RESUMO
OBJECTIVES: To determine the safety, tolerability, pharmacokinetics, and immunomodulatory effects of a 6-week course of atorvastatin in patients with acute Kawasaki disease with coronary artery (CA) aneurysm (CAA). STUDY DESIGN: This was a Phase I/IIa 2-center dose-escalation study of atorvastatin (0.125-0.75 mg/kg/day) in 34 patients with Kawasaki disease (aged 2-17 years) with echocardiographic evidence of CAA. We measured levels of the brain metabolite 24(S)-hydroxycholesterol (24-OHC), serum lipids, acute-phase reactants, liver enzymes, and creatine phosphokinase; peripheral blood mononuclear cell populations; and CA internal diameter normalized for body surface area before atorvastatin treatment and at 2 and 6 weeks after initiation of atorvastatin treatment. RESULTS: A 6-week course of up to 0.75 mg/kg/day of atorvastatin was well tolerated by the 34 subjects (median age, 5.3 years; IQR, 2.6-6.4 years), with no serious adverse events attributable to the study drug. The areas under the curve for atorvastatin and its metabolite were larger in the study subjects compared with those reported in adults, suggesting a slower rate of metabolism in children. The 24-OHC levels were similar between the atorvastatin-treated subjects and matched controls. CONCLUSIONS: Atorvastatin was safe and well tolerated in our cohort of children with acute Kawasaki disease and CAA. A Phase III efficacy trial is warranted in this patient population, which may benefit from the known anti-inflammatory and immunomodulatory effects of this drug.
Assuntos
Atorvastatina/administração & dosagem , Aneurisma Coronário/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Administração Oral , Adolescente , Atorvastatina/efeitos adversos , Atorvastatina/farmacocinética , Criança , Pré-Escolar , Aneurisma Coronário/etiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Masculino , Síndrome de Linfonodos Mucocutâneos/complicaçõesRESUMO
INTRODUCTION: Kawasaki disease (KD) is the leading cause of acquired heart disease in children. The 12-lead electrocardiogram (ECG) changes in patients during the acute phase of KD include flattened T waves and prolonged corrected QT intervals (QTc). We set out to determine the 12-lead ECG and vectorcardiography predictors for identification of patients with KD and which of these predictors would be clinically useful for early identification of those with coronary artery anomalies (CAA). METHODS: A blinded, retrospective case-control study of patients with KD and age-matched controls was performed. Deep Q waves, QTc, spatial QRS-T angles, and T-wave vector magnitude (root mean square of the T wave, RMS-T) were assessed. Comparisons between groups were performed to test for significant differences. RESULTS: Fifty patients with KD (mean age 3.1 ± 3.1 years, 26% female) were compared to 50 previously healthy control patients (mean age 3.8 ± 2.9 years, 44% female). Of the KD patients, 32 (64%) were diagnosed as incomplete KD and 28 (56%) of them had CAA. When compared to the control group, KD patients had abnormal Q waves (72% vs 44% P = 0.005), shorter QTc values (395.1 ± 24.7 ms vs 410.4 ± 34.7 ms, P = 0.013), and lower RMS-T (0.42 ± 0.02 mV vs 0.63 ± 0.03 mV P < 0.001), respectively. Incomplete KD was also discriminated from controls by the same parameters. No differences were noted between KD patients with versus without CAA. CONCLUSION: The RMS-T differentiates complete and incomplete KD from controls. KD patients with CAA were not differentiated from those without CAA.
Assuntos
Doença da Artéria Coronariana/etiologia , Eletrocardiografia , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Vetorcardiografia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the clinical utility of tissue Doppler imaging (TDI) in assessment of disease severity and prognostic value in children with idiopathic pulmonary arterial hypertension (PAH). STUDY DESIGN: A prospective study was performed to evaluate TDI velocities (systolic myocardial velocity, early diastolic myocardial relaxation velocity [Em], late diastolic myocardial velocity associated with atrial contraction), brain natriuretic peptide, New York Heart Association (NYHA) functional class, and hemodynamics in 51 children (mean age; 11.6 years) with idiopathic PAH. Fifty-one healthy children with comparable demographics served as controls. RESULTS: Em, Em/late diastolic myocardial velocity associated with atrial contraction ratio, and systolic myocardial velocity at mitral annulus, septum, and tricuspid annulus in PAH were significantly reduced compared with controls. Tricuspid Em had significant inverse correlations with plasma brain natriuretic peptide levels (r = -0.60, P < .001), right ventricular end-diastolic pressure (r = -0.79, P < .001), and mean pulmonary arterial pressure (r = -0.67, P < .001). Statistically significant differences were observed in tricuspid Em between NYHA functional class II vs combined III and IV (mean and SD; 11.9 ± 4.2 cm/s vs 8.2 ± 3.6 cm/s, respectively, P = .002). Cumulative event-free survival rate was significantly lower when tricuspid Em was ≤8 cm/s (log-rank test, P < .001) CONCLUSIONS: Tricuspid Em velocity correlated with NYHA functional class as disease severity and may serve as a useful prognostic marker in children with idiopathic PAH. The present study is the initial report to evaluate TDI velocities against midterm outcome variables in a relatively large pediatric PAH population.