. Conventional stress echocardiography is the most used imaging modality in evaluating myocardial contractile reserve of patients, however, conventional parameter left ventricular ejection fraction (LVEF) limited by algorithm of LV geometry assumption cannot be used to detect myocardial contractile reserve subclinical dysfunction [ 10 , 11 ]. Compared with conventional stress echocardiography, speckle-tracking stress echocardiography by tracing the displacement characteristics of myocardium during different cardiac cycles is more accurate and sensitive for detecting myocardial contractile reserve abnormality in patients with high feasibility and reproducibility [ 10 – 13 ]. Previous studies regarding on the assessment of myocardial contractile reserve in KD patients were mainly focused on short period after illness onset by conventional stress echocardiography [ 14 – 16 ], nevertheless, the characteristics of myocardial contractile reserve assessed by speckle-tracking stress echocardiography in patients with KD during late convalescent phase are not clear. In this study, we hypothesized that myocardial contractile reserve abnormality existed in KD patients during late convalescent phase, and we aimed to evaluate the feasibility of speckle-tracking stress echocardiography in detecting myocardial contractile reserve abnormality in KD patients. Subjects and Methods Study population Patients with KD during late convalescent phase who referred to our laboratory for a follow-up echocardiographic examination were consecutively enrolled from January 2018 to January 2024.The control subjects with age and gender matched who presented to our hospital due to cardiac murmur but ultimately diagnosed with structurally and functionally normal hearts were recruited. The inclusion criteria for KD patients were as follows: (1) study population or their guardians gave consent to adenosine triphosphate (AT) stress echocardiography. (2) patients with KD met diagnostic criteria established by the American Heart Association (AHA) with the course of disease at least 4 years; (3) all patients had normal LVEF from disease onset to follow-up period; (4) a combination of high dose of IVIG (2 g/kg) and aspirin (80 mg/kg/day) were given to patients in the acute phase. The exclusion criteria for study population included severe cardiac arrhythmia, severe hypertension, known cardiovascular disease, uncooperative during stress test and low image quality which cannot met offline analysis. Patients with KD were divided into groups with or without CALs based coronary artery status. CALs was defined as a Z score of ≥ 2.5 (SD units from the coronary artery internal diameter normalized for body surface area) in the right coronary artery, left coronary artery and left anterior descending coronary artery according to the recommendation by AHA [ 1 ]. Patients with CALs were confirmed by echocardiography, computed tomography angiography (CTA), cardiac magnetic resonance angiography (CMRA) or coronary artery angiography as appropriate. This study was approved by the Ethics Review Committee of Gansu Provincial Hospital (2018GSPH006), and written informed consent was obtained from the subjects or subjects of their guardians. AT Stress Protocol AT (160 µg/kg/min) used by high-flow infusion pump was intravenously given to the study subjects. The dose of AT was reduced to 140 or 100 mg/kg/min, when mild side effects such as dyspnea occurred in subjects. After 6 minutes of AT infusion, atropine (0.02mg/kg, up to 2mg) was intravenously administered to study subjects to increase heart rate. Blood pressure and electrocardiogram were monitored throughout the test. The termination criteria for test was as follows [ 17 ]: (1) age-adjusted target heart rate; (2) systolic blood pressure > 240mmHg; (3) abnormal blood pressure response or severe cardiac arrhythmias; (4) severe ischemic electrocardiographic manifestations; (5) occurrence of wall motion abnormality; (6) unable to cooperate during the examination; (7) angina pectoris. Conventional echocardiographic analysis Study subjects underwent transthoracic echocardiography using a commercially available ultrasonic machine (Philips EPIQ 7C, Andover, Massachusetts, USA) equipped with a S8-3 or S5-1 transducer as appropriate. At rest and under peak stress, all participants underwent comprehensive conventional echocardiography by two experienced investigators who were blinded to status of participants. The digital images consisted of three consecutive cardiac cycles from apical views (apical-4 chamber view, apical-3 chamber view and apical-2 chamber view) and parasternal LV short-axis views (basal-level, mid-level and apical-level) were acquired and stored for subsequent analysis. According to the guideline from the American Society of Echocardiography [ 18 ], the LV ejection fraction (LVEF) based on biplane Simpson's method and LV shortening fraction (LVSF) were calculated. Speckle-tracking echocardiography analysis Dynamic images with three consecutive cardiac cycles obtained by conventional echocardiography were imported into dedicated strain analysis workstation (Qlab version 10.6, Speckle Tracking, Philips, Andover, Massachusetts, USA). All longitudinal and circumferential strains were obtained by the recommended guideline [ 19 ]. At rest and under peak stress, the dynamic images for the three standard apical views and the three parasternal short-axis views with the best display of the LV wall were selected. After manual delineation of the endocardial borders of LV, global longitudinal strain (GLS) derived from apical-3 view, apical-2 view and apical-4 view and global circumferential strain (GCS) (Fig. 1 d) derived from basal level (Fig. 1 a), middle level (Fig. 1 b) and apical level (Fig. 1 c) were automatically calculated. Segments not suitable for strain analysis due to poor tracking quality were excluded. All measurements were analyzed and interpreted by an experienced investigator blinded to participant diagnosis. Global LV myocardial contractile reserve was defined as the change of values at rest and under peak stress (ΔLVEF, ΔGLS and ΔGCS). Reproducibility of speckle-tracking echocardiography To evaluate intra-observer variability, strain parameters including GLS and GCS from 25 randomly assigned patients were reanalyzed by the same investigator 1 month after the initial analysis. The same patients with the same designated cardiac cycles were analyzed by a second investigator to determine inter- observer variability. All observers were blinded to participant diagnosis. Statistical analysis SPSS 22.0 (Statistical Product and Service Solutions Company, Chicago) was used for all calculations. All strain parameters were shown in absolute values to facilitate statistical analysis and comparisons between groups. Mean ± standard deviation were reported for continuous data. The categorical data were summarized as the count and percentages. The continuous variables were first assessed by Kolmogorov–Smirnov test for normality. A chi-square analysis was used for categorical data. Comparisons among the CALs group, NCALs group and normal control group were made by one-way ANOVA for normal distributed parameters and by Kruskal-Wallis nonparametric test for nonnormal distribution parameters respectively. Test reliability was assessed by calculating intra-observer variability, inter-observer variability, and intraclass correlation coefficients (ICCs) with a 95% confidence interval [ 20 ]. A P -value < .05 was considered statistically significant. Results General characteristics in the study population The demographics of KD patients with or without CALs and normal controls were presented in Table 1 . No significant differences regard to baseline parameters among the three groups were found. Of the 63 patients with KD, 44 had normal coronary artery, and 19 had CALs documented by conventional echocardiography, CTA, CMRA or selective artery angiography as appropriate. The age of KD patients CALs were 9.5 ± 5.8 years (range, 3.2–21.4 years) with a mean follow-up of 7.4 ± 4.7 years (range, 4.1–16.9 years) from the disease onset, and the age of KD patients with NCALs was 9.6 ± 5.7 years (range, 3.3–21.0 years) with a mean follow-up of 7.9 ± 5.0 years (range, 4.0–18.7 years) from the disease onset. The LVEF in KD patients with or without NCALs during the acute phase were normal (64.9 ± 5.3%, 65.6 ± 5.8%, respectively), and no abnormal LV systolic function measurements were detected in the follow-up routine echocardiographic examination. Table 1 Clinical characteristics of patients with KD and normal controls CALs group NCALs group Control group Overall P -value n = 19 n = 44 n = 40 Age, year 9.7 ± 5.7 9.6 ± 5.8 9.9 ± 5.5 0.56 Male, % 10 (52.6) 22 (50) 23 (52.2) 0.62 Height, m 1.5 ± 0.3 1.6 ± 0.5 1.5 ± 0.4 0.41 Body mass, Kg 26.6 ± 5.1 26.1 ± 5.0 25.9 ± 5.3 0.32 Body surface area, m 2 1.03 ± 0.23 1.04 ± 0.20 1.02 ± 0.21 0.60 Body mass index, Kg/m 2 22.4 ± 3.9 22.1 ± 4.0 23.0 ± 3.7 0.57 Total cholesterol, mmoL/L 3.1 ± 0.8 3.4 ± 0.6 3.0 ± 0.5 0.31 LDL cholesterol, mmoL/L 2.0 ± 0.3 2.2 ± 0.2 1.9 ± 0.2 0.49 Data are shown in mean ± standard deviation or as number (percentage). KD: Kawasaki disease, CALs: coronary artery lesions, NCALs: non coronary artery lesions. Conventional echocardiography Conventional echocardiographic parameters at resting condition and under peak stress are shown in Table 2 . When comparing with normal controls, no significant differences regarding to LVSF (Fig. 2 a) and LVEF (Fig. 2 b) in patients with CALs and without CALs were found at rest and under peak stress. In addition, both LVEF (patients with CALs: from 64.3 ± 5.2% to 68.5 ± 4.6%, patients with NCALs: from 66.7 ± 4.6% to 69.1 ± 6.0%, normal controls: from 67.6 ± 5.1% to 71.0 ± 5.5%) and LVSF (patients with CALs: from 35.8 ± 4.6% to 37.9 ± 4.8%, patients with NCALs: from 37.0 ± 4.9% to 39.6 ± 5.0%, normal controls: from 36.6 ± 5.1% to 39.3 ± 4.7%) in the three groups increased significantly from rest to peak stress (Table 2 ), with comparable ΔLVSF (Fig. 3 a) as well as ΔLVEF among three groups (Fig. 3 b). No significant differences were found in baseline characteristics and other conventional echocardiographic parameters among three groups. Table 2 Clinical and conventional echocardiographic parameters in KD patients at resting condition and under peak stress CALs group NCALs group Control group Overall P -value n = 19 n = 44 n = 40 LVEDV, mL Rest 87.4 ± 19.2 84.8 ± 17.9 81.9 ± 20.0 0.29 Peak dose 92.0 ± 18.4 91.2 ± 19.0 85.7 ± 18.6 0.42 LVESV, mL Rest 40.1 ± 11.8 39.2 ± 12.0 37.9 ± 14.1 0.58 Peak dose 36.8 ± 12.9 34.5 ± 13.1 32.9 ± 12.8 0.46 LVEF, % Rest 64.3 ± 5.2 66.7 ± 4.6 67.6 ± 5.1 0.55 Peak dose 68.5 ± 4.6 69.1 ± 6.0 71.0 ± 5.5 0.37 ΔLVEF 4.6 ± 2.1 4.2 ± 1.9 4.5 ± 2.3 0.28 LVSF, % Rest 35.8 ± 4.6 37.0 ± 4.9 36.6 ± 5.1 0.22 Peak dose 37.9 ± 4.8 39.6 ± 5.0 39.3 ± 4.7 0.50 ΔLVSF 2.9 ± 1.6 2.8 ± 1.8 3.1 ± 1.4 0.38 Heart rate, bpm Rest 89 ± 9 84 ± 8 88 ± 8 0.58 Peak dose 120 ± 18 117 ± 16 119 ± 19 0.54 SBP, mmHg Rest 108 ± 12 113 ± 10 110 ± 13 0.33 Peak dose 100 ± 11 107 ± 13 106 ± 11 0.36 DBP, mmHg Rest 69 ± 9 72 ± 11 74 ± 10 0.29 Peak dose 65 ± 8 67 ± 9 70 ± 10 0.33 Data are presented with mean ± standard deviation. KD: Kawasaki disease, CALs: coronary artery lesions, NCALs: non coronary artery lesions, LVEDV: left ventricular end-diastolic volume, LVESV: left ventricular end-systolic volume, LVEF: left ventricular ejection fraction, LVSF: left ventricular shortening fraction, SBP: systolic blood pressure, DBP: diastolic blood pressure. Speckle-tracking echocardiography Results of speckle-tracking strain-based analysis at rest and under peak stress are summarized in Table 3 . Compared with normal controls, both KD patients with and those without CALs had decreased GLS (Fig. 2 c) and GCS (Fig. 2 d) at resting condition as well as peak stress which were statistically significant difference. When comparing with patients with NCALs, both GLS at rest as well as peak stress (Fig. 2 c) and GCS under peak stress (Fig. 2 d) in CALs group were significantly lower. As expected, all speckle-tracking strain measurements significantly increased in response to AT in normal controls (GLS from 21.68 ± 1.50% to 24.96 ± 1.13%; GCS from 28.03 ± 3.45% to 30.87 ± 3.46%) (Fig. 3 c and 3 d). However, both GLS (Fig. 3 c) and GCS (Fig. 3 d) in patients with CALs at peak stress when compared with the resting condition significantly decreased (GLS from 17.01 ± 1.39% to 16.16 ± 1.14%; GCS from 24.76 ± 3.49% to 22.68 ± 3.42%). Although an increase of GLS (from 19.01 ± 1.12% to 20.02 ± 1.09%) and GCS (from 25.00 ± 3.42% to 26.04 ± 3.43%) were observed in KD patients without CALs following stress, improvements were significantly weaker (Fig. 3 c and 3 d). Contractile reserve parameters including ΔGLS (Fig. 3 c) and ΔGCS (Fig. 3 d) in CALs patients (ΔGLS − 1.87 ± 1.21 vs 3.28 ± 1.14, P < 0.001; ΔGCS − 2.08 ± 3.09 vs 2.84 ± 3.11, P < 0.001) and NCAL patients (ΔGLS 0.99 ± 1.30 vs 3.28 ± 1.14, P = 0.020; ΔGCS 1.04 ± 3.15 vs 2.84 ± 3.11, P = 0.027) were both lower than those in normal controls. ΔGLS (Fig. 3 c) as well as ΔGCS (Fig. 3 d) were significantly reduced in patients with CALs (ΔGLS − 1.87 ± 1.21 vs 0.99 ± 1.30, P = 0.011; ΔGCS − 2.08 ± 3.09 vs 1.04 ± 3.15, P = 0.0024) when comparing with patients with NCALs. Table 3 Speckle-tracking derived-parameters in KD patients at resting condition and under peak stress CALs group P1 P2 NCALs group P1 Control group Overall P -value n = 19 n = 44 n = 40 AP4-LS, % Rest 17.24 ± 3.27 0.015 0.58 17.65 ± 3.10 0.021 20.17 ± 2.55 0.024 Peak dose 15.36 ± 4.01 < 0.001 0.040 17.90 ± 4.13 0.016 23.28 ± 4.32 < 0.001 ΔAP4-LS -1.88 ± 3.76 < 0.001 0.022 0.25 ± 3.16 < 0.001 3.11 ± 3.03 < 0.001 AP3-LS, % Rest 18.29 ± 2.31 18.18 ± 1.89 18.91 ± 2.02 0.41 Peak dose 18.31 ± 3.00 0.043 0.29 19.00 ± 2.54 0.33 20.03 ± 2.96 0.039 ΔAP3-LS 0.02 ± 2.54 0.019 0.056 0.82 ± 2.13 0.41 1.12 ± 2.00 0.036 AP2-LS, % Rest 19.65 ± 2.72 20.12 ± 2.10 21.08 ± 2.43 0.29 Peak dose 18.57 ± 2.39 < 0.001 0.036 21.34 ± 2.25 0.041 23.33 ± 2.55 0.028 ΔAP2-LS -1.08 ± 2.03 < 0.001 0.021 1.22 ± 2.10 0.33 2.25 ± 2.07 0.022 GLS, % Rest 17.01 ± 1.39 0.013 0.038 19.01 ± 1.12 0.030 21.68 ± 1.50 0.019 Peak dose 16.16 ± 1.14 < 0.001 0.015 20.02 ± 1.09 0.008 24.96 ± 1.13 < 0.001 ΔGLS -1.87 ± 1.21 < 0.001 0.011 0.99 ± 1.30 0.020 3.28 ± 1.14 < 0.001 Basal-CS, % Rest 20.97 ± 4.32 0.024 0.030 23.01 ± 4.96 0.62 23.17 ± 4.56 0.036 Peak dose 21.03 ± 3.68 < 0.001 0.031 24.01 ± 4.02 0.042 26.33 ± 4.13 0.022 ΔBasal-CS 0.06 ± 3.54 < 0.001 1.54 ± 3.33 0.038 3.16 ± 3.60 0.017 Mid-CS, % Rest 26.01 ± 4.09 25.96 ± 5.02 26.19 ± 5.20 0.49 Peak dose 25.97 ± 4.03 0.028 0.11 26.93 ± 4.11 0.053 28.57 ± 4.19 0.037 ΔMid-CS -1.04 ± 3.86 < 0.001 0.012 0.93 ± 3.93 0.023 2.38 ± 4.02 0.0024 Apical-CS Rest 27.84 ± 5.03 28.10 ± 4.22 0.098 29.71 ± 4.29 0.052 Peak dose 24.87 ± 4.66 < 0.001 0.027 29.03 ± 4.58 0.021 32.54 ± 4.67 0.013 ΔApical-CS -1.15 ± 3.65 < 0.001 0.0067 0.93 ± 3.03 0.011 2.83 ± 3.33 0.0021 GCS, % Rest 24.76 ± 3.49 0.023 0.52 25.00 ± 3.42 0.040 28.03 ± 3.45 0.036 Peak dose 22.68 ± 3.42 < 0.001 0.017 26.04 ± 3.43 0.0012 30.87 ± 3.46 < 0.001 ΔGCS -2.08 ± 3.09 < 0.001 0.0024 1.04 ± 3.15 0.027 2.84 ± 3.11 0.0016 Values are demonstrated as mean ± standard deviation, myocardial strain are expressed as absolute values. KD: Kawasaki disease, CALs: coronary artery lesions, NCALs: non coronary artery lesions, AP4: apical four-chamber view, AP3: apical three-chamber view, AP2: apical two-chamber view, LS: longitudinal strain, CS: circumferential strain, GLS: global longitudinal strain, GCS: global circumferential strain. P 1 values for comparison with normal controls. P 2 values for comparison between CALs group and NCALs group. Representative examples of significant decreased GLS reserve in a patient with CALs (Fig. 4 a and 4 c) and weak improvement of GLS reserve in a patient with no coronary artery involvement (Fig. 4 b and 4 d) when comparing with a control subject (Fig. 4 c and 4 f) in response to stress. Reproducibility The reliability analysis for speckle-tracking strain parameters is summarized in Table 4 . Both the inter-observer and intra-observer concordances were good for GLS and GCS values. Table 4 Reproducibility analysis for speckle-tracking strain parameters Intra-observer Reproducibility Inter-observer reproducibility ICCs 95% CI P ICCs 95% CI P GLS 0.981 0.825–0.992 < 0.001 0.974 0.816–0.999 < 0.001 GCS 0.972 0.815–0.996 < 0.001 0.806 0.638–0.971 0.013 ICCs: intraclass correlation coefficients, CI: confidential interval, GLS: global longitudinal strain, GCS: global circumferential strain. Discussion Our study demonstrated that myocardial contractile function abnormality existed in late convalescent phase KD patients regardless of CALs despite normal LV systolic function measurements by conventional stress echocardiography, and the subclinical dysfunction of myocardial contractile reserve in patients with CALs was more severe than patients with NCALs. Two-dimensional speckle-tracking stress echocardiography is a promising approach in detecting myocardial contractile reserve impairment in KD patients with high sensitivity and reproducibility. Both myocardial systolic dysfunction at resting condition and myocardial contractile reserve abnormality following to stress existed in KD patients irrespective of the presence of CALs. Although coronary artery aneurysm as the most significant CALs complications has received most of the attentions from KD research and clinical practice, KD-induced myocarditis in the acute phase is a far more universal feature than coronary artery involvement which can persist into adulthood [ 21 , 22 ]. Yonesaka et al [ 21 ] evaluated the long-term histopathology of the myocardium in 38 patients > 2 years after disease onset, they found that myocardial changes characterized by inflammatory cell infiltration, interstitial fibrosis, and disarray interstitial fibrosis commonly existed in KD patients. In a large biopsy study of 201 KD patients conducted by Yutani et al[ 22 ], myocardial abnormalities including lymphocyte and plasma cell infiltration, myocardial fibrosis, and disarray of myocardial fibers were observed in every patient during acute phase and recovery period. These histopathologic studies suggested persistent myocardial abnormalities after KD. However, there were lack of researches on these chronic myocardial sequelae effects on myocardial contractile reserve in KD patients during late convalescent phase. Consisted with the above mentioned pathological change, our study results demonstrated that myocardial contractile reserve dysfunction occurred in KD patients during late convalescent phase regardless of coronary artery involvement. Tacke et al [ 23 ] investigated myocardial contractile function by cardiac magnetic resonance imaging (CMRI) during long-term follow-up of KD, and no significant differences in cardiac function between KD patients and control subjects were observed, which was in consisted with our conventional stress echocardiographic measurements. However, myocardial contractile reserve in response to stress was not included in their study. In our study, though normal conventional echocardiographic parameters including LVEF and ΔLVEF in KD patients irrespective of coronary artery involvement, significantly decreased strains at rest and under stress were found in patients when comparing with control subjects. Our study results suggested that myocardial contractile reserve subclinical abnormality has existed in late convalescent stage KD patients though normal LVEF as well as ΔLVEF, and speckle-tracking stress echocardiography is more sensitive in detecting myocardial reserve dysfunction than conventional echocardiography and CMRI. Patients with CALs demonstrated more decreased myocardial contractile reserve impairment than those with normal coronary artery. Liu et al [ 24 ] performed an ultrastructural study on endomyocardial biopsy specimens obtained during follow-ups of 54 patients, and they demonstrated a significantly increased incidence of myocardial and coronary microvascular lesions in CAL + compared to CAL − patients, which persisted after convalescent stage even up to 23 years. In an another study [ 25 ] exploring matrix remodeling in adolescents and young adults with KD late after onset, myocardial fibrosis biomarker amino-terminal propeptide of type III procollagen (PIIINP) in KD patients with CALs was significantly increased when comparing with patients with NCALs, suggesting more enhanced collagen synthesis in adolescents and young adults with coronary artery involvement late after the onset of KD. Our previous study showed that the increased PIIINP was significantly correlated to decreased GLS as well as GCS in convalescent stage KD patients, which suggested myocardial fibrosis in late after onset is an important reason for leading to myocardial contractile dysfunction [ 26 ]. In our present study, we further demonstrated that myocardial contractile reserve impairment in KD patients with CALs was more severe than patients without CALs which was in accordance with the above pathological findings and biomarker results. In addition, the decreased capacity of coronary artery vasodilation due to the destroyed coronary artery wall structure may also play an important role for severe myocardial contractile reserve abnormality in KD patients with CALs. Even KD patients without CALs should be given to additional surveillance on myocardial contractile reserve in the long-term follow-up. While CALs as the most significant complication of KD is a risk factor for myocardial ischemia occurrence which is proposed as the only parameter for the cardiovascular risk stratification in KD patients, and an accurate cardiological follow-up is needed for patients with CALs [ 1 ]. However, researches regarding on long-term management of children without CALs is limited. According to the American Heart Association (AHA) recommendations, KD patients with no coronary artery involvement are only advised to discharge from cardiology care at 4 to 6 weeks after KD onset, and ongoing cardiology follow-up is not indicated [ 1 ], but the recommended cardiology assessment is referred to conventional echocardiography which cannot detect subclinical myocardial dysfunction [ 27 ]. In our study, though normal LVEF and LVSF in KD patients without CALs, significantly decreased GLS and GCS at resting condition and following stress were observed in these patients. Therefore, we suggest that careful long-term follow-up assessment of myocardial contractile reserve function by speckle-tracking stress echocardiography in this subset of KD patients should be warranted. In accordance with our study findings, Zanon et al [ 28 ] explored the frequency and risk factors for long-term myocardial perfusion scintigraphy abnormalities in patients with KD using myocardial single-photon emission computed tomography (SPECT), their study results demonstrated that perfusion alterations can be found in KD patients with or without CALs. However, a small sample volume with only 20 patients with normal coronary artery were enrolled in their study, and SPECT examination procedure is time-consuming and radioactive. Compared to SPECT and conventional stress echocardiography, two-dimensional speckle-tracking stress echocardiography could be an alternative way to provide a new approach for monitoring possible myocardial reserve abnormality noninvasively with high sensitivity and accuracy. Based on our study results, we preliminary raised an important issue regarding the management and follow-up of KD patients during convalescent stage, especially for patients with no coronary artery involvement. Limitations Besides the inherent shortcomings of two-dimensional speckle-tracking echocardiography, there are several additional limitations in our study. First, the myocardial contractile reserve course over time cannot be evaluated due to the lack of speckle-tracking stress echocardiography data of the acute phase. Second, compared with the reported literature of CALs in KD (< 10%) [ 1 ], the study population contains a high percentage of occurrence of patients with CALs. One possible explanation for this difference may be the referral bias because of more severe patients referred to our cardiology center, and patients with CALs need more frequent follow-up echocardiographic examinations. Finally, this was a single center research enrolled a small number of patients with relatively short follow-up, prospective, multicenter with larger patient populations and longer follow-up studies were needed to validate our findings. Conclusions Subclinical abnormality of myocardial contractile reserve existed in KD patients during late convalescent phase regardless of CALs, which can be detected by speckle-tracking stress echocardiography though normal LVEF and ΔLVEF. Even patients without coronary artery involvement need an additional surveillance on myocardial contractile reserve in the long-term follow-up. These novel findings by speckle-tracking stress echocardiographic analysis may have more valuable clinical implications for better understanding and long-term management of KD patients during late convalescent stage when comparing with conventional stress echocardiography. Declarations Author Contribution Haiyong Wang: Design of study, data analysis and interpretation, drafting article, critical revision of article, approval of article, statistics, data collection. Ruiling Yan: Design of study, data analysis and interpretation, drafting article, critical revision of article, approval of article. All authors reviewed the manuscript. Statement of financial support: There is none financial support for this study. Disclosure statement: There are none authors’ financial ties to products in the study or potential/perceived conflicts of interest on the cover page. References McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E, American Heart Association Rheumatic Fever E, Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Y, Council C, Stroke N (2017) Council on Cardiovascular S, Anesthesia, Council on E, Prevention. 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Int J Rheum Dis 21(1):45–49 Tamarappoo BK, Fong Ling L, Cerqueira M, Hachamovitch R (2018) Independent prognostic value of left ventricular contractile reserve and chronotropic response in patients with reduced left ventricular ejection fraction undergoing vasodilator stress myocardial perfusion imaging with rb-82 positron emission tomography. Eur Heart J Cardiovasc Imaging 19(4):442–449 Bavishi C, Trivedi V, Sellke FW, Gordon PC, Abbott JD (2021) Myocardial contractile reserve and mortality in patients with severe aortic stenosis with impaired left ventricular function who underwent transcatheter aortic valve implantation. Am J Cardiol 141:150–152 Bautz J, Stypmann J, Reiermann S, Pavenstädt HJ, Suwelack B, Stegger L, Rahbar K, Reuter S, Schäfers M (2021) Prognostic implication of myocardial perfusion and contractile reserve in end-stage renal disease: A direct comparison of myocardial perfusion scintigraphy and dobutamine stress echocardiography. J Nucl Cardiol Li Z, Li Y, Zhang L, Zhang X, Sullivan R, Ai X, Szeto C, Cai A, Liu L, Xiao W, Li Q, Ge S, Chen X (2017) Reduced myocardial reserve in young x-linked muscular dystrophy mice diagnosed by two-dimensional strain analysis combined with stress echocardiography. J Am Soc Echocardiogr 30(8):815–827e819 Mandoli GE, Cameli M, Minardi S, Crudele F, Lunghetti S, Mondillo S (2018) Layer-specific strain in dipyridamole stress echo: A new tool for the diagnosis of microvascular angina. Echocardiography 35(12):2005–2013 Mandoli GE, Pastore MC, Vasilijevaite K, Cameli P, D'Ascenzi F, Focardi M, Mondillo S, Cameli M (2020) Speckle tracking stress echocardiography: A valuable diagnostic technique or a burden for everyday practice? Echocardiography 37(12):2123–2129 Zamirian M, Afsharizadeh F, Moaref A, Abtahi F, Amirmoezi F, Attar A (2019) Reduced myocardial reserve in cirrhotic patients: An evaluation by dobutamine stress speckle tracking and tissue doppler imaging (tdi) echocardiography. J Cardiovasc Thorac Res 11(2):127–131 Zilberman MV, Goya G, Witt SA, Glascock B, Kimball TR (2003) Dobutamine stress echocardiography in the evaluation of young patients with kawasaki disease. Pediatr Cardiol 24(4):338–343 Pahl E, Sehgal R, Chrystof D, Neches WH, Webb CL, Duffy CE, Shulman ST, Chaudhry FA (1995) Feasibility of exercise stress echocardiography for the follow-up of children with coronary involvement secondary to kawasaki disease. Circulation 91(1):122–128 Okçün B, Ozhan H, Baran T, Saltik L, Mutlu H, Uner S, Küçükoğlu MS (2002) Utility of dobutamine stress echocardiography in kawasaki disease: A case report and review of the literature. Turk J Pediatr 44(3):251–253 Pellikka PA, Arruda-Olson A, Chaudhry FA, Chen MH, Marshall JE, Porter TR, Sawada SG (2020) Guidelines for performance, interpretation, and application of stress echocardiography in ischemic heart disease: From the american society of echocardiography. J Am Soc Echocardiography: official publication Am Soc Echocardiography 33(1):1–41e48 Mitchell C, Rahko PS, Blauwet LA, Canaday B, Finstuen JA, Foster MC, Horton K, Ogunyankin KO, Palma RA, Velazquez EJ (2018) Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: Recommendations from the american society of echocardiography. Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography Voigt JU, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R, Pedri S, Ito Y, Abe Y, Metz S, Song JH, Hamilton J, Sengupta PP, Kolias TJ, d'Hooge J, Aurigemma GP, Thomas JD, Badano LP (2015) Definitions for a common standard for 2d speckle tracking echocardiography: Consensus document of the eacvi/ase/industry task force to standardize deformation imaging. Eur Heart J Cardiovasc Imaging 16(1):1–11 Arciniegas Calle MC, Sandhu NP, Xia H, Cha SS, Pellikka PA, Ye Z, Herrmann J, Villarraga HR (2018) Two-dimensional speckle tracking echocardiography predicts early subclinical cardiotoxicity associated with anthracycline-trastuzumab chemotherapy in patients with breast cancer. BMC Cancer 18(1):1037 Yonesaka S, Takahashi T, Eto S, Sato T, Otani K, Ueda T, Sato A, Kitagawa Y, Konno Y, Kinjo M (2010) Biopsy-proven myocardial sequels in kawasaki disease with giant coronary aneurysms. Cardiol Young 20(6):602–609 Yutani C, Go S, Kamiya T, Hirose O, Misawa H, Maeda H, Kozuka T, Onishi S (1981) Cardiac biopsy of kawasaki disease. Arch Pathol Lab Med 105(9):470–473 Tacke CE, Romeih S, Kuipers IM, Spijkerboer AM, Groenink M, Kuijpers TW (2013) Evaluation of cardiac function by magnetic resonance imaging during the follow-up of patients with kawasaki disease. Circ Cardiovasc Imaging 6(1):67–73 Liu AM, Ghazizadeh M, Onouchi Z, Asano G (1999) Ultrastructural characteristics of myocardial and coronary microvascular lesions in kawasaki disease. Microvasc Res 58(1):10–27 Lin MT, Chen SJ, Ho YL, Huang KC, Chen CA, Chiu SN, Sun LC, Lee WJ, Chen HC, Wang JK, Wu MH (2008) Abnormal matrix remodeling in adolescents and young adults with kawasaki disease late after onset. Clin Chem 54(11):1815–1822 Wang H, Tong M, Mu J, Wu T, Ruan L (2021) Assessment of myocardial function by two-dimensional speckle tracking echocardiography in patients with kawasaki disease: A mid-term follow-up study. Coron Artery Dis 32(6):500–508 Katsi V, Georgiopoulos G, Laina A, Koutli E, Parissis J, Tsioufis C, Nihoyannopoulos P, Tousoulis D (2017) Left ventricular ejection fraction as therapeutic target: Is it the ideal marker? Heart Fail Rev 22(6):641–655 Zanon G, Zucchetta P, Varnier M, Vittadello F, Milanesi O, Zulian F (2009) Do kawasaki disease patients without coronary artery abnormalities need a long-term follow-up? A myocardial single-photon emission computed tomography pilot study. J Paediatr Child Health 45(7–8):419–424 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Dec, 2024 Read the published version in Pediatric Cardiology → Version 1 posted Editorial decision: Revision requested 21 Nov, 2024 Reviews received at journal 21 Nov, 2024 Reviews received at journal 19 Nov, 2024 Reviewers agreed at journal 16 Nov, 2024 Reviewers agreed at journal 16 Nov, 2024 Reviewers invited by journal 14 Nov, 2024 Editor assigned by journal 14 Nov, 2024 Submission checks completed at journal 14 Nov, 2024 First submitted to journal 11 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5433121","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":381127219,"identity":"1f1dc567-c257-40fd-bb56-9e4cfaca1722","order_by":0,"name":"Haiyong Wang","email":"","orcid":"","institution":"Gansu Provincial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Haiyong","middleName":"","lastName":"Wang","suffix":""},{"id":381127220,"identity":"dd3dcfe3-5837-41a1-8bb7-c54e83b26be6","order_by":1,"name":"Xiaoli Long","email":"","orcid":"","institution":"The First People Hospital of Lanzhou","correspondingAuthor":false,"prefix":"","firstName":"Xiaoli","middleName":"","lastName":"Long","suffix":""},{"id":381127221,"identity":"a50879f1-bc17-49f6-802c-d9de8a46ba41","order_by":2,"name":"Zhiming Han","email":"","orcid":"","institution":"Gansu Provincial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhiming","middleName":"","lastName":"Han","suffix":""},{"id":381127222,"identity":"f4e5e3af-9ad5-492e-a152-7a8df34d7081","order_by":3,"name":"Xin Dong","email":"","orcid":"","institution":"Gansu Provincial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Dong","suffix":""},{"id":381127223,"identity":"55e9278a-1f01-43b4-925b-320c06c9682f","order_by":4,"name":"Ruiling Yan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtUlEQVRIiWNgGAWjYBACgwMM7J+BtBwbe/sBorWwSQNpYz6eMwnEaZFsgGhJnCfhYECcFn72s8ekGWrq0tskGBIYflRsI6yFjScv/TPDscO5bdKNBxh7ztwmQgtDjvlhxoYDuW0yBxKYGduI0cL/xiyZsaEunU0iwYBILRI5ZsaMDcwJpGh5YyYN9IthGzCQDxLnF/4cM+kfNXXy8u3tBx/8qCBCCwo4QKL6UTAKRsEoGAW4AAAVHzYY6SlnFAAAAABJRU5ErkJggg==","orcid":"","institution":"Tianyou Hospital of Shanghai","correspondingAuthor":true,"prefix":"","firstName":"Ruiling","middleName":"","lastName":"Yan","suffix":""}],"badges":[],"createdAt":"2024-11-11 15:08:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5433121/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5433121/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00246-024-03751-y","type":"published","date":"2024-12-27T15:57:34+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71736111,"identity":"87b385cf-666c-4e10-a828-3007ae2b9fee","added_by":"auto","created_at":"2024-12-18 07:33:38","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1159097,"visible":true,"origin":"","legend":"\u003cp\u003eExample curves of left ventricular systolic circumferential strain for 17 segments acquired from short-axial view at basal-level (a), mid-level (b) and apical-level (c). Then, global circumferential strain was generated by the calculation of the 17-segment of circumferential strain demonstrated in the Bull’s eye plot (d). HR: heart rate, SAX B C: short axis basal circumferential, SAX A C: short axis apical circumferential, SAX B C: short axis middle circumferential, C: circumferential.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5433121/v1/ae86a2affbcf9a9b5ac3bfb2.jpg"},{"id":71736110,"identity":"60ad6658-ce86-426a-b1b4-2dcbc5f55899","added_by":"auto","created_at":"2024-12-18 07:33:38","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":468248,"visible":true,"origin":"","legend":"\u003cp\u003eComparison results of LVSF (a), LVEF (b), GLS (c) and GCS (d) among patients with CALs, patients with NCALs and normal controls at resting condition and peak stress. LVSF: left ventricular shortening fraction, LVEF: left ventricular ejection fraction, GLS: global longitudinal strain, GCS: global circumferential strain, CALs: coronary artery lesions, NCALs: non coronary artery lesions.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5433121/v1/1b3aaf28ba1217598621750e.jpg"},{"id":71735263,"identity":"60effcc5-5eaa-4f06-8d98-e93a25a1b4cd","added_by":"auto","created_at":"2024-12-18 07:25:38","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":562663,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in LVSF (a), LVEF (b), GLS (c) and GCS (d) from baseline to peak stress in patients with CALs, patients with NCALs and normal controls. LVSF: left ventricular shortening fraction, LVEF: left ventricular ejection fraction, GLS: global longitudinal strain, GCS: global circumferential strain, CALs: coronary artery lesions, NCALs: non coronary artery lesions. Δ was defined as the absolute increases in LVEF, GLS and GCS from rest to peak stress.\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5433121/v1/c10466cb1403156e284e6480.jpg"},{"id":71735267,"identity":"151c95e4-64d4-4cfc-8336-27283c67a3b2","added_by":"auto","created_at":"2024-12-18 07:25:38","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":993604,"visible":true,"origin":"","legend":"\u003cp\u003eExamples of GLS reserve in a patient with CALs, a NCALs patient and a normal control subject at rest (a-c) and in response to peak stress (d-f). Note the significant decrease in GLS (from -17.8% to -16.2%) in the patient with CALs and weak improvement of GLS (from -19.2% to -19.8%) in the patient with NCALs when comparing with control (from -20.2% to -26.8%) following peak stress. CALs: coronary artery lesions, NCALs: non coronary artery lesions, GLS: global longitudinal strain.\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5433121/v1/0080092811a36df2bc803628.jpg"},{"id":72640642,"identity":"b45b5570-b19c-44de-9d32-a15c4ecae1d0","added_by":"auto","created_at":"2024-12-30 16:07:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4004694,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5433121/v1/1dc34f7a-e172-4d22-ace6-f7e46ae17e3b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Myocardial contractile reserve impairment in patients with Kawasaki disease during convalescent phase: a study based on two-dimensional speckle-tracking stress echocardiography","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKawasaki disease (KD) characterized by acute systemic vasculitis as the main pathological feature is the leading cause of acquired coronary artery disease in children in developed countries [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, the etiology and pathogenesis of KD is still unclear until now. Coronary artery lesions (CALs) including coronary artery aneurysm, coronary artery stenosis and coronary thrombosis occurred in 20\u0026ndash;25% in patients untreated with intravenous immunoglobulin (IVIG), and the occurrence of CALs can be decreased to 5% in patients timely treated with IVIG [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Nevertheless, 20\u0026ndash;25% of patients are still resistant to IVIG treatment, and the occurrence risk of CALs in these patients is up to 9 times higher than that in IVIG responsive patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough the development of CALs during acute phase received intensive attentions, KD-induced myocarditis in acute phase is more prevalent than CALs which can persist into adulthood [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Myocardial contractile reserve as the principal part of cardiac reserve is an important prognostic indicator for many cardiovascular diseases, early detection of myocardial contractile reserve abnormality is crucial for clinicians to make optimal treatments and improve the prognosis of patients [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, whether the progression of chronic myocardial injury over time in KD patients will lead to myocardial contractile reserve dysfunction during late convalescent phase is not fully delineated.\u003c/p\u003e \u003cp\u003eConventional stress echocardiography is the most used imaging modality in evaluating myocardial contractile reserve of patients, however, conventional parameter left ventricular ejection fraction (LVEF) limited by algorithm of LV geometry assumption cannot be used to detect myocardial contractile reserve subclinical dysfunction [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Compared with conventional stress echocardiography, speckle-tracking stress echocardiography by tracing the displacement characteristics of myocardium during different cardiac cycles is more accurate and sensitive for detecting myocardial contractile reserve abnormality in patients with high feasibility and reproducibility [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Previous studies regarding on the assessment of myocardial contractile reserve in KD patients were mainly focused on short period after illness onset by conventional stress echocardiography [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], nevertheless, the characteristics of myocardial contractile reserve assessed by speckle-tracking stress echocardiography in patients with KD during late convalescent phase are not clear. In this study, we hypothesized that myocardial contractile reserve abnormality existed in KD patients during late convalescent phase, and we aimed to evaluate the feasibility of speckle-tracking stress echocardiography in detecting myocardial contractile reserve abnormality in KD patients.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003ePatients with KD during late convalescent phase who referred to our laboratory for a follow-up echocardiographic examination were consecutively enrolled from January 2018 to January 2024.The control subjects with age and gender matched who presented to our hospital due to cardiac murmur but ultimately diagnosed with structurally and functionally normal hearts were recruited. The inclusion criteria for KD patients were as follows: (1) study population or their guardians gave consent to adenosine triphosphate (AT) stress echocardiography. (2) patients with KD met diagnostic criteria established by the American Heart Association (AHA) with the course of disease at least 4 years; (3) all patients had normal LVEF from disease onset to follow-up period; (4) a combination of high dose of IVIG (2 g/kg) and aspirin (80 mg/kg/day) were given to patients in the acute phase. The exclusion criteria for study population included severe cardiac arrhythmia, severe hypertension, known cardiovascular disease, uncooperative during stress test and low image quality which cannot met offline analysis.\u003c/p\u003e \u003cp\u003ePatients with KD were divided into groups with or without CALs based coronary artery status. CALs was defined as a Z score of \u0026ge;\u0026thinsp;2.5 (SD units from the coronary artery internal diameter normalized for body surface area) in the right coronary artery, left coronary artery and left anterior descending coronary artery according to the recommendation by AHA [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Patients with CALs were confirmed by echocardiography, computed tomography angiography (CTA), cardiac magnetic resonance angiography (CMRA) or coronary artery angiography as appropriate. This study was approved by the Ethics Review Committee of Gansu Provincial Hospital (2018GSPH006), and written informed consent was obtained from the subjects or subjects of their guardians.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAT Stress Protocol\u003c/h3\u003e\u003cp\u003eAT (160 \u0026micro;g/kg/min) used by high-flow infusion pump was intravenously given to the study subjects. The dose of AT was reduced to 140 or 100 mg/kg/min, when mild side effects such as dyspnea occurred in subjects. After 6 minutes of AT infusion, atropine (0.02mg/kg, up to 2mg) was intravenously administered to study subjects to increase heart rate. Blood pressure and electrocardiogram were monitored throughout the test. The termination criteria for test was as follows [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]: (1) age-adjusted target heart rate; (2) systolic blood pressure\u0026thinsp;\u0026gt;\u0026thinsp;240mmHg; (3) abnormal blood pressure response or severe cardiac arrhythmias; (4) severe ischemic electrocardiographic manifestations; (5) occurrence of wall motion abnormality; (6) unable to cooperate during the examination; (7) angina pectoris.\u003c/p\u003e\n\u003ch3\u003eConventional echocardiographic analysis\u003c/h3\u003e\n\u003cp\u003eStudy subjects underwent transthoracic echocardiography using a commercially available ultrasonic machine (Philips EPIQ 7C, Andover, Massachusetts, USA) equipped with a S8-3 or S5-1 transducer as appropriate.\u003c/p\u003e \u003cp\u003eAt rest and under peak stress, all participants underwent comprehensive conventional echocardiography by two experienced investigators who were blinded to status of participants. The digital images consisted of three consecutive cardiac cycles from apical views (apical-4 chamber view, apical-3 chamber view and apical-2 chamber view) and parasternal LV short-axis views (basal-level, mid-level and apical-level) were acquired and stored for subsequent analysis. According to the guideline from the American Society of Echocardiography [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], the LV ejection fraction (LVEF) based on biplane Simpson's method and LV shortening fraction (LVSF) were calculated.\u003c/p\u003e\n\u003ch3\u003eSpeckle-tracking echocardiography analysis\u003c/h3\u003e\n\u003cp\u003eDynamic images with three consecutive cardiac cycles obtained by conventional echocardiography were imported into dedicated strain analysis workstation (Qlab version 10.6, Speckle Tracking, Philips, Andover, Massachusetts, USA). All longitudinal and circumferential strains were obtained by the recommended guideline [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. At rest and under peak stress, the dynamic images for the three standard apical views and the three parasternal short-axis views with the best display of the LV wall were selected. After manual delineation of the endocardial borders of LV, global longitudinal strain (GLS) derived from apical-3 view, apical-2 view and apical-4 view and global circumferential strain (GCS) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed) derived from basal level (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea), middle level (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb) and apical level (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec) were automatically calculated. Segments not suitable for strain analysis due to poor tracking quality were excluded. All measurements were analyzed and interpreted by an experienced investigator blinded to participant diagnosis. Global LV myocardial contractile reserve was defined as the change of values at rest and under peak stress (ΔLVEF, ΔGLS and ΔGCS).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eReproducibility of speckle-tracking echocardiography\u003c/h3\u003e\n\u003cp\u003eTo evaluate intra-observer variability, strain parameters including GLS and GCS from 25 randomly assigned patients were reanalyzed by the same investigator 1 month after the initial analysis. The same patients with the same designated cardiac cycles were analyzed by a second investigator to determine inter- observer variability. All observers were blinded to participant diagnosis.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eSPSS 22.0 (Statistical Product and Service Solutions Company, Chicago) was used for all calculations. All strain parameters were shown in absolute values to facilitate statistical analysis and comparisons between groups. Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation were reported for continuous data. The categorical data were summarized as the count and percentages. The continuous variables were first assessed by Kolmogorov\u0026ndash;Smirnov test for normality. A chi-square analysis was used for categorical data. Comparisons among the CALs group, NCALs group and normal control group were made by one-way ANOVA for normal distributed parameters and by Kruskal-Wallis nonparametric test for nonnormal distribution parameters respectively. Test reliability was assessed by calculating intra-observer variability, inter-observer variability, and intraclass correlation coefficients (ICCs) with a 95% confidence interval [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. A \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eGeneral characteristics in the study population\u003c/h2\u003e \u003cp\u003eThe demographics of KD patients with or without CALs and normal controls were presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. No significant differences regard to baseline parameters among the three groups were found. Of the 63 patients with KD, 44 had normal coronary artery, and 19 had CALs documented by conventional echocardiography, CTA, CMRA or selective artery angiography as appropriate. The age of KD patients CALs were 9.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8 years (range, 3.2\u0026ndash;21.4 years) with a mean follow-up of 7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7 years (range, 4.1\u0026ndash;16.9 years) from the disease onset, and the age of KD patients with NCALs was 9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7 years (range, 3.3\u0026ndash;21.0 years) with a mean follow-up of 7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0 years (range, 4.0\u0026ndash;18.7 years) from the disease onset. The LVEF in KD patients with or without NCALs during the acute phase were normal (64.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3%, 65.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8%, respectively), and no abnormal LV systolic function measurements were detected in the follow-up routine echocardiographic examination.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of patients with KD and normal controls\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCALs group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCALs group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOverall \u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;19\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;44\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;40\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (52.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight, m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass, Kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody surface area, m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index, Kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal cholesterol, mmoL/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL cholesterol, mmoL/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are shown in mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or as number (percentage). KD: Kawasaki disease, CALs: coronary artery lesions, NCALs: non coronary artery lesions.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eConventional echocardiography\u003c/h2\u003e \u003cp\u003eConventional echocardiographic parameters at resting condition and under peak stress are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. When comparing with normal controls, no significant differences regarding to LVSF (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea) and LVEF (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb) in patients with CALs and without CALs were found at rest and under peak stress. In addition, both LVEF (patients with CALs: from 64.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2% to 68.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6%, patients with NCALs: from 66.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6% to 69.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0%, normal controls: from 67.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1% to 71.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5%) and LVSF (patients with CALs: from 35.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6% to 37.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8%, patients with NCALs: from 37.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9% to 39.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0%, normal controls: from 36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1% to 39.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7%) in the three groups increased significantly from rest to peak stress (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), with comparable ΔLVSF (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea) as well as ΔLVEF among three groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). No significant differences were found in baseline characteristics and other conventional echocardiographic parameters among three groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical and conventional echocardiographic parameters in KD patients at resting condition and under peak stress\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCALs group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCALs group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOverall \u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;19\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;44\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;40\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDV, mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e87.4\u0026thinsp;\u0026plusmn;\u0026thinsp;19.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e84.8\u0026thinsp;\u0026plusmn;\u0026thinsp;17.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e81.9\u0026thinsp;\u0026plusmn;\u0026thinsp;20.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e92.0\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e91.2\u0026thinsp;\u0026plusmn;\u0026thinsp;19.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e85.7\u0026thinsp;\u0026plusmn;\u0026thinsp;18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVESV, mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e40.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e39.2\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e37.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e36.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e34.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e32.9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e64.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e66.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e67.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e68.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e69.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e71.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔLVEF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVSF, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e35.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e37.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e37.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e39.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e39.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔLVSF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart rate, bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e89\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e84\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e88\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e120\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e117\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e119\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e108\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e113\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e110\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e100\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e107\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e106\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e69\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e72\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e74\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e65\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e67\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e70\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are presented with mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. KD: Kawasaki disease, CALs: coronary artery lesions, NCALs: non coronary artery lesions, LVEDV: left ventricular end-diastolic volume, LVESV: left ventricular end-systolic volume, LVEF: left ventricular ejection fraction, LVSF: left ventricular shortening fraction, SBP: systolic blood pressure, DBP: diastolic blood pressure.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSpeckle-tracking echocardiography\u003c/h2\u003e \u003cp\u003eResults of speckle-tracking strain-based analysis at rest and under peak stress are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Compared with normal controls, both KD patients with and those without CALs had decreased GLS (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec) and GCS (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed) at resting condition as well as peak stress which were statistically significant difference. When comparing with patients with NCALs, both GLS at rest as well as peak stress (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec) and GCS under peak stress (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed) in CALs group were significantly lower. As expected, all speckle-tracking strain measurements significantly increased in response to AT in normal controls (GLS from 21.68\u0026thinsp;\u0026plusmn;\u0026thinsp;1.50% to 24.96\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13%; GCS from 28.03\u0026thinsp;\u0026plusmn;\u0026thinsp;3.45% to 30.87\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed). However, both GLS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec) and GCS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed) in patients with CALs at peak stress when compared with the resting condition significantly decreased (GLS from 17.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39% to 16.16\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14%; GCS from 24.76\u0026thinsp;\u0026plusmn;\u0026thinsp;3.49% to 22.68\u0026thinsp;\u0026plusmn;\u0026thinsp;3.42%). Although an increase of GLS (from 19.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12% to 20.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09%) and GCS (from 25.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.42% to 26.04\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43%) were observed in KD patients without CALs following stress, improvements were significantly weaker (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed). Contractile reserve parameters including ΔGLS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec) and ΔGCS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed) in CALs patients (ΔGLS \u0026minus;\u0026thinsp;1.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21 vs 3.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; ΔGCS \u0026minus;\u0026thinsp;2.08\u0026thinsp;\u0026plusmn;\u0026thinsp;3.09 vs 2.84\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and NCAL patients (ΔGLS 0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30 vs 3.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020; ΔGCS 1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;3.15 vs 2.84\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027) were both lower than those in normal controls. ΔGLS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec) as well as ΔGCS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed) were significantly reduced in patients with CALs (ΔGLS \u0026minus;\u0026thinsp;1.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21 vs 0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011; ΔGCS \u0026minus;\u0026thinsp;2.08\u0026thinsp;\u0026plusmn;\u0026thinsp;3.09 vs 1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;3.15, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0024) when comparing with patients with NCALs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSpeckle-tracking derived-parameters in KD patients at resting condition and under peak stress\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCALs group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP1\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP2\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNCALs group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP1\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOverall \u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;19\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;44\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;40\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAP4-LS, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e17.24\u0026thinsp;\u0026plusmn;\u0026thinsp;3.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e17.65\u0026thinsp;\u0026plusmn;\u0026thinsp;3.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e20.17\u0026thinsp;\u0026plusmn;\u0026thinsp;2.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e15.36\u0026thinsp;\u0026plusmn;\u0026thinsp;4.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e17.90\u0026thinsp;\u0026plusmn;\u0026thinsp;4.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e23.28\u0026thinsp;\u0026plusmn;\u0026thinsp;4.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔAP4-LS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e-1.88\u0026thinsp;\u0026plusmn;\u0026thinsp;3.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.25\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e3.11\u0026thinsp;\u0026plusmn;\u0026thinsp;3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAP3-LS, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e18.29\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e18.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e18.91\u0026thinsp;\u0026plusmn;\u0026thinsp;2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e18.31\u0026thinsp;\u0026plusmn;\u0026thinsp;3.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e19.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e20.03\u0026thinsp;\u0026plusmn;\u0026thinsp;2.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔAP3-LS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;2.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAP2-LS, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e19.65\u0026thinsp;\u0026plusmn;\u0026thinsp;2.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e20.12\u0026thinsp;\u0026plusmn;\u0026thinsp;2.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e21.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e18.57\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e21.34\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e23.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔAP2-LS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e-1.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;2.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e2.25\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLS, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e17.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e19.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e21.68\u0026thinsp;\u0026plusmn;\u0026thinsp;1.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e16.16\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e20.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e24.96\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔGLS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e-1.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e3.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasal-CS, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e20.97\u0026thinsp;\u0026plusmn;\u0026thinsp;4.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e23.01\u0026thinsp;\u0026plusmn;\u0026thinsp;4.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e23.17\u0026thinsp;\u0026plusmn;\u0026thinsp;4.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e21.03\u0026thinsp;\u0026plusmn;\u0026thinsp;3.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e24.01\u0026thinsp;\u0026plusmn;\u0026thinsp;4.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e26.33\u0026thinsp;\u0026plusmn;\u0026thinsp;4.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔBasal-CS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.06\u0026thinsp;\u0026plusmn;\u0026thinsp;3.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.54\u0026thinsp;\u0026plusmn;\u0026thinsp;3.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e3.16\u0026thinsp;\u0026plusmn;\u0026thinsp;3.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMid-CS, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e26.01\u0026thinsp;\u0026plusmn;\u0026thinsp;4.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e25.96\u0026thinsp;\u0026plusmn;\u0026thinsp;5.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e26.19\u0026thinsp;\u0026plusmn;\u0026thinsp;5.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e25.97\u0026thinsp;\u0026plusmn;\u0026thinsp;4.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e26.93\u0026thinsp;\u0026plusmn;\u0026thinsp;4.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e28.57\u0026thinsp;\u0026plusmn;\u0026thinsp;4.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔMid-CS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e-1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;3.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;3.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e2.38\u0026thinsp;\u0026plusmn;\u0026thinsp;4.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.0024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApical-CS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e27.84\u0026thinsp;\u0026plusmn;\u0026thinsp;5.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e28.10\u0026thinsp;\u0026plusmn;\u0026thinsp;4.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e29.71\u0026thinsp;\u0026plusmn;\u0026thinsp;4.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e24.87\u0026thinsp;\u0026plusmn;\u0026thinsp;4.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e29.03\u0026thinsp;\u0026plusmn;\u0026thinsp;4.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e32.54\u0026thinsp;\u0026plusmn;\u0026thinsp;4.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔApical-CS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e-1.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0067\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.0021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e24.76\u0026thinsp;\u0026plusmn;\u0026thinsp;3.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e25.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e28.03\u0026thinsp;\u0026plusmn;\u0026thinsp;3.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e22.68\u0026thinsp;\u0026plusmn;\u0026thinsp;3.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e26.04\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e30.87\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔGCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e-2.08\u0026thinsp;\u0026plusmn;\u0026thinsp;3.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;3.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e2.84\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.0016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eValues are demonstrated as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, myocardial strain are expressed as absolute values. KD: Kawasaki disease, CALs: coronary artery lesions, NCALs: non coronary artery lesions, AP4: apical four-chamber view, AP3: apical three-chamber view, AP2: apical two-chamber view, LS: longitudinal strain, CS: circumferential strain, GLS: global longitudinal strain, GCS: global circumferential strain.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003eP\u003c/em\u003e1 values for comparison with normal controls.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003eP\u003c/em\u003e2 values for comparison between CALs group and NCALs group.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRepresentative examples of significant decreased GLS reserve in a patient with CALs (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec) and weak improvement of GLS reserve in a patient with no coronary artery involvement (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ed) when comparing with a control subject (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ef) in response to stress.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eReproducibility\u003c/h2\u003e \u003cp\u003eThe reliability analysis for speckle-tracking strain parameters is summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Both the inter-observer and intra-observer concordances were good for GLS and GCS values.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReproducibility analysis for speckle-tracking strain parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eIntra-observer Reproducibility\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eInter-observer reproducibility\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eICCs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eICCs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.981\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.825\u0026ndash;0.992\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.816\u0026ndash;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.815\u0026ndash;0.996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.638\u0026ndash;0.971\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eICCs: intraclass correlation coefficients, CI: confidential interval, GLS: global longitudinal strain, GCS: global circumferential strain.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study demonstrated that myocardial contractile function abnormality existed in late convalescent phase KD patients regardless of CALs despite normal LV systolic function measurements by conventional stress echocardiography, and the subclinical dysfunction of myocardial contractile reserve in patients with CALs was more severe than patients with NCALs. Two-dimensional speckle-tracking stress echocardiography is a promising approach in detecting myocardial contractile reserve impairment in KD patients with high sensitivity and reproducibility.\u003c/p\u003e \u003cp\u003eBoth myocardial systolic dysfunction at resting condition and myocardial contractile reserve abnormality following to stress existed in KD patients irrespective of the presence of CALs. Although coronary artery aneurysm as the most significant CALs complications has received most of the attentions from KD research and clinical practice, KD-induced myocarditis in the acute phase is a far more universal feature than coronary artery involvement which can persist into adulthood [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Yonesaka et al [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] evaluated the long-term histopathology of the myocardium in 38 patients\u0026thinsp;\u0026gt;\u0026thinsp;2 years after disease onset, they found that myocardial changes characterized by inflammatory cell infiltration, interstitial fibrosis, and disarray interstitial fibrosis commonly existed in KD patients. In a large biopsy study of 201 KD patients conducted by Yutani et al[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], myocardial abnormalities including lymphocyte and plasma cell infiltration, myocardial fibrosis, and disarray of myocardial fibers were observed in every patient during acute phase and recovery period. These histopathologic studies suggested persistent myocardial abnormalities after KD. However, there were lack of researches on these chronic myocardial sequelae effects on myocardial contractile reserve in KD patients during late convalescent phase. Consisted with the above mentioned pathological change, our study results demonstrated that myocardial contractile reserve dysfunction occurred in KD patients during late convalescent phase regardless of coronary artery involvement. Tacke et al [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] investigated myocardial contractile function by cardiac magnetic resonance imaging (CMRI) during long-term follow-up of KD, and no significant differences in cardiac function between KD patients and control subjects were observed, which was in consisted with our conventional stress echocardiographic measurements. However, myocardial contractile reserve in response to stress was not included in their study. In our study, though normal conventional echocardiographic parameters including LVEF and ΔLVEF in KD patients irrespective of coronary artery involvement, significantly decreased strains at rest and under stress were found in patients when comparing with control subjects. Our study results suggested that myocardial contractile reserve subclinical abnormality has existed in late convalescent stage KD patients though normal LVEF as well as ΔLVEF, and speckle-tracking stress echocardiography is more sensitive in detecting myocardial reserve dysfunction than conventional echocardiography and CMRI.\u003c/p\u003e \u003cp\u003ePatients with CALs demonstrated more decreased myocardial contractile reserve impairment than those with normal coronary artery. Liu et al [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] performed an ultrastructural study on endomyocardial biopsy specimens obtained during follow-ups of 54 patients, and they demonstrated a significantly increased incidence of myocardial and coronary microvascular lesions in CAL\u003csup\u003e+\u003c/sup\u003e compared to CAL\u003csup\u003e\u0026minus;\u003c/sup\u003e patients, which persisted after convalescent stage even up to 23 years. In an another study [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] exploring matrix remodeling in adolescents and young adults with KD late after onset, myocardial fibrosis biomarker amino-terminal propeptide of type III procollagen (PIIINP) in KD patients with CALs was significantly increased when comparing with patients with NCALs, suggesting more enhanced collagen synthesis in adolescents and young adults with coronary artery involvement late after the onset of KD. Our previous study showed that the increased PIIINP was significantly correlated to decreased GLS as well as GCS in convalescent stage KD patients, which suggested myocardial fibrosis in late after onset is an important reason for leading to myocardial contractile dysfunction [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In our present study, we further demonstrated that myocardial contractile reserve impairment in KD patients with CALs was more severe than patients without CALs which was in accordance with the above pathological findings and biomarker results. In addition, the decreased capacity of coronary artery vasodilation due to the destroyed coronary artery wall structure may also play an important role for severe myocardial contractile reserve abnormality in KD patients with CALs.\u003c/p\u003e \u003cp\u003eEven KD patients without CALs should be given to additional surveillance on myocardial contractile reserve in the long-term follow-up. While CALs as the most significant complication of KD is a risk factor for myocardial ischemia occurrence which is proposed as the only parameter for the cardiovascular risk stratification in KD patients, and an accurate cardiological follow-up is needed for patients with CALs [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, researches regarding on long-term management of children without CALs is limited. According to the American Heart Association (AHA) recommendations, KD patients with no coronary artery involvement are only advised to discharge from cardiology care at 4 to 6 weeks after KD onset, and ongoing cardiology follow-up is not indicated [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], but the recommended cardiology assessment is referred to conventional echocardiography which cannot detect subclinical myocardial dysfunction [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In our study, though normal LVEF and LVSF in KD patients without CALs, significantly decreased GLS and GCS at resting condition and following stress were observed in these patients. Therefore, we suggest that careful long-term follow-up assessment of myocardial contractile reserve function by speckle-tracking stress echocardiography in this subset of KD patients should be warranted. In accordance with our study findings, Zanon et al [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] explored the frequency and risk factors for long-term myocardial perfusion scintigraphy abnormalities in patients with KD using myocardial single-photon emission computed tomography (SPECT), their study results demonstrated that perfusion alterations can be found in KD patients with or without CALs. However, a small sample volume with only 20 patients with normal coronary artery were enrolled in their study, and SPECT examination procedure is time-consuming and radioactive. Compared to SPECT and conventional stress echocardiography, two-dimensional speckle-tracking stress echocardiography could be an alternative way to provide a new approach for monitoring possible myocardial reserve abnormality noninvasively with high sensitivity and accuracy. Based on our study results, we preliminary raised an important issue regarding the management and follow-up of KD patients during convalescent stage, especially for patients with no coronary artery involvement.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eBesides the inherent shortcomings of two-dimensional speckle-tracking echocardiography, there are several additional limitations in our study. First, the myocardial contractile reserve course over time cannot be evaluated due to the lack of speckle-tracking stress echocardiography data of the acute phase. Second, compared with the reported literature of CALs in KD (\u0026lt;\u0026thinsp;10%) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], the study population contains a high percentage of occurrence of patients with CALs. One possible explanation for this difference may be the referral bias because of more severe patients referred to our cardiology center, and patients with CALs need more frequent follow-up echocardiographic examinations. Finally, this was a single center research enrolled a small number of patients with relatively short follow-up, prospective, multicenter with larger patient populations and longer follow-up studies were needed to validate our findings.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eSubclinical abnormality of myocardial contractile reserve existed in KD patients during late convalescent phase regardless of CALs, which can be detected by speckle-tracking stress echocardiography though normal LVEF and ΔLVEF. Even patients without coronary artery involvement need an additional surveillance on myocardial contractile reserve in the long-term follow-up. These novel findings by speckle-tracking stress echocardiographic analysis may have more valuable clinical implications for better understanding and long-term management of KD patients during late convalescent stage when comparing with conventional stress echocardiography.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eHaiyong Wang: Design of study, data analysis and interpretation, drafting article, critical revision of article, approval of article, statistics, data collection. Ruiling Yan: Design of study, data analysis and interpretation, drafting article, critical revision of article, approval of article. All authors reviewed the manuscript.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStatement of financial support:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere is none financial support for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure statement:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere are none authors\u0026rsquo; financial ties to products in the study or potential/perceived conflicts of interest on the cover page.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMcCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E, American Heart Association Rheumatic Fever E, Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Y, Council C, Stroke N (2017) Council on Cardiovascular S, Anesthesia, Council on E, Prevention. Diagnosis, treatment, and long-term management of kawasaki disease: A scientific statement for health professionals from the american heart association. Circulation. ;135(17):e927-e999\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFurusho K, Sato K, Soeda T, Matsumoto H, Okabe T, Hirota T, Kawada S (1983) High-dose intravenous gammaglobulin for kawasaki disease. Lancet 2(8363):1359\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWallace CA, French JW, Kahn SJ, Sherry DD (2000) Initial intravenous gammaglobulin treatment failure in kawasaki disease. Pediatrics 105(6):E78\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuthusami P, Luining W, McCrindle B, van der Geest R, Riesenkampff E, Yoo SJ, Seed M, Manlhiot C, Grosse-Wortmann L (2018) Myocardial perfusion, fibrosis, and contractility in children with kawasaki disease. 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Circulation 91(1):122\u0026ndash;128\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOk\u0026ccedil;\u0026uuml;n B, Ozhan H, Baran T, Saltik L, Mutlu H, Uner S, K\u0026uuml;\u0026ccedil;\u0026uuml;koğlu MS (2002) Utility of dobutamine stress echocardiography in kawasaki disease: A case report and review of the literature. Turk J Pediatr 44(3):251\u0026ndash;253\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePellikka PA, Arruda-Olson A, Chaudhry FA, Chen MH, Marshall JE, Porter TR, Sawada SG (2020) Guidelines for performance, interpretation, and application of stress echocardiography in ischemic heart disease: From the american society of echocardiography. J Am Soc Echocardiography: official publication Am Soc Echocardiography 33(1):1\u0026ndash;41e48\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitchell C, Rahko PS, Blauwet LA, Canaday B, Finstuen JA, Foster MC, Horton K, Ogunyankin KO, Palma RA, Velazquez EJ (2018) Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: Recommendations from the american society of echocardiography. Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVoigt JU, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R, Pedri S, Ito Y, Abe Y, Metz S, Song JH, Hamilton J, Sengupta PP, Kolias TJ, d'Hooge J, Aurigemma GP, Thomas JD, Badano LP (2015) Definitions for a common standard for 2d speckle tracking echocardiography: Consensus document of the eacvi/ase/industry task force to standardize deformation imaging. 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Clin Chem 54(11):1815\u0026ndash;1822\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Tong M, Mu J, Wu T, Ruan L (2021) Assessment of myocardial function by two-dimensional speckle tracking echocardiography in patients with kawasaki disease: A mid-term follow-up study. Coron Artery Dis 32(6):500\u0026ndash;508\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatsi V, Georgiopoulos G, Laina A, Koutli E, Parissis J, Tsioufis C, Nihoyannopoulos P, Tousoulis D (2017) Left ventricular ejection fraction as therapeutic target: Is it the ideal marker? Heart Fail Rev 22(6):641\u0026ndash;655\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZanon G, Zucchetta P, Varnier M, Vittadello F, Milanesi O, Zulian F (2009) Do kawasaki disease patients without coronary artery abnormalities need a long-term follow-up? A myocardial single-photon emission computed tomography pilot study. J Paediatr Child Health 45(7\u0026ndash;8):419\u0026ndash;424\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"myocardial contractile reserve, two-dimensional speckle-tracking echocardiography, late convalescent stage","lastPublishedDoi":"10.21203/rs.3.rs-5433121/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5433121/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePersistent myocardial impairment proved by histopathologic studies universally existed in patients with Kawasaki disease (KD), however, the long-term effects on myocardial contractile reserve in KD patients, especially on patients without coronary artery lesions (CALs), is still unknown. The aim of this study was to investigate myocardial contractile reserve in KD patients during late convalescent stage by speckle-tracking adenosine triphosphate (AT) echocardiography.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 63 antecedent KD patients at least 4 years after the disease onset and 40 age- and gender-matched normal controls were prospectively enrolled. Based on coronary artery status, patients were further divided into CALs group and non-CALs (NCALs) group. Left ventricular ejection fraction (LVEF), speckle-tracking derived-global longitudinal strain (GLS) and global circumferential strain (GCS) were evaluated at rest and during AT peak stress. Myocardial contractile reserve parameters including ΔLVEF, ΔGLS and ΔGCS were defined as the absolute increases in LVEF, GLS and GCS from rest to peak stress.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eKD patients regardless of CALs had lower GLS and GCS than normal controls at resting condition. Significant decreases in ΔGLS and ΔGCS were observed in patients with CALs compared to normal controls under peak stress. While ΔGLS and ΔGCS increased in patients without CALs following stress, improvements were significantly weaker than those in normal controls. However, no significant differences in LVEF at rest and ΔLVEF under peak stress between KD patients irrespective of CALs and normal controls were found. In additional, when comparing with patients with NCALs, patients with CALs had lower GLS and GCS at rest, lower ΔGLS and ΔGCS in response to stress.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eSubclinical abnormality of myocardial contractile reserve existed in KD patients during late convalescent phase. Even patients without CALs need an additional surveillance on myocardial contractile reserve in the long-term follow-up. These novel findings by speckle-tracking stress echocardiographic analysis may provide more valuable clinical implications for better understanding and long-term management of such patients.\u003c/p\u003e","manuscriptTitle":"Myocardial contractile reserve impairment in patients with Kawasaki disease during convalescent phase: a study based on two-dimensional speckle-tracking stress echocardiography","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-18 07:25:33","doi":"10.21203/rs.3.rs-5433121/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-21T22:27:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-21T14:38:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-19T21:24:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"163160511447478401096604934831835314727","date":"2024-11-17T04:30:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66926384833861083839964636150291872447","date":"2024-11-16T18:18:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-14T20:30:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-14T11:38:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-14T11:36:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Cardiology","date":"2024-11-11T15:03:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8bcb9e55-7d88-492e-80a2-abad5a8a4cfd","owner":[],"postedDate":"December 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-30T16:01:49+00:00","versionOfRecord":{"articleIdentity":"rs-5433121","link":"https://doi.org/10.1007/s00246-024-03751-y","journal":{"identity":"pediatric-cardiology","isVorOnly":false,"title":"Pediatric Cardiology"},"publishedOn":"2024-12-27 15:57:34","publishedOnDateReadable":"December 27th, 2024"},"versionCreatedAt":"2024-12-18 07:25:33","video":"","vorDoi":"10.1007/s00246-024-03751-y","vorDoiUrl":"https://doi.org/10.1007/s00246-024-03751-y","workflowStages":[]},"version":"v1","identity":"rs-5433121","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5433121","identity":"rs-5433121","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}