Remodeling of ECM patch into functional myocardium in an ovine model: A pilot study.

BACKGROUND: Previous studies have demonstrated that surgical patches comprised of small intestinal submucosa-derived extracellular matrix (ECM) have biological remodeling potential. This pilot study investigated histological, mechanical, and bioelectrical properties of an ECM patch implanted in the ovine right-ventricular outflow tract (RVOT). MATERIALS AND METHODS: ECM patches (2 × 2 cm2 ) were implanted in four Western Range sheep (wether males, 37-49 kg, age <1 year) and explanted at 5 months (n = 2) and 8 months (n = 2). In vivo analysis included epicardial echocardiography and contact electrical mapping. Optical mapping was used to map electrical activity of two hearts on a Langendorff preparation. Mechanical testing quantified stiffness. Histological stains characterized structure, neovascularization, and calcification; immunohistochemistry (IHC) assessed cell phenotype. RESULTS: In vivo analysis showed that ECM patch tissue was contractile by M-mode and two-dimensional echocardiographic evaluation. In vivo electrical mapping, and optical mapping confirmed that ECM conducted an organized electrical signal. Mechanical testing of native and ECM patched RVOT tissue showed an elastic modulus of the implanted patch comparable to native tissue stiffness. CONCLUSIONS: At 5 and 8 months, the ECM had undergone extracellular matrix remodeling and neovascularization without calcification. The ECM was populated with locally aligned muscle cells positive for sarcomeric alpha-actinin, CD45, and troponin I and T. In sheep, the ECM patch appears to have the potential of remodeling to resemble native, functional ventricular tissue as evidenced by histological, mechanical, and electrical properties. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1713-1720, 2016.

Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations.

BACKGROUND: Mutations in the transforming growth factor beta receptor type I and II genes (TGFBR1 and TGFBR2) cause Loeys-Dietz syndrome (LDS), characterised by thoracic aortic aneurysms and dissections (TAAD), aneurysms and dissections of other arteries, craniosynostosis, cleft palate/bifid uvula, hypertelorism, congenital heart defects, arterial tortuosity, and mental retardation. TGFBR2 mutations can also cause TAAD in the absence of features of LDS in large multigenerational families, yet only sporadic LDS cases or parent-child pairs with TGFBR1 mutations have been reported to date. METHODS: The authors identified TGFBR1 missense mutations in multigenerational families with TAAD by DNA sequencing. Clinical features of affected individuals were assessed and compared with clinical features of previously described TGFBR2 families. RESULTS: Statistical analyses of the clinical features of the TGFBR1 cohort (n = 30) were compared with clinical features of TGFBR2 cohort (n = 77). Significant differences were identified in clinical presentation and survival based on gender in TGFBR1 families but not in TGFBR2 families. In families with TGFBR1 mutations, men died younger than women based on Kaplan-Meier survival curves. In addition, men presented with TAAD and women often presented with dissections and aneurysms of arteries other than the ascending thoracic aorta. The data also suggest that individuals with TGFBR2 mutations are more likely to dissect at aortic diameters <5.0 cm than individuals with TGFBR1 mutations. CONCLUSION: This study is the first to demonstrate clinical differences between patients with TGFBR1 and TGFBR2 mutations. These differences are important for the clinical management and outcome of vascular diseases in these patients.

Safety of magnetic resonance imaging immediately following Palmaz stent implant: a report of three cases.

Magnetic resonance imaging (MRI) can provide important information on patients with congenital heart defects. There is some reluctance to perform MRI acutely following intravascular stent implant, due to concerns of distortion or movement of the stent in the magnetic field. We report on three patients who underwent MRI evaluation less than 14 days following Palmaz stent implant in the pulmonary arteries and superior vena cava, with no acute adverse outcome or long-term problems.

Cardiac catheterization in diagnosis and management of congenital heart disease in thoracopagus conjoined twins.

Over the last two decades, surgical separation of thoracopagus conjoined twins has become increasingly feasible. Delineation of the degree of cardiac involvement is essential to establish the feasibility of surgical separation. We describe our experience of cardiac catheterization both in the diagnosis and management of nine sets of thoracopagus twins who presented to a single center over three decades and discuss its role in conjunction with other modern diagnostic modalities.

Three- and four-dimensional visualization of magnetic resonance imaging data sets in pediatric cardiology.

The purpose of medical imaging technology in pediatric cardiology is to provide clear representations of the underlying anatomy and physiology of the cardiovascular system--representations that are easily understood and that facilitate clinical decision making. However, standard projective and tomographic imaging methods often yield results that are intelligible only to imaging specialists. Three- and four-dimensional reconstructions from projective and tomographic data sets are an alternative form of image display. Often, these reconstructions are more readily comprehensible as representations of the reality apparent in the operating room or the pathology laboratory than are the original data sets. Furthermore, viewing of these reconstructions is much more time efficient than viewing hundreds of separate tomographic images. Magnetic resonance imaging inherently provides three-, four-, and even higher dimensional data, and magnetic resonance data sets are commonly used to generate volumetric reconstructions. This review will focus on the practical application of magnetic resonance imaging to yield three- and four-dimensional reconstructions of pediatric cardiovascular disorders.

Double aortic arch in D-transposition of the great arteries: confirmation of dominant arch by magnetic resonance imaging.

We report the case of a female infant who had the rare combination of double aortic arch and D-transposition of the great arteries. The double aortic arch was diagnosed at the time of her arterial switch procedure. Magnetic resonance imaging identified the left arch as dominant, and the right arch was successfully ligated.

Evaluation of left ventricular wall motion, volumes, and ejection fraction by gated myocardial tomography with technetium 99m-labeled tetrofosmin: a comparison with cine magnetic resonance imaging.

BACKGROUND: Whether left ventricular function can be assessed accurately by gated single photon emission computed tomography (SPECT) in patients with myocardial infarction and severe perfusion defects is not well known. METHODS AND RESULTS: Twenty-five patients with an acute myocardial infarction underwent 99mTc-labeled tetrofosmin (99mTc-tetrofosmin) gated SPECT and cine magnetic resonance imaging (MRI). Wall motion was assessed in 13 left ventricular segments using a 5-point scoring system ranging from 3 (normal) to -1 (dyskinetic). Exact agreement for wall motion scores between gated SPECT and MRI was excellent (92%, kappa = 0.82). Furthermore, correlations between the two techniques were also good for end-diastolic volume (r = 0.81, P < .0001), end-systolic volume (r = 0.92, P < .0001), and ejection fraction (r = 0.93, P < .0001). CONCLUSION: In patients with a recent myocardial infarction, 99mTc-tetrofosmin gated SPECT provides reliable evaluation of global and regional ventricular function and volumes.

Single therapeutic catheterization to treat coexisting coarctation of the aorta and patent ductus arteriosus.

A case of a pediatric patient found to have coexisting coarctation of the aorta and patent ductus arteriosus who underwent balloon dilation of the coarctation and coil occlusion of the ductus in a single cardiac catheterization is presented. Review of the English literature revealed no previous reports of this combination of transcatheter interventions during a single catheterization procedure.

Update on new technologies in pediatric echocardiography.

Advances in ultrasound technology will continue to expand the utility of echocardiography in the assessment of structural and functional cardiac disease in children. Tissue Doppler imaging and dobutamine stress echocardiography are 2 promising clinical applications that are expected to become increasingly used with time. Advances in data compression technology, including JPEG and MPEG techniques, will significantly affect digital archival and transmission of echocardiograms, which also have clinical implications, particularly in the expanding use of telemedicine. Continued research and clinical experience will further define the ultimate roles of these technologies in the future.

Use of intravascular stents in systemic venous and systemic venous baffle obstructions. Short-term follow-up results.

BACKGROUND: Balloon-expandable intravascular stents are well accepted in the management of arterial obstructions. This study was undertaken to detail the immediate and short-term results of intravascular stent implantation in systemic venous and systemic venous baffle obstructions in children. METHODS AND RESULTS: Between September 1991 and June 1994, 12 patients had 21 stents implanted in 13 systemic venous obstructions, 1 patient having stents placed in 2 separate obstructions. In the baffle group, 4 of 13 obstructions were at the superior vena cava/right atrial junction after atrial baffling for transposition of the great arteries. One of 4 patients had complete obstruction requiring transseptal needle perforation before stent implantation. There was an immediate gradient reduction from 12 +/- 8.4 mm Hg (range, 4 to 20 mm Hg) to 1.3 +/- 1.9 mm Hg (range, 0 to 4 mm Hg, P = .05). The obstructed segment diameter increased from 3.5 +/- 3.9 mm (range, 0 to 8.5 mm) to 16 +/- 2.7 mm (range, 14 to 20 mm, P = .002). In the central vein group, 9 of 13 obstructions were in large central veins. Three of 9 patients had complete obstruction requiring transseptal needle perforation before stent implantation. There was an immediate gradient reduction from 10.3 +/- 8.5 mm Hg (range, 0 to 20 mm Hg) to 0.8 +/- 1.1 mm Hg (range, 0 to 3 mm Hg, P = .005). The obstructed segment diameter increased from 1.3 +/- 1.1 mm (range, 0 to 2.8 mm) to 9.4 +/- 1.7 mm (range, 7.6 to 12 mm, P < .001). There were no acute complications in either group. In the follow-up group, patients were scheduled for clinical follow-up at 3, 6, and 12 months with echocardiography or magnetic resonance imaging (MRI) at 3 or 6 months and for repeat cardiac catheterization at 12 months. All stents were patent by echocardiography or MRI when studied at follow-up. Cardiac catheterization in 6 of 12 patients, 2 to 13 months after stent, demonstrated that all stents remained patent without compression or fracture. Follow-up and immediate poststent gradients were not significantly different (1 +/- 1.6 versus 0.7 +/- 1.2 mm Hg, P = NS). Neointimal hyperplasia (5 of 6 patients) reduced the stent lumen only from 12.5 +/- 4.7 mm (range, 8 to 20 mm) to 10.6 +/- 4.7 mm (range, 4.5 to 17.7 mm, P = NS). No stents required redilation. One of 18 stents placed in series had "unlocked" and rotated in the venous lumen but remained fully patent to flow. CONCLUSIONS: Balloon-expandable intravascular stents can be safely and effectively used to relieve systemic venous and systemic venous baffle obstructions, even when obstruction is complete. Short-term follow-up suggests excellent continued patency, but further follow-up is required to observe for progression of neointimal hyperplasia. We postulate that balloon-expandable intravascular stents will become the treatment of choice for the relief of selected systemic venous and venous baffle obstructions in the pediatric population.

Role of spin echo and cine magnetic resonance imaging in presurgical planning of heterotaxy syndrome. Comparison with echocardiography and catheterization.

BACKGROUND: Patients with heterotaxy syndrome frequently have complex congenital cardiac and noncardiac malformations requiring detailed diagnostic evaluation by noninvasive as well as invasive imaging modalities for management planning. Recent advances in magnetic resonance imaging (MRI) techniques allow detailed delineation of cardiovascular anatomy and blood flow in young infants with rapid heart rates. The present study was undertaken to prospectively evaluate the role of MRI in the presurgical evaluation of patients with heterotaxy syndrome. METHODS AND RESULTS: Between January 1 and December 31, 1992, 14 consecutive patients with heterotaxy syndrome and complex congenital heart disease were enrolled in a prospective protocol. After evaluation by echocardiography and cardiac catheterization, a tentative management plan was recorded. Subsequently, a MRI study was performed and surgical planning was reevaluated. MRI was found to be comparable to echocardiography in terms of length of examination and sedation requirements. Surgical planning was altered in four patients because MRI provided additional data not evident on echocardiography and catheterization. Comparison of diagnostic yield between echocardiography, catheterization, and MRI showed that MRI is superior to echocardiography and often to catheterization in delineation of systemic and pulmonary venous anatomy and their relation to mediastinal structures. When the anatomic and hemodynamic data obtained by echocardiography and MRI were considered together, cardiac catheterization data were necessary only to determination of pulmonary vascular resistance before Fontan operation. CONCLUSIONS: MRI provides excellent anatomic and functional information that in some patients was not available by echocardiography or catheterization. Combined with echocardiography, MRI provides the high-quality diagnostic information necessary for management planning in most patients with heterotaxy syndrome. Cardiac catheterization is indicated when determination of pulmonary vascular resistance is necessary for decision making or when an interventional procedures is indicated.

Comparison of gradient echo with spin echo magnetic resonance imaging and echocardiography in the evaluation of major aortopulmonary collateral arteries.

This study compared gradient echo magnetic resonance imaging, spin echo magnetic resonance imaging, echocardiography, and echocardiography with x-ray cineangiography in the evaluation of major aortopulmonary collateral arteries. Twelve patients (ages 9 months to 35 years, mean 11 +/- 11 years) with known or suspected major aortopulmonary collateral arteries were studied. The aortic insertion and proximal course of 29 major aortopulmonary collateral arteries demonstrated by x-ray contrast angiography were shown in all 29 cases by gradient echo magnetic resonance imaging but in only 23 of the 29 cases by spin echo magnetic resonance imaging. Color Doppler-echocardiography detected aortopulmonary collateral arteries in four patients but did not define the proximal course or distal anatomy. Gradient echo images of distal aortopulmonary collateral anatomy were qualitatively superior to spin echo images. The contrast-to-noise ratio between the vessel lumen and adjacent lung was greater for gradient echo (6.06 +/- 2.91) than for spin echo (1.45 +/- 1.13)(p < 0.05). Gradient echo magnetic resonance imaging is a useful method for identification and characterization of aortopulmonary collateral arteries in patients of all ages and is superior to spin echo magnetic resonance imaging and echocardiography.

Balloon expandable intravascular stents: aortic implantation and late further dilation in growing minipigs.

Intravascular stents have been implanted in children with congenital and acquired vascular stenoses. Little information is known regarding the long-term results in growing patients, the implantation of multiple stents (in series), and the feasibility of further dilation. Nine stents were implanted in the abdominal aortas of 6 mini-pigs; in 3 pigs, 2 stents were implanted in series. Five pigs were recatheterized 196 +/- 17 days after stent implant. All stents were patent, with mild narrowing at the stent relative to the adjacent aorta; further stent dilation was performed. The stent diameter increased from 8.3 +/- 0.6 mm to 11.2 +/- 1.3 mm (p = 0.002), and the narrowing was relieved. These five pigs were catheterized 253 +/- 73 days after stent redilation. Each stent was patent without narrowing or pressure gradient. We conclude that intravascular stents do not interfere with normal growth, can be implanted in series, and can be further dilated.

The long QT syndrome in children. An international study of 287 patients.

BACKGROUND: The Pediatric Electrophysiology Society studied children with the long QT syndrome (LQTS) to describe the features of LQTS in patients less than 21 years old, define potential "low-risk" and "high-risk" subpopulations, and determine optimal treatment. METHODS AND RESULTS: Patients less than 21 years old were included if either QTc was more than 0.44; they had unexplained syncope, seizures, or cardiac arrest preceded by emotion or exercise; or family history of LQTS. We found 287 patients from 26 centers in seven countries. Mean +/- SD age at presentation was 6.8 +/- 5.6; 9% presented with cardiac arrest, 26% with syncope, and 10% with seizures. Of those with symptoms, 67% had symptoms related to exercise. Family history was positive for long QT interval in 39% and for sudden death in 31%. Hearing loss was present in 4.5%. A normal QTc was present in 6%, and QTc of more than 0.60 was in 13%. Atrioventricular block occurred in 5%, but 13 of 15 patients had second-degree atrioventricular block (2:1), and only two of 287 had complete atrioventricular block. Ventricular arrhythmias were found on 16% of initial routine ECGs: 4% uniform premature ventricular contractions, 5% multiform premature ventricular contractions, 1% monomorphic ventricular tachycardia, and 6% torsade de pointes. Overall, treatment was effective for symptoms in 76% and for ventricular arrhythmias in 60%. There was no difference between propranolol and other beta-blockers in effective treatment. Left stellectomy was performed in nine patients, and defibrillators were implanted in four; no sudden death occurred in these 13 patients. In follow-up (duration, 5.0 +/- 4 years; age, 10.9 +/- 6.3 years), 5% had cardiac arrest, 4% had syncope, and 1% had seizures. The two multivariate predictors of symptoms at follow-up were symptoms at presentation and propranolol failure. Sudden death occurred in 8%; multivariate predictors of sudden death were length of QTc at presentation of more than 0.60 and medication noncompliance. CONCLUSIONS: The appearance of 2:1 atrioventricular block, multiform premature ventricular contractions, and torsade de pointes are relatively more common in children with LQTS than other children and should raise the index of suspicion for LQTS. Because 9% of patients presented with cardiac arrest and no preceding symptoms, perhaps prophylactic treatment in asymptomatic children is indicated. Asymptomatic patients with normal QTc and positive family history may be a low-risk group. Patients with QTc of more than 0.60 are at particularly high risk for sudden death, and if treatment is not effective, consideration should be given to cardiac sympathetic denervation, pacemaker implantation, and perhaps implantation of a defibrillator.