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Background: Clinical manifestations of children's coronavirus disease-2019 (COVID-19) were initially considered less severe compared with adult patients. However, there is now increasing evidence of a "long-tail" of COVID-19 related symptoms lasting for several months after recovery from the acute infection. Long COVID-19-related symptoms and mechanisms are poorly characterized and understood, with several phenotypes reported, often driven by long-term tissue damage (such as lung, heart and brain) and pathological inflammation due to viral persistence and/or immune deregulation. Purpose(s): The objective of this study was to evaluate atrio-ventricular mechanics, by means of two-dimensional speckle-tracking echocardiography, in previously healthy children recovered from asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term followup. Method(s): We analysed a cohort of 157 paediatric patients, mean age 7 +/- 4 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study 148 +/- 68 days after diagnosis. One hundred seven age, sex, and body surface area comparable healthy subjects were used as control group. Result(s): Left ventricular ejection fraction was within normal limits in postCOVID-19 cases and CTRL with no significant differences between the two groups (postCOVID-19: 65.6 +/- 4% vs CTRL: 65.0 +/- 5%, p = 0.182).Left ventricular (LV) global longitudinal strain (postCOVID-19: -20.5 +/- 2.9%;CTRL: -21.8 +/- 1.7%;p < 0.001) was significantly reduced in cases compared with CTRLs. An amount of 11 (7%) postCOVID-19 cases showed impaired GLS values < -17% and 95 subjects (60%) presented with a strain lower than -16% in more than 2 segments. These subjects did not show any difference regarding symptoms or serological findings. Moreover, GLS was significantly reduced in children with disease's onset during the second wave of COVID-19 pandemic, compared with those during the first wave (second wave: -20.2 +/- 2.6%;first wave: -21.2 +/- 3.4%;p = 0.048). Finally, peak left atrial systolic strain was within the normal range in the postCOVID-19 group with no significant differences compared to CTRL (postCOVID-19: 49.1 +/- 12%;CTRL: 49.5 +/- 18%). Conclusion(s): SARS-CoV-2 infection may affect left ventricular deformation in children despite an asymptomatic or only mildly symptomatic acute illness. Our data show an amount of 60% of children, recovering from asymptomatic or mildly symptomatic COVID-19, with still mild subclinical systolic cardiac impairment in the midand long-term follow-up after the infection. This subtle impairment was seen to be worse in children recovering from the second wave of COVID-19 compared to the first one. A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes.
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Background: Clinical manifestations of children's coronavirus disease-2019 (COVID-19) were initially considered less severe compared with adult patients. However, there is now increasing evidence of a “long-tail” of COVID-19 related symptoms lasting for several months after recovery from the acute infection. Long COVID-19-related symptoms and mechanisms are poorly characterized and understood, with several phenotypes reported, often driven by long-term tissue damage (such as lung, heart and brain) and pathological inflammation due to viral persistence and/or immune deregulation. Purpose: The objective of this study was to evaluate atrio-ventricular mechanics, by means of two-dimensional speckle-tracking echocardiography, in previously healthy children recovered from asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term follow-up. Methods: We analysed a cohort of 157 paediatric patients, mean age 7±4 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study 148±68 days after diagnosis. One hundred seven age, sex, and body surface area comparable healthy subjects were used as control group. Results: Left ventricular ejection fraction was within normal limits in postCOVID-19 cases and CTRL with no significant differences between the two groups (postCOVID-19: 65.6±4% vs CTRL: 65.0±5%, p=0.182).Left ventricular (LV) global longitudinal strain (postCOVID-19: −20.5±2.9%;CTRL: −21.8±1.7%;p<0.001) was significantly reduced in cases compared with CTRLs. An amount of 11 (7%) postCOVID-19 cases showed impaired GLS values < −17% and 95 subjects (60%) presented with a strain lower than −16% in more than 2 segments. These subjects did not show any difference regarding symptoms or serological findings. Moreover, GLS was significantly reduced in children with disease's onset during the second wave of COVID-19 pandemic, compared with those during the first wave (second wave: −20.2±2.6%;first wave: −21.2±3.4%;p=0.048). Finally, peak left atrial systolic strain was within the normal range in the postCOVID-19 group with no significant differences compared to CTRL (postCOVID-19: 49.1±12%;CTRL: 49.5±18%). Conclusions: SARS-CoV-2 infection may affect left ventricular deformation in children despite an asymptomatic or only mildly symptomatic acute illness. Our data show an amount of 60% of children, recovering from asymptomatic or mildly symptomatic COVID-19, with still mild subclinical systolic cardiac impairment in the mid- and long-term follow-up after the infection. This subtle impairment was seen to be worse in children recovering from the second wave of COVID-19 compared to the first one.A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes. Funding Acknowledgement: Type of funding sources: None.
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Background and Aim: Growing evidence has documented a severe systemic hyperinflammation syndrome affecting children previ-ously exposed to SARS-CoV-2, known as Multisystem Inflammatory Syndrome in Children (MIS-C). Cardiovascular manifestations in MIS-C are frequent (34%-82%). The aim of our study was to describe the early and late cardiac abnormalities in patients with MIS-C, assessed by standard echocardiography, speckle tracking echocardiography (STE), and cardiac MRI (CMR). Method(s): 32 consecutive patients (21M, 11F), mean age 8.25 +/- 4years (range 1.3-17.7), with confirmed MIS-C diagnosis were enrolled in this study. Clinical, laboratory and microbiological data were collected. At disease onset, all children underwent standard transthoracic echocardiography, STE with analysis of left ventricle global longitudinal strain (GLS) and 23 (75%) of them performed CMR. Patients underwent complete cardiological evaluation, including echocardiography and STE at two months (T1) and six months (T2) after diagnosis. CMR was repeated at six months after diagnosis. Result(s): Cardiovascular symptoms were present in 45.8% of cases. Thirteen children (40.6%) shared Kawasaki Disease-like symp-toms, and 5 (15.6%) needed ICU admission. Early survival was 100%. All patients showed an hyperinflammatory state. Tn-I was elevated in 20 (62.5%) and BNP in 28 (87.5%) patients. Mean LVEF at baseline was 58.8 +/- 10% with 10 patients (31%) below 55%. STE showed reduced mean LV GLS (-17.4 +/- 4%). On CMR, LGE with nonischemic pattern was evident in 8/23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 +/- 7.5 vs. 58.8 +/- 10.6%, p value 0.044) with only three patients (10%) below <= 55% at T1 and one (4%) at T2. LV GLS remained impaired at T1 (-17.2 +/- 2.7 vs.-17.4 +/- 4, p value 0.71), and significantly improved at T2 (-19 +/- 2.6% vs.-17.4 +/- 4%, p value 0.009). LV GLS was impaired (gt;-18%) in 53% of patients at baseline and T1, while only 13% showed persistent LV GLS reduc-tion at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. Conclusion(s): Even though, early cardiac involvement significantly improves during follow-up, subclinical myocardial damage seems to be still detectable 6 months follow up in one third of MIS-C patients.
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Background and Aim: Clinical manifestations of children's corona-virus disease-2019 (COVID-19) are generally considered less severe compared with adult patients. The objective of this study was to evaluate cardiac involvement in healthy children with asymptomatic or mildly symptomatic severe acute respiratory syn-drome coronavirus-2 (SARS-CoV-2) infection. Method(s): We analysed a cohort of 210 paediatric patients, mean age 7 +/- 4 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study 138 +/- 65 days after diagnosis. Seventy-two age, sex, and body sur-face area comparable healthy subjects were used as control group. Result(s): Left ventricular ejection fraction was within normal limits but significantly lower in the cases group compared to controls (62 +/- 4% vs. 65 +/- 5%;P = 0.012). Left ventricular (LV) global longi-tudinal strain (-20,91 +/- 2,83 % vs.-22,73 +/- 2,51 %;P lt;0.001) was significantly reduced in cases compared with CTRLs. Regional LV strain analysis showed a significant reduction of the LV mid-wall segments strain among cases compared to controls. Furthermore, in the cases group, there were 25% of subjects with a regional peak systolic strain below-16% (-2.5 Z score in our healthy cohort) in at least two segments. These subjects did not show any difference regarding symptoms or serological findings. Conclusion(s): SARS-CoV-2 infection may affect left ventricular deformation in 26% of children despite an asymptomatic or only mildly symptomatic acute illness. A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes.
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AIMS: Multisystem inflammatory syndrome in children (MIS-C) with cardiovascular manifestations are frequent. However, there is lacking evidence regarding cardiological follow-up of this cohort of patients. The aim of our study was to describe the early and mid-term cardiac abnormalities assessed by standard and speckle-tracking echocardiography (STE), and cardiac MRI (CMR). METHODS AND RESULTS: We enrolled 32 patients (21 male, 11 female), mean age 8.25 ± 4years, with diagnosis of MIS-C. During admission, all children underwent TTE, STE with analysis of left ventricle global longitudinal strain (GLS) and CMR. Patients underwent cardiological evaluation at 2 (T1) and 6 months (T2) after discharge. Cardiac MRI was repeated at 6 months after discharge. Mean left ventricular ejection fraction (LVEF) at baseline was 58.8 ± 10% with 10 patients (31%) below 55%. Speckle-tracking echocardiography showed reduced mean LV GLS (-17.4 ± 4%). On CMR, late gadolinium enhancement (LGE) with non-ischaemic pattern was evident in 8 of 23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 ± 7.5 vs. 58.8 ± 10.6%, P-value 0.044) with only three patients (10%) below ≤ 55% at T1. Left ventricular (LV) GLS remained impaired at T1 (-17.2 ± 2.7 vs.-17.4 ± 4, P-value 0.71) and significantly improved at T2 (-19 ± 2.6% vs. -17.4 ± 4%, P-value 0.009). LV GLS was impaired (>-18%) in 53% of patients at baseline and T1, whereas only 13% showed persistent LV GLS reduction at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. CONCLUSION: Early cardiac involvement significantly improves during follow-up of MIS-C patients. However, subclinical myocardial dysfunction seems to be still detectable after 6 months of follow-up in a not negligible proportion of them.
Subject(s)
Heart Defects, Congenital , Ventricular Dysfunction, Left , COVID-19/complications , Child , Child, Preschool , Contrast Media , Echocardiography/methods , Female , Follow-Up Studies , Gadolinium , Humans , Magnetic Resonance Imaging , Magnetic Resonance Imaging, Cine/methods , Male , Stroke Volume , Systemic Inflammatory Response Syndrome , Ventricular Function, LeftABSTRACT
Introduction: Evidence suggests that, compared with adult patients, clinical manifestations of children's COVID-19 may be less severe. However, multiple reports have raised concern about the so called pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) which resembles other inflammatory conditions (i.e. Kawasaki disease, toxic shock). Patients affected by PIMS-TS showed cardiac involvement with myocardial injury, reduced left ventricle systolic function and coronary artery abnormalities, and in some cases, need for inotropes/ vasopressors and extracorporeal life support (ECLS). Little is known regarding cardiac involvement in pediatric patients with SARS-CoV-2 infection and none or only mild symptoms of disease. Methods: We analyzed 52 pediatric patients (29males, 56%) with diagnosis of SARS-CoV-2 infection based on either PCR analysis of nasopharingeal swab (NPS), or serological finding of IgG on blood sample and asymptomatic (23%) or only mildly symptomatic (77%) for COVID-19. Patients underwent transthoracic echocardiogram (TTE) after a median time of 3.6 months from diagnosis and negative NPS for SARS-CoV-2. Offline analysis with GE EchoPAC software to measure global longitudinal strain (GLS) of the LV using 2D speckle tracking imaging. Therefore, we compared the results with an age-matched group of 32 controls (18males, 56%). Results: Cases and controls were similar regarding age and gender. LV biplane EF was significantly lower in the cases group, although still in the normal range (62.4±4.1% vs. 65.2±5.5%, p=0.012). TAPSE and LV-GLS were comparable between the two groups. GLS analysis showed significant strain reduction of the LV midwall segments and of the basal anterior, posterior and septal inferior segments among cases compared to controls. On the other hand, apical segments showed higher deformation in cases compared to controls. Furthermore, in the case group there were 14 subjects (27%) with a strain below 16% (mean value minus 2.5 SD) in at least 2 segments. Conclusions: SARS-CoV-2 infection may affect LV deformation in asymptomatic or only mildly symptomatic children, showing a peculiar pattern with lower longitudinal strain in all mid-wall segments of LV compared to control subjects. The clinical significance of this findings is unclear and follow-up is needed to verify the reversibility of this alterations.
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Introduction: Among all western countries, Italy was the first to be strongly affected by COVID-19 pandemic, and one of the first to apply the “hard” lockdown. In order to limit the in-hospital infections and to re-distribute the healthcare professionals, all healthcare elective activities were reduced or cancelled, and among them, cardiac percutaneous interventions in Pediatric and Adult Congenital Heart Disease (ACHD) patients were limited to urgent or emergent ones. The aim of this paper is to describe the impact of COVID-19 pandemic on Pediatric and ACHD cath lab activity during the so called “hard lockdown” in Italy. Methods: On behalf of the interventional working group of the Italian Society of Pediatric Cardiology, 11 out of 12 Italian Institutions with a dedicated Invasive Cardiology Unit in Congenital Heart Disease actively participated to the survey. The institutions were distributed over all the national territory, 5 in the northern regions, 3 in the central and 3 in the southern ones. The data from each center were collected using a self-completion questionnaire containing 41 multiple choices questions. Results: Most of the hospitals were affected by the COVID-19 pandemic, either actively, with direct management of infected patients, or passively due to decrease of routinely clinical activities. The majority of institutions stated a change in the cath lab usual workflow plan and accessibility. Most of the centers had to cease at least temporarily the Cath lab practice, and the overall reduction of procedures number ranged between 50% and 75%. This reduction was more pronounced for teenagers and ACHD compared to neonates and children. Interestingly, there was an evident discrepancy in the management of the lock-down, irrespective of the number of COVID-19 positive cases registered, with higher reduction in Southern Italy compared to the most affected Regions Conclusions: COVID-19 pandemic has significantly affected the activity of 11 different pediatric cardiology and ACHD units all over Italy. Cath lab services were deeply impacted due to decline in outpatient clinic consultations and referrals from local hospitals. ACHD cath lab procedures suffered the biggest drop. However, overall activity reduction was not consistent with the severity of outbreak in the different Italian regions.
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Background/Introduction: In recent years there has been a growing interest in artificial intelligence (AI) applications in the echocardiography field. This is in order to simplify, reduce time and amplify the use of advanced analyses in the echo lab. Purpose: to compare results of the fully automated analysis and manual tracing analysis using a new intuitive software. Methods: 28 consecutive previously healthy patients less than 18 years old who were screened at our Center for cardiac evaluation within 6 months after an asymptomatic or paucisymptomatic COVID19 infection were enrolled. All they were in sinus rhythm. Standard transthoracic echocardiography (TTE) was performed for each patient using Canon Aplio i900, software 2D Wall Motion Tracking. Optimized apical 4-, 3- and 2- chamber views, mitral valve inflow pattern and LVOT Doppler interrogation were collected. Off-line data analysis of each examination was performed by both fully automated analysis (AI) and pediatric cardiologists with experience in echocardiography i.e. by manual tracing, evaluation and adjustment of the track by the operator (Echocardiographers). Operators were blinded to the AI analysis. To measure intraobserver variability, evaluations of 16 patients datasets were performed twice by both operators and AI. Results: Patients' demographic data were: age 9,8+/-4,7 years;males 22 (78%);height 134,3+/- 34,9 cm;weight 41,8+/-28,7 kg;BSA 1,2+/-0,4 mq, HR 85+/-15/min. The time taken for off-line analysis by AI and echocardiographers was 4-5 and 13-20 minutes, respectively. Reproducibility of echocardiographers' analysis was found to be excellent for left ventricle assessment (IC from 0,88 to 0,98);moderate for LVOT mean gradient (IC 0,73), RV end diastolic area (IC 0,69) and right atrial strain (IC 0,59);poor for deceleration time (IC 0,5), left ventricle strain (IC 0,49), RV FAC and strain (IC from 0,27 to 0,45). Conversely, reproducibility of the AI analysis was found to be excellent for any parameter (ICC from 0,87 to 0,99) (Table 1). About the mitralic valve inflow pattern assessment, despite the excellent reproducibility of AI analysis, the margin of error was found to be high. Particularly, a systematic error was observed with a tendency of the AI to overestimate deceleration time (DT-AI 176,6 ± 63,8 vs DTEcocardiographers 150,4 ± 24,3). Conclusion(s): Fully automated analysis is technically simple, less time consuming and highly reproducible. AI analysis of the mitralic inflow pattern should be optimized, having found a systematic error in the calculation of deceleration time. Reproducibility is the strong point of AI. This reduces the variability of manual measurements between different sonographers and at different times.
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Background/Introduction: Ejection fraction (EF) is a parameter widely used in Echolab to evaluate left ventricular function. Recently, in parallel with the growing interest in artificial intelligence (AI), attemps have been made to create automated systems for EF assessment, in order to reduce time and improve the accuracy of the analysis. Purpose: to compare results of different methods of EF assessment: visual estimation (visual EF), manual and fully automated analysis. Methods: 28 consecutive pediatric patients were enrolled. This cohort of previously healthy patients was screened at our Center for cardiac evaluation within 6 months after an asymptomatic or paucisymptomatic COVID19 infection. All they were in sinus rhythm. Optimized apical 4- and 2- chamber views were collected for each patient using Canon Aplio i900. Off-line EF assessment was first evaluated visually by pediatric cardiologists with experience in echocardiography, then performed by both fully automated analysis (AI) using two different methods (Automatic Simpson -AI Simpson- and Wall Motion Tracking -AI WMT-) and pediatric cardiologists through manual tracing of endocardial border (Manual Simpson and Manual WMT respectively). Operators were blinded to the AI analysis. To measure intraobserver variability, evaluations of 16 patients' datasets were performed twice by both operators and AI. Results: Patients' demographic data were: age 9,8+/-4,7 years;males 22 (78%);height 134,3+/- 34,9 cm;weight 41,8+/-28,7 kg;BSA 1,2+/-0,4 mq, HR 85+/-15/min. The time taken for off-line analysis was 0.3-0.7 minutes, 1-1.5 minutes, 1-3 minutes and 3-4 minutes, respectively for AI WMT, AI Simpson, Manual WMT and Manual Simpson. As expected, visual EF showed high intraobserver variability and a poor reproducibility (ICC 43%). AI analysis revealed a good to excellent reproducibility (ICC from 80% to 99%, depending on the method used). WMT methods had the best reproducibility both for manual tracing of endocardial border and fully automated analysis (Table 1). The comparison between different methods (Table 2) showed a good agreement between AI Simpson and AI WMT (mean bias 2,9, from -3,2 to 9,0, ICC 86%). A moderate correlation was found between different methods of AI analysis while only poor correlation was found between manual Simpson and manual WMT (Table 2). Conclusion(s): Automatic Simpson and Wall Motion Tracking are two different fully automated methods which can be used for left ventricular function assessment. AI reproducibility is high for both methods, higher for WMT. WMT method is also less time consuming and improves reproducibility of manual tracing of endocardial borderd analysis.
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Introduction: Multisystem Inflammatory Syndrome in Children (MISC) is a known severe condition affecting children previously exposed to SARS-CoV-2. Cardiovascular manifestations in MIS-C are quite common and include myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. Severe cases can present even with cardiogenic shock. To date, little is known about the very early myocardial abnormalities in pediatric patients with MIS-C. The Speckle Tracking Echocardiography (STE) and cardiac MRI (cMRI) have shown to be potential candidate for identifying regional ventricular dysfunctions in early stages of inflammatory COVID-related conditions [1,2]. Objectives: To describe the early cardiac findings in patients with MIS-C, evaluated by two advanced cardiovascular imaging, STE and cMRI. Methods: Consecutive patients with MIS-C underwent standard transthoracic echocardiography (TTE), speckle-tracking echocardiography (STE) with analysis of left ventricle (LV) global longitudinal strain (GLS) and cardiac MRI (cMRI). Clinical and laboratory data, including markers of systemic inflammation, Troponin I (TnI) and Brain Natriuretic Peptide (BNP) were also collected at onset and during follow up. All patients received intravenous immunoglobulins (IVIGs), intravenous corticosteroids (methylprednisolone) and antiplatelet therapy (aspirin). The use of biological agents (Anakinra) was reserved to patients with severe or critical illness. The need for Intensive Care Unit (ICU) was based on clinical and hemodynamic status at presentation. Results: Twenty-three patients (13M, 10F), mean age 8.1±4years (range 5.4-15.7), all with positive clinical and/or serological evidence of previous SARS-COV2 infection, entered the study. The majority (78.2%) was caucasian. All presented high degree fever, gastrointestinal symptoms and rash. Conjunctivitis and cardiovascular symptoms, as hypotension, thoracic pain or dysrhythmia, were present in 10 (43.5%). Nine children (39.1%) shared Kawasaki Disease-like symptoms. Four patients (17.4%) needed ICU admission and 3 required inotropic support. Short-term survival was 100%. All patients showed an hyperinflammatory state with elevated CRP, ESR, and D-Dimer. Tn- I was abnormal (>34 ng/L) in 15 patients (65.2%), BNP was significantly elevated in 20 (86.9%). Median time to STE evaluation was 8 days and to cMRI was 18 days since fever onset. Mean LVEF and RVEF were respectively 59±10% and 45±7%. Coronary dilation was observed in 6 (26.1%) patients. STE showed reduced mean LVGLS (-17±4.3%). LVEF on cMR was 60±13%, LGE with non-ischemic pattern was evident in 6/16 patients (37.5%) and pericardial effusion in 2 (12.5%). Conclusion: MIS-C can occur in a small but not negligible proportion of children previously affected by COVID-19 and affects the heart in a significant proportion of them. STE and cMRI were shown to be very sensitive tools to evaluate and monitor the early cardiac dysfunctions in patients with MIS-C. The elevation of myocardial necrosis markers, the myocardial injury confirmed by reduced LVGLS and presence of LGE on cMR in about a quarter of the patients support the pathogenetic hypothesis of a post-viral immuno-mediated myocarditis.
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Background: Evidence suggests that, compared with adult patients, clinical manifestations of children's COVID-19 may be less severe. However, multiple reports have raised concern about the so called pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) which resembles other inflammatory conditions (i.e. Kawasaki disease, toxic shock). Patients affected by PIMS-TS showed cardiac involvement with myocardial injury, reduced left ventricle systolic function and coronary artery abnormalities, and in some cases, need for inotropes/vasopressors and extracorporeal life support (ECLS). Little is known regarding cardiac involvement in pediatric patients with SARS-CoV-2 infection and none or only mild symptoms of disease. Methods: We analyzed 52 pediatric patients (29males, 56%) with diagnosis of SARS-CoV-2 infection based on either PCR analysis of nasopharingeal swab (NPS), or serological finding of IgG on blood sample and asymptomatic (23%) or only mildly symptomatic (77%) for COVID-19. Patients underwent transthoracic echocardiogram (TTE) after a median time of 3.6 months from diagnosis and negative NPS for SARS-CoV-2. Offline analysis with GE EchoPAC software to measure global longitudinal strain (GLS) of the LV using 2D speckle tracking imaging. Therefore, we compared the results with an age-matched group of 32 controls (18males, 56%). Results: Cases and controls were similar regarding age and gender. LV biplane EF was significantly lower in the cases group, although still in the normal range (62.4±4.1% vs. 65.2±5.5%, p=0.012). TAPSE and LV-GLS were comparable between the two groups. GLS analysis showed significant strain reduction of the LV mid-wall segments and of the basal anterior, posterior and septal inferior segments among cases compared to controls. On the other hand, apical segments showed higher deformation in cases compared to controls. Furthermore, in the case group there were 14 subjects (27%) with a strain below 16% (mean value minus 2.5 SD) in at least 2 segments. Conclusion: SARS-CoV-2 infection may affect LV deformation in asymptomatic or only mildly symptomatic children, showing a peculiar pattern with lower longitudinal strain in all mid-wall segments of LV compared to control subjects. The clinical significance of this findings is unclear and follow-up is needed to verify the reversibility of this alterations.
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Background: Recent evidences suggest that SARS-CoV-2 neutralizing antibodies (Nabs) may persist over time, however lack of knowledge still regards the pediatric population. Methods: A single-centre, prospective observational study evaluated family clusters of COVID-19 attending the Pediatric Department, University Hospital of Padua (Italy). Confirmed COVID-19 was defined by positive SARS-CoV-2 molecular detection and/or serology;patients/family symptom's and virological positivity were considered to define the infection onset (baseline). Blood samples were analyzed in pair to detect Nabs through Plaque Reduction Neutralization Test (PRNT), and IgG through chemiluminescent immuneenzymatic assay (CLIA) MAGLUMI™ 2000 Plus;IgG >1.1 kAU/L and/or PRNT≥1:10 were considered positive. SARS-CoV-2 viral load (VL) was quantified by multiplex quantitative assay based on One-Step RT-ddPCR. Geometric mean titers (GMT) and 95% Confidence Intervals of IgG/PRNT were evaluated, stratified by age and time from baseline to sample collection. Trends over time of immune-virological response were assessed. P-value <0.05 was considered statistically significant. Results: Among 213 subjects (57 families) evaluated, 155 had confirmed COVID-19 including 73 (47%) children/older siblings of 8 years median age (IQR 4-13) and 82 (53%) parents aged 42 years (IQR 34-46);93.5% had asymptomatic/mild COVID-19. From the cumulative analysis of 194 blood samples, Nabs persisted over a median period of 95 days (IQR, 67-133) from baseline. Children showed significantly higher NAbs than older subjects, with children <3 years ranging from a 4-fold difference at 1-2 months to 8.8-fold difference at 3-6 months after baseline, compared to adults (table). The longitudinal assessment of 42 subjects sampled at 60 days (SD+/-9.9) and at 150 days (SD+/-24.2) showed a 2-fold increase in NAbs in children <6 years (PRNT 144, 95% C.I. 74.42-277.94 versus 303, 95% C.I. 196.43-468.57) and a substantial stability in Nabs among older subjects. CLIA IgG significantly decreased over time for all age classes, becoming negative in 13/42 subjects (31%), compared to 1/42 subjects detected by PRNT. Among 32 individuals checked for VL within 4 days from baseline, VL directly correlated with PRNT titers in subjects >15 years (Pearson Coefficient =0.70, p=0,0349) but not in pediatric cases. Conclusion: Asymptomatic/mild COVID-19 disease triggers in children a superior and persistent humoral response compared to adults.
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Introduction: The paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and Kawasaki disease (KD) have overlapping features. This study aimed to describe the strain segmental analysis among both entities. Methods: Retrospective review of strain segmental analysis within 4 weeks of presentation of symptoms among children diagnosed with PIMS-TS between April and June 2020 and a historic cohort of typical KD from the Royal Brompton Hospital, London. Results: We included 33 PIMS-TS patients (23 males, 69.7%) at a mean age of 8 ± 4,9 years old and 45 KD patients (31 males, 68,9%) at a mean age of 5,8 ± 4,5 years old. PIMS-TS patients were older at presentation (p = 0.038). Left ventricle ejection fraction (LVEF) was normal in both groups (63,3% vs 63,5%;p= 0,89), 4/33 PIMS-TS children (12,1%) had coronary arteries abnormalities (CAA), whereas 100% of KD cohort had CAA. Both groups had a normal global longitudinal strain (GLS),but in PIMS-TS it was significantly reduced compared to the KD group (-20% vs -22%;p = 0,008). Basal segments were the most affected in PIMS-TS with significant difference in the basal anterior and anterolateral strain compared to KD (respectively -18,2% vs -23,4%;p < 0,001 and - 16,7% vs -22,7%;p < 0,001). PIMS-TS had a greater anterior, anterolateral and posterior segments involvement with a significant reduction in the anterolateral mid-wall longitudinal strain (-18,3% vs -22%;p = 0,002). Apical segments were less involved, with significant difference only in the septal and inferior apical strain (respectively p = 0.001 and p = 0,032). Conclusions: These preliminary data showed that after 4 weeks from the onset of symptoms, all PIMS-TS patients had a normal LVEF but they had a significant reduction in GLS and different segmental involvement compared to KD cohort. We hypothesize that these findings may be related to direct myocardial damage in PIMS-TS rather than caused by coronaries perfusion abnormalities.
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Background: Evidence suggests that clinical manifestations of children's COVID-19 may be less severe. However, it has been described the pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) which resembles other inflammatory conditions (i.e. Kawasaki disease). Patients affected by PIMS-TS showed cardiac involvement with myocardial injury, reduced left ventricle systolic function and coronary artery abnormalities. Little is known regarding cardiac involvement in pediatric patients with asymptomatic or mildly symptomatic SARS-CoV-2 infection. Methods: We analyzed 23 pediatric patients (13males, 56%) with diagnosis of SARS-CoV-2 infection based on PCR analysis of nasopharin-geal swab (NPS), and asymptomatic or only mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram (TTE) within 2-3 month from diagnosis and after negative NPS for SARS-CoV-2. We performed offline analysis with GE EchoPAC software to measure global longitudinal strain (GLS) of the LV using 2D speckle tracking imaging. Therefore, we compared the results with a matched group of 23 controls (13males, 56%). Results: Cases and controls were similar regarding age (5.9 ± 4.1years vs. 6.4 ± 4.4 years, p = 0.63), body surface area (0.98 ± 0.3m2 vs. 0.8 ± 0.4m2, p = 0.17), LV FS (37.9 ± 5.9% vs. 36.4 ± 8.3%, p = 0.74) and LV biplane EF (63.9 ± 5.2% vs. 66.4 ± 5.3%, p = 0.11). GLS analysis showed significant strain reduction of the LV mid-wall segments and of the basal anterior, posterior and septal inferior segments among cases compared to controls. Furthermore, in the case group there were 7 subjects (30%) with a strain below 16.5% in at least 3 segments. Conclusion: SARS-CoV-2 infection may affect LV deformation in asymptomatic or only mildly symptomatic children, showing a peculiar pattern with lower longitudinal strain in all mid-wall segments of LV compared to control subjects. The clinical significance of this findings is unclear and follow-up is needed to verify the reversibility of this alterations.
ABSTRACT
Introduction. CHB is a rare disease due to the immune-mediated injury of the conduction system, as result of the transplacental passage of maternal anti-SSA/Ro and anti-SSB/La autoantibodies to the fetus. High rates of mortality and pacemaker (PM) implantation have been observed. Specific long-term management recommendations are not yet available. Methods. Consecutive patients with autoimmune-mediated CHB referred to our Center from 2008 to 2019 were prospectively enrolled. In utero diagnosis was assessed by fetal echocardiography and confirmed at birth by electrocardiography (ECG). Serial clinical evaluation, ECG-monitoring and echocardiography were performed during follow-up. In patients with PM, a periodical device-monitoring was obtained. The aim of the study was to evaluate the long-term cardiovascular outcome and the clinical management of CHB. Data on self-perception of exercise tolerance were considered. CHB degree and mean ventricular heart rate (HR) in utero, at birth and during the latest follow-up were assessed. Pacing characteristics and device-related adverse events were also evaluated, involving LV dyssynchrony obtained by echocardiography. Results. 22 cases of CHB from 21 anti-SSA/Ro antibody-positive mothers were enrolled (67% III-degree CHB at fetal diagnosis;33% II-degree CHB). One intra-uterine death occurred. 16 cases were treated with a combination therapy protocol of steroids, plasmapheresis and intravenous immunoglobulin infusion. Among the 20 live births, 5 cases of incomplete CHB were observed (3 cases of I-degree and 2 cases of II-degree CHB). Patients with III-degree CHB at birth most often presented LV dilation (p=0,03;incomplete CHB 1 vs III-degree CHB 15 patients). HR at birth was for I-degree 135 bpm [127,5-147,5], for II-degree 75 bpm [72,5-77,5] and for III-degree CHB 58 bpm [50-65]. Long-term follow-up was obtained in 21 patients (one late-diagnosis presented to our Institution at the age of 8 years) at 6,9 years [4,3-8,5]. HR remained stable over time (I-degree p=0,1;II-degree p=0,18;III-degree CHB p=0,14). No cases of impaired exercise tolerance were observed. LV dilation was detected in 4 patients. 1 patient with severe LV dilation and preserved ejection fraction presented non-sustained ventricular tachycardia. A borderline QT interval was observed in a child with LV dilation. No cases of R-R interval >3 sec were revealed. QRS interval was normal in all patients with spontaneous rhythm. 6 patients underwent PM implantation (5 within the first year and 1 within the fifth year): 2 epicardial dual chamber DDD, 1 endocardial dual chamber DDD, 1 epicardial biventricular CRT-P PM and 2 epicardial single-chamber VVI-R PM were implanted. Last device follow-up showed a range of ventricular pacing of 98-100%. PM dependency was confirmed in all cases. An early abdominal PM pocket infection was successfully treated with antibiotics. Endocarditis, pneumothorax and macroscopic lead fracture or dislodgment have all been excluded. All patients presented a recovery of LV dilation and no cases of LV dyssynchrony were observed. Conclusions. In our experience, autoimmune-mediated CHB presented with a favorable long-term cardiovascular outcome. An adequate exercise tolerance was observed also in patients with spontaneous rhythm. Considering the stability of HR over time, an accurate selection of patients that need for PM should be performed. Long-term management of CHB should evaluate LV dyssynchrony in patients with PM and the presence of ventricular arrhythmias and LV dilation/dysfunction in patients with spontaneous rhythm. COVID-19.
ABSTRACT
Introduction: During SARS-COV-2 pandemic, different reports have been published regarding children who developed hyperinflammatory syndrome with certain or probable relationship with SARS-COV-2. These patients presented incomplete or atypical manifestations of Kawasaki disease (KD), particularly abdominal pain, myocarditis and macrophage activation syndrome features. Objectives: To report a case of SARS-COV-2-related Kawasaki-like disease with severe cardiac involvement. Methods: case report description. Results: A 10-year-old previously healthy girl presented progressively worsening abdominal pain, high grade fever for 3 days and vomiting. Lab tests showed WBC 11680/mmc, N 9370/mmc, Creactive protein (CRP) 329 mg/L, procalcitonin (PCT) 0,74 ug/L, PT-INR 1,35 and elevated D-dimer and fibrinogen levels (817 ug/L and 9,45 g/L respectively). Abdomen ultrasound revealed lymphadenopathies and hyperechogenic mesentery in the right lower quadrant, although the appendix was not visualized. She underwent laparoscopy showing moderate quantity of free fluid and appendectomy was performed. Thereafter she continued to complain of high-grade fever, abdominal pain and diarrhoea, despite broad-spectrum antibiotics. Blood, urine and stool cultures were negative. Bilateral non-exudative conjunctivitis was present. Moreover, the lab tests showed persistent marked elevation of CRP (370 mg/L), WBC 15590/mmc, N 14070/mmc, hypoalbuminemia (23 g/L), elevated ferritin and triglycerides (458 ug/L and 221 mg/dl). By taking into consideration the concomitant SARS-COV-2 pandemic, nasopharyngeal and rectal swabs were taken with negative results. Conversely, serological test showed anti-SARS-COV-2 IgG antibodies and absence of IgM. The family medical history showed that the mother had presented fever, cough, ageusia and anosmia one month before, preceded by a contact with a SARS-COV-2 positive case, while the patient was asymptomatic at that time. Suspecting a KD-like disease she was referred to our Paediatric Rheumatology Unit: cardiological assessment revealed negative Twaves in V4-V5-V6 on EKG while standard and advanced echocardiography showed mild mitral and tricuspid insufficiencies, mild dilatation of the left main coronary artery (LMCA, z score +2), normal global function (FEVS 2D 58%) but reduced longitudinal strain (GLS-16%). Lab tests confirmed myocardial injury with troponin (TnI) 100,1 ng/l and brain natriuretic peptide (P-BNP) 593 ng/L. A single infusion of intravenous immunoglobulin 2 g/kg associated with methylprednisolone (1 mg/kg/day) led to a rapid clinical improvement with apyrexia and resolution of abdominal pain and conjunctivitis. Blood test confirmed gradual normalization of inflammatory markers, ferritin, troponin and BNP and EKG showed positive T-waves. Shortly after the discharge, while she was on prednisone 0.5 mg/kg/day and acetylsalicylic acid 100 mg/day, she referred some episodes of heart pounding, lasting about ten minutes with spontaneous resolution. Three weeks after onset, cardiac MRI was normal, however, speckle tracking echocardiography showed persistent dilatation of LMCA and reduction of global longitudinal strain (GLS-14%). 24-hour EKG-Holter detected episodes of supraventricular tachycardia and several ventricular and supraventricular extrasystoles. Thus, oral atenolol therapy was started. Conclusion: In our patient SARS-COV-2 induced a possible postinfectious antibody or immune-complex mediated reaction that led to KD-like disease with acute surgical abdomen presentation and persistent myocardial damage and arrythmias. Speckle tracking echocardiography appears more reliable than MRI in early detection of myocardial damage in patients with preserved left ventricular ejection fraction.