Kawasaki disease: a review with emphasis on cardiovascular complications

Kawasaki disease (KD) is an acute systemic vasculitis that is currently the leading cause of acquired heart disease in childhood in the United States. Cardiovascular complications are the major cause of morbidity, are responsible for virtually all deaths from KD and should be evaluated as soon as possible after the acute phase to establish the baseline status, in order to predict disease progression and determine adequate treatment. In selected patients, electrocardiography (ECG)-gated cardiac computed tomography (CT) and magnetic resonance (MR) imaging are valuable non-invasive techniques that can be used to help diagnose the cardiovascular complications associated with KD. In this article, we review the epidemiology, aetiology and pathogenesis, histopathology, clinical features, cardiovascular complications and imaging, focusing on the role of cardiac CT and MR on the initial assessment and follow-up of the cardiovascular complications of KD

Significance of myeloperoxidase plasma levels as a predictor for cardiac resynchronization therapy response

Objectives This study aimed to determine if changes in myeloperoxidase (MPO) levels correlate with response to cardiac resynchronization therapy (CRT) and the potential role of MPO as a predictor of response to CRT. Background CRT is a well-established treatment option in chronic heart failure (CHF) with 50-80% of patients benefiting. Inflammation and oxidative stress play a key role in CHF pathophysiology. Previous studies have demonstrated increased levels of MPO in CHF patients, but the correlation with CRT response remains incompletely understood. Methods Fifty-three patients underwent CRT implantation. During follow-up, patients were divided into two groups, responders and non-responders to CRT, based on improved physical capacity and NYHA classification. Levels of MPO and NT-pro-brain-natriuretic-peptide (NT-proBNP) were determined prior to implantation, 30 and 90 days after. Physical capacity, including a 6-min walking-test, NYHA class, and LVEF were evaluated at baseline and during follow-up. Results Thirty-four patients (64%) responded to CRT, showing improved physical capacity and LVEF. All responders revealed a significant decrease of MPO levels (503.8 ng/ml vs. 188.4 ng/ml;p < 0.001). Non-responding patients did not show any significant changes in clinical parameters or MPO levels (119.6 ng/ml vs. 134.3 ng/ml;p = 0.672) during follow-up. At baseline, physical capacity and NYHA class, as well as MPO levels differed significantly between both groups (p < 0.001). A ROC analysis identified an MPO cut-off value for response to CRT of 242 ng/ml with a sensitivity of 93.5% and specificity of 71.4%. There was a strong correlation between MPO and improvement of LVEF (Spearman's rho: - 0.453;p = 0.005) and physical capacity (Spearman's rho: - 0.335;p = 0.042). Conclusions Response to CRT and course of MPO levels correlate significantly. MPO levels differ between responders and non-responders prior to CRT, which may indicate an additional value of MPO as a predictor for CRT response. Further randomized studies are required to confirm our data in larger patient cohorts

Protective Effects of 10-nitro-oleic Acid in a Hypoxia-Induced Murine Model of Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) is characterized by adverse remodeling of pulmonary arteries. Although the origin of the disease and its underlying pathophysiology remain incompletely understood, inflammation has been identified as a central mediator of disease progression. Oxidative inflammatory conditions support the formation of electrophilic fatty acid nitroalkene derivatives, which exert potent anti-inflammatory effects. The current study investigated the role of 10-nitro-oleic acid (OA-NO2) in modulating the pathophysiology of PAH in mice. Mice were kept for 28 days under normoxic or hypoxic conditions, and OA-NO2 was infused subcutaneously. Right ventricular systolic pressure (RVPsys) was determined, and right ventricular and lung tissue was analyzed. The effect of OA-NO2 on cultured pulmonary artery smooth muscle cells (PASMCs) and macrophages was also investigated. Changes in RVPsys revealed increased pulmonary hypertension in mice on hypoxia, which was significantly decreased by OA-NO2 administration. Right ventricular hypertrophy and fibrosis were also attenuated by OA-NO2 treatment. The infiltration of macrophages and the generation of reactive oxygen species were elevated in lung tissue of mice on hypoxia and were diminished by OA-NO2 treatment. Moreover, OA-NO2 decreased superoxide production of activated macrophages and PASMCs in vitro. Vascular structural remodeling was also limited by OA-NO2. In support of these findings, proliferation and activation of extracellular signal-regulated kinases 1/2 in cultured PASMCs was less pronounced on application of OA-NO2. Our results show that the oleic acid nitroalkene derivative OA-NO2 attenuates hypoxia-induced pulmonary hypertension in mice. Thus, OA-NO2 represents a potential therapeutic agent for the treatment of PAH

Inhaled epoprostenol therapy for pulmonary hypertension: Improves oxygenation index more consistently in neonates than in older children

The purpose of this study was to determine the efficacy of inhaled epoprostenol for treatment of acute pulmonary hypertension (PH) in pediatric patients and to formulate a plan for a prospective, randomized study of pulmonary vasodilator therapy in this population. Inhaled epoprostenol is an effective treatment for pediatric PH. A retrospective chart review was conducted of all pediatric patients who received inhaled epoprostenol at a tertiary care hospital between October 2005 and August 2007. The study population was restricted to all patients under 18 years of age who received inhaled epoprostenol for greater than 1 hour and had available data for oxygenation index (OI) calculation. Arterial blood gas values and ventilator settings were collected immediately prior to epoprostenol initiation, and during epoprostenol therapy (as close to 12 hours after initiation as possible). Echocardiograms were reviewed during two time frames: Within 48 hours prior to therapy initiation and within 96 hours after initiation. Of the 20 patients in the study population, 13 were neonates, and the mean OI for these patients improved during epoprostenol administration (mean OI before and during therapy was 25.6±16.3 and 14.5±13.6, respectively, P=0.02). Mean OI for the seven patients greater than 30 days of age was not significantly different during treatment (mean OI before and during therapy was 29.6±15.0 and 25.6±17.8, P=0.56). Improvement in echocardiographic findings (evidence of decreased right-sided pressures or improved right ventricular function) was demonstrated in 20% of all patients. Inhaled epoprostenol is an effective therapy for the treatment of selected pediatric patients with acute PH. Neonates may benefit more consistently from this therapy than older infants and children. A randomized controlled trial is needed to discern the optimal role for inhaled prostanoids in the treatment of acute PH in childhood