Multiple vascular anomalies and refractory pericardial effusion in a young patient with Cantu syndrome: a case report and review of the literature.

BACKGROUND: Cantu syndrome is a rare and complex multisystem disorder characterized by hypertrichosis, facial dysmorphism, osteochondroplasia and cardiac abnormalities. With only 150 cases reported worldwide, Cantu syndrome is now gaining wider recognition due to molecular testing and a growing body of literature that further characterizes the syndrome and some of its most important features. Cardiovascular pathology previously described in the literature include cardiomegaly, pericardial effusion, vascular dilation and tortuosity, and other congenital heart defects. However, cardiovascular involvement is highly variable amongst individuals with Cantu syndrome. In some instances, it can be extensive and severe requiring surgical management and long term follow up. CASE PRESENTATION: Herein we report a case of a fourteen-year-old female who presented with worsening pericardial effusion of unknown etiology, and echocardiographic findings of concentric left ventricular hypertrophy, a mildly dilated aortic root and ascending aorta. Her medical history was notable for hemoptysis and an episode of pulmonary hemorrhage secondary to multiple aortopulmonary collaterals that were subsequently embolized in early childhood. She was initially managed with Ibuprofen and Colchicine but continued to worsen, and ultimately required a pericardial window for the management of refractory pericardial effusion. Imaging studies obtained on subsequent visits revealed multiple dilated and tortuous blood vessels in the head, neck, chest, and pelvis. A cardiomyopathy molecular studies panel was sent, and a pathogenic variant was identified in the ABCC9 gene, confirming the molecular diagnosis of autosomal dominant Cantu syndrome. CONCLUSIONS: Vascular anomalies and significant cardiac involvement are often present in Cantu syndrome, however there are currently no established screening recommendations or surveillance protocols in place. The triad of hypertrichosis, facial dysmorphism, and unexplained cardiovascular involvement in any patient should raise suspicion for Cantu syndrome and warrant further investigation. Initial cardiac evaluation and follow up should be indicated in any patient with a clinical and/or molecular diagnosis of Cantu syndrome. Furthermore, whole body imaging should be utilized to evaluate the extent of vascular involvement and dictate long term monitoring and care.

A Race Against Time-Changing the Natural History of CRIM Negative Infantile Pompe Disease.

We report the clinical course of the first prenatally diagnosed cross-reactive immunologic material (CRIM)-negative infantile Pompe disease (IPD) patient [homozygous for c.2560C>T (p.Arg854X) variant in the GAA gene] to undergo prophylactic immune tolerance induction (ITI) and enzyme replacement therapy (ERT) within the first 2 days of life. Both parents were found to be carriers of the c.2560C>T (p.Arg854X) variant through prenatal carrier screening. Fetal echocardiogram at 31 weeks of gestation showed left ventricular hypertrophy. An echocardiogram on the 1st day of life revealed marked biventricular hypertrophy. Physical exam was significant for macroglossia and hypotonia. A short course of Prophylactic ITI with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) in conjunction with ERT at a dose of 20 mg/kg every other week was started on day 2 of life. The patient completed the ITI protocol safely and complete B-cell recovery, based on CD19 count, was noted by 3 months of age. The patient never developed anti-rhGAA IgG antibodies to ERT. Vaccinations were initiated at 9 months of age, with adequate response noted. Complete recovery of cardiac function and left ventricular mass was seen by 11 weeks of age. At 8 months of age, the patient developmentally measured at 75-90% on the Alberta Infant Motor Scale, walked at 11 months and continues to develop age-appropriately at 50 months of age based on the Early Learning Accomplishment Profile. ERT dosing was increased to 40 mg/kg every 2 weeks at 32 months of age and frequency increased to 40 mg/kg every week at 47 months of age. Patient continues to have undetectable antibody titers, most recently at age 50 months and urine Hex4 has remained normal. To our knowledge, this is the first report of successful early ERT and ITI in a prenatally diagnosed CRIM-negative IPD patient and the youngest IPD patient to receive ITI safely. With the addition of Pompe disease to the Recommended Uniform Screening Panel(RUSP) and its addition to multiple state newborn screening programs, our case highlights the benefits of early diagnosis and timely initiation of treatment in babies with Pompe disease, who represent the most severe end of the disease spectrum.

The Right Axillary Incision: A Potential New Standard of Care for Selected Congenital Heart Surgery.

Although the median sternotomy has been the traditional approach for congenital heart surgery, young patients and their families often find the midline scar to be cosmetically unappealing. At our center, a right transverse axillary incision has become the standard approach for many congenital cardiac lesions because of its safety, versatility, and unsurpassed aesthetic result. We present our experience with the axillary approach for a diverse array of congenital defects. A retrospective review of patients receiving a right transverse axillary incision for congenital cardiac surgery between 2005 and 2016 was conducted. The right transverse axillary incision was performed in 358 patients for 24 unique procedures. Median age was 5 years (range 1 month-60 years) and 225 patients (63%) were female. Median weight was 17 kg (range 4-124 kg), with 19 patients (5%) weighing less than 6 kg. The most common lesions were atrial septal defects (n = 244, 68%) and ventricular septal defects (n = 72, 20%). As experience with this approach increased, other repairs included subvalvular aortic membrane resection (n = 10, 3%), tetralogy of Fallot repair (n = 7, 2%), ventricular assist device placement (n = 3, 1%), and mitral valve repair (n = 2, 1%). There were no intraoperative deaths or conversions to sternotomy. In-hospital complications included mortality (n = 1, 0.3%), reoperations for bleeding (n = 5, 1%), pneumothorax or pleural effusion (n = 6, 2%), and permanent pacemaker (n = 4, 1%). The right axillary incision allows a safe and effective repair for a broad range of congenital heart defects and is a potential new standard of care for many patients.

Cardiac mechanics in patients with human immunodeficiency virus: a study of systolic myocardial deformation in children and young adults.

Human immunodeficiency virus (HIV) infection causes dysfunction of different organ systems. Myocardial diastolic dysfunction has been reported previously in an adult HIV population. Our aim was to study myocardial strain in children and young adults infected by HIV who have apparently normal ejection fraction. Forty HIV-infected patients (mean age 20.6 ± 1.5 years) with normal ejection fraction and 55 matched normal controls (mean age 17 ± 1.5 years) were studied by two-dimensional echocardiogram. The images were stored then exported to velocity vector imaging software for analysis. Measures considered were left-ventricular peak global systolic strain (LV S) and strain rate (LV SR) as well as right-ventricular peak global systolic strain (RV S) and strain rate (RV SR). Circumferential measures of the left ventricle included the following: LV circumferential peak global systolic strain (LV circ S), strain rate (LV circ SR), radial velocity (LV rad vel), and rotational velocity (LV rot vel) at the level of the mitral valve. Statistical significance was set at p < 0.05. The means of all longitudinal deformation parameters were significantly lower in HIV patients compared with normal controls: LV S (-14.15 vs. -19.31), LV SR (-0.88 vs. -1.30), RV S (-19.58 vs. -25.09), and RV SR (-1.34 vs. -2.13), respectively (p < 0.05). LV rot vel was lower in patients compared with controls (43.23 vs. 51.71, p = 0.025). LV circ S, LV circ SR, and LV rad vel showed no significant difference between the two groups (p ≥ 0.05). HIV infection affects longitudinal systolic cardiac strain and strain rate in children and young adults. Normal ejection fraction might be attributed to preserved circumferential myocardial deformation. Strain and strain rate may help identify HIV patients at high risk for cardiac dysfunction and allow early detection of silent myocardial depression.

Point-of-care testing for B-type natriuretic peptide in premature neonates with patent ductus arteriosus.

Patent ductus arteriosus (PDA) is highly prevalent in pre-term neonates (PTN) and has been recognized as a neonatal co-morbidity. The purpose of this study was to determine if levels of brain (or B-type) natriuretic peptide (BNP), a peptide secreted by ventricular myocytes in response to volume or pressure overload, correlate with the size of the PDA. In a prospective design, 52 PTN (no PDA: n=24; PDA: n=28) were studied after obtaining parental consent. Those with genetic anomalies and congenital heart disease, except for PDA and patent foramen ovale, were excluded. Echocardiographic estimates of the diameters of the PDA (or absence of PDA) were made concurrently with capillary blood collection for BNP assay. BNP levels in samples from PTN without PDA were 23.6 ng/L (median); 13.1 to 32.3 ng/L (IQR); initial samples (between days 3 and 7 of life) with small PDA (n=11), median 66.1 ng/L; 55.5 to 85.3 ng/L (IQR); with moderate PDA (n=6) median 284 ng/L; 204 to 622 ng/L (IQR); and with large PDA (n=11) 2410 ng/L median; 420 to 2770 ng/L (IQR). (p< 0.0001 for ANOVA; groupwise: p<0.05 for both no PDA vs. moderate and large PDA); Trend analysis suggested a strong association of BNP with size of PDA (p<0.001). Of 17 subjects with moderate to large PDA, pre and post-treatment (Ibuprofen; per standard protocol) data were obtained on 12 subjects. Pre-treatment BNP ranged from 111 to 5000 ng/L; post-treatment BNP decreased to 5.0 to 262 ng/L (p = 0.0005). Estimates of decision levels for treatment were made by examining dichotomized groups, i.e., no-to-small vs. moderate-to-large and using receiver-operator characteristic (ROC) curve analysis yielding a value of 123 ng/L. BNP may obviate repeated echocardiography as follow up after treatment, or to monitor future course of respiratory distress secondary to PDA in PTN.

Varicella myopericarditis mimicking myocardial infarction in a 17-year-old boy.

Varicella (chickenpox), a common childhood infection caused by the varicella-zoster virus, is self-limiting and usually benign. Although atypical manifestations of the virus are occasionally seen, it rarely presents with cardiovascular sequelae. Cardiovascular complications of varicella can include pericarditis, myocarditis, or endocarditis. Herein, we report the case of a 17-year-old boy who had varicella infection and severe chest pain. Examination revealed atypical electrocardiographic findings of pericarditis and remarkably elevated cardiac biomarker levels: peak cardiac troponin I, 37.2 ng/mL; total creatine kinase, 1,209 U/L; and creatine kinase-MB fraction, 133.6 ng/mL. After results of coronary angiography reliably excluded ischemia and myocardial infarction, the diagnosis was varicella myopericarditis. The patient was placed on a medical regimen during and after 5 days of hospitalization. In 2 weeks, he was asymptomatic, and at 6 months, he was doing well and had normal electrocardiographic and echocardiographic results.To our knowledge, cardiac enzyme elevations to these levels have not been reported in cases of cardiovascular sequelae of varicella. We discuss the diagnostic challenges of this atypical case and suggest that clinicians be aware that varicella disease is most often, but not always, benign.

Transcatheter closure of patent foramen ovale in older adults.

OBJECTIVES: Comparing results of patent foramen ovale (PFO) closure in older and younger patient cohorts. BACKGROUND: The literature pertaining to stroke and PFO has focused on patients <55 years of age. METHODS: Between March 2000 and December 2003, 456 consecutive stroke/transient ischemic attack (TIA) patients (14.2-91.1 years, mean 51.4 +/- 15.5) underwent successful closure of PFO with a CardioSEAL Septal Occluder by one operator at five hospitals. Of the 456 patients, 184 (40.4%) were >55 years of age at the time of the procedure (mean 66.9 +/- 8.3 years) and comprise the subject group (OLDER). The remaining 272 patients (mean 41.1 +/- 7.7) comprise the control group (YOUNGER). Data were collected prospectively in a registry type format. RESULTS: Minor procedural complications were comparable: 7/184 (3.8%) OLDER vs. 12/272 (4.4%) YOUNGER (P = NS). In the follow-up period (1-45 months, mean = 17.8 +/- 11.1), there was no significant difference in the rate of recurrent stroke/TIA, headaches, or late unrelated death. Forty OLDER patients and 47 YOUNGER developed new onset atrial arrhythmia (P = NS). The incidence of new onset atrial fibrillation (AF), however, was significantly higher in OLDER (14/40 OLDER and only 2/47 YOUNGER, P < 0.025). All patients who were in normal sinus rhythm (NSR) before the procedure are in NSR at last follow-up. CONCLUSIONS: Older patients should not be excluded from PFO closure. The procedure seems as safe and effective in preventing recurrent stroke in the older, as in the younger population. Older patients seem more prone to developing AF.