Transcatheter Pulmonary Valve Replacement With the Sapien Prosthesis.

BACKGROUND: There are limited published data focused on outcomes of transcatheter pulmonary valve replacement (TPVR) with either a Sapien XT or Sapien 3 (S3) valve. OBJECTIVES: This study sought to report short-term outcomes in a large cohort of patients who underwent TPVR with either a Sapien XT or S3 valve. METHODS: Data were entered retrospectively into a multicenter registry for patients who underwent attempted TPVR with a Sapien XT or S3 valve. Patient-related, procedural, and short-term outcomes data were characterized overall and according to type of right ventricular outflow tract (RVOT) anatomy. RESULTS: Twenty-three centers enrolled a total of 774 patients: 397 (51%) with a native/patched RVOT; 183 (24%) with a conduit; and 194 (25%) with a bioprosthetic valve. The S3 was used in 78% of patients, and the XT was used in 22%, with most patients receiving a 29-mm (39%) or 26-mm (34%) valve. The implant was technically successful in 754 (97.4%) patients. Serious adverse events were reported in 67 patients (10%), with no difference between RVOT anatomy groups. Fourteen patients underwent urgent surgery. Nine patients had a second valve implanted. Among patients with available data, tricuspid valve injury was documented in 11 (1.7%), and 9 others (1.3%) had new moderate or severe regurgitation 2 grades higher than pre-implantation, for 20 (3.0%) total patients with tricuspid valve complications. Valve function at discharge was excellent in most patients, but 58 (8.5%) had moderate or greater pulmonary regurgitation or maximum Doppler gradients >40 mm Hg. During limited follow-up (n = 349; median: 12 months), 9 patients were diagnosed with endocarditis, and 17 additional patients underwent surgical valve replacement or valve-in-valve TPVR. CONCLUSIONS: Acute outcomes after TPVR with balloon-expandable valves were generally excellent in all types of RVOT. Additional data and longer follow-up will be necessary to gain insight into these issues.

Recent advances in transcatheter pulmonary valve delivery.

PURPOSE OF REVIEW: Transcatheter pulmonary valve replacement has only been both approved and widely available for most congenital heart disease centers for a few years; its use and familiarity for interventionalists have greatly expanded our knowledge of its applicability to a multitude of clinical situations. Expanded worldwide use and longer time from implant have both served to better understand procedural limits and uncommon late adverse events. RECENT FINDINGS: Although currently approved for implantation in the USA only in dysfunctional and circumferential right ventricle to pulmonary artery conduits, with expanded experience operators have been able to adapt the delivery of this valve in a large number of additional clinical scenarios. Rare technical limitations of the procedure, most importantly coronary compression, are now being better defined. Although not frequent, a significant number of infective endocarditis episodes have been reported, but more recently several studies have deepened our understanding of this late adverse event for the most commonly implanted transcatheter pulmonary valve prosthesis. SUMMARY: Expanded and widened use has extended our understanding of who may benefit from transcatheter pulmonary valve implantation (TPVI), the current limits of TPVI, and uncommon but important late issues following TPVI.

Outcomes in highly sensitized pediatric heart transplant patients using current management strategies.

BACKGROUND: Previous studies have suggested that children with pre-formed anti-HLA antibodies (PRA) undergoing orthotopic heart transplantation (OHT) have increased risk for rejection, coronary artery vasculopathy (CAV) and death. In 2005, our program started utilizing aggressive desensitization (including plasmapheresis, IVIg, pulse cytoxan and rituximab) with the goal of improving outcomes for these patients. The purpose of this study was to compare outcomes with this new strategy in recipients with pre-OHT high PRA (>10%) vs low PRA ≤10%). METHODS: A retrospective study of 70 consecutive pediatric OHT patients was undertaken between January 2005 and July 2013 to identify patients with pre-OHT PRA >10% (high PRA), or PRA ≤10% (low PRA). Demographic/data information and detailed post-OHT outcomes, including rejection, 30-day and overall mortality, freedom from significant rejection, and CAV, were analyzed. RESULTS: Fourteen (20%) patients had high PRA and 56 (80%) did not. There was a significant decrease in PRA values before and after desensitization. Thirty-day and overall mortality and the proportion of patients with rejections or CAV were lower in the high PRA group, although the difference was not statistically significant. Kaplan-Meier survival analysis revealed no significant difference in survival between the two groups. There was a significant difference in survival in our sensitized patients before 2005 vs after 2005. CONCLUSIONS: We identified no significant differences in outcomes between high or low PRA patients. These preliminary findings may suggest improvement in OHT outcomes for high PRA patients as a result of aggressive desensitization. A larger study is warranted to confirm these findings.

Impact of pre-stage II hemodynamics and pulmonary artery anatomy on 12-month outcomes in the Pediatric Heart Network Single Ventricle Reconstruction trial.

OBJECTIVE: To compare the interstage cardiac catheterization hemodynamic and angiographic findings between shunt types for the Pediatric Heart Network Single Ventricle Reconstruction trial. The trial, which randomized subjects to a modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery shunt (RVPAS) for the Norwood procedure, demonstrated the RVPAS was associated with a smaller pulmonary artery diameter but superior 12-month transplant-free survival. METHODS: We analyzed the pre-stage II catheterization data for the trial subjects. The hemodynamic variables and shunt and pulmonary angiographic data were compared between shunt types; their association with 12-month transplant-free survival was also evaluated. RESULTS: Of 549 randomized subjects, 389 underwent pre-stage II catheterization. A smaller size, lower aortic and superior vena cava saturation, and higher ventricular end-diastolic pressure were associated with worse 12-month transplant-free survival. The MBTS group had a lower coronary perfusion pressure (27 vs 32 mm Hg; P<.001) and greater pulmonary blood flow/systemic blood flow ratio (1.1 vs 1.0, P=.009). A greater pulmonary blood flow/systemic blood flow ratio increased the risk of death or transplantation only in the RVPAS group (P=.01). The MBTS group had fewer shunt (14% vs 28%, P=.004) and severe left pulmonary artery (0.7% vs 9.2%, P=.003) stenoses, larger mid-main branch pulmonary artery diameters, and greater Nakata indexes (164 vs 134, P<.001). CONCLUSIONS: Compared with the RVPAS subjects, the MBTS subjects had more hemodynamic abnormalities related to shunt physiology, and the RVPAS subjects had more shunt or pulmonary obstruction of a severe degree and inferior pulmonary artery growth at pre-stage II catheterization. A lower body surface area, greater ventricular end-diastolic pressure, and lower superior vena cava saturation were associated with worse 12-month transplant-free survival.

Transcatheter pulmonary valve insertion, expanded use (beyond large conduits from the right ventricle to pulmonary artery), and future directions.

Transcatheter pulmonary valve insertion is the most important advance in congenital interventional cardiology since atrial septal defect devices became commonly available 15 years ago. It has changed the way we look at a number of diverse diagnoses and changes how we plan, diagnose, operate, and follow-up patients. It has changed how we counsel families expecting a child that may benefit from it. Expanded use of the Melody® valve, outside its United States Food and Drug Administration approved indications, has helped numerous additional patients. The use of transcatheter pulmonary valve insertion in selected patients following surgical Gore-tex® bileaflet in valve right ventricular outflow tract reconstruction and those with a history of prior small homograft conduits will be discussed.

Transcatheter pulmonary valve insertion, expanded use and future directions.

Transcatheter pulmonary valve replacement with the Melody® valve is an accepted alternative to surgical replacement of the pulmonary valve for some patients and therefore a complementary strategy in the long-term management of several groups of patients with congenital heart disease. It allows at least extending the time between sternotomies and possibly improving late outcomes. With a combined surgical and percutaneous approach, late morbidity for some of these patients will likely be diminished. This manuscript will review the current expanded applications for this technology, demonstrate several examples of its use and discuss future directions for this evolving equipment.

Management of adults with Tetralogy of Fallot.

Tetralogy of Fallot is the most common form of cyanotic congenital cardiac disease. Patients with previously repaired tetralogy of Fallot are the most common patients seen in the Program for Adults with Congenital Heart Disease at The Johns Hopkins All Children's Heart Institute. Guidelines for the management of these patients are available from multiple sources including The American College of Cardiology (ACC) and The American Heart Association (AHA), The Canadian Cardiovascular Society, and The European Society of Cardiology (ESC). These guidelines describe multiple components related to the care for these patients including strategies for medical follow-up, the management of arrhythmias and electrophysiological diseases, and the treatment of chronic pulmonary insufficiency and stenosis. Several new strategies are available for replacement of the pulmonary valve including transcatheter replacement of the pulmonary valve and replacement of the pulmonary valve with a self-manufactured bicuspid polytetrafluoroethylene pulmonary valve.

Transcatheter pulmonary valve insertion: when, how, and why.

Transcatheter pulmonary valve replacement is fast becoming an accepted alternative to repeat surgical pulmonary valve replacement for selected patients and therefore a complementary strategy in the long-term management of those requiring surgical pulmonary valve replacement. With a combined surgical and percutaneous approach, late morbidity for some of these patients may be diminished. This manuscript will review the current indications for this procedure, its limitations, and its benefits.

The hybrid approach--current knowns and unknowns: the perspective of cardiology.

The hybrid approach to the treatment of patients with hypoplastic left heart syndrome most commonly includes transcatheter placement of a stent in the arterial duct and surgical placement of bands on the branch pulmonary arteries via median sternotomy. This manuscript will review the concept of hybrid palliation and discuss topics related to several time intervals: peri-procedural, post-procedural, interstage, and comprehensive stage 2.

Management of children undergoing cardiac transplantation with high Panel Reactive Antibodies.

Highly sensitised children in need of cardiac transplantation have overall poor outcomes because of increased risk for dysfunction of the cardiac allograft, acute cellular and antibody-mediated rejection, and vasculopathy of the cardiac allograft. Cardiopulmonary bypass and the frequent use of blood products in the operating room and cardiac intensive care unit, as well as the frequent use of homografts, have predisposed potential recipients of transplants to allosensitisation. The expansion in the use of ventricular assist devices and extracorporeal membrane oxygenation has also contributed to increasing rates of allosensitisation in candidates for cardiac transplantation. Antibodies to Human Leukocyte Antigen can be detected before transplantation using several different techniques, the most common being the "complement-dependent lymphocytotoxicity assays". "Solid-phase assays", particularly the "Luminex® single antigen bead method", offer improved specificity and more detailed information regarding specificities of antibodies, leading to improved matching of donors with recipients. Allosensitisation prolongs the time on the waiting list for potential recipients of transplantation and increases the risk of complications and death after transplantation. Aggressive reduction of antibodies to Human Leukocyte Antigen in these high-risk patients is therefore of vital importance for long-term survival of the patient and cardiac allograft. Strategies to decrease Panel Reactive Antibody or percent reactive antibody before transplantation include plasmapheresis, intravenous administration of immunoglobulin, and specific treatment to reduce B-cells, particularly Rituximab. These strategies have resulted in varying degrees of success. Antibody-mediated rejection and cardiac allograft vasculopathy are two of the most important complications of transplantation in patients with high Panel Reactive Antibody. The treatment of antibody-mediated rejection in recipients of cardiac transplants is largely empirical and includes the use of high-dose corticosteroids, plasmapheresis, intravenous administration of immunoglobulins, anti-thymocyte globulin, and Rituximab. Cardiac allograft vasculopathy is believed to be secondary to chronic complement-mediated endothelial injury and chronic vascular rejection. The use of proliferation signal inhibitors, such as sirolimus and everolimus, has been shown to delay the progression of cardiac allograft vasculopathy. In some non-sensitised recipients of cardiac transplants, the de novo formation of antibodies to Human Leukocyte Antigen after transplantation may increase the likelihood of adverse clinical outcomes. The use of serial testing for donor-specific antibodies after cardiac transplantation may be advisable in patients with frequent episodes of rejection and patients with history of sensitisation. Allosensitisation before transplantation can negatively influence outcomes after transplantation. A high incidence of antibody-mediated rejection and graft vasculopathy can result in graft failure and decreased survival. Current strategies to decrease allosensitisation have helped to expand the pool of donors, improve times on the waiting list, and decrease mortality. Centres of transplantation offering desensitisation are currently using plasmapheresis to remove circulating antibodies; intravenous immunoglobulin to inactivate antibodies; cyclophosphamide to suppress B-cell proliferation; and Rituximab to deplete B-lymphocytes. Similar approaches are also used to treat antibody-mediated rejection after transplantation with promising results.

Pediatric catheterization laboratory anticoagulation with bivalirudin.

BACKGROUND: Pediatric physicians regularly face the problem of uncertain procedural anticoagulation in children, especially in neonates. We sought to evaluate the safety, plasma concentration (pharmacokinetics, PK), pharmacodynamics (PD), and dosing guidelines of bivalirudin when used as a procedural anticoagulant in pediatric percutaneous intravascular procedures. METHODS AND RESULTS: Pediatric subjects undergoing percutaneous intravascular procedures for congenital heart disease were enrolled and received the current weight-based dose used in percutaneous coronary interventions (0.75 mg/kg bolus, 1.75 mg/kg/hr infusion). Blood samples for PK/PD analyses were drawn, and safety was evaluated by monitoring bleeding and thrombosis events. A total of 110 patients (11 neonates, 33 infants, 32 young children, and 34 older children) were enrolled; 106 patients received the protocol dose. The PK/PD response of bivalirudin was predictable and behaved in a manner similar to that in adults. Weight-normalized bivalirudin clearance rates were more rapid in neonates and decreased with increasing age. Bivalirudin concentrations were slightly lower in neonates, with a trend to an increase with age. Activating clotting time response was consistent with adult studies and prolonged in all age groups, and there was reasonable correlation between activating clotting time and bivalirudin plasma concentrations across all age groups. There were few major bleeding (2 of 110, 1.8%) or thrombotic events (9 of 110, 8.2%) reported. CONCLUSIONS: PK/PD response of bivalirudin in the pediatric population is predictable and behaves in a manner similar to that in adults. Using adult dosing, bivalirudin safely provided the expected anticoagulant effect in the pediatric population undergoing intravascular procedures for congenital heart disease.

Plasma profiling determinants of matrix homeostasis in paediatric dilated cardiomyopathy.

OBJECTIVE: Dilated cardiomyopathy is an important cause of cardiac failure in both children and adults, but is more progressive in children. In adult dilated cardiomyopathy, left ventricular remodelling is associated with changes in the plasma levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases. Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinase changes in paediatric dilated cardiomyopathy have not been examined. This study developed a low blood volume, high-sensitivity assay to test the hypothesis that unique and differential plasma matrix metalloproteinases and tissue inhibitors of metalloproteinase profile exist in patients with paediatric dilated cardiomyopathy. METHODS/RESULTS: A systemic blood sample (1 millilitre) was obtained from seven children aged 8 plus or minus 7 years with dilated cardiomyopathy and 26 age-matched normal volunteers. Using a high-throughput multiplex suspension immunoassay, plasma levels were quantified for collagenases (matrix metalloproteinase-8), gelatinases (matrix metalloproteinase-2 and -9), lysins (matrix metalloproteinase-3 and -7), and tissue inhibitor of metalloproteinases-1, -2, and -4. The matrix metalloproteinase to tissue inhibitors of metalloproteinases ratios were also calculated. The plasma matrix metalloproteinase-2, -7, -8, and -9 levels were increased by greater than twofold in patients with dilated cardiomyopathy than normal patients (with p less than 0.05). Patients with dilated cardiomyopathy also had significantly higher tissue inhibitors of metalloproteinases-1 and -4 (298% and 230%; with p less than 0.05). CONCLUSIONS: These unique findings show that a specific plasma matrix metalloproteinase/tissue inhibitor of metalloproteinase profile occurs in paediatric dilated cardiomyopathy when compared to the cases of normal children. These distinct differences in the determinants of myocardial matrix structure and function may contribute to the natural history of dilated cardiomyopathy in children and may provide a novel biomarker platform in paediatric dilated cardiomyopathy.

Rejection with hemodynamic compromise in the current era of pediatric heart transplantation: a multi-institutional study.

BACKGROUND: Survival after pediatric heart transplant has improved over time, as has the incidence of overall rejection. We studied the effect of era on the occurrence and outcome of rejection with hemodynamic compromise (HC). METHODS: Data from 2227 patients who received allografts between 1993 and 2006 at 36 centers in the Pediatric Heart Transplant Study were analyzed to determine incidence, outcome, and risk factors for rejection with HC in early (1993-1999) and recent (2000-2006) eras. Rejection with HC was classified as severe (RSHC) when inotropes were used for circulatory support and mild (RMHC) when inotropes were not used. RESULTS: Of 1217 patients with any episode of rejection, 541 had rejection with HC. Freedom from RMHC improved at 1 year (81% vs 90%, p < 0.001) and at 5 years (74% vs 85%, p < 0.001) in the early vs recent eras, but freedom from RSHC was similar between eras (93% vs 95% at 1 year and 85% vs 87% at 5 years, p = 0.24). Survival after RSHC (63% at 1 year and 49% at 5 years) was worse than after RMHC (87% at 1 year and 72% at 5 years, p < 0.001) and did not change over time. Risk factors for RSHC were non-white race (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.29-2.32, p < 0.01), older age (HR, 2.85; 95% CI, 1.24-6.53; p = 0.01), and non-A blood type (HR, 1.51;, 95% CI, 1.11-2.04,; p = 0.01), but the only risk factor for RMHC was earlier era of transplant (HR, 1.94; 95% CI, 1.56-2.41; p < 0.001). CONCLUSIONS: The incidence of RMHC has declined over time but the same era effect has not occurred with RSHC. Close follow-up after RSHC is crucial because mortality is so high.

Determinants of extracellular matrix remodelling are differentially expressed in paediatric and adult dilated cardiomyopathy.

AIMS: The left ventricular phenotype of idiopathic dilated cardiomyopathy (DCM) can appear similar in paediatric and adult patients. However, the aetiology of paediatric DCM is usually idiopathic, and often leads an aggressive clinical course. A structural underpinning of DCM is extracellular matrix changes, which are determined by a balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). This study tested the hypothesis that different MMP/TIMP profiles occur in paediatric and adult DCM patients. METHODS AND RESULTS: Left ventricular samples from paediatric (age 9 ± 5 years; n = 10) and adult (age 62 ± 3 years; n = 20) DCM (at time of transplant) were subjected to an MMP/TIMP multiplex array and immunoassay in order to measure the MMP subclasses; collagenases (MMP-8, -13), gelatinases (MMP-2, -9), stromelysin/matrilysin (MMP-3, -7), membrane type (MT1-MMP), as well as for the four known TIMPs. MMP-8 and -9 levels increased by over 150% (P < 0.05), whereas MMP-3 and -7 levels decreased by over 30% (P < 0.05) in paediatric DCM when compared with adult DCM. TIMP-1 and -2 levels increased two-fold (P < 0.05), but TIMP-3 fell by 41% (P < 0.05) in paediatric DCM. Myocardial levels of specific interleukins (IL-1beta, IL-2, IL-8) were increased by approximately 50% in paediatric DCM. CONCLUSIONS: These unique findings demonstrated that a specific MMP/TIMP profile occurs in paediatric DCM when compared with adult DCM, and that local cytokine induction may contribute to this process. These distinct differences in the determinants of myocardial matrix structure and function may contribute to the natural history of DCM in children.

Evaluation of the myocardial performance index and tissue doppler imaging by comparison to near-simultaneous catheter measurements in pediatric cardiac transplant patients.

BACKGROUND: Parameters derived from Doppler echocardiography, such as the myocardial performance index (MPI) and the ratio of peak velocity of early diastolic prograde flow (E) across the atrioventricular valve (AVV) divided by the peak velocity of early diastolic tissue motion at the AVV annulus (E') (E:E' ratio), are routinely used to assess ventricular function. However, they have not been compared with measurements obtained by cardiac catheterization (CC) in children. METHODS: We prospectively studied post-cardiac transplant children undergoing CC with near-simultaneous echocardiographic imaging for MPI and E:E'. CC data included right atrial pressure (RAp), pulmonary artery wedge pressure (PAWp) and cardiac index (CI). One investigator, who was blinded to the CC data, measured right ventricular (RV) and left ventricular (LV) MPI and E:E' offline. Correlations between echocardiographic and catheter measurements were calculated. Receiver-operating-characteristics (ROC) curves were created to evaluate the utility of echocardiographic measurements that exhibited statistically significant correlations with CC measurements. RESULTS: Twenty-four patients (age range 0.8 to 21 years) underwent 142 CCs during the study period. Of the 12 correlations studied, 3 met statistical significance (p < 0.05) (RV E:E' vs RAp, RV E:E' vs PAWp and LV MPI vs CI). The ROC areas for these correlations were 0.38, 0.42 and 0.68, respectively. There were no cut-off points where both the sensitivity and specificity for any measurement were >0.80. CONCLUSIONS: Our data suggest that MPI and E:E' are poor predictors of simultaneously obtained, catheter-derived hemodynamic parameters in post-transplant children. These limitations should be carefully considered before ascribing diagnostic value to these measurements.

Etoposide-related cardiotoxicity in a child with haemophagocytic lymphohistiocytosis.

We report a male child with haemophagocytic lymphohistiocytosis who developed myocardial infarction after receiving etoposide. He recovered well with supportive measures and after discontinuation of etoposide. We discuss the possible mechanisms and differential diagnoses of myocardial infarction in our patient.

Novel minimally invasive, intrapericardial implantable cardioverter defibrillator coil system: a useful approach to arrhythmia therapy in children.

BACKGROUND: Current approaches to implantable cardioverter defibrillator (ICD) implantation in children remain challenging. Transvenous access may be limited due to patient size or anatomy, while epicardial patches require sternotomy or thoracotomy. We present an alternative approach; minimally invasive placement of a transvenous ICD coil within the pericardial space with active fixation. METHODS: Between August 2005 and October 2008, 7 children meeting indications for ICD therapy for ventricular tachyarrhythmias underwent intrapericardial placement of an ICD coil system. Median age was 5 years (range, 1 to 17), weight was 14 kg (range, 8 to 46), and 4 patients weighed less than 20 kg. The ICD system was composed of a single or dual defibrillation coil, an active can, and either ventricular or dual chamber epicardial sense-pace leads. All implantations were performed through a small subxiphoid incision and pericardial window without sternotomy. The coil lead was actively fixated in the transverse sinus under fluoroscopic guidance, and the generator placed in a subrectus pocket in the upper abdomen through the same incision. RESULTS: There were no perioperative complications, and no early or late deaths. All implants had acceptable defibrillation energies (range, 5 to 15 J) that were successfully tested intraoperatively, and none required energy increase or lead revision during follow-up (range, 1 to 39 months; median, 20 months). Impedance between the active can and the defibrillation coil remained stable in all. There were no inappropriate discharges. Thirty-six successful ICD discharges in 4 patients were recorded. Two patients underwent subsequent orthotopic heart transplantation and ICD system removal. CONCLUSIONS: Intrapericardial placement of an ICD coil system can be safely and successfully carried out through a minimally invasive subxiphoid approach in small infants and children. This novel ICD configuration demonstrates excellent performance, and provides a particularly efficacious approach to ventricular tachyarrhythmia therapy in pediatric patients.

Usefulness of live three-dimensional transesophageal echocardiography in a congenital heart disease center.

Three-dimensional (3D) transesophageal echocardiography (TEE) has numerous potential applications in the care of patients with congenital heart disease (CHD). However, there were few data examining its utility in this setting. The aim was to describe the initial experience and feasibility of this modality at a tertiary CHD center. Twenty-seven 3D-TEE studies using the x7-2t live 3D matrix TEE transducer with an iE33 echocardiographic scanner (Philips Medical Systems, Bothell, Washington) were attempted. The utility of this method was examined in the 3 settings of interventional catheterizations (n = 16), intraoperative studies (n = 4), and diagnostic studies (n = 7). The probe was successfully inserted in 26 of 27 patients (weight 22.6 to 110 kg). In conclusion, the current matrix-array 3D-TEE probe was found to have a wide variety of clinical applications in a CHD center.