Intravascular Ultrasound Characterization of a Tissue-Engineered Vascular Graft in an Ovine Model.

Patients who undergo implantation of a tissue-engineered vascular graft (TEVG) for congenital cardiac anomalies are monitored with echocardiography, followed by magnetic resonance imaging or angiography when indicated. While these methods provide data regarding the lumen, minimal information regarding neotissue formation is obtained. Intravascular ultrasound (IVUS) has previously been used in a variety of conditions to evaluate the vessel wall. The purpose of this study was to evaluate the utility of IVUS for evaluation of TEVGs in our ovine model. Eight sheep underwent implantation of TEVGs either unseeded or seeded with bone marrow-derived mononuclear cells. Angiography, IVUS, and histology were directly compared. Endothelium, tunica media, and graft were identifiable on IVUS and histology at multiple time points. There was strong agreement between IVUS and angiography for evaluation of luminal diameter. IVUS offers a valuable tool to evaluate the changes within TEVGs, and clinical translation of this application is warranted.

Design and Implementation of a Prospective Adult Congenital Heart Disease Biobank.

BACKGROUND: Adults with congenital heart disease (ACHD) comprise a growing, increasingly complex population. The Boston Adult Congenital Heart Disease Biobank is a program for the collection and storage of biospecimens to provide a sustainable resource for scientific biomarker investigation in ACHD. METHODS: We describe a protocol to collect, process, and store biospecimens for ACHD or associated diagnoses developed based on existing literature and consultation with cardiovascular biomarker epidemiologists. The protocol involves collecting urine and ∼48.5 mL of blood. A subset of the blood and urine undergoes immediate clinically relevant testing. The remaining biospecimens are processed soon after collection and stored at -80°C as aliquots of ethylenediaminetetraacetic acid (EDTA) and lithium heparin plasma, serum, red cell and buffy coat pellet, and urine supernatant. Including tubes with diverse anticoagulant and clot accelerator contents will enable flexible downstream use. Demographic and clinical data are entered into a database; data on biospecimen collection, processing, and storage are managed by an enterprise laboratory information management system. RESULTS: Since implementation in 2012, we have enrolled more than 650 unique participants (aged 18-80 years, 53.3% women); the Biobank contains over 11,000 biospecimen aliquots. The most common primary CHD diagnoses are single ventricle status-post Fontan procedure (18.8%), repaired tetralogy of Fallot with pulmonary stenosis or atresia (17.6%), and left-sided obstructive lesions (17.5%). CONCLUSIONS: We describe the design and implementation of biospecimen collection, handling, and storage protocols with multiple levels of quality assurance. These protocols are feasible and reflect the size and goals of the Boston ACHD Biobank.

Pheochromocytoma and paraganglioma in cyanotic congenital heart disease.

CONTEXT: Aberrant cellular oxygen sensing is a leading theory for development of pheochromocytoma (PHEO) and paraganglioma (PGL). OBJECTIVE: The objective of the study was to test the hypothesis that chronic hypoxia in patients with cyanotic congenital heart disease (CCHD) increases the risk for PHEO-PGL. DESIGN/SETTING/PARTICIPANTS: We investigated the association between CCHD and PHEO-PGL with two complementary studies: study 1) an international consortium was established to identify congenital heart disease (CHD) patients with a PHEO-PGL diagnosis confirmed by pathology or biochemistry and imaging; study 2) the 2000-2009 Nationwide Inpatient Survey, a nationally representative discharge database, was used to determine population-based cross-sectional PHEO-PGL frequency in hospitalized CCHD patients compared with noncyanotic CHD and those without CHD using multivariable logistic regression adjusted for age, sex, and genetic PHEO-PGL syndromes. RESULTS: In study 1, we identified 20 PHEO-PGL cases, of which 18 had CCHD. Most presented with cardiovascular or psychiatric symptoms. Median cyanosis duration for the CCHD PHEO-PGL cases was 20 years (range 1-57 y). Cases were young at diagnosis (median 31.5 y, range 15-57 y) and 7 of 18 had multiple tumors (two bilateral PHEO; six multifocal or recurrent PGL), whereas 11 had single tumors (seven PHEO; four PGL). PGLs were abdominal (13 of 17) or head/neck (4 of 17). Cases displayed a noradrenergic biochemical phenotype similar to reported hypoxia-related PHEO-PGL genetic syndromes but without clinical signs of such syndromes. In study 2, hospitalized CCHD patients had an increased likelihood of PHEO-PGL (adjusted odds ratio 6.0, 95% confidence interval 2.6-13.7, P < .0001) compared with those without CHD; patients with noncyanotic CHD had no increased risk (odds ratio 0.9, P = .48). CONCLUSIONS: There is a strong link between CCHD and PHEO-PGL. Whether these rare diseases coassociate due to hypoxic stress, common genetic or developmental factors, or some combination requires further investigation.

Single ventricle anatomy is associated with increased frequency of nonalcoholic cirrhosis.

BACKGROUND: Single ventricle (SV) patients with Fontan physiology have multiple risk factors for liver disease but the prevalence of liver disease remains unknown in this population. We sought to determine whether hospitalized patients with a SV diagnosis have higher rates of nonalcoholic cirrhosis than patients without congenital heart disease. METHODS: We used the 1998-2009 Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, a nationally representative dataset, to identify patients 18-49 years old admitted to an acute care hospital. We compared the rate of nonalcoholic cirrhosis between those with a SV diagnosis and patients without congenital heart disease. RESULTS: There were 7968 hospitalizations of patients with a SV diagnosis and 13,602,149 hospitalizations of patients without congenital heart disease. SV patients were more likely to have nonalcoholic cirrhosis than those without congenital heart disease (4.3 ± 0.7 vs. 0.3 ± 0.01%, univariate OR 15.2, 95%CI 10.9-21.3), even after adjusting for viral or chronic hepatitis and other cirrhosis risk factors (multivariable OR 21.6, 95%CI 4.3-32.5). The proportion of all hospitalizations among SV patients for nonalcoholic cirrhosis increased by 173% between 1998/9 and 2008/9, from 2.3% to 6.2% (p=0.009). Among those with nonalcoholic cirrhosis, SV patients were more likely to have congestive hepatopathy (6.6 ± 3.1 vs. 0.1 ± 0.0001%, OR 63.2, 95%CI 19.2-207.8), longer hospital stays and higher hospital charges. CONCLUSIONS: A single ventricle diagnosis is associated with markedly higher risk for nonalcoholic cirrhosis in a population-based sample of hospitalized patients. The proportion of patients with single ventricle anatomy admitted for nonalcoholic cirrhosis or its complications is increasing rapidly.