Edward C. Kirkpatrick

Etanercept as adjunctive treatment for acute kawasaki disease: Study design and rationale

BACKGROUND Kawasaki disease (KD) is a multisystem vasculitis affecting coronary arteries in children. Patients, refractory to standard treatment with intravenous immunoglobulin and aspirin, show higher rates of coronary artery dilation. Early tumor necrosis factor α receptor antagonism in KD may provide effective adjunctive therapy. STUDY DESIGN The EATAK trial is a multicenter, double-blind, randomized, and placebo-controlled trial intended to assess the efficacy of etanercept in reducing the intravenous immunoglobulin refractory rate during treatment of acute KD. Each arm will enroll 110 patients who will receive 3 doses of study drug over 2 weeks in conjunction with standard therapy. Coronary artery dilation parameters will serve as secondary end points. DISCUSSION The EATAK trial will test a new paradigm for treatment of acute KD involving tumor necrosis factor α antagonism by etanercept.

Role of the Egami Score in Predicting Intravenous Immunoglobulin Resistance in Kawasaki Disease Among Different Ethnicities.

Early treatment with intravenous immunoglobulin (IVIG) is necessary to help reduce the risk of coronary artery abnormalities, such as coronary artery aneurysms and to help alleviate symptoms, in Kawasaki disease. Some patients, however, do not respond to an initial dose of IVIG and require additional doses. Prediction of these IVIG nonresponders may be of assistance in altering initial therapy to make it more effective. The Egami score has been validated in the Japanese population to predict IVIG nonresponders but has shown to be ineffective in US populations. This study evaluates the Egami score in a Midwest US population, subdividing patients by race and the diagnosis of typical or atypical type of Kawasaki disease. Patients were included in the study if they met criteria for Kawasaki disease and received IVIG in the inpatient setting. A total of 182 patients were studied, and in all studied groups, the Egami score had poor sensitivity at predicting IVIG nonresponders. Sensitivity of the score differed between races and differed between typical and atypical Kawasaki disease. The Egami score, as well as other systems, have been validated to predict IVIG nonresponders. These, however, lack sensitivity in the US population. Other scores developed in the United States have also lacked sensitivity, likely due to the absence of race or Kawasaki disease classification as variables. The development of a sensitive scoring system to predict IVIG nonresponders in US populations will require the incorporation of race and Kawasaki disease classification, factors that seem to alter IVIG response.

Echocardiography in Pediatric Pulmonary Hypertension

Pediatric pulmonary hypertension is a complicated disease with multiple etiologies and high mortality. Echocardiography is at the forefront of evaluation as a noninvasive, portable imaging modality that can yield diagnostic and prognostic information regarding this disease. Echocardiography is known for its ability to give an anatomic assessment of the heart and proximal blood vessels. With the additional use of Doppler echocardiography and myocardial motion assessment, the effects of elevated pulmonary pressures on the heart can be evaluated. This can allow for estimation of pulmonary artery pressures and resistances and assessment of ventricular systolic and diastolic functions. However despite its advantages, echocardiography is still an indirect assessment of pulmonary hypertension and not a substitute for cardiac catheterization. The purpose of this review is to discuss common techniques for the assessment of pulmonary hypertension by echocardiography as well as their limitations.

A Rare Case of Hypoplastic Left Heart Syndrome and Scimitar Syndrome: Value of Neonatal Cardiac Magnetic Resonance Imaging

A 3-day-old neonate born at 37 weeks gestation was referred to our clinic for evaluation of a heart murmur. She was noted to have tachypnea with feeds but had no diaphoresis or cyanosis. At presentation, she was nondysmorphic and had minimal distress, with heart rate of 166 beats/min, a variable respiratory rate of 24–87 breaths/min, a blood pressure 60/30, and an oxygen saturation of 95% in room air. She weighed 2.4 kg (24th percentile). Her cardiovascular examination was significant for a right ventricular tap, with a grade 3/6 systolic ejection murmur best heard at the left midsternal border. There were no gallops or rubs. No organomegaly was noted. The patient’s chest X-ray showed cardiomegaly and an elevated right hemidiaphragm. The 12-lead electrocardiogram (ECG) showed sinus rhythm with right atrial enlargement, left axis deviation, and a paucity of left-sided forces. A transthoracic echocardiogram (TTE) showed hypoplastic left heart syndrome with aortic atresia and mitral atresia. The right pulmonary artery appeared to be hypoplastic. The left-sided pulmonary veins appeared to drain to the left atrium, and at least one right-sided pulmonary vein was seen draining to the inferior vena cava. The TTE and chest X-ray findings raised suspicion for scimitar syndrome associated with hypoplastic left heart syndrome (HLHS). The baby was admitted to the neonatal intensive care unit and started on prostaglandins. Cardiac magnetic resonance (CMR) imaging with magnetic resonance angiography (MRA) (Siemens Magnetom Symphony magnet, Munich, Germany) was performed with the patient under general anesthesia to define further the right lung arterial supply and the pulmonary venous drainage. The CMR confirmed the diagnosis of HLHS with mitral and aortic atresia as well as the rare finding of associated scimitar syndrome. The CMR also showed dextroposition of the heart with hypoplastic right lung (50% of normal size), anomalous drainage of the right pulmonary veins to the inferior vena cava (Fig. 1), a small right pulmonary artery, and a single aortopulmonary (AP) collateral (thought to be similar in size to the celiac artery) supplying the right lower lung from the descending abdominal aorta (Fig. 2). Functional information, provided by CMR, showed the right ventricular ejection fraction to be low normal (47%),

Myocardial Infarction Late After Mustard Procedure

This case report discusses a young man with d-transposition of the great arteries who suffered three myocardial infarctions late after his Mustard procedure. The etiology was found to be a coronary embolism, with a mural thrombus in the systemic ventricle as the probable nidus. The risk factors of coronary embolism are discussed, and it is concluded that Mustard patients are at risk for coronary embolization and myocardial infarction, which can be a cause of sudden death.

A novel FOXF1 mutation associated with alveolar capillary dysplasia and coexisting colobomas and hemihyperplasia

Alveolar capillary dysplasia (ACD) is a rare and lethal cause of hypoxic respiratory failure in the neonate. Here we describe a term neonate with ACD that was found with a previously unreported p.Arg86Pro mutation in the FOXF1 (Forkhead Box-F1) gene and coexisting congenital anomalies, including colobomas of the iris and hemihyperplasia. This unique clinical presentation may indicate a novel, yet unconfirmed disease association for mutations in the FOXF1 gene. Rapid mutation analysis in FOXF1 may provide noninvasive early confirmation of ACD in neonates with respiratory failure and can aid in clinical decision making.

Diagnostic Challenges in Pediatric Pulmonary Hypertension

As with any rare disease, a low prevalence in the population is a setup for missed diagnosis. Pulmonary hypertension (PH) can occur at any age during childhood and like in adults, a delay in diagnosis is common.1 Historical outcomes for idiopathic pulmonary arterial hypertension are worse than adults, with a mean survival of 10 months after diagnosis.2 This highlights the need for accurate workup for a potential pediatric PH diagnosis. Generally the evaluation process has paralleled the adult guidelines.3,4 However, adult guidelines lack evidence-based support in pediatrics.5 Recently the American Heart Association and American Thoracic Society created guidelines for the diagnosis and management of pediatric PH.6 The guidelines offer a diagnostic algorithm needed to verify the diagnosis and work up potential etiologies (Figure 1). They provide the best evidence-based support for the workup and rationale involved. However, the guidelines are still hindered in that the majority of the evidence to support th...

An Unusual Case of Severe Stenosis of the Coronary Sinus Ostium in Association With Double Inlet Left Ventricle

We present a patient with complex single ventricle physiology who was subsequently diagnosed with atresia of the coronary sinus ostium in the setting of myocardial dysfunction following operative palliation. Although a rare cardiac defect, awareness is important as the coronary venous system will often drain to a left superior vena cava (LSVC). If the LSVC is ligated without knowing of this defect, cardiac dysfunction and death can occur.