Inability of Asian risk scoring systems to predict intravenous immunoglobulin resistance and coronary lesions in Kawasaki disease in an Italian cohort.

Since resistance to intravenous immunoglobulin (IVIG) is associated with coronary lesions (CALs) in Kawasaki disease (KD), it is crucial to identify patients at risk to protect them from coronary involvement. The available risk scores to predict IVIG resistance were developed in Asian populations in whom their effectiveness has been proven, but data on non-Asian children are limited. The aim of this study is to evaluate the ability of the Kobayashi, Egami, and Formosa risk scores to predict IVIG resistance and CALs in Italian patients with KD. A multicenter retrospective analysis involving children with KD diagnosed between 2000 and 2015 was carried out: 257 patients were enrolled (57.9% boys, 89.9% Caucasian); 43 patients were IVIG resistant (16.7%). The scores have low sensitivity and specificity in predicting IVIG resistance: respectively, KS 64% and 62.5%, ES 41.4% and 77.4%, and FS 70.8% and 44.9%. The predictive value of the 3 scores for predicting CALs was also poor.Conclusion: Kobayashi, Egami, and Formosa Scores are ineffective in predicting IVIG resistance and coronary involvement in a predominantly Caucasian cohort. A specific score system for mostly Caucasian children with KD is needed enable the early identification of those at risk for CALs who could benefit from intensified treatment. What is Known: • There are several risk scores developed in the Asian population to early identify patients with KD at risk for immunoglobulin-resistance and thus for coronary lesions. • Data are scarce on their effectiveness in non-Asian children. What is New: • We present a comprehensive analysis of the ability of 3 Asian risk scores in a cohort of mostly Caucasian children to predict immunoglobulin resistance and coronary involvement. • Low sensitivity and specificity of the Asian scores for immunoglobulin-resistance and coronary lesions suggest the need for criteria specific for different ethnicities.

Coronary Arteries Lesions in Kawasaki Disease: Risk Factors in an Italian Cohort.

Background: Kawasaki disease (KD) is a systemic vasculitis of medium arteries, particularly involving coronary arteries. Coronary artery lesions (CALs) is the most serious complication in the acute stage, potentially leading to ischemic cardiomyopathy, myocardial infarction and sudden death. Environmental factors and genetic background contribute to individual susceptibility to develop CALs. The aim of this study was to define the risk factors for CALs in an Italian cohort. Methods: Data of KD patients from 10 Italian sites were registered into a REDCap database where demographic and clinical data, laboratory findings and coronary status were recorded. KD was diagnosed according to AHA definition. We used multiple logistic regression analysis to identify independent risk factors for CALs. Results: A total of 517 patients were enrolled, mainly Caucasians (83.6%). Presentation was complete in 321 patients (62.8%) and IVIG responsiveness in 360 (70%). CALs developed in 136/517 (26.31%). Gender, age, ethnicity, clinical presentation, fever duration, non-coronary cardiac events, Hb, albumin and CRP were significantly different between patients with and without CALs, while seasonality was not. Male gender, age < 18 months, Asian ethnicity, incomplete presentation and fever > 10 days were independent risk factors for CALs. Conclusions: Age younger than 18 months, incomplete KD and longer fever duration are risk factors for CALs. Asian ethnicity also represents a risk factor in our Italian Cohort.

Spectrum of Cardiovascular Diseases in Children During High Peak Coronavirus Disease 2019 Period Infection in Northern Italy: Is There a Link?

BACKGROUND: Children with coronavirus disease-2019 (COVID-19) have a milder clinical course than adults. We describe the spectrum of cardiovascular manifestations during a COVID-19 outbreak in Emilia-Romagna, Italy. METHODS: A cross-sectional multicenter study was performed, including all patients diagnosed with Kawasaki disease (KD), myocarditis, and multisystem inflammatory syndrome in children (MIS-C) from February to April 2020. KD patients were compared with those diagnosed before the epidemic. RESULTS: KD: 8 patients (6/8 boys, all negative for severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]): complete presentation in 5/8, 7/8 immunoglobulin (IVIG) responders, and 3/8 showed transient coronary lesions (CALs). Myocarditis: one 5-year-old girl negative for SARS-CoV-2 and positive for parvovirus B19. She responded to IVIG. MIS-C: 4 SARS-CoV-2-positive boys (3 patients with positive swab and serology and 1 patient with negative swab and positive serology): 3 presented myocardial dysfunction and pericardial effusion, and 1 developed multicoronary aneurysms and hyperinflammation; all responded to treatment. The fourth boy had mitral and aortic regurgitation that rapidly regressed after steroids. CONCLUSIONS: KD, myocarditis, and MIS-C were distinguishable cardiovascular manifestations. KD did not show a more aggressive form compared with previous years: coronary involvement was frequent but always transient. MIS-C and myocarditis rapidly responded to treatment without cardiac sequelae despite high markers of myocardial injury at the onset, suggesting a myocardial depression due to systemic inflammation rather than focal necrosis. Evidence of actual or previous SARS-CoV-2 infection was documented only in patients with MIS-C.

Non-coronary cardiac events, younger age, and IVIG unresponsiveness increase the risk for coronary aneurysms in Italian children with Kawasaki disease.

OBJECTIVES: Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. METHODS: Multicenter retrospective and prospective study including 372 consecutive children (58% boys; mean age 34.3 ± 30.3 months, Caucasian 85%) was diagnosed with KD. We divided the cohort into 2 groups according to the presence of coronary anomalies (CAA) and aneurysms. We compared the groups and studied the risk factors for CAA and for aneurysms, the most severe lesions. RESULTS: Children with CAA were 91/372 (24.46%, aneurysms 20/372, 5.37%). Children with CAA were more likely to have a longer duration of fever (p < 0.001), later day of treatment (p < 0.001), to be IVIG non-responders and late treated (p < 0.001), while age, clinical presentation, and seasonality were not different. They also had significantly higher WBC and neutrophils, lower lymphocytes, Hb and Na during the acute stage, and slower resolution of inflammation. Age, IVIG unresponsiveness, and presence of non-coronary cardiac findings were independent risk factors for CAA and for aneurysms, while neutrophils just for CAA. Age under 6 months was a risk factor for the aneurysm. Aneurysms occurred more frequently in the first quartile of the age of KD onset (under 14 months). CONCLUSION: Very young children with non-coronary cardiac findings are at increased risk for a more severe form of KD with aneurysms. These children could benefit from adjunctive therapy beside IVIG, especially if they have higher markers of inflammation, particularly neutrophils. Key points • Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. • Risk factors for coronary involvement have been extensively studied in the Asian population, and others have been validated in cohorts with mixed ethnicities. • In our predominantly Caucasian population, non-coronary cardiac findings, age younger than 6 months, and IVIG unresponsiveness are independent risk factors for a more severe form of KD with aneurysms.

Neonatal diagnosis of isolated absence of the right pulmonary artery: a case report and review of the literature.

BACKGROUND: Unilateral absence of the pulmonary artery (UAPA) is a rare congenital malformation often associated with other cardiac anomalies; however it may occur as an isolated lesion. Isolated absence of the right pulmonary artery is twice more frequent than that of the left pulmonary artery. Patients with isolated UAPA are usually asymptomatic at birth; thereafter they may develop a progression of symptoms such as exercise intolerance, dyspnea, chest pain, hemoptysis and recurrent pulmonary infections. As patients may remain asymptomatic or have vague symptoms, the diagnosis of isolated UAPA can be difficult to make in infancy. Indeed, most cases described in literature are adults. Due to the rarity of neonatal presentation, there is no consensus regarding the treatment of this malformation. CASE PRESENTATION: Herein, the case of a two-day-old term female infant, born after uneventful pregnancy, who required a cardiological assessment for a light murmur, is reported; an echocardiogram demonstrated an isolated unilateral absence of the right pulmonary artery, confirmed by means of magnetic resonance imaging (MRI) performed 1 month after child's birth. Besides this finding, MRI showed a slightly increased lumen and size of the main and left pulmonary arteries. The right lung was shown to be perfused by some systemic collateral arteries. In the absence of any other cardiovascular malformation, our patient did not need any treatment. As symptoms may occur later in life, a thorough clinical and cardiological follow up was immediately started. Three years later, she is still asymptomatic, showing adequate growth, without any sign of pulmonary hypertension. CONCLUSIONS: Isolated UAPA is a very rare malformation with a diverse clinical presentation. To the best of our knowledge, this is the second case of neonatal presentation of UAPA reported in literature to date. We believe that our case report supports the opinion that a prompt cardiological evaluation is needed whenever a newborn shows signs and/or symptoms of cardiorespiratory concern. Any missed neonatal diagnosis of UAPA may contribute to the later age at presentation, with resultant higher risk of morbidity and mortality and greater therapeutical difficulties.

Gastrointestinal presentation of Kawasaki disease: A red flag for severe disease?

BACKGROUND: Kawasaki disease (KD) is a febrile systemic vasculitis of unknown etiology and the main cause of acquired heart disease among children in the developed world. To date, abdominal involvement at presentation is not recognized as a risk factor for a more severe form of the disease. OBJECTIVE: To evaluate whether presenting abdominal manifestations identify a group at major risk for Intravenous immunoglobulin (IVIG)-resistance and coronary lesions. METHODS: Retrospective study of KD patients diagnosed between 2000 and 2015 in 13 pediatric units in Italy. Patients were divided into 2 groups according to the presence or absence of abdominal manifestations at onset. We compared their demographic and clinical data, IVIG-responsiveness, coronary ectasia/aneurysms, laboratory findings from the acute and subacute phases. RESULTS: 302 patients (181 boys) were enrolled: 106 patients with, and 196 patients without presenting abdominal features. Seasonality was different between the groups (p = 0.034). Patients with abdominal manifestations were younger (p = 0.006) and more frequently underwent delayed treatment (p = 0.014). In the acute phase, patients with abdominal presentation had higher platelet counts (PLT) (p = 0.042) and lower albuminemia (p = 0.009), while, in the subacute phase, they had higher white blood cell counts (WBC) and PLT (p = 0.002 and p < 0.005, respectively) and lower red blood cell counts (RBC) and hemoglobin (Hb) (p = 0.031 and p 0.009). Moreover, the above mentioned group was more likely to be IVIG-resistant (p < 0.005) and have coronary aneurysms (p = 0.007). In the multivariate analysis, presenting abdominal manifestations, age younger than 6 months, IVIG- resistance, delayed treatment and albumin concentration in the acute phase were independent risk factors for coronary aneurysms (respectively p<0.005, <0.005, = 0.005 and 0.009). CONCLUSIONS: This is the first multicenter report demonstrating that presenting gastrointestinal features in KD identify patients at higher risk for IVIG-resistance and for the development of coronary aneurysms in a predominantly Caucasian population. CLINICAL TRIAL REGISTRATION: 8/20014/O/OssN.

Lack of tight association between quality of life and exercise capacity in pulmonary arterial hypertension.

BACKGROUND: In pulmonary arterial hypertension (PAH) health-related quality of life (HRQOL) has been investigated over the short-term (weeks) but little is known about patient's perspective over the medium and long term. OBJECTIVE: To analyze how patients on specific PAH therapies do over one year of observation in terms of HRQOL, and to investigate if possible associations between the exercise capacity (EC) and HRQOL persist over the medium term. METHODS: Thirty-four patients on PAH therapies (bosentan and/or sildenafil) were enrolled (age 14 to 58 years, median 35.5 years, functional class II or III), and evaluated at baseline, and 3, 6, 9 and 12 months subsequently using the six-minute walk test and the SF-36 HRQOL questionnaire. RESULTS: The six minute walked distance did not change over the follow-up (387-432 meters, median values, p=0.2775), the same for the functional class and peripheral oxygen saturation. The SF-36 scores also remained stable, with physical health always worse than mental health. Of 40 possible associations between EC and HRQOL, only 12 were significant (30%, p<0.05). Prediction of severely depressed HRQOL based on a walked distance of <235 meters was >90% specific but <43% sensitive. CONCLUSION: Patients with PAH who remain stable in terms of EC also seem to do so in terms of HRQOL. However, EC and HRQOL are not consistently tied over time, and should be analyzed as different perspectives in the individual patient.

[Two-year follow-up of pulmonary arterial hypertension patients treated with sildenafil]. / Seguimento de dois anos em pacientes com hipertensão arterial pulmonar sob tratamento com sildenafila.

BACKGROUND: The long-term effects of drugs developed for the control of pulmonary arterial hypertension (PAH) are little known, since multicenter studies usually last 12 to 16 weeks. OBJECTIVE: To evaluate the two-year outcome of PAH patients receiving monotherapy with sildenafil (a phosphodiesterase-5 inhibitor), with regard to their functional capacity. METHODS: Twenty four patients (ages between 8 and 54 years) with idiopathic PAH (IPAH, n = 9) or congenital heart disease-associated PAH (CHD-PAH, n = 15) were treated with sildenafil for two years, with daily oral doses ranging from 60 to 225 mg (tid). Physical capacity was assessed by the distance walked in the 6-minute walk test (DW6M) and by the degree of dyspnea at the end of the walk (Borg scale); peripheral oxygen saturation was also recorded (SpO(2)6M, pulse oximetry). RESULTS: In the 18 patients who completed the two-year follow-up, there was a progressive and sustained increase in DW6M, both in the IPAH group (from 239 +/- 160 m to 471 +/- 66 m, p = 0.0076) and in the CHD-PAH group (from 361 +/- 144 m to 445 +/- 96 m, p = 0.0031), with improvement of dyspnea at the end of the walk (p<0.05 for both groups). No decrease in SpO(2)6M was observed in the groups; in patients with CHD-PAH, in particular, SpO(2)6M went from 77 +/- 20% to 79 +/- 16% (p = 0.5248). Five deaths occurred (three in the IPAH group) and one patient was lost to follow-up during the study period. CONCLUSION: In a two-year follow-up, sildenafil proved useful in the control of the functional status of PAH patients, with significant improvement in both groups considered.

Ausência de estreita associação entre qualidade de vida e capacidade de exercício na hipertensão arterial pulmonar / Lack of tight association between quality of life and exercise capacity in pulmonary arterial hypertension

FUNDAMENTO: Na hipertensão arterial pulmonar (HAP) a qualidade de vida relacionada saúde (QVRS) tem sido investigada em curtos períodos de tempo (semanas), mas pouco se sabe sobre a perspectiva do paciente no médio e longo prazo. OBJETIVO: Analisar o estado de pacientes em terapias específicas de HAP durante um ano de observação, em termos de QVRS, e investigar se possíveis associações entre a capacidade de exercício (CE) e a QVRS persistem no médio prazo. MÉTODOS: Trinta e quatro pacientes em terapias para a HAP (bosentan e/ou sildenafil) foram selecionados (idade de 14 a 58 anos, mediana de 35,5 anos, classe funcional II ou III), e avaliados no momento basal, e 3, 6, 9 e 12 meses depois, usando o teste de caminhada de 6 minutos e questionário SF-36 de QVRS. RESULTADOS: A distância percorrida nos seis minutos não mudou durante o acompanhamento (387 - 432 metros, valores da mediana, p=0.2775), o mesmo para a classe funcional e saturação periférica de oxigênio. Os escores SF-36 também se mantiveram estáveis, com a saúde física sempre pior que a saúde mental. Das 40 possíveis associações entre a CE e QVRS, apenas 12 foram significativas (30%, p<0,05). A previsão de uma QVRS severamente deprimida com base em uma distância percorrida de 235 metros foi específica em >90%, mas sensível em <43%. CONCLUSÃO: Os pacientes com HAP que se mantêm estáveis em termos da CE também parecem fazê-lo em termos de QVRS. Contudo, CE e QVRS não têm ligação consistente com o tempo, e devem ser analisadas como diferentes perspectivas no paciente individual.

BACKGROUND: In pulmonary arterial hypertension (PAH) health-related quality of life (HRQOL) has been investigated over the short-term (weeks) but little is known about patient's perspective over the medium and long term. OBJECTIVE: To analyze how patients on specific PAH therapies do over one year of observation in terms of HRQOL, and to investigate if possible associations between the exercise capacity (EC) and HRQOL persist over the medium term. METHODS: Thirty-four patients on PAH therapies (bosentan and/or sildenafil) were enrolled (age 14 to 58 years, median 35.5 years, functional class II or III), and evaluated at baseline, and 3, 6, 9 and 12 months subsequently using the six-minute walk test and the SF-36 HRQOL questionnaire. RESULTS: The six minute walked distance did not change over the follow-up (387-432 meters, median values, p=0.2775), the same for the functional class and peripheral oxygen saturation. The SF-36 scores also remained stable, with physical health always worse than mental health. Of 40 possible associations between EC and HRQOL, only 12 were significant (30%, p<0.05). Prediction of severely depressed HRQOL based on a walked distance of <235 meters was >90% specific but <43% sensitive. CONCLUSION: Patients with PAH who remain stable in terms of EC also seem to do so in terms of HRQOL. However, EC and HRQOL are not consistently tied over time, and should be analyzed as different perspectives in the individual patient.

Seguimento de dois anos em pacientes com hipertensão arterial pulmonar sob tratamento com sildenafila / Two-year follow-up of pulmonary arterial hypertension patients treated with sildenafil

FUNDAMENTO: Os efeitos de longo prazo das drogas desenvolvidas para o controle da hipertensão arterial pulmonar (HAP) são pouco conhecidos, já que os estudos multicêntricos em geral têm duração de 12 a 16 semanas. OBJETIVO: Avaliar a evolução de dois anos, em pacientes com HAP submetidos à monoterapia com sildenafila (inibidor da fosfodiesterase-5), com respeito à capacidade funcional. MÉTODOS: Vinte e quatro pacientes (idade entre 8 e 54 anos) com HAP idiopática (HAPI, n = 9) ou associada a cardiopatias congênitas (HAP-CCg, n = 15) foram tratados com sildenafila por dois anos, com doses diárias que variaram de 60 a 225 mg (três tomadas), por via oral. A capacidade física foi avaliada pela distância caminhada no teste de 6 minutos (DC6M) e pelo grau de dispneia ao final da caminhada (escala de Borg), sendo também registrada a saturação periférica de oxigênio (SpO(2)6M, oximetria de pulso). RESULTADOS: Nos 18 pacientes que completaram dois anos de seguimento, houve incremento progressivo e sustentado na DC6M, tanto no grupo HAPI (de 239 ± 160 m para 471 ± 66 m, p = 0,0076) como no grupo HAP-CCg (de 361 ± 144 m para 445 ± 96m, p = 0,0031), com melhora da dispneia ao final da caminhada (p < 0,05 em ambos). Não houve decréscimo na SpO(2)6M nos grupos considerados; em particular, pacientes com HAP-CCg evoluíram de 77 ± 20 por cento para 79 ± 16 por cento (p = 0,5248). Houve 5 óbitos (três no grupo HAPI) e uma perda de seguimento no período. CONCLUSÃO: Em dois anos de seguimento, a sildenafila mostrou-se útil no controle da condição funcional de pacientes com HAP, com melhora significante nas duas etiologias consideradas.

BACKGROUND: The long-term effects of drugs developed for the control of pulmonary arterial hypertension (PAH) are little known, since multicenter studies usually last 12 to 16 weeks. OBJECTIVE: To evaluate the two-year outcome of PAH patients receiving monotherapy with sildenafil (a phosphodiesterase-5 inhibitor), with regard to their functional capacity. METHODS: Twenty four patients (ages between 8 and 54 years) with idiopathic PAH (IPAH, n = 9) or congenital heart disease-associated PAH (CHD-PAH, n = 15) were treated with sildenafil for two years, with daily oral doses ranging from 60 to 225 mg (tid). Physical capacity was assessed by the distance walked in the 6-minute walk test (DW6M) and by the degree of dyspnea at the end of the walk (Borg scale); peripheral oxygen saturation was also recorded (SpO(2)6M, pulse oximetry). RESULTS: In the 18 patients who completed the two-year follow-up, there was a progressive and sustained increase in DW6M, both in the IPAH group (from 239 ± 160 m to 471 ± 66 m, p = 0.0076) and in the CHD-PAH group (from 361 ± 144 m to 445 ± 96m, p = 0.0031), with improvement of dyspnea at the end of the walk (p<0.05 for both groups). No decrease in SpO(2)6M was observed in the groups; in patients with CHD-PAH, in particular, SpO(2)6M went from 77 ± 20 percent to 79 ± 16 percent (p = 0.5248). Five deaths occurred (three in the IPAH group) and one patient was lost to follow-up during the study period. CONCLUSION: In a two-year follow-up, sildenafil proved useful in the control of the functional status of PAH patients, with significant improvement in both groups considered.

Qualidade de vida em hipertensão arterial pulmonar e sua relação com o desempenho físico: avaliação longitudinal / Health-related quality of life in pulmonary arterial hypertension and its relationship with the exercise capacity: a longitudinal study

A qualidade de vida relacionada à saúde tem aparecido, com frequência, entre as metas dos estudos clínicos destinados ao desenvolvimento de novos tratamentos para a hipertensão arterial pulmonar (HAP). Embora os novos tratamentos melhorem o desempenho ao exercício na fase inicial de 12 - 16 semanas, não se sabe se existe associação entre tolerância ao exercício e qualidade de vida (QV), sobretudo em médio e longo prazo. Os objetivos do estudo foram: a) verificar, em pacientes com HAP, a existência ou não de correlação entre a QV e desempenho físico; b) verificar como as possíveis associações entre QV e desempenho ao exercício se comporta ao longo de um ano de observação sob tratamento medicamentoso específico; c) verificar se a aplicação de um protocolo de orientação de enfermagem, especificamente planejado para pacientes com HAP, poderia exercer impacto sobre a QV e o desempenho físico. Foram incluídos 34 pacientes no estudo, adolescentes ou adultos com o diagnóstico de HAP idiopática, hereditária ou associada a cardiopatias congênitas. Para o comprimento do terceiro objetivo, os pacientes foram organizados em pares, seguindo-se randomização para o tipo de seguimento a que seriam submetidos: apenas orientação médica ou orientação médica seguida de consulta de enfermagem. O acompanhamento constou de cinco visitas, a saber, no início, e aos três, seis, nove e 12 meses. Nas visitas, foram avaliados o desempenho físico, através da classe funcional e do teste de caminhada de seis minutos, e a QV mediante aplicação do questionário SF-36. A idade variou entre 14 e 58 anos (mediana de 35,5 anos). Houve dez pacientes com o diagnostico de hipertensão arterial pulmonar idiopática, dois na forma hereditária e 22 indivíduos com a forma associada a cardiopatias congênitas. Com relação à classe funcional, 25 pacientes estavam em classe II e nove em classe III. A distância caminhada inicialmente foi 177 a 564 metros (mediana 399 metros). A saturação periférica de oxigênio...

Health-related quality of life (HRQOL) has been explored as an additional end point in clinical studies for development of new therapies in pulmonary arterial hypertension (PAH). Although treatments have been shown to improve the exercise capacity in 12-16 weeks, little is known of how patients do over the medium and long term on these therapies, in terms of HTQOL. The objectives of the present study were: 1- to observe how PAH patients do on specific therapies over 12 months of follow-up in terms of the exercise capacity and HRQOL; 2- to test for possible associations between the exercise capacity and HRQOL, and determine if such associations persist over the medium term (12 months); 3- to examine if a PAH-specific nursing approach (following conventional visits to the doctor) has a positive impact on patients exercise capacity and quality of life. Thirty-four patients were enrolled, with PAH associated with congenital heart disease (N=22) or idiopathic/hereditary PAH (N=12). Patients were seen at baseline, and three, six, nine and twelve months thereafter. The exercise capacity was assessed by performing the six-minute walk test, and the quality of life using the SF-36 questionnaire. The functional class was recorded according to the World Health Organization classification. The age range was 14 to 58 years (median 35.5 years). Patients were in functional class II (N=25) or III (N=9), and baseline six-minute walked distance was 177 to 564 meters (median 399 meters). Peripheral oxygen saturation was 63% to 98% (median 94.5%) at rest, and 38% to 98% (median 84%) at the end of the exercise. At baseline, in two of the eight domains of the SF-36 questionnaire (physical functioning and physical role), median score were lower than 50 (0-100 scale, 100 indicating best health). In 31 patients who completed the follow-up, there were no statistically significant changes in the functional class, six-minute walked distance, peripheral oxygen saturation and SF-36 scores...