Biomedical subjects

John E Mayer

Publications and source records attributed to John E Mayer.

At least 19 recordsLinked to original sources

PubMed2007

Measurement of technical performance in congenital heart surgery: a pilot study.

BACKGROUND: Although adequacy of repair after congenital heart surgery is a crucial determinant of clinical outcome, there is no current method of assessment. We sought to develop a process to measure the adequacy of repair for a diverse group of congenital heart procedures. METHODS: Selected surgical procedures, consisting of repair of ventricular septal defect (VSD), tetralogy of Fallot (TOF), complete common atrioventricular canal (CAVC), and arterial switch operation, were divided into component subprocedures, each of which was assessed separately. Three outcome categories of "optimal," "adequate," and "inadequate" were defined by consensus according to postprocedure echocardiographic assessment. Outcome categories for conduction disturbance were also created. All patients undergoing one of the four procedures in 2004 were identified, and each subprocedure was assessed. Other clinical data were obtained from medical records. Repairs were scored as "optimal" if all attempted subprocedures and conduction were optimal, and "inadequate" if any was inadequate. RESULTS: A total of 138 procedures were included. VSD repair was done in 46 patients (33%), TOF repair in 33 (24%), arterial switch operation in 36 (26%), and CAVC repair in 23 (17%). Optimal technical score was found in 28 (20%), adequate in 106 (77%), and inadequate in 4 (3%) (2 VSD, 1 TOF, 1 CAVC). Median length of stay was 8 days, and no patients died. CONCLUSIONS: Despite procedural diversity and complexity, technical adequacy of repair can be assessed for congenital heart surgery.

Cardiac Surgical Procedures↗

PubMed2007

Physician payment for 2007: a description of the process by which major changes in valuation of cardiothoracic surgical procedures occurred.

Throughout the last 3 years, the Society of Thoracic Surgeons (STS) has put forth a major effort towards more accurate valuation of the work performed by cardiothoracic surgeons. The culmination of these efforts was realized on November 1, 2006, when the Centers for Medicare & Medicaid Services published the Final Rule which markedly increased the physician work values for the most frequently performed cardiothoracic surgery procedures. This article recounts the innovative approach taken by the STS during these extended efforts.

Cardiac Surgical Procedures↗

PubMed2006

Cyclic flexure and laminar flow synergistically accelerate mesenchymal stem cell-mediated engineered tissue formation: Implications for engineered heart valve tissues.

Bone marrow-derived mesenchymal stem cells (BMSCs) are relatively accessible and exhibit a pluripotency suitable for cardiovascular applications such as tissue-engineered heart valves (TEHVs). Recently, Sutherland et al. [From stem cells to viable autologous semilunar heart valve. Circulation 2005; 111(21): 2783-91] demonstrated that BMSC-seeded TEHV can successfully function as pulmonary valve substitutes in juvenile sheep for at least 8 months. Toward determining appropriate mechanical stimuli for use in BMSC-seeded TEHV cultivation, we investigated the independent and coupled effects of two mechanical stimuli physiologically relevant to heart valves-cyclic flexure and laminar flow (i.e. fluid shear stress)-on BMSC-mediated tissue formation. BMSC isolated from juvenile sheep were expanded and seeded onto rectangular strips of nonwoven 50:50 blend poly(glycolic acid) (PGA) and poly(l-lactic acid) (PLLA) scaffolds. Following 4 days static culture, BMSC-seeded scaffolds were loaded into a novel flex-stretch-flow (FSF) bioreactor and incubated under static (n=12), cyclic flexure (n=12), laminar flow (avg. wall shear stress=1.1505 dyne/cm(2); n=12) and combined flex-flow (n=12) conditions for 1 (n=6) and 3 (n=6) weeks. By 3 weeks, the flex-flow group exhibited dramatically accelerated tissue formation compared with all other groups, including a 75% higher collagen content of 844+/-278 microg/g wet weight (p<0.05), and an effective stiffness (E) value of 948+/-233 kPa. Importantly, collagen and E values were not significantly different from values measured for vascular smooth muscle cell (SMC) -seeded scaffolds incubated under conditions of flexure alone [Engelmayr et al. The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue. Biomaterials 2005; 26(2): 175-87], suggesting that BMSC-seeded TEHV can be optimized to yield results comparable to SMC-seeded TEHV. We thus demonstrated that cyclic flexure and laminar flow can synergistically accelerate BMSC-mediated tissue formation, providing a basis for the rational design of in vitro conditioning regimens for BMSC-seeded TEHV.

Animals↗

PubMed2006

Transforming growth factor-beta1 modulates extracellular matrix production, proliferation, and apoptosis of endothelial progenitor cells in tissue-engineering scaffolds.

BACKGROUND: Valvular endothelial cells and circulating endothelial progenitor cells (EPCs) can undergo apparent phenotypic change from endothelial to mesenchymal cell type. Here we investigated whether EPCs can promote extracellular matrix formation in tissue engineering scaffolds in response to transforming growth factor (TGF)-beta1. Method and Results- Characterized ovine peripheral blood EPCs were seeded onto poly (glycolic acid)/poly (4-hydroxybutyrate) scaffolds for 5 days. After seeding at 2 x 10(6) cells/cm2, scaffolds were incubated for 5 days in a roller bottle, with or without the addition of TGF-beta1. After seeding at 15 x 10(6) cells/cm2, scaffolds were incubated for 10 days in a roller bottle with or without the addition of TGF-beta1 for the first 5 days. Using immunofluorescence and Western blotting, we demonstrated that EPCs initially exhibit an endothelial phenotype (ie, CD31+, von Willebrand factor+, and alpha-smooth muscle actin (SMA)-) and can undergo a phenotypic change toward mesenchymal transformation (ie, CD31+ and alpha-SMA+) in response to TGF-beta1. Scanning electron microscopy and histology revealed enhanced tissue formation in EPC-TGF-beta1 scaffolds. In both the 10- and 15-day experiments, EPC-TGF-beta1 scaffolds exhibited a trend of increased DNA content compared with unstimulated EPC scaffolds. TGF-beta1-mediated endothelial to mesenchymal transformation correlated with enhanced expression of laminin and fibronectin within scaffolds evidenced by Western blotting. Strong expression of tropoelastin was observed in response to TGF-beta1 equal to that in the unstimulated EPC. In the 15-day experiments, TGF-beta1-stimulated scaffolds revealed dramatically enhanced collagen production (types I and III) and incorporated more 5-bromodeoxyuridine and TUNEL staining compared with unstimulated controls. CONCLUSIONS: Stimulation of EPC-seeded tissue engineering scaffolds with TGF-beta1 in vitro resulted in a more organized cellular architecture with glycoprotein, collagen, and elastin synthesis, and thus noninvasively isolated EPCs coupled with the pleiotropic actions of TGF-beta1 could offer new strategies to guide tissue formation in engineered cardiac valves.

Actins↗

PubMed2006

Extracorporeal membrane oxygenation support of a neonate with percutaneous femoral arterial cannulation.

We describe a neonate with hypoplastic left heart syndrome supported with venoarterial extracorporeal membrane oxygenation with a femoral arterial cannula. A 6-French straight sheath was percutaneously placed in the right femoral artery using the Seldinger technique. Adequate extracorporeal membrane oxygenation flows were achieved, and the patient was successfully de-cannulated. Femoral arterial cannulation in neonates is technically feasible and provides an alternative site for extracorporeal membrane oxygenation cannulation.

Catheterization, Peripheral↗

PubMed2006

Natural history of pulmonary atresia with intact ventricular septum and right-ventricle-dependent coronary circulation managed by the single-ventricle approach.

BACKGROUND: Long-term outcome of patients with pulmonary valvar atresia and intact ventricular septum with right-ventricle-dependent coronary circulation (PA/IVS-RVDCC) managed by staged palliation directed toward Fontan circulation is unknown, but should serve as a basis for comparison with management protocols that include initial systemic-to-pulmonary artery shunting followed by listing for cardiac transplantation. METHODS: Retrospective review of patients admitted to our institution with the diagnosis of PA/IVS-RVDCC from 1989 to 2004. All angiographic imaging studies, operative reports, and follow-up information were reviewed. Right-ventricle-dependent coronary circulation was defined as situations in which ventriculocoronary fistulae with proximal coronary stenosis or atresia were present, putting significant left ventricle myocardium at risk for ischemia with right ventricle decompression. RESULTS: Thirty-two patients were identified with PA/IVS-RVDCC. All underwent initial palliation with modified Blalock-Taussig shunt (BTS). Median tricuspid valve z-score was -3.62 (-2.42 to -5.15), and all had moderate (n = 13) or severe (n = 19) right ventricular hypoplasia. Median follow-up was 5.1 years (9 months to 14.8 years). Overall mortality was 18.8% (6 of 32), with all deaths occurring within 3 months of BTS. Aortocoronary atresia was associated with 100% mortality (3 of 3). Of the survivors (n = 26), 19 have undergone Fontan operation whereas 7, having undergone bidirectional Glenn shunt, currently await Fontan. Actuarial survival by the Kaplan-Meier method for all patients was 81.3% at 5, 10, and 15 years, whereas mean survival was 12.1 years (95% confidence interval: 10.04 to 14.05). No late mortality occurred among those surviving beyond 3 months of age. CONCLUSIONS: In patients with PA/IVS-RVDCC, early mortality appears related to coronary ischemia at the time of BTS. Single-ventricle palliation yields excellent long-term survival and should be the preferred management strategy for these patients. Those with aortocoronary atresia have a particularly poor prognosis and should undergo cardiac transplantation.

Cohort Studies↗

PubMed2006

Analysis of surgical outcome in complex double-outlet right ventricle with heterotaxy syndrome or complete atrioventricular canal defect.

BACKGROUND: Double-outlet right ventricle encompasses a broad spectrum of anomalies. Heterotaxy syndrome, which is often associated with total anomalous pulmonary venous connection and complete atrioventricular canal defect, has been considered a risk factor for surgical repair of double-outlet right ventricle. METHODS: From January 1992 to May 1999, medical records of 96 patients (50 males, 46 females) who had complex double-outlet right ventricle with heterotaxy and/or complete atrioventricular canal defect were reviewed (median age at initial surgery 3 months). Seventeen patients were neonates requiring surgery. Follow-up ranged from 1 day to 7.4 years (median, 16 months). RESULTS: Sixty-eight patients had heterotaxy syndrome (27 with total anomalous pulmonary venous connection). Eighty-three had complete atrioventricular canal defect, 22 with moderate to severe atrioventricular valve regurgitation at the time of surgical repair. Eight patients had two-ventricle repair, and 88 patients were considered for single-ventricle management (bidirectional Glenn, 37; Fontan, 44). One patient had heart transplantation after bidirectional Glenn. There were 16 deaths including 10 early (<30 days postoperatively). Overall survival (95% confidence interval) estimated by the Kaplan-Meier method was 89% (83% to 96%) at 1 month, 84% (76% to 91%) at 1 year, and 81% (73% to 89%) at 5 years. Multivariate analysis revealed that neonatal presentation requiring surgery (p < 0.0001), moderate to severe atrioventricular valve regurgitation (p = 0.03), and pulmonary venous obstruction (p = 0.02) were risk factors for death. CONCLUSIONS: Atrioventricular valve regurgitation, pulmonary venous obstruction, and neonatal presentation are risk factors for mortality in patients with complex double-outlet right ventricle. Early surgical intervention in symptomatic neonates and infants, including those with pulmonary venous obstruction, may reduce mortality and improve outcome after staged operation.

Abnormalities, Multiple↗

PubMed2006

Aortic atresia or severe left ventricular outflow tract obstruction with ventricular septal defect: results of primary biventricular repair in neonates.

BACKGROUND: Aortic atresia or severe aortic stenosis and left ventricular outflow tract obstruction is a frequent component of complex congenital heart disease. Aortic atresia or severe aortic stenosis and left ventricular outflow tract obstruction with two adequate ventricles is sometimes treated by Norwood palliation followed by late biventricular repair. We reviewed our experience with primary biventricular repair in this group of neonates. METHODS: Retrospective review identified 17 neonates (10 males) with aortic atresia or severe left ventricular outflow tract obstruction with ventricular septal defect and an adequate left ventricle undergoing primary biventricular repair between 1986 and 2002. Mean age was 7.7 +/- 2.9 days, weight 3.3 +/- 0.7 kg, and body surface area 0.21 +/- 0.04 kg/m2. Associated anomalies included arch hypoplasia, 7 (41%); aortic atresia, 7 (41%); and coarctation, 5 (29%). Results are reported as mean +/- standard deviation. RESULTS: Median follow-up was 6 years (range, 1 to 17.7 years). Three of the 17 (18%) died within 30 days. There were no deaths in this series since 1992. Nine patients (38.9%) required one reoperation, 7 of which were for conduit stenosis, 1 for left ventricular outflow tract obstruction, and 1 for residual ventricular septal defect with left ventricle-to-right atrium shunt. Freedom from death at 10 years was 82% by Kaplan-Meier estimate. CONCLUSIONS: Excellent long-term survival can be achieved by primary biventricular repair as corroborated by our survival rate of 82%. Primary biventricular repair is an effective operation for aortic atresia and severe left ventricular outflow tract obstruction with adequate sized left ventricle that avoids interstage attrition associated with Norwood palliation and is our procedure of choice.

Aortic Valve↗

PubMed2006

Determinants of left ventricular dysfunction after anatomic repair of congenitally corrected transposition of the great arteries.

BACKGROUND: Early results for anatomic repair of congenitally corrected transposition of the great arteries are excellent with respect to right ventricular and tricuspid valve function. However, development of left ventricular (systemic ventricle) dysfunction late after repair remains a concern. In this study we sought to determine factors leading to late impairment in left ventricular performance. METHODS: From August 1992 to July 2005, 44 patients (median age at surgery, 1.6 years; range, 0.6 to 39.6 years) with congenitally corrected transposition of the great arteries had anatomic repair. Left ventricular function and mitral regurgitation were evaluated by echocardiography at follow-up. Twenty-three patients had a Rastelli procedure, and 21 underwent an arterial switch. Twelve patients (27%) were pacemaker dependent at latest follow-up. RESULTS: Early mortality was 4.5% (n = 2) with 1 late death as a result of leukemia. Median follow-up was 3.0 years (range, 7 days to 12.4 years). Left ventricular function remained unchanged (normal) in 35 patients, improved in 1 patient, and deteriorated in 8 patients (18%). Mitral regurgitation was unchanged in 30 patients, improved in 6 patients, and worsened in 8 patients (18%). Development of left ventricular dysfunction was significantly associated with pacemaker implantation (p = 0.005) and a widened QRS (>20% > 98% percentile of normal; p = 0.03). CONCLUSIONS: Anatomic repair of congenitally corrected transposition can be performed with low operative mortality. However, late left ventricular dysfunction is not uncommon, with higher incidence in those requiring pacing and with a prolonged QRS. Resynchronization may be of value in patients requiring a pacemaker.

Adolescent↗

PubMed2006

Regional low-flow perfusion versus circulatory arrest in neonates: one-year neurodevelopmental outcome.

BACKGROUND: Regional low-flow perfusion of the brain is a bypass technique commonly used during stage 1 reconstruction in neonates with hypoplastic left heart syndrome and related variants. The neurodevelopmental outcome of these children is unknown. METHODS: Twenty-nine infants (22 boys, 7 girls) with hypoplastic left heart syndrome or variant requiring single ventricle palliation and aortic arch reconstruction were studied between 1999 and 2004. Mental Developmental Index (MDI) and Psychomotor Developmental Index were assessed using Bayley Scales of Infant Development and correlated with intraoperative and perioperative variables. Results are reported as mean +/- standard deviation. RESULTS: Average age at stage 1 operation and at bidirectional Glenn was 7 +/- 8 days and 6.0 +/- 2 months, respectively. The MDI was in the low average range (87.7 +/- 13.2). The Psychomotor Developmental Index was in the mildly delayed range (75.2 +/- 14.5). Regional low-flow perfusion was used in 31% (9 of 29 patients), with an average circulatory arrest time of 23.5 +/- 13.4 minutes. Deep hypothermia and circulatory arrest was used as the primary operative strategy in 69% of patients (20 of 29 patients), with an average circulatory arrest time of 44.3 +/- 15.3 minutes (p = 0.003). No differences in MDI or Psychomotor Developmental Index scores were observed between the regional low-flow perfusion and non-regional low-flow perfusion groups (MDI, 88.0 +/- 12.1 versus 87.6 +/- 14.0; p = 0.93, respectively; Psychomotor Developmental Index, 75.5 +/- 15.1 versus 75.0 +/- 14.6; p = 0.93, respectively). Lowest operative temperature (<16 degrees C) and birth order (<2 versus >3) significantly related to MDI (89.6 versus 72.8; p = 0.047). CONCLUSIONS: At 1 year of age, neurodevelopmental outcomes of patients undergoing stage 1 using regional low-flow perfusion were similar to outcomes observed in children exposed to circulatory arrest. The association of birth order and MDI suggests that early intervention may benefit these patients.

Cardiac Surgical Procedures↗

PubMed2006

Early postoperative outcomes in a series of infants with hypoplastic left heart syndrome undergoing stage I palliation operation with either modified Blalock-Taussig shunt or right ventricle to pulmonary artery conduit.

OBJECTIVE: Previous publications using nonconcurrent series of patients indicate improved survival for patients with hypoplastic left heart syndrome (HLHS) undergoing stage I palliation with a right ventricle to pulmonary artery conduit (NW-RVPA) vs. a modified Blalock-Taussig shunt (NW-BT). We compared postoperative outcomes in a concurrent series of patients with HLHS undergoing an NW-BT procedure vs. NW-RVPA procedure. DESIGN: Perioperative data from 66 consecutive patients who underwent NW-BT (n = 37) or NW-RVPA (n = 29) procedures were retrospectively analyzed. SETTING: Cardiac intensive care unit in a tertiary pediatric hospital. PATIENTS: Charts were reviewed for all patients with the diagnosis of HLHS undergoing the NW-BT or NW-RVPA procedure between January 2002 and December 2003. RESULTS: Cardiopulmonary bypass time was longer in the NW-BT group than in the NW-RVPA group (152.5 +/- 52.0 vs. 134.5 +/- 36.1 mins; p = .04). Postoperative diastolic pressures were higher and the Pao2 to Fio2 ratio profiles were lower for the NW-RVPA group over the first 72 hrs. Time to sternal closure (2 [1-6] vs. 4 [2-41] days; p = .01), duration of mechanical ventilation (113 [49-386] vs. 136 [84-764] hrs; p = .01), time to establish enteral feeds (4 [2-8] vs. 5 [3-22] days; p = .01), length of intensive care unit stay (11 [7-55] vs. 15 [8-90] days; p = .04), and length of hospital stay (16 [11-67] vs. 27 [12-126] days; p = .01) were shorter in the NW-RVPA group. Postoperative mortality was not significantly different between the NW-RVPA group (7%) and NW-BT group (11%). CONCLUSION: At an experienced institution with low stage I palliation mortality for HLHS, there were no differences in early morbidity and mortality between the NW-RVPA and NW-BT procedures. The primary advantage of the NW-RVPA procedure may be faster recovery following surgery and earlier discharge from the hospital.

Analysis of Variance↗

PubMed2005

Guidance of engineered tissue collagen orientation by large-scale scaffold microstructures.

The tensile strength and stiffness of load-bearing soft tissues are dominated by their collagen fiber orientation. While microgrooved substrates have demonstrated a capacity to orient cells and collagen in monolayer tissue culture, tissue engineering (TE) scaffolds are structurally distinct in that they consist of a three-dimensional (3-D) open pore network. It is thus unclear how the geometry of these open pores might influence cell and collagen orientation. In the current study we developed an in vitro model system for quantifying the capacity of large scale ( approximately 200 microm), geometrically well-defined open pores to guide cell and collagen orientation in engineered tissues. Non-degradable scaffolds exhibiting a grid of 200 microm wide rectangular pores (1:1, 2:1, 5:1, and 10:1 aspect ratios) were fabricated from a transparent epoxy resin via high-resolution stereolithography. The scaffolds (n=6 per aspect ratio) were surface modified to support cell adhesion by covalently grafting GRGDS peptides, sterilized, and seeded with neonatal rat skin fibroblasts. Following 4 weeks of static incubation, the resultant collagen orientation was assessed quantitatively by small angle light scattering (SALS), and cell orientation was evaluated by laser confocal and scanning electron microscopy. Cells adhered to the struts of the pores and proceeded to span the pores in a generally circumferential pattern. While the cell and collagen orientations within 1:1 aspect ratio pores were effectively random, higher aspect ratio rectangular pores exhibited a significant capacity to guide global cell and collagen orientation. Preferential alignment parallel to the long strut axis and decreased spatial variability were observed to occur with increasing pore aspect ratio. Intra-pore variability depended in part on the spatial uniformity of cell attachment around the perimeter of each pore achieved during seeding. Evaluation of diamond-shaped pores [Sacks, M.S. et al., 1997. J. Biomech. Eng. 119(1), 124-127] suggests that they are less sensitive to initial conditions of cell attachment than rectangular pores, and thus more effective in guiding engineered tissue cell and collagen orientation.

Animals↗

PubMed2005

From stem cells to viable autologous semilunar heart valve.

BACKGROUND: An estimated 275,000 patients undergo heart valve replacement each year. However, existing solutions for valve replacement are complicated by the morbidity associated with lifelong anticoagulation of mechanical valves and the limited durability of bioprostheses. Recent advances in tissue engineering and our understanding of stem cell biology may provide a lifelong solution to these problems. METHODS AND RESULTS: Mesenchymal stem cells were isolated from ovine bone marrow and characterized by their morphology and antigen expression through immunocytochemistry, flow cytometry, and capacity to differentiate into multiple cell lineages. A biodegradable scaffold was developed and characterized by its tensile strength and stiffness as a function of time in cell-conditioned medium. Autologous semilunar heart valves were then created in vitro using mesenchymal stem cells and the biodegradable scaffold and were implanted into the pulmonary position of sheep on cardiopulmonary bypass. The valves were evaluated by echocardiography at implantation and after 4 months in vivo. Valves were explanted at 4 and 8 months and examined by histology and immunohistochemistry. Valves displayed a maximum instantaneous gradient of 17.2+/-1.33 mm Hg, a mean gradient of 9.7+/-1.3 mm Hg, an effective orifice area of 1.35+/-0.17 cm2, and trivial or mild regurgitation at implantation. Gradients changed little over 4 months of follow-up. Histology showed disposition of extracellular matrix and distribution of cell phenotypes in the engineered valves reminiscent of that in native pulmonary valves. CONCLUSIONS: Stem-cell tissue-engineered heart valves can be created from mesenchymal stem cells in combination with a biodegradable scaffold and function satisfactorily in vivo for periods of >4 months. Furthermore, such valves undergo extensive remodeling in vivo to resemble native heart valves.

Animals↗

PubMed2005

Heart valve regeneration.

The valves of the heart cannot regenerate spontaneously. Therefore, heart valve disease generally necessitates surgical repair or replacement of the diseased tissue by mechanical or bioprosthetic valve substitutes in order to avoid potentially fatal cardiac or systemic consequences. Although survival and quality of life is enhanced for many patients treated surgically, currently available valve substitutes remain imperfect. This is especially the case in pediatric applications, where physiologically corrective procedures can be successfully performed, but reoperations are frequently required to replace failed valve substitutes or accommodate growth of the patient. While much work is currently underway to incrementally improve existing valve substitutes, a major impact will require radically new technologies, including tissue engineering or regeneration. The use of engineered tissue offers the potential to create a non-obstructive, non-thrombogenic tissue valve substitute containing living cells capable of providing ongoing remodeling and repair of cumulative injury to the extracellular matrix. Ideally, this would allow growth in maturing recipients. The innovative fabrication of materials and the development of sophisticated methods to repair or regenerate damaged or diseased heart valves requires integration of a diverse array of basic scientific principles and enabling technologies. Thus, heart valve tissue engineering requires an understanding of relationships of structure to function in normal and pathological valves (including mechanisms of embryological development, tissue repair and functional biomechanics), and the ability to control cell and tissue responses to injury, physical stimuli and biomaterial surfaces, through chemical, pharmacological, mechanical and potentially genetic manipulations. These approaches created by advances in cell biology raise exciting possibilities for in situ regeneration and repair of heart valves.

Bioprosthesis↗

PubMed2005

Total anomalous pulmonary venous connection: an analysis of current management strategies in a single institution.

BACKGROUND: Repair of total anomalous pulmonary venous connection (TAPVC) continues to be associated with significant mortality. We reviewed patients undergoing consecutive TAPVC repairs over a 10-year period at Children's Hospital Boston. The impact of current surgical and perioperative management strategies on short-term outcomes (postrepair pulmonary venous obstruction and mortality) is evaluated. METHODS: All patients with surgically corrected TAPVC from November 1989 to December 2000 were included. Charts were reviewed for patient demographics, operation variables, and postoperative course. RESULTS: There were 123 patients in the cohort, of which 72 (59%) were male. The median age and weight at operation were 10 days and 3.6 kg, respectively. Sixty-eight (55%) patients presented with pulmonary venous obstruction, and 65 (53%) underwent emergent TAPVC repair. Thirty-nine (32%) had single-ventricle anatomy, and 84 (68%) had two-ventricle anatomy. Thirty patients (24%) died. Kaplan-Meier survival at 1 month was 65% (95% confidence interval [CI], 55% to 75%) for single-ventricle patients versus 90% (95% CI, 90% to 100%) for two-ventricle patients; at 36 months it was 47% (95% CI, 35% to 59%) versus 87% (95% CI, 81% to 93%), respectively. By Cox multivariable regression analysis, a single ventricle (p < 0.001, hazard ratio, 4.8; 95% CI, 2.5 to 9.2) was an independent mortality risk factor. Prerepair pulmonary venous obstruction was a multivariate risk factor for death among single-ventricle patients. Postrepair pulmonary venous obstruction occurred in 11%. If year of operation is used as a predictor, two-ventricle patient survival has significantly improved (p < 0.05). CONCLUSIONS: Despite current interventions, single-ventricle patients continue to have a worse prognosis than two-ventricle patients.

Abnormalities, Multiple↗

PubMed2005

Creation of a brachial arteriovenous fistula for treatment of pulmonary arteriovenous malformations after cavopulmonary anastomosis.

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) occur in approximately 20% of patients after unidirectional superior cavopulmonary anastomosis (CPA), and frequently after bidirectional CPA in patients with polysplenia syndrome. It is hypothesized that exclusion of a growth-modulating factor produced in the liver may predispose to PAVM formation. Resolution of PAVMs after inclusion of hepatic venous effluent into the cavopulmonary circulation has been reported. An upper extremity systemic arteriovenous (AV) fistula may be created to augment pulmonary blood flow and improve oxygenation in hypoxemic patients with CPA, but there has been no systematic investigation of the effects of such fistulas on PAVMs after CPA. METHODS: We studied 11 patients with PAVMs who underwent creation of a brachial AV fistula a median of 11 years after CPA. RESULTS: Eight patients had discontinuous pulmonary arteries or unilateral flow of a bidirectional CPA and were not considered good candidates for Fontan completion; the other 3 patients had polysplenia and unilateral hepatic venous streaming after Fontan completion. Three patients died of progressive complications of their heart disease 4 to 18 months after AV fistula creation. Pulmonary arteriovenous malformations resolved after creation of a brachial AV fistula in 4 of 5 surviving patients with unilateral flow of a superior CPA, but in none of 3 patients with polysplenia who had unilateral hepatic venous streaming after Fontan completion and PAVMs in the contralateral lung. CONCLUSIONS: These findings are consistent with the "hepatic factor" hypothesis, according to which the development of PAVMs is facilitated when an unidentified factor produced or metabolized in the liver does not reach the pulmonary circulation before traversing another capillary bed. Patients with unilateral superior CPA flow and PAVMs who are not considered candidates for Fontan completion may benefit from a brachial AV fistula.

Adolescent↗

PubMed2005

Incorporation of the hepatic veins into the cavopulmonary circulation in patients with heterotaxy and pulmonary arteriovenous malformations after a Kawashima procedure.

BACKGROUND: In patients with polysplenia syndrome and azygous continuation of an interrupted inferior vena cava (IVC), pulmonary arteriovenous malformations (PAVMs) are relatively common after bidirectional cavopulmonary anastomosis (BCPA, Kawashima procedure). Resolution of PAVMs after hepatic vein (HV) inclusion into the cavopulmonary circulation has been reported, but there has been no systematic investigation of the effects of this therapy in a population of more than 3 patients. METHODS: We studied 16 patients with heterotaxy, univentricular congenital heart disease, and azygous continuation of the IVC who underwent incorporation of the HV into the cavopulmonary circuit for treatment of significant PAVMs after a Kawashima procedure. RESULTS: The median preoperative systemic arterial oxygen saturation (SsaO2) was 76% (65%-85%), compared with 89% (85% to 92%) early after BCPA. Among 15 early survivors, the median early postoperative SsaO2 was 76% (56%-85%). In 11 of the 15 survivors, SsaO2 rose to 90% or greater within a year and remained at 93% or greater at follow-up of 2.8 to 10 years. Four patients had persistent hypoxemia and residual PAVMs at follow-up catheterization 1.5 to 8 years postoperatively; these patients had the most severe hypoxemia prior to HV inclusion, and in 2 the residual PAVMs were unilateral, with HV flow streaming to the contralateral lung, in which PAVMs had resolved. CONCLUSIONS: Hypoxemia resolved after cavopulmonary incorporation of the HV in the majority of our patients with PAVMs after the Kawashima operation, presumably due to a combination of PAVM resolution and elimination of hepatic venoatrial right-to-left shunting. These findings support the theory that development of PAVMs is facilitated by exclusion of HV effluent from the pulmonary circulation.

Adolescent↗

PubMed2005

The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue.

Tissue engineered heart valves (TEHV) are being investigated as an alternative to current non-viable prosthetic valves and valved conduits. Studies suggest that pulse duplicator bioreactors can stimulate TEHV development. In the current study, a model system was used to determine if cyclic flexure, a major mode of heart valve deformation, has independent effects on TEHV cell and extracellular matrix (ECM) development. Ovine vascular smooth muscle cells (SMC) were seeded for 30 h onto strips of non-woven 50:50 polyglycolic acid (PGA) and poly-L-lactic acid (PLLA) scaffold. After 4 days of incubation, SMC-seeded and unseeded scaffolds were either maintained under static conditions (static group), or subjected to unidirectional cyclic three-point flexure at a physiological frequency and amplitude in a bioreactor (flex group) for 3 weeks. After seeding or incubation, the effective stiffness (E) was measured, with SMC-seeded scaffolds further characterized by DNA, collagen, sulfated glycosaminoglycan (S-GAG), and elastin content, as well as by histology. The seeding period was over 90% efficient, with a significant accumulation of S-GAG, no significant change in E, and no collagen detected. Following 3 weeks of incubation, unseeded scaffolds exhibited no significant change in E in the flex or static groups. In contrast, E of SMC-seeded scaffolds increased 429% in the flex group (p<0.01) and 351% in the static group (p<0.01), with a trend of increased E, a 63% increase in collagen (p<0.05), increased vimentin expression, and a more homogenous transmural cell distribution in the flex versus static group. Moreover, a positive linear relationship (r2=0.996) was found between the mean E and mean collagen concentration. These results show that cyclic flexure can have independent effects on TEHV cell and ECM development, and may be useful in predicting the mechanical properties of TEHV constructed using novel scaffold materials.

Animals↗