High Time to Consider the Role of Thyroid Function in Single Ventricle Heart Disease.

Herein we respond to the controversial United States Food and Drug Administration (FDA) recommendation to perform thyroid function testing in children up to 3 years of age within 3 weeks of exposure to iodinated contrast media (ICM). Considering the many effects of thyroid hormone on the cardiovascular system, the increased risk of thyroid disease in patients with congenital heart disease, the hemodynamic consequences of the Fontan circulation on the thyroid gland, and the potential clinical significance of subclinical hypothyroidism, we share our perspective that the cardiovascular effects of thyroid hormone may carry more influence for patients with single ventricle heart disease. In our opinion, the FDA statement prompts us to consider routine thyroid hormone surveillance testing in the long-term management of patients with single ventricle heart disease.

Bronchiolitis obliterans organising pneumonia secondary to tacrolimus toxicity in a pediatric cardiac transplant recipient.

BACKGROUND: Bronchiolitis obliterans organising pneumonia is a rare complication associated with calcineurin inhibitors and mammalian target of rapamycin inhibitors. While bronchiolitis obliterans organising pneumonia in adult transplant patients has been reported, it has not been well described in pediatric transplant patients. CASE DESCRIPTION: We present a case of a 19-month-old male patient with dilated cardiomyopathy who underwent orthotropic heart transplantation at 14 months of life for heart failure refractory to medical therapy. Approximately 4 months post-transplant, he presented with diarrhea and vomiting with acute kidney injury secondary to dehydration. His tacrolimus level on admission and first week of hospitalisation was within target range of 10-12 ng/ml. He was diagnosed with esophagitis and prescribed proton pump inhibitors. Our patient subsequently developed significant respiratory distress with initial chest radiograph showing right lower lobe opacities. Repeat tacrolimus at the time of worsening respiratory status was 84.2 ng/dL and his tacrolimus was held. He required intubation due to significant hypoxia with progression of lung to disease and development of diffuse bilateral opacities consistent with acute respiratory distress syndrome. Despite initiation of steroids and aggressive ventilator management, he continued to be hypoxic on maximal respiratory support. After 28 days post admission, support was withdrawn. On autopsy, his lung biopsy findings were consistent with bronchiolitis obliterans organising pneumonia. CONCLUSION: Life-threatening bronchiolitis obliterans organising pneumonia can be seen in pediatric transplant patients on tacrolimus or when transitioning from tacrolimus to sirolimus, highlighting the need for close monitoring of heart transplant patients on immunosuppressive medications presenting with hypoxia.

Emergency Department Management of Pediatric Heart Transplant Recipients: Unique Immunologic and Hemodynamic Challenges.

BACKGROUND: Since the first heart transplant in 1967, there has been significant progress in this field of cardiac transplantation. Approximately 600 pediatric heart transplants are performed every year worldwide. With the increasing number of pediatric heart transplant patients, and given the few tertiary care pediatric transplant centers, adult and pediatric emergency department (ED) providers are increasingly engaged in the care of pediatric heart transplant recipients in the ED. OBJECTIVE: The aim of this article is to review common ED scenarios pertinent to the pediatric heart transplant patients. DISCUSSION: There are complications unique to this population, such as rejection, opportunistic infections, and medication side effects, that require special considerations, and it is helpful for the emergency medicine (EM) provider to have knowledge about them. CONCLUSIONS: The unique immunological challenges in these patients, including rejection and medication side effects and opportunistic infections, make this population fragile, and the knowledge of these challenges is helpful for EM providers.

Pneumocystis pneumonia with hypogammaglobulinemia in a pediatric patient who underwent heart transplantation.

A 23-month-old Caucasian female who had heart transplantation (HT) at 11 days of age was diagnosed with Pneumocystis pneumonia (PCP) in the setting of secondary hypogammaglobulinemia (HGG). She was diagnosed with HGG at 5 months of age and had been receiving monthly intravenous immunoglobulin infusion. This is the first case report describing the clinical course of PCP in a pediatric patient with HGG. She developed PCP 23 months after HT even when she was off steroids and was receiving timely IVIG. The case posed some clinical questions regarding PCP prophylaxis and HGG management.

Infantile-onset pompe disease: a tale of two cases.

Pompe disease is a type-II glycogen storage disease, and clinical manifestations include hypertrophic cardiomyopathy and generalised muscular hypotonia. Enzyme replacement therapy has proven to be effective in reversing the ventricular hypertrophy. The outcomes are variable depending on time to diagnosis and severity of the cardiac disease. We describe two contrasting cases of patients with infantile-onset Pompe disease. The first child was diagnosed late and had severe cardiac hypertrophy with respiratory decompensation and ventilator dependence and eventual death. The second case was diagnosed at birth with early initiation of therapy resulting in a good outcome. Our cases highlight the importance of early initiation of enzyme replacement therapy to improve clinical outcomes.

Left ventricular adaptation following orthotopic heart transplantation in children: A speckle tracking echocardiographic imaging study.

BACKGROUND: Evolution of left ventricle (LV) function in the pediatric OHT population has not been well described. Our hypothesis was that, in children following OHT without any rejection, there would be progressive normalization of LV size and function over 2 years. METHODS: LV function was evaluated using STE and conventional echo parameters at five time points in pediatric OHT patients without any rejection in the first 2 years following OHT and normal controls. LV global peak systolic longitudinal strain (LVPLS) and strain rate, LV peak systolic radial and circumferential strain (LVRS and LVCS), and strain rate were analyzed. RESULTS: We had twenty two patients with median age at OHT of 1.27 years ( IQR 0.19, 5.6 years). The LVPLS (mean ± SD) was abnormal in the post-OHT echocardiograms at 1 week (-12.4 ± 3.7) and 1 month (-13.9 ± 3.7) and significantly improved at 6 months (-15.8 ± 3.2), 1 year (-15.7 ± 3.1), and 2 years (-17.8 ± 2.8). However, LVPLS remained below the normal group even at 2 years following OHT (-21.3 ± 1.76). CONCLUSION: In children following OHT, despite the absence of rejection, strain values are significantly impaired in the initial months, improve progressively over the first 2 years but remain abnormal compared with healthy controls.

Right Ventricular Dysfunction as an Echocardiographic Measure of Acute Rejection Following Heart Transplantation in Children.

Noninvasive biomarkers of acute allograft rejection (AAR) following orthotopic heart transplantation (OHT) are needed. The aim of this study was to investigate the accuracy of echocardiographic (ECHO) right ventricular (RV) global functional and resistance indices in the detection of AAR. This retrospective chart review included children with biopsy-proven AAR (grade ≥ 2R cellular or CD4 + antibody-mediated rejection) following OHT and an ECHO within 12 h of the biopsy. ECHO measures: (a) ratio of systolic to diastolic duration (S/D), (b) RV myocardial performance index (MPI) and (c) tricuspid regurgitant gradient to RV outflow tract velocity time integral ratio (TRG/VTI), were derived at baseline, during AAR and at two follow-ups. Sixteen patients [56% male, mean (SD) age at OHT 3.5 (4.3) years] had 16 AAR episodes. S/D (1.15 vs. 1.60, p < 0.01), RV MPI (0.19 vs. 0.39, p < 0.01) and TRG/VTI (1.05 vs. 1.7, p = 0.01) deteriorated during AAR and, except for diastolic duration, improved significantly at first follow-up. The negative predictive values for S/D, RV MPI and TRG/VTI at cutoffs of 1.3, 0.31 and 1.3 were 97, 97 and 87%, respectively. RV S/D, MPI and TRG/VTI deteriorated during AAR. Their excellent negative predictive values suggest that their incorporation in surveillance may obviate the need for routine biopsies.

New-onset diabetes mellitus after heart transplantation in children - Incidence and risk factors.

Diabetes mellitus is a recognized complication of SOT in adults and is associated with decreased graft and patient survival. Little is known about NOD in pediatric HT recipients. We aimed to characterize the incidence and describe risk factors for development of NOD after HT in children. Children who developed diabetes after HT were identified from the OPTN database. Demographic and clinical data before and after transplant were compared between patients with and without NOD. A total of 2056 children were included, 56% were male, 54% were Caucasian, and 62% had cardiomyopathy prior to HT. NOD developed in 219 children (11%) after HT. The incidence of NOD was 2.4, 9.0, and 10.4% at one, five, and 10 yr after HT, respectively. Obesity (HR: 4.32), dialysis prior to transplant (HR: 2.38), African American race (HR: 1.86), transplant before year 2000 (HR: 1.82), female gender (HR: 1.68), and older age at transplant (HR: 1.28) were independent predictors of NOD. The major modifiable risk factor for NOD is obesity, imparting the maximum hazard. Improved surveillance for diabetes in high-risk patients and specific prevention and intervention strategies are imperative in this population.

Strain and strain rate imaging using speckle tracking in acute allograft rejection in children with heart transplantation.

Acute allograft rejection is a major cause of morbidity and mortality following heart transplantation. There is no reliable noninvasive test to diagnose rejection. We aimed to investigate the accuracy of strain by speckle tracking echocardiography in the detection of acute rejection. We identified acute rejection episodes in patients followed at a single transplant center. Data were collected at baseline, during rejection and two follow-up points. Peak systolic radial and circumferential strain at the level of papillary muscles and peak systolic longitudinal strain from apical four-chamber view were analyzed offline. ANOVA was used for comparison between groups. p value ≤0.05 was considered significant. Fifteen rejection episodes were identified. There were no differences in the fractional shortening, LV posterior wall thickness, E/A, septal E/E', septal S', lateral E/E', lateral S', or MPI during rejection, compared to baseline. There was a significant increase in the LV mass during a rejection episode (47.5 vs. 34.4 g/ht(2.7) [p = 0.03]). The peak systolic radial strain (18.3 vs. 26.5; p = 0.03), longitudinal strain (-11.7 vs. -14.6; p = 0.05), and circumferential strain (-14.4 vs. -21.7; p = 0.05) declined significantly during rejection. In conclusion, peak systolic radial, longitudinal and circumferential strain decline and LV mass increases during an episode of rejection.

Successful Explantation of Berlin Heart Excor in Two Young Children.

Berlin Heart EXCOR ventricular assist device (VAD) implantation in children is widely used as bridge-to-heart transplantation. Berlin left ventricular assist device (LVAD) support as a bridge to recovery is rare. There is a scarcity of literature describing systematic evaluation in pediatric VAD explantation. Patient 1. A 3 month old boy presented with acute heart failure secondary to myocarditis. An echocardiogram demonstrated severely depressed left ventricular function. He required ECMO cannulation and was decannulated 11 days later. He continued to be hemodynamically unstable and required Berlin LVAD implantation with the intent to bridge to transplantation. Patient 2. A 3 month old boy presented initially with a heart rate of 250 beats/min and an electrocardiogram showed multifocal atrial tachycardia. An echocardiogram showed severely decreased left ventricular function. He was placed on ECMO due to unstable hemodynamics. He did not tolerate ECMO decannulation due to persistent chaotic atrial rhythm and underwent Berlin LVAD implantation with the intent to bridge to transplantation. After both patients showed evidence of myocardial recovery, they underwent a weaning protocol that includes: screening, trial-off with echocardiography, and trial-off in the catheterization suite. Our patients met the criteria and underwent successful explantation. Explantation of VAD can be successfully performed even in young children with appropriate candidate selection and a multidisciplinary and systematic approach.

Heart Transplant in Children: What a Primary Care Provider Needs to Know.

Heart transplantation is offered to children with heart failure that is not amenable to medical or surgical therapy. Indications for heart transplant include unrepairable congenital heart disease, failed palliation of congenital heart disease, and cardiomyopathies. There has been tremendous progress in this field since the first heart transplant was performed in 1967. Each year, approximately 500 pediatric heart transplants take place worldwide. Pediatric heart transplant survivors are living longer with their initial transplant. Many pediatric practitioners are faced with caring for these patients before as well as after the heart transplant and, therefore, they should be knowledgeable about basic principles related to heart transplant. There are certain complications that are unique to this population, and medication side-effects, evaluation and management of a febrile illness, opportunistic infections, vaccination, pregnancy, and exercise recommendations are areas that require special consideration. [Pediatr Ann. 2018;47(4):e172-e178.].

Dilated cardiomyopathy with cardiogenic shock in a child with Kearns-Sayre syndrome.

Kearns-Sayre syndrome (KSS) is a mitochondrial myopathy resulting from mitochondrial DNA deletion. This syndrome primarily involves the central nervous system, eyes, skeletal muscles and the heart. The most well-known cardiac complications involve the conduction system; however, there have been case reports describing cardiomyopathy. We describe a case of a child with KSS who presented with decompensated cardiac failure from dilated cardiomyopathy representing cardiomyocyte involvement of KSS. Our patient had a rapidly progressing course, despite maximal medical management, requiring emergent institution of extracorporeal membrane oxygenation and transition to a ventricular assist device. To the best of our knowledge, this is the youngest patient in the literature to have dilated cardiomyopathy in KSS.

Epidemiology, Clinical Presentation, and Outcomes of Kawasaki Disease Among Hospitalized Children in an Inner City Hospital Before and After Publication of the American Academy of Pediatrics/American Heart Association Guidelines for Treatment of Kawasaki Disease: An 11-Year Period.

The effect of 2004 Kawasaki disease (KD) guidelines on diagnosis and outcome of KD is lacking. We studied the epidemiology of KD in our region and compared the incidence, presentation, and outcome of KD before and after publication of the guidelines. A retrospective chart review was conducted for patients admitted with a diagnosis of KD. Demographics, laboratory data, and clinical data were collected. Comparison was made between 2 groups: prepublication (2000-2004) and postpublication (2005-2009) of guidelines. A total of 312 children were included; 64% were African American, 23% White, and 2% Asian; 61% were boys; 79% were complete KD, and 66% were in winter/spring. There was a significant increase in KD cases over the 11 years. There was no significant difference in clinical findings and outcome between the 2 groups. KD admissions in our region significantly increased during the postpublication period. There was no difference in clinical presentation, laboratory findings, or outcome between the 2 groups.

Cocaine-induced relaxation of isolated rat aortic rings and mechanisms of action: possible relation to cocaine-induced aortic dissection and hypotension.

Cocaine HCl is well known for its toxic effects on the cardiovascular system, but little is known about its effects on different regional blood vessels. We designed experiments to determine if cocaine HCl could influence the tension of isolated aortic rings, i.e., induce contraction or relaxation. Surprisingly, cocaine HCl (1 x 10(-5) to 6 x 10(-3) M) relaxed isolated aortic rings precontracted by phenylephrine in a concentration-dependent manner. No significant differences were found between intact or denuded isolated aortic rings (P>0.05). The maximal % relaxations of intact vs. denuded isolated aortic rings were 108.9+/-24.3% vs. 99.5+/-8.3% (P>0.05). Cocaine HCl, 2 x 10(-3) M, was found to inhibit contractions by phenylephrine; EC50s were increased (P<0.01) and Emax's were decreased (51.3+/-16.4% vs. 89.8+/-10.6%, P<0.01). A variety of amine antagonists could not inhibit the relaxant effects of cocaine HCl (P>0.05). The cyclooxygenase-1 inhibitor, indomethacin, also failed to inhibit relaxations induced by cocaine HCl (P>0.05). Neither L-arginine, NG-monomethyl-L-arginine (L-NMMA), nor methylene blue could inhibit the relaxations induced by cocaine HCl (P>0.05), suggesting cocaine HCl does not relax isolated aortic rings by inducing the synthesis or release of nitric oxide (NO) or prostanoids from either endothelial or vascular muscle cells. Inhibitors of cAMP, cGMP and protein kinase G (PKG) also failed to inhibit cocaine-induced relaxations. Cocaine HCl (1 x 10(-5) to 6 x 10(-3) M) could also relax isolated aortic rings precontracted by phenylephrine in high K+ depolarizing buffer. Surprisingly, calyculin A, an inhibitor of myosin light chain (MLC) phosphatase, inhibited cocaine-induced relaxations in a concentration-dependent manner, suggesting the probable importance of cocaine-induced MLC phosphatase activation in rat aortic smooth muscle cells. It was also found that cocaine HCl could dose-dependently inhibit Ca2+-induced contractions of isolated aortic rings in high K+-Ca2+-free buffer, suggesting that cocaine HCl may inhibit Ca2+ influx and/or intracellular release.