Echocardiographic Screening for Postoperative Pericardial Effusion in Children.

Pericardial effusion (PE) after cardiac surgery can be life threatening without timely detection, and the optimal screening method is unknown. We sought to evaluate the role of a surveillance echocardiogram on postoperative day 10 (± 2), determine the incidence of postoperative PE, and identify risk factors. We conducted a retrospective cohort study including all pediatric patients who underwent open heart surgery at a single institution over a 7-month period. To identify risk factors for PE, medical records of patients with PE detected within 6 weeks after surgery (cases) were compared with patients without PE (controls). Of 203 patients, 52 (26%) had PE within 6 weeks; 42 (81%) were trivial-small and 10 (19%) were moderate-large. Twenty-nine (56%) were first detected within 7 days post-operatively, including all cases developing cardiac tamponade (n = 3). An echocardiogram was done 10 (± 2) days post-operatively in 41/52 cases, of which 12/41 (29%) did not have a PE at this time, 24/41 (59%) had a trivial-small PE, and 5/41(12%) had a moderate-large PE; 2 of the latter had no prior detected PE. Closure of an atrial septal defect had the highest incidence of PE (42%). PE cases were associated with postoperative nasopharyngeal detection of a respiratory virus (OR 3.8, p = 0.03). In conclusion, the majority of PE cases were detected within 7 days post-operatively, including all cases subsequently developing cardiac tamponade. Day 10 echocardiography infrequently detected a moderate or large effusion that had previously gone undiagnosed. A positive perioperative nasopharyngeal aspirate for a respiratory virus was associated with postoperative PE.

Pompe Disease: Diagnosis and Management. Evidence-Based Guidelines from a Canadian Expert Panel.

Pompe disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid alpha-glucosidase. Patients have skeletal muscle and respiratory weakness with or without cardiomyopathy. The objective of our review was to systematically evaluate the quality of evidence from the literature to formulate evidence-based guidelines for the diagnosis and management of patients with Pompe disease. The literature review was conducted using published literature, clinical trials, cohort studies and systematic reviews. Cardinal treatment decisions produced seven management guidelines and were assigned a GRADE classification based on the quality of evidence in the published literature. In addition, six recommendations were made based on best clinical practices but with insufficient data to form a guideline. Studying outcomes in rare diseases is challenging due to the small number of patients, but this is in particular the reason why we believe that informed treatment decisions need to consider the quality of the evidence.

Evaluation of single right atrial volume and function with magnetic resonance imaging in children with hypoplastic left heart.

BACKGROUND: Standardized methods to evaluate atrial properties in single ventricles are lacking. OBJECTIVE: To determine the feasibility of quantifying right atrial volumes and function in hypoplastic left heart using MRI. MATERIALS AND METHODS: We studied 15 infants with hypoplastic left heart prior to Glenn surgery (mean age 4.2 months [standard deviation 0.3]) who underwent cardiac MRI with evaluation of atrial volumes and emptying fraction using monoplane two-chamber, monoplane four-chamber, and biplane methods, all of which were compared to the atrial short-axial oblique stack method. We compared atrial end-diastolic volume, end-systolic volume and emptying fraction among these methods. We analyzed reproducibility of the methods using Bland‒Altman plots. RESULTS: Both four-chamber and biplane methods showed high correlations for atrial end-diastolic volume (r = 0.7 and r = 0.8, respectively; P < 0.01) and end-systolic volume (r = 0.8 and r = 0.9, respectively; P < 0.01) with small mean differences (-0.2 ± 2.9 standard deviation [SD] ml and -0.8 ± 1.6 ml, respectively, for atrial end-diastolic volume and -0.8 ± 1.5 ml and -0.9 ± 0.9 ml, respectively, for atrial end-systolic volume). The short-axial oblique method was the most reproducible, followed by the four-chamber method. CONCLUSION: MRI assessment of atrial volume and function is feasible in hypoplastic left heart and might provide further insight into single-ventricle mechanics.

Whole Blood Cardiac Troponin "Triaging" to Improve Early Detection of Myocardial Injury at a Pediatric Hospital.

BACKGROUND: The importance of offering on-site cardiac troponin (cTn) testing at pediatric hospitals may be underappreciated. We developed a rapid rule-in process for myocardial injury at a pediatric hospital experiencing delays in off-site high-sensitivity cardiac troponin T (hs-cTnT) testing. METHODS: Collect-to-verify turnaround times (TATs) for off-site testing were reviewed. Pre-analytic changes to improve TATs were devised, implemented and evaluated, after which a new analyzer was selected and evaluated for on-site cTn testing. Performance of the new analyzer's assay was compared to the off-site hs-cTnT assay, and post go-live TATs for on-site testing were assessed. RESULTS: Median collect-to-verify TAT for short turnaround-time (STAT) priority off-site plasma hs-cTnT testing was 104 min, with 35% of orders having a TAT >120 min. Eliminating serum separator tubes and requiring a separate plasma separator tube did not significantly reduce TATs. A QuidelOrtho Triage® MeterPro whole blood cardiac troponin I (cTnI) assay was implemented to "triage" time-critical and STAT priority specimens collected for off-site hs-cTnT testing. Elevated cTnI (≥0.02 µg/L) had a sensitivity of 91% for clear elevations in hs-cTnT (≥53 ng/L) but a 0% sensitivity for modest elevations (5 to 13 ng/L, 14 to 52 ng/L). An interpretive comment was auto-appended to cTnI results indicating that clinicians should wait for the hs-cTnT result if cTnI was normal. Median collect-to-verify TAT for on-site cTnI testing was <50% the TAT for off-site hs-cTnT testing. CONCLUSIONS: On-site point-of-care whole blood cTn testing can rapidly confirm significant or late-presenting myocardial injury. Combined with simultaneous off-site high-sensitivity cardiac troponin (hs-cTn) testing, this workflow is a viable interim solution for pediatric hospitals without on-site hs-cTn testing.

Optimization of myocardial nulling in pediatric cardiac MRI.

BACKGROUND: Current protocols to determine optimal nulling time in late enhancement imaging using adult techniques may not apply to children. OBJECTIVE: To determine the optimal nulling time in anesthetised children, with the hypothesis that this occurs earlier than in adults. MATERIALS AND METHODS: Sedated cardiac MRI was performed in 12 children (median age: 12 months, range: 1-60 months). After gadolinium administration, scout images at 2, 3, 4 and 10 min and phase sensitive inversion recovery (PSIR) images from 5 to 10 min were obtained. Signal-to-noise ratio (SNR) and inversion time (TI) were determined. Quality of nulling was assessed according to a grading score by three observers. Data was analysed using linear regression, Kruskal-Wallis and quadratic-weighted kappa statistics. RESULTS: One child with a cardiomyopathy had late enhancement. Good agreement in nulling occurred for scout images at 2 (κ = 0.69) and 3 (κ = 0.66) min and moderate agreement at 4 min (κ = 0.57). Agreement of PSIR images was moderate at 7 min (κ = 0.44) and poor-fair at other times. There were significant correlations between TI and scout time (r = 0.61, P < 0.0001), and SNR and kappa (r = 0.22, P = 0.017). CONCLUSION: Scout images at 2-4 min can be used to determine the TI with little variability. Image quality for PSIR images was highest at 7 min and SNR optimal at 7-9 min. TI increases with time and should be adjusted frequently during imaging. Thus, nulling times in children differ from nulling times in adults when using standard adult techniques.

Abnormal flow in the posterior descending artery: an echo Doppler clue to the anomalous origin of left anterior descending coronary artery from the pulmonary trunk.

Anomalous origin of the left anterior descending coronary (LAD) from the pulmonary trunk is a rare lesion. We describe a neonate with anomalous origin of the LAD from the pulmonary artery and the circumflex artery arising normally from the left-facing sinus. The finding of a tortuous and dilated posterior descending coronary artery suggested increased intercoronary collateral flow and provided a clue to the identification of the anomaly in an otherwise asymptomatic neonate. Interrogation of the posterior descending coronary artery should be included in the routine echocardiographic examination of children, as unusual flow patterns may help identify aberrant coronary artery connections.

Impact of a Pediatric Cardiology Clinical Program on Congenital Heart Disease Outcomes in Guyana.

Background: Children with congenital heart disease (CHD) in Guyana have not historically been managed with timely intervention, increasing the likelihood of serious, irreversible complications. In 2014, a pediatric cardiology clinical program (Guyana Paediatric Cardiology Steering Committee [GPCSC]) and partnership with International Children's Heart Foundation (BabyHeart) was developed to improve CHD care. Objectives: To describe the characteristics of CHD in Guyanese children and to determine the impact of GPCSC on CHD outcomes. Methods: Qualitative comparison between CHD patients sent for surgery prior to GPCSC (pre-GPCSC cohort) and those managed through GPCSC (post-GPCSC cohort). Findings: Eighty-eight pre-GPHC patients were identified from 2005 to 2014. A total of 319 CHD patients were referred post-GPCSC. In all, 114 patients required surgical or catheterization procedures, with 74 patients prioritized for interventions within 29 months post-GPCSC. Mean age at surgery was 77 months in both cohorts, with younger children represented in the post-GPCSC cohort. Postoperative follow-up was more frequent post-GPCSC (100% vs 35%). Vital status of 48% of pre-GPCSC patients is unknown, with more pre-GPCSC patients known to be deceased compared with post-GPCSC (9% vs 5%). Pre-GPCSC patients had more incorrect diagnosis and inoperable disease when sent for surgery. Interpretation: Patients undergoing surgery post-GPCSC had more appropriate and timely interventions, better follow-up, and increased survival. The feasibility and positive impact of this collaborative pediatric cardiology clinical program in Guyana is demonstrated, with potential applicability for other low- and middle-income countries. Obstacles to referral of children with CHD in Guyana can begin to be addressed, with the goal of more complete access to timely intervention, and improved outcomes for these children.

Echocardiographic Image Quality Deteriorates with Age in Children and Young Adults with Duchenne Muscular Dystrophy.

BACKGROUND: Advances in medical care for patients with Duchenne muscular dystrophy (DMD) have resulted in improved survival and an increased prevalence of cardiomyopathy. Serial echocardiographic surveillance is recommended to detect early cardiac dysfunction and initiate medical therapy. Clinical anecdote suggests that echocardiographic quality diminishes over time, impeding accurate assessment of left ventricular systolic function. Furthermore, evidence-based guidelines for the use of cardiac imaging in DMD, including cardiac magnetic resonance imaging (CMR), are limited. The objective of our single-center, retrospective study was to quantify the deterioration in echocardiographic image quality with increasing patient age and identify an age at which CMR should be considered. METHODS: We retrospectively reviewed and graded the image quality of serial echocardiograms obtained in young patients with DMD. The quality of 16 left ventricular segments in two echocardiographic views was visually graded using a binary scoring system. An endocardial border delineation percentage (EBDP) score was calculated by dividing the number of segments with adequate endocardial delineation in each imaging window by the total number of segments present in that window and multiplying by 100. Linear regression analysis was performed to model the relationship between the EBDP scores and patient age. RESULTS: Fifty-five echocardiograms from 13 patients (mean age 11.6 years, range 3.6-19.9) were systematically reviewed. By 13 years of age, 50% of the echocardiograms were classified as suboptimal with ≥30% of segments inadequately visualized, and by 15 years of age, 78% of studies were suboptimal. Linear regression analysis revealed a negative correlation between patient age and EBDP score (r = -2.49, 95% confidence intervals -4.73, -0.25; p = 0.032), with the score decreasing by 2.5% for each 1 year increase in age. CONCLUSION: Echocardiographic image quality declines with increasing age in DMD. Alternate imaging modalities may play a role in cases of poor echocardiographic image quality.

Non-invasive Investigations for the Diagnosis of Fontan-Associated Liver Disease in Pediatric and Adult Fontan Patients.

Fontan-associated liver disease (FALD) is a serious complication related to the chronically elevated venous pressure and low cardiac output of this abnormal circulation. However, diagnostic markers for this condition are limited. We hypothesized that specific tests for fibrosis developed for other chronic liver diseases would identify a higher prevalence of FALD than ultrasound and standard laboratory tests and that identified abnormalities would correlate with time post-Fontan. In this cross-sectional study, we assessed 19 children (average age 8.4 ± 4.3 and 5.4 ± 4.1 years post-Fontan) and 8 adults (average age 31.5 ± 8.9 and 21.1 ± 4 years post-Fontan) using standard serum laboratory investigations assessing hepatic integrity and function, the FibroTest, liver ultrasound, and transient elastography (FibroScan). In adult Fontan patients, hemoglobin, C-reactive protein, and gamma-glutamyl transpeptidase were significantly increased, and white blood cell and platelet counts were significantly decreased in comparison to the pediatric cohort. International normalized ratio was mildly elevated in both children and adults. FibroTest results were suggestive of fibrosis regardless of time post-Fontan. FibroScan measurements were significantly correlated with time post-Fontan, but the incidence of ultrasound-detected liver abnormalities was variable. No cases of hepatocellular carcinoma were identified. Abnormalities suggestive of FALD occur in both children and adults post-Fontan. Select laboratory tests, and possibly ultrasound and FibroScan in some patients, appear to have the most promise for the non-invasive detection of FALD.

Identification of chloride intracellular channel proteins in spermatozoa.

We have identified for the first time the presence of chloride intracellular channel (CLIC) proteins in bovine epididymal spermatozoa. CLIC1 was discovered during microsequencing of proteins that co-purified with protein phosphatase 1, PP1gamma2, in sperm extracts. In addition to CLIC1, Western blot showed that two additional CLIC family members, CLIC4 and CLIC5, are also present in spermatozoa. CLIC fusion proteins, GST-CLIC1, GST-CLIC4 and GST-CLIC5, were all able to bind to PP1gamma2 in sperm extracts during pull-down assays. Immunofluorescence microscopy revealed that each of the three isoforms occupies a distinct location within the cell. Given that PP1gamma2 is a key enzyme regulating sperm motility, PP1gamma2-binding proteins, such as the CLIC proteins, are likely to play significant roles in sperm function.

Late intervention in an asymptomatic pediatric patient with anomalous left coronary artery.

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is most commonly diagnosed within the first year of life with congestive heart failure symptomatology reflecting left ventricle (LV) dysfunction. The late diagnosis of ALCAPA is presented in a 5-year-old without significant LV dysfunction, mild LV dilatation and only mild mitral regurgitation that did not change significantly after surgery. The timing of surgical intervention in the late diagnosis of ALCAPA remains unclear despite risks of significant ongoing myocardial injury secondary to coronary artery hypoperfusion and progressive mitral valve dysfunction. Intervention in this case allows for revascularization which may reverse ventricular and valvular dysfunction.

Insights into the evolution of myocardial dysfunction in the functionally single right ventricle between staged palliations using speckle-tracking echocardiography.

BACKGROUND: The long-term prognosis of hypoplastic left heart syndrome is limited by progressive right ventricular dysfunction. The aim of this study was to determine the trends in single right ventricular systolic function between staged palliative surgeries using speckle-tracking and conventional echocardiography. METHODS: There were 76 patients with functionally single right ventricles at the (1) pre-Norwood (n = 26), (2) pre-bidirectional cavopulmonary anastomosis (BCPA; n = 19), (3) pre-Fontan (n = 16), and (4) post-Fontan (n = 15) stages, compared with 30 controls of similar ages. Speckle-tracking-derived longitudinal and circumferential strain and strain rate, postsystolic strain index, and mechanical dyssynchrony index were compared with conventional measures of ventricular function. Differences between stages were analyzed using analysis of variance (P < .05). RESULTS: Strain rate was highest at the pre-Norwood stage and decreased at the other stages (longitudinal P < .0001, circumferential P = .0002), as opposed to controls, in whom strain rate was maintained. Longitudinal strain was significantly decreased at the pre-BCPA stage compared with the pre-Norwood stage (P = .004), but circumferential strain was maintained, resulting in a corresponding decrease in the ratio of longitudinal to circumferential strain, which failed to resemble that of controls. Longitudinal (P = .003) and circumferential (P = .002) postsystolic strain indices were greatest at the pre-BCPA stage. CONCLUSIONS: A decline in contractility occurred at the pre-BCPA stage. Although there was evidence of adaptation of the single right ventricle, this failed to resemble the normal left ventricle and may be insufficient to handle the chronic volume load or insult from previous surgery. These findings suggest an intrinsic inability of the single right ventricular myocardium to fully adapt to chronic systemic pressures.

Noninvasive assessment of vascular function and hydraulic power and efficiency in pediatric Fontan patients.

BACKGROUND: Invasive studies have shown that children with Fontan palliation have abnormal arterial stiffness, impedance, and hydraulic power and efficiency. The aim of this study was to assess these indexes noninvasively in a cohort of children with Fontan circulation using Doppler echocardiography and compare their results with those of healthy peers. METHODS: This was a case-control study of 22 Fontan patients and 31 healthy control children. Using standard two-dimensional, M-mode, and Doppler echocardiographic imaging and carotid artery applanation tonometry, aortic flows, dimensions, and pulse-wave velocity were measured, and vascular impedance and arterial stiffness were calculated. Hydraulic power and efficiency were calculated from standard fluid dynamics formulae. RESULTS: The median age was similar between groups. Stroke volume index (39 vs 39 mL/min/m(2)) and cardiac index (2.6 vs 2.5 L/min/m(2)) were similar. Aortic cross-sectional area (3.3 vs 2.8 cm(2)), peak aortic flow (302 vs 261 cm(3)/sec), and myocardial performance index (0.47 vs 0.25) were higher and ejection fraction (50% vs 66%) was lower in Fontan patients. Input impedance (61 vs 83 dyne · sec/cm(5)/m(2)) was lower in Fontan patients. Pulse-wave velocity (488 vs 364 cm/sec), elastic pressure-strain modulus (305 vs 263 torr), and stiffness index (4.15 vs 3.04) were higher in Fontan patients. Total arterial compliance (1.29 vs 1.32 mL/torr/m(2)) and mean power (606 vs 527 mW/m(2)) were similar and total hydraulic power (716 vs 627 mW/m(2)) was higher in Fontan patients. Efficiency and the power cost per unit of forward flow were similar. CONCLUSIONS: Despite stiffer aortas, Fontan patients generate more hydraulic power associated with decreased ventricular function to achieve a similar hydraulic efficiency. In Fontan patients, therapy that is given to improve ventricular function may need to target vascular stiffness as well. This technique may be used to monitor the efficacy of therapeutic interventions.

Benign cardiac tumours, malignant arrhythmias.

Four cases of pediatric cardiac tumours (PCTs) associated with ventricular arrhythmias are reported. Sudden cardiac death attributable to the tumour occurred in two children. A third child received an implantable cardioverter defibrillator and the fourth had persistent ventricular arrhythmia despite medical therapy. Most PCTs are considered benign; however, the development of malignant arrhythmias may complicate the management of these tumours in some patients. The literature regarding the arrhythmogenic potential of PCTs and the use of implantable cardioverter defibrillators in these patients is reviewed. The series highlights the deficiency of prognostic information for this cohort.

Proteomic analysis of bovine sperm YWHA binding partners identify proteins involved in signaling and metabolism.

Posttranslational modification of proteins by phosphorylation is involved in regulation of sperm function. Protein phosphatase 1 gamma isoform 2 (PPP1CC_v2) and protein YWHA (also known as 14-3-3) are likely to be key molecules in pathways involving sperm protein phosphorylation. We have shown that phosphorylated PPP1CC_v2 is bound to protein YWHAZ in spermatozoa. In somatic cells, protein YWHA is known to bind a number of phosphoproteins involved in signaling and energy metabolism. Thus, in addition to PPP1CC_v2, it is likely that sperm contain other YWHA-binding proteins. A goal of the present study was to identify these sperm YWHA-binding proteins. The binding proteins were isolated by affinity chromatography with GST-YWHAZ followed by elution with a peptide, R-11, which is known to disrupt YWHA complexes. The YWHA-binding proteins in sperm can be classified as those involved in fertilization, acrosome reaction, energy metabolism, protein folding, and ubiquitin-mediated proteolysis. A subset of these putative YWHA-binding proteins contain known amino acid consensus motifs, not only for YWHA binding but also for PPP1C binding. Identification of sperm PPP1CC_v2-binding proteins by microcystin-agarose chromatography confirmed that PPP1CC_v2 and YWHA interactomes contain several common proteins. These are metabolic enzymes phosphoglycerate kinase 2, hexokinase 1, and glucose phosphate isomerase; proteins involved in sperm-egg fusion; angiotensin-converting enzyme, sperm adhesion molecule, and chaperones; heat shock 70-kDa protein 5 (glucose-regulated protein 78 kDa; and heat shock 70-kDa protein 1-like. These proteins are likely to be phosphoproteins and potential PPP1CC_v2 substrates. Our data suggest that in addition to potential regulation of a number of important sperm functions, YWHA may act as an adaptor molecule for a subset of PPP1CC_v2 substrates.

Regulation of sperm function by protein phosphatase PP1gamma2.

The intracellular mediators cyclic AMP, calcium and pH regulate sperm function through changes in protein phosphorylation. Protein phosphorylation is the net result of the actions of protein kinases and phosphatases. The protein phosphatase isoform, PPlgamma2, with a unique C-terminus extension is highly enriched in spermatozoa and testis. Changes in PPlgamma2 catalytic activity, its phosphorylation, and binding to its regulatory proteins change during epididymal maturation. Thus PPgamma2 is a key protein in sperm motility regulation; decreased enzyme activity is associated with increased motility. This review summarizes the current knowledge of this sperm protein phosphatase. The biochemical properties of its regulatory proteins, sds22 and protein 14-3-3, among others, are discussed. Future studies will elucidate sperm signalling pathways involving PP1gamma2 and determine if the unique structure of PP1gamma2 is critical to normal male gamete development and function. Understanding the role of PP1gamma2 will not only contribute to the basic understanding of male gamete functions but also has practical applications in clinical andrology and in the development of male contraceptives.

Protein 14-3-3zeta binds to protein phosphatase PP1gamma2 in bovine epididymal spermatozoa.

The protein phosphatase PP1gamma2 is critical in the regulation of sperm motility and fertility. Its activity is regulated by its binding proteins and by phosphorylation. We have recently shown that PP1gamma2 is phosphorylated and that the amount of phosphorylated PP1gamma2 increases during sperm epididymal maturation (Huang et al., Biol Reprod 2004; 70:439-447). Microsequencing revealed that protein 14-3-3 coeluted with phosphorylated PP1gamma2 during column chromatography of bovine sperm extracts. Western blot analyses confirmed the presence of protein 14-3-3 not only in bovine spermatozoa but also in spermatozoa of diverse species-bull, hamster, horseshoe crab, monkey, rat, turkey, and Xenopus. The binding between PP1gamma2 and protein 14-3-3 was confirmed by coimmunoprecipitation experiments and in pull-down assays with recombinant GST-14-3-3. Western blot analysis and protein 14-3-3 immunoprecipitates with antibodies against the consensus binding domain of protein 14-3-3 reveal that, in addition to PP1gamma2, at least two other protein 14-3-3 binding partners are present in spermatozoa. Fluorescence immunocytochemistry results indicate that phosphorylated PP1gamma2 and protein 14-3-3 both localize to the postacrosomal region of the head and principal piece of bovine spermatozoa. Together, these results provide conclusive evidence that protein 14-3-3 is present in mature spermatozoa and that PP1gamma2 is one of its binding partners.