Segmental and global longitudinal strain differences between Kawasaki disease and multi-system inflammatory syndrome in children.

BACKGROUND: Multi-system inflammatory syndrome in children and Kawasaki disease have overlapping clinical features but comparative echocardiographic studies are lacking. METHODS: We reviewed echocardiography findings of all multi-system inflammatory syndrome cases between 1st April and 31st July, 2020 and typical Kawasaki disease patients with coronary arteries abnormalities consecutively followed between 1st October, 2016 and June 30th, 2019. RESULTS: We included 40 multi-system inflammatory syndrome children (25 males, 62.5%) and 45 Kawasaki disease patients (31 males, 68.9%) at a mean age of 6.4 years old and 8 years old, respectively. Four out of 40 multi-system inflammatory syndrome children had coronary arteries abnormalities. Left ventricle ejection fraction was normal in both groups. Global longitudinal strain was normal although Kawasaki disease group had significantly lower values (-20.0 versus -21.7%; p = 0.02). Basal segments were the most affected in Kawasaki disease patients with significant differences in the basal anterior, anterolateral, and anteroseptal strain: -18.2 versus -23.0% (p = 0.002), -16.7 versus -22.0% (p < 0.001), -16.7 versus -19.5% (p = 0.034), respectively. The basal anterolateral and anteroseptal segments in Kawasaki disease patients were the only ones with an absolute reduction of longitudinal strain (-16.7% both) consistent with the greater left main coronary involvement in this cohort. CONCLUSIONS: Our findings are consistent with the transient cardiac involvement in multi-system inflammatory syndrome, as opposed to the subtle and chronic myocardial involvement in Kawasaki disease children with coronary arteries abnormalities. We speculate that the mechanism of cardiac impairment in the few multi-system inflammatory syndrome children with reduced global longitudinal strain is not related to coronary arteries abnormalities.

Total isovolumic time relates to exercise capacity in patients with transposition of the great arteries late after atrial switch procedures.

BACKGROUND: Systemic right ventricular systolic dysfunction is common late after atrial switch surgery for transposition of the great arteries. Total isovolumic time is the time that the ventricle is neither ejecting nor filling and is calculated without relying on geometric assumptions. We assessed resting total isovolumic time in this population and its relationship to exercise capacity. METHODS: A total of 40 adult patients with transposition of the great arteries after atrial switch - and 10 healthy controls - underwent transthoracic echocardiography and cardiopulmonary exercise testing from January, 2006 to January, 2009. Resting total isovolumic time was measured in seconds per minute: 60 minus total ejection time plus total filling time. RESULTS: The mean age was 31.6 plus or minus 7.6 years, and 38.0% were men. There were 16 patients (40%) who had more than or equal to moderate systolic dysfunction of the right ventricle. Intra- and inter-observer agreement was good for total isovolumic time, which was significantly prolonged in patients compared with controls (12.0 plus or minus 3.9 seconds per minute versus 6.0 plus or minus 1.8 seconds per minute, p-value less than 0.001) and correlated significantly with peak oxygen consumption (r equals minus 0.63, p-value less than 0.001). The correlation strengthened (r equals minus 0.73, p-value less than 0.001) after excluding seven patients with exercise-induced cyanosis. No relationship was found between exercise capacity and right ventricular ejection fraction or long-axis amplitude. CONCLUSION: Resting isovolumic time is prolonged after atrial switch for patients with transposition of the great arteries. It is highly reproducible and relates well to exercise capacity.

Echocardiographic Normal Reference Ranges for Non-invasive Myocardial Work Parameters in Pediatric Age: Results From an International Multi-Center Study.

Aims: This international multi-center study aimed to demonstrate the feasibility and reliability of non-invasive myocardial work (MW) parameters in the pediatric population, and to provide normal reference ranges for this useful echocardiographic tool in this specific subset of patients. Methods and Results: In this retrospective multi-center study involving three pediatric laboratories, 150 healthy children and adolescents (mean age of 10.6 ± 4.5, 91 males) were enrolled. A complete echocardiographic examination has been performed, including global longitudinal strain (GLS) assessment. The following parameters of non-invasive MW have been obtained through a dedicated software: global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE), using left ventricular (LV) strain loops and non-invasive brachial artery cuff pressure values. The lowest expected values were for GWI 1,723 mmHg% in males and 1,682 mmHg% in females, for GCW 2,089 and 2,106 mmHg%, for GWE 95.9 and 95.5% whereas the highest expected value for GWW was 78 mmHg% in men and 90 mmHg% in women. The univariable and multivariable analysis showed significant associations between either GWI or GCW with SBP (ß coefficient = 0.446, p < 0.001; ß coefficient = 0.456, p < 0.001, respectively) and LV GLS (ß coefficient = -0.268, p = 0.001; ß coefficient = -0.233, p = 0.003, respectively). Inter- and intra-observer variability showed good reproducibility of non-invasive MW parameters. Conclusion: Non-invasive MW parameters were feasible and reliable in the pediatric population. This study provided normal reference ranges of these useful echocardiographic indices.

Abnormal myocardial work in children with Kawasaki disease.

Kawasaki disease (KD) can be associated with high morbidity and mortality due to coronary artery aneurysms formation and myocardial dysfunction. Aim of this study was to evaluate the diagnostic performance of non-invasive myocardial work in predicting subtle myocardial abnormalities in Kawasaki disease (KD) children with coronary dilatation (CADL). A total of 100 patients (age 8.7 ± 5 years) were included: 45 children with KD and CADL (KD/CADL) (Z-score > 2.5), 45 age-matched controls (CTRL) and, finally, an additional group of 10 children with KD in absence of coronary dilatation (KD group). Left ventricular (LV) systolic function and global longitudinal strain (GLS) were assessed. Global myocardial work index (MWI) was calculated as the area of the LV pressure-strain loops. From MWI, global Constructive Work (MCW), Wasted Work (MWW) and Work Efficiency (MWE) were estimated. Despite normal LV systolic function by routine echocardiography, KD/CADL patients had lower MWI (1433.2 ± 375.8 mmHg% vs 1752.2 ± 265.7 mmHg%, p < 0.001), MCW (1885.5 ± 384.2 mmHg% vs 2175.9 ± 292.4 mmHg%, p = 0.001) and MWE (994.0 ± 4.8% vs 95.9 ± 2.0%, p = 0.030) compared to CTRL. Furthermore, MWI was significantly reduced in children belonging to the KD group in comparison with controls (KD: 1498.3 ± 361.7 mmHg%; KD vs CTRL p = 0.028) and was comparable between KD/CADL and KD groups (KD/CADL vs KD p = 0.896). Moreover, KD/CADL patients with normal GLS (n = 38) preserved significant differences in MWI and MCW in comparison with CTRL. MWI, MCW and MWE were significantly reduced in KD children despite normal LVEF and normal GLS. These abnormalities seems independent from CADL. Thus, in KD with normal LVEF and normal GLS, estimation of MWI may be a more sensitive indicator of myocardial dysfunction.

Serial changes in longitudinal strain are associated with outcome in children with hypoplastic left heart syndrome.

INTRODUCTION: Hypoplastic Left Heart Syndrome (HLHS) has high mortality and morbidity and systemic right ventricle (RV) dysfunction may play a key-role. Study aim is to evaluate the accuracy of speckle-tracking echocardiographic (STE) assessment of RV deformation and 2D standard echo parameters in predicting outcome in HLHS patients. METHODS: We studied 27 HLHS patients (17 male) who successfully completed Norwood palliation. All the patients underwent in-hospital interstage stay. Serial echocardiographic assessment was performed: baseline, one-month after Norwood, three-months after Norwood, one-week before bidirectional cavopulmonary anastomosis (BCPA) and two-months after BCPA. From the apical view we measured: tricuspid annulus peak systolic excursion (TAPSE), fractional area change (FAC), longitudinal strain (LS) and strain rate (LSR). RESULTS: After a mean follow-up of 1.18 (± 1.16) years, 8 out of 27 of the included patients met the composite endpoint of death/heart transplant (HT). At pre-Norwood assessment, there was no difference in echo measurements between survivors and patients with events. In death/HT group TAPSE and LS declined already one-month after Norwood procedure: TAPSE ≤5 mm had good sensitivity (85.71%) and moderate specificity (63.16%) for death/HT (AUC = 0.767); a decrease of LS > 8.7% vs baseline showed 100% sensitivity and 84.21% specificity for death/HT (AUC = 0.910). At multivariate analysis, one-month-after-Norwood LS drop >8.7% was the best predictor of outcome (P = 0.01). CONCLUSIONS: RV dysfunction in HLHS carries prognostic value. Our findings encourage serial measurements of RV function to identify the subgroup of HLHS patients at higher risk. In our experience, ∆ LS showed the best predictive value.

Echocardiography and cardiac magnetic resonance in children with repaired tetralogy of Fallot: New insights in cardiac mechanics and exercise capacity.

BACKGROUND: Pulmonary regurgitation (PR) and right ventricular (RV) dilatation and disfunction are common in patients with repaired Tetralogy of Fallot (r-TOF). AIMS: To compare Echo data with the gold standard CMR in a paediatric population of r-TOF with significant PR, to assess the reliability of standard and advanced echo parameters. In addition, to evaluate their correlation with peak oxygen consumption (VO2). METHODS AND RESULTS: All patients underwent standard echo-Doppler study, speckle tracking analysis, and CMR to assess PR and RV size and function. Thirty-six patients underwent also cardiopulmonary exercise test. Fourty-six patients (aged 13.7 ± 3.0) were included. Echo derived RV areas correlated with CMR RV volumes (p < .0001, r = 0.72). RV end-diastolic area > 21.9 cm2/m2 had a good sensitivity (83.3%) and specificity (73.5%) to identify a RV end-diastolic volume ≥ 150 ml/m2. RVEF was preserved in all patients, while TAPSE was reduced in 78.2% and RVGLS in 60.8%. Flow-reversal in pulmonary branches showed a sensitivity of 95.8% and a specificity of 59.1% to identify CMR pulmonary regurgitant fraction (RF) ≥ 35%. None of the CMR parameters correlated with peak VO2. Among the Echo data only right atrial strain (RAS) correlated with peak VO2. CONCLUSION: In children, flow-reversal in pulmonary branches identifies hemodynamically significant RF with a good sensitivity but poor specificity. RV area by echocardiogram is a valid first-line parameter to screen RV dilation. RV longitudinal systolic dysfunction coexists with a still preserved EF. RAS correlates strongly with peak VO2 and should be added in their follow up.

Left Atrial Strain to Identify Diastolic Dysfunction in Children with Cardiomyopathies.

BACKGROUND: Left ventricular (LV) diastolic dysfunction (DD) carries worse prognosis in childhood. 2-dimensional (2-D) left atrial (LA) strain accurately categorizes DD in adults but its role in children is unknown. Thus, the aim of this study is to investigate whether LA strain and strain rate could diagnose and classify DD in children with dilated (CMD), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies (CM). METHODS AND RESULTS: The study includes 136 children (aged 8.8 ± 6 years): 44 with DCM, 40 with HCM, 7 with RCM and 45 healthy controls (CTRL). They underwent standard echocardiographic examination and 2-D speckle-tracking analyses (LV longitudinal peak systolic strain (LS), LA peak systolic strain and strain rate). No significant differences in mitral E/A and pulmonary S/D ratios were observed among the four groups. Although E/E' and indexed left atrial volumes were found to be significantly higher in HCM, DCM and RCM compared to CTRL (p < 0.001), they showed no significant difference among the three CM groups. LV LS values were significantly reduced in CM vs CTRL (p < 0.001) and in DCM vs HCM (p < 0.01), with no other differences between the remaining groups. LA peak systolic strain and strain rate values showed a steady and significant decrease with worsening of DD. Receiver Operating Characteristics (ROC) curves showed area under the curve of 0.976 (p < 0.001) for LA strain and 0.946 (p < 0.001) for LA strain rate, to distinguish CTRL from CMs. CONCLUSIONS: LA strain and strain rate could be a promising tool to better understand and classify DD in children with cardiomyopathies, opening the way to its clinical use.

Left Ventricular Twist Mechanics to Identify Left Ventricular Noncompaction in Childhood.

BACKGROUND: Left ventricular noncompaction cardiomyopathy (LVNC) is associated with poor clinical outcome in childhood. Standard diagnostic criteria are still controversial, especially in young patients. Recent studies in adults demonstrated that left ventricular (LV) twist is abnormal in LVNC, but it has not been investigated in pediatric patients to date. Our aim was to assess LV cardiac mechanics, LV twist, and the prevalence of rigid body rotation, using 2-dimensional speckle tracking echocardiography, in young patients with LVNC and LV hypertrabeculation. METHODS: Forty-seven children (age range: 0-18 years) were assessed for suspected LVNC. All patients underwent 2-dimensional speckle tracking echocardiography and cardiovascular magnetic resonance imaging at 1.5 Tesla (T). Twenty-three patients fulfilled the cardiovascular magnetic resonance imaging diagnostic criteria for LVNC (LVNC group), while the remaining 24 did not and were included in the LV hypertrabeculation group. Forty-seven age- and sex-matched healthy volunteers were used as controls. RESULTS: The average LV twist was significantly reduced in LVNC compared with control and LV hypertrabeculation. Rigid body rotation was recognized in 13 (56%) children with LVNC and in 1 (4%) child with LV hypertrabeculation and a strong family history for LVNC. Multivariable analysis demonstrated that LV twist is an independent predictor of LVNC ( P=0.006; coefficient=0.462). The receiver operating characteristics curve showed that LV twist had optimal predictive value to discriminate patients with LVNC (cutoff value <5.8°; sensitivity, 82%; specificity, 92%; area under the curve=0.914). CONCLUSIONS: LV twist has good predictive value in diagnosing LVNC in young patients. Our findings strongly support the routine use of 2-dimensional speckle tracking echocardiography in the evaluation of young patients with suspected LVNC.

Pure Aortic Regurgitation in Pediatric Patients.

Aortic regurgitation (AR) continues to be an important cause of morbidity and mortality in pediatric patients. Although echocardiographic parameters are well established for the adults, there are no clear cut-off values for AR severity in children. Cardiac magnetic resonance (CMR) imaging is considered a "gold standard" for a quantitative evaluation of the AR, but it is not widely available. This study assesses which echo parameter can accurately define AR severity as assessed by CMR in pediatric patients. A total of 27 pediatric patients (12 ± 3 years, range 6 to 18 years) with different degree of AR underwent echo assessment within an average of 35 days from CMR. CMR included phase-contrast velocity-encoded imaging for the measurement of regurgitant fraction (RF). Severe AR was defined as RF >33%. Echo evaluation included vena contracta, pressure half time, the ratio between the AR jet and the left ventricular outflow tract diameter (jet/left ventricular outflow tract), presence of holodiastolic reversal flow in abdominal aorta, the ratio between the velocity-time integral of the reversal flow over the forward flow in descending aorta (echoRF). Among the studied parameters, the strongest predictor of severe AR, as assessed by CMR, was echoRF. Receiver-operating characteristic curve showed, for a cutoff >0.38, an area under the curve of 0.886 (p <0.0001), a sensitivity of 71%, and a specificity of 100%. Correlation coefficient between echoRF and RF was R = 0.929 (p <0.0001). In conclusion, echoRF is a strong echo-Doppler marker of severe AR in the pediatric population. This parameter should be routinely added in the standard echo evaluation of pediatric patients with AR.

Prognostic value of echocardiographic parameters in pediatric patients with Ebstein's anomaly.

BACKGROUND: Accurate risk stratification of patients with Ebstein's anomaly (EA) is crucial. Aim of the study was to assess the prognostic value of echocardiography, including 2D speckle tracking (STE) derived myocardial deformation indices, for predicting outcome in pediatric and young adult unrepaired EA patients. METHODS: Fifty consecutive EA patients (1 day-18 years, 52% males) underwent echocardiography and were followed for a mean follow-up of 60 ±â€¯41 months for clinical outcome (ventricular tachyarrhythmia, heart failure, need for surgery and/or death). Clinical and instrumental features of EA patients with stable disease were compared with those of EA patients with progressive disease. RESULTS: Twenty-four (48%) EA patients had progressive disease. A more severe grade of tricuspid valve (TV) displacement [59.7 mm/m2 (IQR 27.5-83) vs 28.4 mm/m2 (IQR 17.5-47); p = 0.002], a lower functional right ventricle (RV) fractional area change (FAC) (29.2 ±â€¯7.7% vs 36.7 ±â€¯9.6%; p = 0.004), a higher Celermajer index [0.8 (IQR 0.7-0.98) vs 0.55 (IQR 0.4-0.7); p = 0.000], a lower functional RV-longitudinal strain (-10.2 ±â€¯6.2% vs -16.2 ±â€¯7.3%; p = 0.003) and a lower right atrium peak systolic strain (RA-PALS) (25.2 ±â€¯13.5% vs 36.3 ±â€¯12.5%; p = 0.004) were detected in progressive disease group compared to stable one, respectively. Functional RV-FAC and RA-PALS were independent predictors of progressive disease at multivariate analysis. CONCLUSION: Our study demonstrated for the first time the prognostic role of RV-FAC and RA-PALS in a long-term follow-up of EA young patients. A complete echocardiographic evaluation should be regular part in the evaluation and risk-stratification of EA children.

Geometry of the left ventricular outflow tract in fixed subaortic stenosis and intact ventricular septum: an echocardiographic study in children and adults.

OBJECTIVE: We compared the echocardiographic geometry of the preoperative and postoperative left ventricular outflow tract in children and adults with isolated fixed subaortic stenosis with age- and weight-matched controls to elucidate whether the geometry can be modified when surgical intervention is performed at a younger age. METHODS: The mitral-aortic valve distance, aortic valve diameter, aorto-left ventricular septal angle, degree of aortic valve dextroposition, aortic valve-subaortic stenosis distance, width of left ventricular outflow tract, left ventricle wall thickness, and septal thickness were determined preoperatively and postoperatively in 21 patients and 21 controls. The measurements were indexed to body surface area. Patients were divided into 3 age groups: group 1 comprised 9 patients aged 1 to 10 years, group 2 comprised 8 patients aged 11 to 20 years, and group 3 comprised 4 patients aged 21 years or more. RESULTS: Compared with controls, patients had a significantly wider mitral-aortic separation (group 1, P = .003; group 2, P = .02), a steeper aortoseptal angle (group 1, P = .02; group 3, P = .03), a smaller left ventricular outflow tract width (group 1, P = .003; group 2, P = .01), a marked aortic valve dextroposition (groups 1 and 3), an increased left ventricle wall thickness (group 1, P = .03), and an increased septal thickness (group 1, P = .01). There was a significant difference between preoperative and postoperative values in aortoseptal angle and left ventricular outflow tract width in patients up to 10 years of age (P = .02 and P = .01, respectively). CONCLUSIONS: Hearts with isolated subaortic stenosis have abnormal left ventricular outflow tract geometry that postoperatively showed changes in left ventricular outflow tract width and aortoseptal angle. Compared with controls, the aortoseptal angle does not "normalize" when surgery is performed in older patients, suggesting that left ventricular outflow tract geometry may be remodeled in younger patients.