Safety and Short-Term Outcomes for Infants < 2.5 kg Undergoing PDA Device Closure: A C3PO Registry Study.

To evaluate short-term procedural outcomes and safety for infants < 2.5 kg who underwent catheterization with intended patent ductus arteriosus (PDA) device closure in a multi-center registry, as performance of this procedure becomes widespread. A multi-center retrospective review was performed using data from the Congenital Cardiac Catheterization Project on Outcomes (C3PO) registry. Data were collected for all intended cases of PDA closure in infants < 2.5 kg from April 2019 to December 2020 at 13 participating sites. Successful device closure was defined as device placement at the conclusion of the catheterization. Procedural outcomes and adverse events (AE) were described, and associations between patient characteristics, procedural outcomes and AEs were analyzed. During the study period, 300 cases were performed with a median weight of 1.0 kg (range 0.7-2.4). Successful device closure was achieved in 98.7% of cases with a 1.7% incidence of level 4/5 AEs, including one periprocedural mortality. Neither failed device placement nor adverse events were significantly associated with patient age, weight or institutional volume. Higher incidence of adverse events associated with patients who had non-cardiac problems (p = 0.017) and cases with multiple devices attempted (p = 0.064). Transcatheter PDA closure in small infants can be performed with excellent short-term outcomes and safety across institutions with variable case volume.

Palliative stenting of the venous duct in a premature neonate with obstructed infradiaphragmatic total anomalous pulmonary venous connection.

In infracardiac, infradiaphragmatic total anomalous pulmonary venous connection, all four pulmonary veins connect to a descending vertical vein that usually drains to the portal vein or one of its tributaries. Obstruction is common, and definitive treatment is surgical repair. We present a case of late-diagnosed infradiaphragmatic total anomalous pulmonary venous connection in a premature neonate who was too high risk for surgery and underwent palliative stenting of the venous duct. We demonstrate the feasibility of a transhepatic approach when umbilical access is no longer available.

Transcatheter Tricuspid Valve-in-Valve Implantation for the Treatment of Dysfunctional Surgical Bioprosthetic Valves: An International, Multicenter Registry Study.

BACKGROUND: Off-label use of transcatheter aortic and pulmonary valve prostheses for tricuspid valve-in-valve implantation (TVIV) within dysfunctional surgical tricuspid valve (TV) bioprostheses has been described in small reports. METHODS AND RESULTS: An international, multicenter registry was developed to collect data on TVIV cases. Patient-related factors, procedural details and outcomes, and follow-up data were analyzed. Valve-in-ring or heterotopic TV implantation procedures were not included. Data were collected on 156 patients with bioprosthetic TV dysfunction who underwent catheterization with planned TVIV. The median age was 40 years, and 71% of patients were in New York Heart Association class III or IV. Among 152 patients in whom TVIV was attempted with a Melody (n=94) or Sapien (n=58) valve, implantation was successful in 150, with few serious complications. After TVIV, both the TV inflow gradient and tricuspid regurgitation grade improved significantly. During follow-up (median, 13.3 months), 22 patients died, 5 within 30 days; all 22 patients were in New York Heart Association class III or IV, and 9 were hospitalized before TVIV. There were 10 TV reinterventions, and 3 other patients had significant recurrent TV dysfunction. At follow-up, 77% of patients were in New York Heart Association class I or II (P<0.001 versus before TVIV). Outcomes did not differ according to surgical valve size or TVIV valve type. CONCLUSIONS: TVIV with commercially available transcatheter prostheses is technically and clinically successful in patients of various ages across a wide range of valve size. Although preimplantation clinical status was associated with outcome, many patients in New York Heart Association class III or IV at baseline improved. TVIV should be considered a viable option for treatment of failing TV bioprostheses.

Transcatheter valve implantation for right atrium-to-right ventricle conduit obstruction or regurgitation after modified Björk-fontan procedure.

BACKGROUND: The most common reason for reintervention after a Björk modification of the Fontan procedure, in which the right ventricle (RV) is incorporated into the pulmonary circulation by connecting the right atrial (RA) appendage to the RV directly or with an extra-anatomic graft, is obstruction or regurgitation of the RA-RV connection. Transcatheter implantation of a valved stent is an appealing option for the treatment of RA-RV conduit dysfunction in these patients. In the present study, we assessed early and intermediate results after transcatheter valve implantation within an obstructed or regurgitant RA-RV modified Fontan pathway. METHODS: Through a retrospective multicenter registry, we collected data from 16 patients with a modified Fontan circulation who were treated with percutaneous Melody or Sapien valve implantation for dysfunction of an extra-anatomic RA-RV conduit or valve. RESULTS: All patients had successful and uncomplicated implantation of a Melody (n = 15) or Sapien 3 (n = 1) valve with hemodynamic and, in most cases, clinical improvement. During a median follow-up of 3.3 years, 3 patients died of cardiovascular causes unrelated to the procedure or the valve, and no major valve dysfunction was observed. CONCLUSION: Percutaneous transcatheter valve deployment to treat a dysfunctional RA-RV connection after a Björk modification of the Fontan procedure is a viable alternative to surgery, with low procedural risk, and appears to offer good early and intermediate results.© 2016 Wiley Periodicals, Inc.

Thrombolytic-Enhanced Extracorporeal Cardiopulmonary Resuscitation After Prolonged Cardiac Arrest.

OBJECTIVE: To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest. DESIGN: Laboratory investigation. SETTING: University laboratory. SUBJECTS: Pigs. INTERVENTIONS: Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40% ± 15% vs 18% ± 21%). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of electroencephalogram signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages. CONCLUSIONS: In a porcine model of prolonged cardiac arrest, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.

Severely regurgitant left ventricle to ascending aorta conduit in a failing fontan patient treated with a vascular endograft and melody transcatheter pulmonary valve via hybrid approach.

A 28-year-old male with single ventricular heart disease status post Fontan palliation and subsequent placement of left ventricle to ascending aorta (LV-AAo) valved conduit developed ascites and edema. Diagnostic catheterization revealed elevated ventricular end diastolic pressures (EDP) secondary to severe LV-AAo conduit regurgitation. Given the unique anatomy, surgical access via the right axillary artery provided optimal route for transcatheter valve implantation within the conduit. The procedure resulted in significant hemodynamic improvement with no complications. © 2016 Wiley Periodicals, Inc.

Contained rupture of patched right ventricular outflow tracts during balloon sizing for percutaneous pulmonary valve implantation.

Transcatheter pulmonary valves are being used off-label to treat pulmonary insufficiency in patched right ventricular outflow tracts (RVOTs). We describe the first reported cases of patched RVOT rupture, during balloon sizing for percutaneous pulmonary valve implantation, in two patients with tetralogy of Fallot status post repair. Both RVOTs were too large for subsequent catheter-based intervention. The ruptures remained stable over time, and both patients were managed conservatively with follow-up imaging.

Factors associated with the internal jugular venous approach for Melody™ Transcatheter Pulmonary Valve implantation.

BACKGROUND: Transcatheter pulmonary valve implantation is usually performed from a femoral venous - transfemoral - approach, but this may not be the optimal vascular access option in some patients. This study aimed to determine which group of patients might benefit from an internal jugular - transjugular - approach for transcatheter pulmonary valve implantation. METHODS: This multicentre retrospective study included all patients who underwent attempted transcatheter pulmonary valve placement in the right ventricular outflow tract between April 2010 and June 2012 at two large congenital heart centres. Patients were divided into two groups based on venous access site - transfemoral or transjugular. Patient characteristics, procedural outcomes, and complications were compared between groups. RESULTS: Of 81 patients meeting the inclusion criteria (median age 16.4 years), the transjugular approach was used in 14 patients (17%). The transjugular group was younger (median age 11.9 versus 17.3 years), had lower body surface area (mean 1.33 versus 1.61 m2), more often had moderate or greater tricuspid regurgitation (29% versus 7%), and had a higher ratio of right ventricle-to-systemic systolic pressure (mean 82.4 versus 64.7). Patients requiring a transjugular approach after an unsuccessful transfemoral approach had longer fluoroscopic times and procedure duration. CONCLUSIONS: The transjugular approach for transcatheter pulmonary valve implantation is used infrequently but is more often used in younger and smaller patients. Technical limitations from a transfemoral approach may be anticipated if there is moderate or greater tricuspid regurgitation or higher right ventricular pressures. In these patients, a transjugular approach should be considered early.

The Utility of Intracardiac Echocardiography Following Melody™ Transcatheter Pulmonary Valve Implantation.

The aim of this study was to determine the utility of intracardiac echocardiography (ICE) in assessing Melody™ transcatheter pulmonary valve (TPV) function immediately following valve implantation. ICE is used increasingly in percutaneous cardiac interventions. At our center, ICE is routinely utilized to evaluate valve function following Melody TPV implantation, but the utility of this practice remains unclear. A retrospective review of all Melody valves placed in the right ventricular outflow tract from April 2010 to September 2013 was performed. The clinical utility of ICE was described, along with the relationship between ICE data and traditional hemodynamic/angiographic data. ICE was performed in 54 cases and provided excellent Melody TPV visualization with no complications. ICE did not change clinical management but did provide supplemental information in two cases. In one case, angiography showed severe catheter-related Melody insufficiency. Subsequent ICE confirmed no insufficiency and prevented the need for additional angiography. In the second case, ICE allowed characterization of the mechanism of a residual gradient. ICE did not detect any clinically significant paravalvar leaks or valvar insufficiency not seen by angiography. The peak catheterization gradient was more closely approximated by the mean ICE gradient (median difference -7.4 % between measurements) than by the peak ICE gradient (median difference 58.3 %; p < 0.0001). ICE provides excellent and safe visualization following Melody TPV implantation but did not provide new clinical information impacting management in this series. Selective use of ICE in cases with more than expected valve insufficiency or larger than expected residual gradients may streamline use while maintaining optimal clinical outcomes.

Self-Expanding Transcatheter Pulmonary Valve Implant in the Right Pulmonary Artery.

Newer self-expanding transcatheter pulmonary valves (TPVs) are approved for the treatment of severe pulmonary regurgitation in patients with large right ventricular outflow tracts. We present a patient with Tetralogy of Fallot whose right ventricular outflow tract was too large for self-expanding TPV, who was treated successfully with a self-expanding TPV in the right pulmonary artery. (Level of Difficulty: Advanced.).

Update on percutaneous and perventricular device closure of congenital ventricular septal defect.

INTRODUCTION: Ventricular septal defect is the most common congenital heart defect. Surgical repair has been standard therapy for symptomatic ventricular septal defects since the 1950s. Catheter-based device closure of ventricular septal defects emerged in the 1980s and has become a safe and effective alternative in select patients. AREAS COVERED: This review focuses on patient selection and procedural techniques for device closure of ventricular septal defects, including percutaneous and hybrid perventricular approaches. The available devices used for these procedures and outcomes of their use are reviewed. EXPERT OPINION: Percutaneous and perventricular device closure of ventricular septal defects is safe and effective in select patients. However, the majority of ventricular septal defects requiring closure continue to be managed with conventional surgery. Further development and investigation of transcatheter and hybrid surgical approaches for closing ventricular septal defects is required.

Sterilization effects on poly(glycerol dodecanedioate): A biodegradable shape memory elastomer for biomedical applications.

Biodegradable shape memory polymers provide unique regenerative medicine approaches in minimally invasive surgeries. Once heated, thermally responsive shape memory polymer devices can be compressed, programmed to fit within a small profile, delivered in the cold programmed state, and expanded when heated to body temperature. We have previously developed a biodegradable shape memory elastomer (SME), poly(glycerol dodecanedioate) (PGD), with transition temperatures near 37°C exhibiting nonlinear elastic properties like numerous soft tissues. Using SMEs in the clinic requires disinfection and sterilization methods that conserve physiochemical, thermomechanical, and shape recovery properties. We evaluated disinfection protocols using 70% ethanol and UV254 nm for research applications and ethylene oxide (EtO) gas sterilization for clinical applications. Samples disinfected with ethanol for 0.5 and 1 min showed no changes in physiochemical material properties, but after 15 min showed slower recovery rates than controls (p < .05). EtO sterilization at 54.4°C decreased transition temperatures and shape recovery rate compared to EtO sterilization at 37.8°C (p < .01) and controls (p < .05). Aging samples for 9 months in a vacuum desiccator significantly reduced shape recovery, and the recovery rate in EtO sterilized samples compared to controls (p < .001). Cytotoxicity testing (ISO-10993.5C:2012) revealed media extractions from EtO sterilized samples, sterilized at 37.8°C, and high-density polyethylene negative control samples exhibit lower cytotoxicity (IC50) than Ethanol 1 min, UV 2 h, and EtO 54.4°C. Cell viability of NIH3T3 fibroblasts on sterilized surfaces was equivalent on EtO 37.7°C, EtO 54.4°C and Ethanol sterilized substrates. Finally, chromogenic bacterial endotoxin testing showed endotoxin levels were below the FDA prescribed levels for devices contacting blood and lymphatic tissues for ethanol 1 min, UV 120 min, EtO 37.7°C, EtO 54.4°C. These findings outline various disinfection and sterilization processes for research and pre-clinical application and provide a pathway for developing custom sterilization cycles for the translation of biomedical devices utilizing PGD shape memory polymers.

Percutaneous delivery and degradation of a shape memory elastomer poly(glycerol dodecanedioate) in porcine pulmonary arteries.

Shape memory biodegradable elastomers are an emergent class of biomaterials well-suited for percutaneous cardiovascular repair requiring nonlinear elastic materials with facile handling. We have previously developed a chemically crosslinked shape memory elastomer, poly (glycerol dodecanedioate) (PGD), exhibiting tunable transition temperatures around body temperature (34-38 °C), exhibiting nonlinear elastic properties approximating cardiac tissues, and favorable degradation rates in vitro. Degree of tissue coverage, degradation and consequent changes in polymer thermomechanical properties, and inflammatory response in preclinical animal models are unknown material attributes required for translating this material into cardiovascular devices. This study investigates changes in the polymer structure, tissue coverage, endothelialization, and inflammation of percutaneously implanted PGD patches (20 mm × 9 mm x 0.5 mm) into the branch pulmonary arteries of Yorkshire pigs for three months. After three months in vivo, 5/8 samples exhibited (100%) tissue coverage, 2/8 samples exhibited 85-95% tissue coverage, and 1/8 samples exhibited limited (<20%) tissue coverage with mild-moderate inflammation. PGD explants showed a (60-70%) volume loss and (25-30%) mass loss, and a reduction in polymer crosslinks. Lumenal and mural surfaces and the cross-section of the explant demonstrated evidence of degradation. This study validates PGD as an appropriate cardiovascular engineering material due to its propensity for rapid tissue coverage and uneventful inflammatory response in a preclinical animal model, establishing a precedent for consideration in cardiovascular repair applications.

In-vivo evaluation of molybdenum as bioabsorbable stent candidate.

Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drug-eluting stents for the treatment of obstructive coronary artery disease. Any bioresorbable or biodegradable scaffold material needs to possess optimal mechanical properties and uniform degradation behavior that avoids local and systemic toxicity. Recently, molybdenum (Mo) has been investigated as a potential novel biodegradable material for this purpose. With its proven moderate degradation rate and excellent mechanical properties, Mo may represent an ideal source material for clinical cardiac and vascular applications. The present study was performed to evaluate the mechanical performance of metallic Mo in vitro and the biodegradation properties in vivo. The results demonstrated favorable mechanical behavior and a uniform degradation profile as desired for a new generation ultra-thin degradable endovascular stent material. Moreover, Mo implants in mouse arteries avoided the typical cellular response that contributes to restenosis. There was minimal neointimal hyperplasia over 6 months, an absence of excessive smooth muscle cell (SMC) proliferation or inflammation near the implant, and avoidance of significant harm to regenerating endothelial cells (EC). Qualitative inspection of kidney sections showed a potentially pathological remodeling of kidney Bowman's capsule and glomeruli, indicative of impaired filtering function and development of kidney disease, although quantifications of these morphological changes were not statistically significant. Together, the results suggest that the products of Mo corrosion may exert beneficial or inert effects on the activities of inflammatory and arterial cells, while exerting potentially toxic effects in the kidneys that warrant further investigation.

Perventricular Transcatheter Pulmonary Valve Implantation in a Symptomatic 3-Year-Old Child With Repaired Tetralogy of Fallot.

In select patients, transcatheter pulmonary valve replacement through a percutaneous approach can be challenging because of complicated anatomy or small patient size. In these patients, especially those weighing <20 kg, hybrid perventricular valve delivery may provide a preferred alternative approach. (Level of Difficulty: Intermediate.).

Modulating nonlinear elastic behavior of biodegradable shape memory elastomer and small intestinal submucosa(SIS) composites for soft tissue repair.

Structural repair of soft tissue for regenerative therapies can be advanced by developing biocompatible and bioresorbable materials with mechanical properties similar to the tissue targeted for therapy. Developing new materials modeling soft tissue mechanics can mitigate many limitations of material based therapies, specifically concerning the mechanical stress and deformation the material imposes on surrounding tissue structures. However, many elastomeric materials used in soft tissue repair lack the ability to be delivered through minimally invasive surgical (MIS) or transcatheter routes and require open surgical approaches for placement and application. We have developed a biocompatible and fully biodegradable shape memory elastomer, poly-(glycerol dodecanedioate) (PGD), which fulfills the requirements for hyperelasticity and exhibits shape memory behavior to serve as a novel substrate material for regenerative therapy in minimally invasive clinical procedures. Our previous work demonstrated control over the tangent modulus at 12.5% compressive strain between 1 and 3 MPa by increasing the crosslinking density in the polymer. In order to improve control over a broader range of mechanical properties, nonlinear behavior, and toughness, we 1) varied PGD physical crosslink density, 2) incorporated sheets of porcine small intestinal submucosa (SIS, Cook Biotech, Inc.) with varying thickness, and 3) mixed lyophilized SIS particulates into PGD at different weight percentages. Tensile testing (ASTM D412a) revealed PGD containing SIS sheets of were stiffer than controls (p < 0.01). Incorporating lyophilized SIS particulates into PGD increased the strain to failure (p < 0.001) compared to PGD controls. Test specimens with 1 ply sheets had greater tear strength (ASTM D624c) compared to PGD tear specimens prepared control specimens (p < 0.001). However, incorporating SIS particulates decreased tear strength of PGD-SIS 0.5 wt% particulate composites (p < 0.01) compared to PGD controls. Incorporating 2 ply and 4 ply sheets and 0.5 wt% particulates into PGD decreased the fixity and recovery of composite materials compared to controls (p < 0.01). Nonlinear modeling of stress strain curves under uniaxial tension demonstrated tunability of PGD-SIS composite materials to model various nonlinear soft tissues. These findings support the use of shape memory PGD-SIS composite materials towards the design of implantable devices for a variety of soft tissue regeneration applications by minimally invasive surgery.

Degradation properties of a biodegradable shape memory elastomer, poly(glycerol dodecanoate), for soft tissue repair.

Development of biodegradable shape memory elastomers (SMEs) is driven by the growing need for materials to address soft tissue pathology using a minimally invasive surgical approach. Composition, chain length and crosslinking of biocompatible polymers like PCL and PLA have been investigated to control mechanical properties, shape recovery and degradation rates. Depending on the primary mechanism of degradation, many of these polymers become considerably stiffer or softer resulting in mechanical properties that are inappropriate to support the regeneration of surrounding soft tissues. Additionally, concerns regarding degradation byproducts or residual organic solvents during synthesis accelerated interest in development of materials from bioavailable monomers. We previously developed a biodegradable SME, poly(glycerol dodecanoate) (PGD), using biologically relevant metabolites and controlled synthesis conditions to tune mechanical properties for soft tissue repair. In this study, we investigate the influence of crosslinking density on the mechanical and thermal properties of PGD during in vitro and in vivo degradation. Results suggest polymer degradation in vivo is predominantly driven by surface erosion, with no significant effects of initial crosslinking density on degradation time under the conditions investigated. Importantly, mechanical integrity is maintained during degradation. Additionally, shifts in melt transitions on thermograms indicate a potential shift in shape memory transition temperatures as the polymers degrade. These findings support the use of PGD for soft tissue repair and warrant further investigation towards tuning the molecular and macromolecular properties of the polymer to tailor degradation rates for specific clinical applications.

Zn2+-dependent suppression of vascular smooth muscle intimal hyperplasia from biodegradable zinc implants.

Biodegradable arterial implants based on zinc have been found to suppress neointimal hyperplasia, suggesting that biodegradable materials containing zinc may be used to construct vascular implants with a reduced rate of restenosis. However, the molecular mechanism has remained unclear. In this report, we show that zinc-containing materials can be used to prevent neointimal formation when implanted into the rat aorta. Indeed, neointimal cells were significantly more TUNEL positive and alpha-actin negative at the interface of biodegradable zinc vs. biostable platinum implants, in association with greater caspase-3 activity. Although zinc stimulated extensive neointimal smooth muscle cell (SMC) death, macrophage and proinflammatory markers CD68 and iNOS were not increased in neointimal tissue relative to biostable platinum control implants. Using arterial explants, ionic zinc was confirmed to promote SMC apoptosis by activating the caspase apoptotic signaling pathway. These observations suggest that zinc-containing materials can be used to construct vascular implants such as stents with reduced neointimal hyperplasia.

Novel method for delivering the Amplatzer muscular VSD occluder in a patient with double outlet right ventricle after bidirectional Glenn procedure and pulmonary artery band.

We report the first use of bilateral femoral venovenous rail creation for the delivery of an Amplatzer Muscular Ventricular Septal Defect Occluder in a patient with a large mid-to-apical muscular ventricular septal defect before Rastelli operation. The presence of a right-sided bidirectional Glenn shunt, a banded main pulmonary artery, and double outlet right ventricle anatomy precluded the use of standard delivery techniques. The patient underwent successful transcatheter device placement followed by Rastelli operation on the following day.