Anomalous Pulmonary Venous Return: Insights Into Prenatal Detection.

OBJECTIVES: To review all cases of total anomalous pulmonary venous return (TAPVR) or partial anomalous pulmonary venous return (PAPVR) identified prenatally or postnatally at a single institution and to identify factors that may lead to a correct or missed diagnosis in both high- and low-risk fetuses on screening examinations. METHODS: Fetal images from 16 cases of prenatally or postnatally diagnosed T/PAPVR were retrospectively reviewed to analyze factors that influenced interpretations and diagnoses. RESULTS: Sixteen diagnoses of T/PAPVR were made, with a final number of 10 confirmed cases, 1 of which was PAPVR. Ten fetuses with a presumptive diagnosis of T/PAPVR before delivery were at an average gestational age of 24.7 weeks, with 5 cases diagnosed postnatally. None of the diagnoses of isolated TAPVR were made during a screening examination. Twelve of the pregnancies were complicated by complex cardiac defects, including 6 with heterotaxy syndromes. Of the 5 abnormal cases identified in the postpartum period, 3 had isolated TAPVR. In the 3 patients with isolated defects, prenatal echocardiography was not performed; the anatomy scan interpretations were confounded by multiple factors. In retrospect, there was no obvious sonographic evidence of TAPVR in these patients; however, color flow Doppler imaging of the pulmonary veins was not performed on any of them. CONCLUSIONS: Although fetal echocardiography has improved the overall detection of TAPVR or PAPVR, this abnormality continues to elude prenatal diagnosis during screening in both low- and high-risk patients. We hypothesize that the use of color flow Doppler imaging in the 4-chamber view may assist in diagnosing TAPVR in screening low-risk patients, especially in those with difficult scans.

Tissue plasminogen activator for neonatal coronary thrombosis presenting with mitral valve regurgitation and impaired ventricular function.

OBJECTIVE: Neonatal coronary thrombosis is a rarely reported disorder, with variable outcomes described. This study assessed the feasibility and safety of an institutional protocol using tissue plasminogen activator (tPA) administration for the treatment of neonatal coronary artery thrombi. METHODS: They reviewed the outcome of three neonates with clinical evidence of myocardial infarction secondary to coronary thrombosis. All three underwent the tPA treatment protocol. RESULTS: The three described cases presented at 5 hours, 15 hours, and 10 days of life. The patients identified underwent the tPA protocol at least once. There was clinical evidence of improvement in coronary flow, as well as demonstration of increased left ventricular function and decreased mitral regurgitation. No major adverse events occurred. CONCLUSION: Thrombolytic therapy with this tPA protocol may be safe and effective in treating neonates with coronary thrombosis.

Preprocedural Transthoracic Echocardiography Can Predict Amplatzer Septal Occluder Device Size for Transcatheter Atrial Septal Defect Closure.

OBJECTIVE: To evaluate whether preprocedural transthoracic echocardiography (TTE) can be used to predict Amplatzer septal occluder (ASO) size for device closure of atrial septal defect (ASD). DESIGN: Retrospective review of patients who underwent ASD device closure at our institution between August 2006 and August 2013 was performed. Patients with complex congenital heart disease, devices other than the ASO, multiple devices, or inadequate TTE images were excluded. Those who had transesophageal echocardiography (TEE)-guided device placement were evaluated. A blinded observer reviewed their preprocedural TTE images and applied a scaled formula to predict device size. RESULTS: A total of 186 patients underwent ASO placement during the study period, 87 had TEE guidance, of which 45 met inclusion criteria. The mean predicted device size by the scaled formula was 18.0 ± 5.11 mm, compared to the mean implanted device size of 18.8 ± 5.22 mm. The mean absolute difference between each predicted and final deployed device size was 1.44 mm with 95% CI [1.08, 1.81]. The Pearson correlation showed that the predicted device size had a positive correlation coefficient of 0.94. CONCLUSION: Preprocedural TTE assessment of ASD size using a scaling formula in patients with adequate TTE windows can accurately predict ASO device size and aid in device selection.

Cardiovascular biomarkers in acute Kawasaki disease.

BACKGROUND: Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of acute Kawasaki disease (KD). METHODS: We investigated biochemical evidence of myocardial strain, oxidative stress, and cardiomyocyte injury in 55 acute KD subjects (30 with paired convalescent samples), 54 febrile control (FC), and 50 healthy control (HC) children by measuring concentrations of cardiovascular biomarkers. RESULTS: Levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) were elevated in acute vs. convalescent KD, FC, and HC (p≤0.002), while γ-glutamyl transferase and alanine amino transferase as measures of oxidative stress were increased in acute vs. FC (p≤0.0002). Cardiac troponin I (cTnI) levels, using a highly sensitive assay, were elevated in 30% and 40% of paired acute and convalescent KD subjects, respectively, and normalized within two years of disease onset. NT-proBNP and sST2 negatively correlated with deceleration time, but only NT-proBNP correlated with MV E:A ratio and internal diameter of the coronary arteries (RCA/LAD Zworst). CONCLUSIONS: NT-proBNP and sST2 were elevated in acute KD subjects and correlated with impaired myocardial relaxation. These findings, combined with elevated levels of cTnI, suggest that both cardiomyocyte stress and cell death are associated with myocardial inflammation in acute KD.

Coronary artery dilation in acute Kawasaki disease and acute illnesses associated with Fever.

BACKGROUND: In the absence of a specific test, the diagnosis of clinically incomplete Kawasaki disease (KD) can be challenging. The 2004 American Heart Association guidelines state that the diagnosis of KD is supported by the presence of coronary artery dilation documented by echocardiography. However, the specificity of coronary artery dilation and its prevalence in children with other acute illnesses associated with fever has not been studied. METHODS: A 2-center, prospective study compared the internal diameters and Z-scores (standard deviation [SD] units from the mean internal diameter normalized for body surface area) of the proximal left anterior descending and right coronary arteries measured by echocardiography in febrile children (FC) and children with KD. RESULTS: The median Z-score (interquartile range) of the left anterior descending coronary artery was -0.05 (-0.86, 0.62) and 1.06 (0.36, 2.06) SD units for the 45 FC and the 145 KD patients, respectively (P < 0.0001). For the right coronary artery, the median Z-score was 0.21 (-0.20, 0.87) and 1.04 (0.31, 1.85) SD units for the FC and KD patients, respectively (P < 0.0001). There was no correlation between body temperature at the time of echocardiography and coronary artery Z-score. No febrile child had a coronary artery Z-score ≥ 2.5 SD units. CONCLUSIONS: Z-scores ≥ 2.5 SD units were not observed in our cohort of FC. Therefore, echocardiographic evidence of coronary artery dilation can be used to support the diagnosis of KD.

Pericardiocentesis of noncircumferential effusions using nonstandard catheter entry sites guided by echocardiography and fluoroscopy.

OBJECTIVE: Classically pericardiocentesis has been described and performed through the subxiphiod approach, which is feasible if the pericardial fluid is circumferential or collected inferior or anterior to the heart. However, not uncommonly, the collection of fluid is at the base of the heart or in the posterior or apical portion of the pericardium, necessitating a different approach. The purpose of this study is to describe echo and fluoroscopic guided pericardiocentesis to evacuate noncircumferential effusions, which are not accessible from the standard subcostal approach. METHODS: Retrospective review of all patients with localized/noncircumferential effusions at Rady Children's Hospital San Diego between May 2007 and February 2010 was performed. During these procedures, effusions were identified at the point closest to the skin. The pericardial drains were introduced, directed, and advanced under echocardiographic and fluoroscopic guidance while avoiding major organs. RESULTS: Ten patients were identified (age ranged from 20 days to 22 years, weight ranged from 1.6 kg to 94 kg). All procedures were successful in draining the pericardial effusions with minimal residual fluid and no complications. CONCLUSION: Echocardiographic and fluoroscopic guided pericardiocentesis is a feasible, relatively safe, and reliable technique to drain loculated pericardial effusions using nonstandard entry sites.

Transforming growth factor-beta signaling pathway in patients with Kawasaki disease.

BACKGROUND: Transforming growth factor (TGF)-ß is a multifunctional peptide that is important in T-cell activation and cardiovascular remodeling, both of which are important features of Kawasaki disease (KD). We postulated that variation in TGF-ß signaling might be important in KD susceptibility and disease outcome. METHODS AND RESULTS: We investigated genetic variation in 15 genes belonging to the TGF-ß pathway in a total of 771 KD subjects of mainly European descent from the United States, the United Kingdom, Australia, and the Netherlands. We analyzed transcript abundance patterns using microarray and reverse transcriptase-polymerase chain reaction for these same genes, and measured TGF-ß2 protein levels in plasma. Genetic variants in TGFB2, TGFBR2, and SMAD3 and their haplotypes were consistently and reproducibly associated with KD susceptibility, coronary artery aneurysm formation, aortic root dilatation, and intravenous immunoglobulin treatment response in different cohorts. A SMAD3 haplotype associated with KD susceptibility replicated in 2 independent cohorts and an intronic single nucleotide polymorphism in a separate haplotype block was also strongly associated (A/G, rs4776338) (P=0.000022; odds ratio, 1.50; 95% confidence interval, 1.25 to 1.81). Pathway analysis using all 15 genes further confirmed the importance of the TGF-ß pathway in KD pathogenesis. Whole-blood transcript abundance for these genes and TGF-ß2 plasma protein levels changed dynamically over the course of the illness. CONCLUSIONS: These studies suggest that genetic variation in the TGF-ß pathway influences KD susceptibility, disease outcome, and response to therapy, and that aortic root and coronary artery Z scores can be used for phenotype/genotype analyses. Analysis of transcript abundance and protein levels further support the importance of this pathway in KD pathogenesis.

Recognition of a Kawasaki disease shock syndrome.

OBJECTIVE: We sought to define the characteristics that distinguish Kawasaki disease shock syndrome from hemodynamically normal Kawasaki disease. METHODS: We collected data prospectively for all patients with Kawasaki disease who were treated at a single institution during a 4-year period. We defined Kawasaki disease shock syndrome on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of > or =20%, or clinical signs of poor perfusion. We compared clinical and laboratory features, coronary artery measurements, and responses to therapy and analyzed indices of ventricular systolic and diastolic function during acute and convalescent Kawasaki disease. RESULTS: Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the definition for Kawasaki disease shock syndrome. All received fluid resuscitation, and 7 (54%) required vasoactive infusions. Compared with patients without shock, patients with Kawasaki disease shock syndrome were more often female and had larger proportions of bands, higher C-reactive protein concentrations, and lower hemoglobin concentrations and platelet counts. Evidence of consumptive coagulopathy was common in the Kawasaki disease shock syndrome group. Patients with Kawasaki disease shock syndrome more often had impaired left ventricular systolic function (ejection fraction of <54%: 4 of 13 patients [31%] vs 2 of 86 patients [4%]), mitral regurgitation (5 of 13 patients [39%] vs 2 of 83 patients [2%]), coronary artery abnormalities (8 of 13 patients [62%] vs 20 of 86 patients [23%]), and intravenous immunoglobulin resistance (6 of 13 patients [46%] vs 32 of 174 patients [18%]). Impairment of ventricular relaxation and compliance persisted among patients with Kawasaki disease shock syndrome after the resolution of other hemodynamic disturbances. CONCLUSIONS: Kawasaki disease shock syndrome is associated with more-severe laboratory markers of inflammation and greater risk of coronary artery abnormalities, mitral regurgitation, and prolonged myocardial dysfunction. These patients may be resistant to immunoglobulin therapy and require additional antiinflammatory treatment.