Christopher Ratnasamy

Associations between neurohormonal and inflammatory activation and heart failure in children

BACKGROUND Adult heart failure (HF) has been shown to be associated with neuroendocrine and inflammatory activation. We hypothesize that neuroendocrine and inflammatory activation also associate with symptom severity and echocardiographic measurements in pediatric HF. METHODS Nineteen children with HF were divided into 3 symptom severity groups. Measurements were made of left ventricular (LV) ejection fraction, LV shortening fraction (LVSF), LV shortening fraction Z score (LVSFz), and LV end-systolic (LVSDz) and diastolic diameter Z scores. Blood levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha, and soluble tumor necrosis factor receptor II were measured. RESULTS NT-proBNP and hsCRP were significantly elevated with more severe symptoms (P < or = .003) and discriminated between clinical severity groups (volume under the receiver operating characteristic surface = 0.58 and 0.62, P = .007 and P = .002, respectively). NT-proBNP was negatively associated with LV ejection fraction, LVSF, and LVSFz (P < or = .05) and positively associated with LVSDz (P < .001). High-sensitivity C-reactive protein was negatively associated with LVSF (P = .02) and positively associated with NT-proBNP (P = .03). Tumor necrosis factor alpha was negatively associated with LVSF and LVSFz (P < or = .03) and positively associated with LVSDz and NT-proBNP (P < or = .02). Soluble tumor necrosis factor receptor II was negatively associated with LVSFz (P = .03). CONCLUSIONS Neuroendocrine and inflammatory activation are associated with more severe symptoms and worse cardiac characteristics in pediatric HF. Blood levels of these biomarkers could be used to better assess the severity of HF in children.

Serial Measurements of Serum NT-proBNP as Markers of Left Ventricular Systolic Function and Remodeling in Children with Heart Failure

BACKGROUND Increasing serum levels of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) are associated with worsening heart failure (HF) in adults. We determined whether changes in NT-proBNP level are associated with changes in symptoms and left ventricular (LV) systolic function and remodeling in children with HF secondary to dilated cardiomyopathy. METHODS We retrospectively examined associations between serum NT-proBNP levels and NYHA/Ross functional class, LV systolic and diastolic diameter (LVSD-z and LVDD-z), LV ejection fraction (LVEF), and LV shortening fraction (LVSF-z) using generalized linear mixed models. Fluctuation in functional class of subjects was also modeled using logistic regression and receiver operating characteristic (ROC) curves. RESULTS In 36 children (14 males), a 10-fold increase in NT-proBNP serum levels was associated (P < .001) with a 9.8% decrease in LVEF, a 3.25-unit drop in LVSF-z, a 1.53-unit increase in LVDD-z, a 2.64-unit increase in LVSD-z, and an increased odds of being in functional class III/IV (OR 85.5; 95% CI, 10.9 to 671.0). An NT-proBNP level greater than 1000 pg/mL identified children constantly or intermittently in functional class III-IV with 95% sensitivity and 80% specificity. The reliability of a single NT-proBNP value was 0.61, but the means for two and three NT-proBNP values were 0.76 and 0.82, respectively. CONCLUSIONS In children with HF, NT-proBNP is associated with cardiac symptoms and indices of LV systolic dysfunction and remodeling. NT-proBNP >1000 pg/mL identifies highly symptomatic children. Within subject serial measurements of NT-proBNP are needed for a reliable and accurate determination of disease status and/or course.

Cardiac anomalies in the setting of the Abernethy malformation of the portal vein.

We describe a child with tricuspid atresia associated with a porto-systemic shunt and complete absence of the portal vein, the latter known as the Abernethy malformation. As far as we are aware, this association has not previously been reported. We review the various cardiac defects that have been reported in children with the Abernethy malformation, emphasizing the interesting clinical presentations of this rare malformation of the portal venous system.

Pharmacological Therapy in Children with Atrioventricular Reentry: Which Drug?

Atrioventricular reentrant tachycardia (AVRT) is the most common cause of supraventricular tachycardia in young children. In nearly 70% of cases, there is manifest preexcitation on electrocardiogram. In the rest, the accessory pathway is concealed. Drugs control AVRT by affecting conduction through the atrioventricular node (beta-blockers, digoxin, verapamil) or accessory pathway (flecainide, propafenone) or both (sotalol, amiodarone). Adenosine is the drug of choice in acute management of AVRT in hemodynamically stable children. In adenosine-resistant cases, intravenous flecainide, procainamide, esmolol, propafenone and amiodarone are other treatment options. Hypotension and bradycardia can occur during administration of these drugs. Verapamil may be used to treat AVRT using a concealed pathway. Verapamil should be avoided in infants and in patients with decreased cardiac function. In chronic management, catheter ablation is the preferred treatment in older children with frequent AVRT. In infants and small children, ablation is associated with higher risk, and pharmacologic management is recommended. Beta-blockers are the preferred first line drugs for chronic management. In patients with concealed accessory pathway, digoxin and calcium channel blockers are alternative options. Sotalol, flecainide, propafenone and amiodarone can be prescribed in resistant cases. Flecainide and propafenone should be avoided in children with structurally abnormal hearts because of a higher risk of proarrhythmia. The initiation of flecainide, propafenone and sotalol therapy is recommended in an inpatient setting to monitor for proarrhythmias.