Faculty Bibliography

OBJECTIVE:In this Consensus Statement, we review the etiology and pathophysiology of inflammatory processes seen in critically ill children with cardiac disease. Immunomodulatory therapies aimed at improving outcomes in patients with myocarditis, heart failure, and transplantation are extensively reviewed. DATA SOURCES/METHODS:The author team experience and along with an extensive review of the medical literature were used as data sources. DATA SYNTHESIS/RESULTS:The authors synthesized the data in the literature to present current immumodulatory therapies. For each drug, the physiologic rationale, mechanism of action, and pharmacokinetics are synthesized, and the evidence in the literature to support the therapy is discussed. CONCLUSIONS:Immunomodulation has a crucial role in the treatment of certain pediatric cardiac diseases. Immunomodulatory treatments that have been used to treat myocarditis include corticosteroids, IV immunoglobulin, cyclosporine, and azathioprine. Contemporary outcomes of pediatric transplant recipients have improved over the past few decades, partly related to improvements in immunomodulatory therapy to prevent rejection of the donor heart. Immunosuppression therapy is commonly divided into induction, maintenance, and acute rejection therapy. Common induction medications include antithymocyte globulin, muromonab-CD3, and basiliximab. Maintenance therapy includes chronic medications that are used daily to prevent rejection episodes. Examples of maintenance medications are corticosteroids, cyclosporine, tacrolimus, sirolimus, everolimus, azathioprine, and mycophenolate mofetil. Rejection of the donor heart is diagnosed either by clinically or by biopsy and is treated with intensification of immunosuppression.

BACKGROUND:The association of cardiorenal syndrome (CRS) with mortality in children with dilated cardiomyopathy (DCM) is unknown. METHODS:With a modified Schwartz formula, we estimated glomerular filtration rates (eGFR) for children ≥1 year of age with DCM enrolled in the Pediatric Cardiomyopathy Registry at the time of DCM diagnosis and annually thereafter. CRS was defined as an eGFR of <90 mL/min/1.73 m(2). Children with and without CRS were compared on survival and serum creatinine concentrations (SCr). The association between eGFR and echocardiographic measures was assessed with linear mixed-effects regression models. RESULTS:Of 285 eligible children with DCM diagnosed at ≥1 year of age, 93 were evaluable. CRS was identified in 57 of these 93 children (61.3%). Mean (standard deviation) eGFR was 62.0 (22.6) mL/min/1.73 m(2) for children with CRS and 108.0 (14.0) for those without (P < 0.001); median SCr concentrations were 0.9 and 0.5 mg/dL, respectively (P < 0.001). The mortality hazard ratio of children with CRS versus those with no CRS was 2.4 (95% confidence interval 0.8-7.4). eGFR was positively correlated with measures of left ventricular function and negatively correlated with age. CONCLUSIONS:CRS in children newly diagnosed with DCM may be associated with higher 5-year mortality. Children with DCM, especially those with impaired left ventricular function, should be monitored for renal disease.

OBJECTIVES/OBJECTIVE:This study sought to determine the incidence and predictors of recovery of normal echocardiographic function among children with idiopathic dilated cardiomyopathy (DCM). BACKGROUND:Most children with idiopathic DCM have poor outcomes; however, some improve. METHODS:We studied children <18 years of age from the Pediatric Cardiomyopathy Registry who had both depressed left ventricular (LV) function (fractional shortening or ejection fraction z-score <-2) and LV dilation (end-diastolic dimension [LVEDD] z-score >2) at diagnosis and who had at least 1 follow-up echocardiogram 30 days to 2 years from the initial echocardiogram. We estimated the cumulative incidence and predictors of normalization. RESULTS:Among 868 children who met the inclusion criteria, 741 (85%) had both echocardiograms. At 2 years, 22% had recovered normal LV function and size; 51% had died or undergone heart transplantation (median, 3.2 months), and 27% had persistently abnormal echocardiograms. Younger age (hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.88 to 0.97) and lower LVEDD z-score (HR: 0.78; 95% CI: 0.70 to 0.87) independently predicted normalization. Nine children (9%) with normal LV function and size within 2 years of diagnosis later underwent heart transplantation or died. CONCLUSIONS:Despite marked LV dilation and depressed function initially, children with idiopathic DCM can recover normal LV size and function, particularly those younger and with less LV dilation at diagnosis. Investigations related to predictors of recovery, such as genetic associations, serum markers, and the impact of medical therapy or ventricular unloading with assist devices are important next steps. Longer follow-up after normalization is warranted as cardiac failure can recur. (Pediatric Cardiomyopathy Registry; NCT00005391).

In normal pediatric echocardiograms, the distance from the junction of superior vena cava (SVC) and right atrium to inferior vena cava (IVC) and right atrium is linearly related to height. We examine this relation in children listed for heart transplant with idiopathic dilated cardiomyopathy (IDC) compared with the previously defined normal distribution of SVC-IVC to improve matching of heart sizes. Measurements of SVC-IVC and left ventricular end-diastolic diameter in 55 pediatric patients with IDC were correlated with height, weight, and body surface area. Regression analyses were performed to find the best-fit equation and correlation coefficient. Generalized linear modeling compared SVC-IVC in patients with IDC with normal SVC-IVC values from 254 patients. There was a strong linear relation in patients with IDC between SVC-IVC and height (R2=0.84) and a logarithmic relation to weight (R2=0.80). Left ventricular end-diastolic diameter did not correlate with SVC-IVC or any other parameter. In 87% of patients with IDC, SVC-IVC was over 2 SDs above predicted normal values (mean z-score=4.3±2.1). In conclusion, predicted SVC-IVC in patients with IDC was different from published norms (p<0.001). SVC-IVC in pediatric patients with IDC, although linearly related to height, is consistently above normal values.

High pulmonary vascular resistance index (PVRI) can lead to right ventricular dysfunction and failure of the donor heart early after pediatric heart transplantation. Oral pulmonary vasodilators such as sildenafil have been shown to be effective modifiers of pulmonary vascular tone. We performed a retrospective, observational study comparing patients treated with sildenafil ("sildenafil group") to those not treated with sildenafil ("nonsildenafil group") after heart transplantation from 2007 to 2012. Pre- and posttransplant data were obtained, including hemodynamic data from right heart catheterizations. Twenty-four of 97 (25%) transplant recipients were transitioned to sildenafil from other systemic vasodilators. Pretransplant PVRI was higher in the sildenafil group (6.8 ± 3.9 indexed Woods units [WU]) as compared to the nonsildenafil group (2.5 ± 1.7 WU, p=0.002). In the sildenafil group posttransplant, there were significant decreases in systolic pulmonary artery pressure, mean pulmonary artery pressure, transpulmonary gradient and PVRI (4.7 ± 2.9 WU before sildenafil initiation to 2.7 ± 1 WU on sildenafil, p=0.0007). While intubation time, length of inotrope use and time to hospital discharge were longer in the sildenafil group, survival was similar between both groups. Oral sildenafil was associated with a significant improvement in right ventricular dysfunction and invasive hemodynamic measurements in pediatric heart transplant recipients with high PVRI early after transplant.