Brian Reemtsen

Berlin Heart EXCOR Pediatric Ventricular Assist Device for Bridge to Heart Transplantation in US Children

Background— Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection. Methods and Results— This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device at 47 centers from May 2007 through December 2010. Multiphase nonproportional hazards modeling was used to identify risk factors for early (<2 months) and late mortality. Of 204 children supported with the EXCOR, the median duration of support was 40 days (range, 1–435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death. Conclusions— Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.

Force required to elevate the sternum of pectus excavatum patients.

Pectus excavatum (PE) is one of the most common surgically correctable major congenital malformations, occurring in approximately 1 in every 400 births. Although operative procedures to correct PE deformities have been available for more than five decades, the techniques have varied greatly, as have the number of complications and the longterm results. Despite the frequency of PE, the number of patients undergoing repair was small until 1997, when the technique of minimally invasive repair of PE (MIRPE) was first reported by Nuss and associates. Variations of the modified Ravitch repair, which had been used widely by most surgeons before 1997, include subperichondrial resection of deformed costal cartilages; transverse wedge sternal osteotomy; and anterior fixation of the sternum with a variety of temporary internal support struts, prostheses, or an external harness. The MIRPE avoids cartilage resection and sternal osteotomy by placing a convex steel bar under the sternum through bilateral thoracic incisions and then forcefully turning the bar over to elevate the deformed sternum and costal cartilages to the desired position. The bar is left in place for 2 to 4 years, depending on the age of the patient and the severity of the deformity. The initial reports of favorable clinical experience with the MIRPE included primarily young children (mean age approximately 5 years). During the ensuing years, the MIRPE has been extended to older patients, including occasional adults. Although there has been initial great enthusiasm from both patients and surgeons for the MIRPE, some recent reports have indicated that although the operating time is shorter with the MIRPE than with the modified Ravitch repair, the complication rate, length of hospitalization, and severity of postoperative pain might be considerably higher with the MIRPE. The majority of patients undergoing MIRPE receive epidural analgesia for a few days and oral analgesic medications for several weeks. A major complication of the MIRPE has been flipping of the substernal bar onto the heart, which has been presumed to be related to the weight of the sternum in older patients pushing downward on the bar. The force necessary to elevate the deformed costal cartilages and sternum of PE patients to the desired level has not been previously reported. The relationship between the severity and duration of pain associated with the MIRPE and the force necessary to elevate the anterior chest to the desired level is unclear. Occasional patients have experienced such severe persistent pain after the MIRPE that they have requested early removal of the convex bar. The present study was undertaken to measure the force necessary to elevate the sternum of PE patients of varying ages and severity to the desired position. Consent for the study was granted by the Medical Center Institutional Review Board.

Arrhythmia Recurrence in Adult Patients with Single Ventricle Physiology Following Surgical Fontan Conversion: Arrhythmia Recurrence Following Fontan Conversion

OBJECTIVES To evaluate the incidence of atrial tachy-arrhythmia (AT) recurrence following conversion from right atrial-pulmonary artery (RA-PA) Fontan to total cavopulmonary connection (TCPC) in adults. BACKGROUND AT is a recognized sequel of Fontan palliation, especially in RA-PA Fontans, and is associated with significant morbidity. While catheter ablation achieves fairly reliable short-term success with low morbidity, conversion to TCPC with arrhythmia surgery is a highly effective treatment option for the classical Fontan patients with incessant AT. METHODS Single center retrospective review. RESULTS Twenty-seven adults underwent Fontan conversion from RA-PA to TCPC, mostly for AT indications (n = 24). Nine (33%) underwent conversion to a lateral tunnel (LT) and 18 (67%) to an extracardiac (EC) Fontan. Two patients died <30 days post-operatively. Both had liver failure and had been turned down for cardiac/liver transplantation. In-hospital complications occurred in 15/27 patients (55%), including recurrence of AT requiring cardioversion in six patients (22%) and persistent pleural effusions in 4 (15%). Mean follow-up was 4.2 years (range 3 months-14 years). Functional capacity improved from mean New York Heart Association (NYHA) class 1.8 pre-conversion to 1.2 post-conversion (P= 0.008). Twenty-one patients had concomitant arrhythmia surgery (MAZE in 12 patients with IART and Cox-MAZE in nine patients with A-Fib +/- IART). Of these, 3/21 (14%) had AT recurrence >3 months following conversion. CONCLUSIONS Conversion from RA-PA Fontan to TCPC, with arrhythmia surgery, decreases AT recurrence and improves functional capacity. The risk of peri-operative mortality is highest in patients with cirrhosis. AT recurred in 14% of patients.

Histologic examination of decellularized porcine intestinal submucosa extracellular matrix (CorMatrix) in pediatric congenital heart surgery

BACKGROUND CorMatrix is a decellularized porcine small intestinal submucosa extracellular matrix that has gained attention as a promising alternative to current materials used in cardiac repair. While animal models demonstrate integration of CorMatrix material with host tissue, the histologic characteristics of CorMatrix used in humans are less well-characterized. In this retrospective study, we report our experience with CorMatrix material used in pediatric congenital heart surgery and describe the histology of CorMatrix material and of surrounding native tissue in explanted specimens. METHODS Records were reviewed of all pediatric patients implanted with CorMatrix from a single institution (2011-2014). Histologic examinations were performed on CorMatrix and other tissues removed. Explanted samples of CorMatrix and adherent tissues were evaluated for inflammation (acute and chronic), fibrosis, necrosis, degenerative changes, eosinophil response, foreign-body giant cell reaction, neovascularization, and calcification of tissues on a semiquantitative basis (0, none; 1, mild; 2, moderate; 3, marked). Presence of degeneration within CorMatrix and necrosis of surrounding tissue were noted. RESULTS CorMatrix was utilized in 532 pediatric heart reconstruction procedures since 2011. Twelve explanted CorMatrix specimens from 11 pediatric patients including 4 valves (2 mitral and 2 aortic) and 8 outflow/septal/conduit patches were identified and evaluated. Six cases (5 patients) demonstrated clinical evidence of graft failure prior to surgery (n=6, 1%). Chronic inflammation was seen in adjacent native tissue in 11/12 cases and consisted predominantly of a mixed population of lymphocytes, macrophages, and plasma cells. Acute inflammation was seen in three cases (3/12). Fibrosis of the surrounding native tissue was seen in all CorMatrix specimens. Eosinophils were present in 6/12 cases. Calcification in surrounding tissue was present in 3/12 cases. Giant cell reaction in adjacent native tissue was seen in 8/12 cases. Neovascularization was seen in surrounding native tissue in 5/12 cases. Degeneration of CorMatrix material was seen in 9/12 cases. Necrosis of surrounding tissue was also identified in 5/12 cases. CorMatrix was not resorbed and no cases demonstrated any remodeling of CorMatrix material by integration of native mesenchymal cells or myocytes. CONCLUSION CorMatrix may be associated with a marked inflammatory response, including a foreign-body giant cell reaction and fibrosis of the surrounding native tissue. Degenerative changes of CorMatrix material are also seen in a majority of explanted specimens. No histologic differences were seen between patients with clinical evidence of graft failure versus patients requiring graft removal due to other factors. Additionally, no cases showed evidence of tissue integration or recellularization of patch material. Our overall clinical experience with CorMatrix demonstrates a favorable outcome for pediatric patients undergoing cardiac reconstructive surgery. However, there is no histologic evidence that CorMatrix acts as a scaffold for reconstitution of the native cardiovascular structures.

Hemidiaphragm plication after repair of congenital heart defects in children : Quantitative return of diaphragm function over time

OBJECTIVE Phrenic nerve injury resulting in hemidiaphragm paresis leads to morbidity in children undergoing repair of congenital heart defects. Previous studies have documented short-term benefits of diaphragm plication, but little is known about the return of diaphragm function. METHODS We reviewed 46 consecutive patients undergoing hemidiaphragm plication after repair of congenital heart defects. The function of plicated diaphragms was measured at follow-up fluoroscopy using excursion of the unplicated side as a control. RESULTS The median age at the procedure resulting in phrenic nerve injury was 6.4 months (0-62 months). Among the 46 patients, 29 (63%) and 17 (37%) had repair for single and 2-ventricle defects, respectively. Hemidiaphragm paresis occurred on the left side in 32 patients (70%). Phrenic nerve injury was documented at a median of 8 days (1-84 days) after operation. The median time from diagnosis to plication was 2 days (0-21 days). Five patients required prolonged ventilation after plication. One patient died 10 weeks later, and 4 patients required tracheostomy. The remaining 41 patients were extubated within 2 days (0-19 days). In 17 patients, fluoroscopy assessing diaphragm motion was performed at a mean interval of 16.4 months after plication. Excursion of the plicated diaphragm was 77% of the contralateral side. There was a trend toward improved function over time. CONCLUSIONS Hemidiaphragm paresis results in significant morbidity after repair of congenital heart defects. Early diagnosis and plication result in timely extubation. The plicated diaphragm demonstrates return of function that may improve over time. This is the first study to numerically quantitate the degree of diaphragm recovery.

Allochimeric class I MHC molecules prevent chronic rejection and attenuate alloantibody responses

BACKGROUND We have shown that treatment with molecularly engineered, allochimeric [alpha1 hl/u]-RT1.Aa class I MHC antigens bearing donor-type Wistar-Furth (WF, RT1.Au) amino acid substitutions for host-type ACI (RTI.Aa) sequences in the alpha1-helical region induces donor-specific tolerance to cardiac allografts in rat recipients. This study examined the effect of allochimeric molecules on the development of chronic rejection. METHODS Allochimeric [alpha1 hl/u]-RT1.Aa class I MHC antigenic extracts (1 mg) were administered via the portal vein into ACI recipients of WF hearts on the day of transplantation in conjunction with subtherapeutic oral cyclosporine (CsA, 10 mg/kg/day, days 0-2). Control groups included recipients of syngeneic grafts and ACI recipients of WF heart allografts treated with high-dose CsA (10 mg/kg/day, days 0-6). RESULTS WF hearts in ACI rats receiving 7 days of CsA exhibited myocardial fibrosis, perivascular inflammation, and intimal hyperplasia at day 80. At day 120, these grafts displayed severe chronic rejection with global architectural disorganization, ventricular fibrosis, intimal hyperplasia, and progressive luminal narrowing. In contrast, WF hearts in rats treated with [alpha1 hl/u]-RT1.Aa molecules revealed only mild perivascular fibrosis, minimal intimal thickening, and preserved myocardial architecture. Alloantibody analysis demonstrated no IgM alloantibodies in all groups. An attenuated, but detectable, anti-WF IgG response was present in recipients receiving allochimeric molecules, with IgG1 and IgG2a subclasses predominating. Immunohistochemical analysis of allografts demonstrated minimal T cell infiltration and IgG binding to vascular endothelium. CONCLUSION Treatment with allochimeric molecules prevents the development of chronic rejection. Such effect may be in part caused by deviation of host alloantibody responses.

MRI with ferumoxytol: A single center experience of safety across the age spectrum

To summarize our single‐center safety experience with the off‐label use of ferumoxytol for magnetic resonance imaging (MRI) and to compare the effects of ferumoxytol on monitored physiologic indices in patients under anesthesia with those of gadofosveset trisodium.

Stage I palliation for hypoplastic left heart syndrome: Norwood versus Sano modification.

Purpose of review Advancements in surgical technique and perioperative care have significantly improved the survival of infants born with hypoplastic left heart syndrome. A recent modification to the Norwood procedure is being adopted by many centers to improve postoperative hemodynamic stability and survival to stage II palliation. The late effects of this modification, however, are speculated and have not been investigated. Recent findings Center-specific improved short-term outcomes have been reported in a few small, nonrandomized studies of a new approach to the Norwood procedure, which utilizes a right ventricle to pulmonary artery shunt or Sano modification to provide pulmonary blood flow rather than the standard modified Blalock-Taussig shunt. Summary The classic Norwood procedure and Sano modification each have specific advantages and disadvantages in both the short and long term. Data comparing the two techniques are nonrandomized, contradictory, and utilize historical controls. The optimal shunt to improve survival to the second-stage palliation is unknown. A multicenter randomized clinical trial comparing the Sano with the modified Blalock-Taussig shunt in hypoplastic left heart syndrome or variants is currently in progress and should hopefully provide future guidelines for shunt selection based on clinical presentation.

Mechanical Occlusion of the Inferior Vena Cava: An Unusual Complication After Repair of Pectus Excavatum Using the Nuss Procedure

We describe the case of a 13-year-old girl with a pectus excavatum in whom acute occlusion of the inferior vena cava developed after a nuss repair. In this hemodynamically unstable patient, we evaluated the possibility of a penetrating injury to the thoracic and abdominal structures before confirming the diagnosis of inferior vena cava obstruction with a venogram. Removal of the nuss bar relieved the unexpected problem.

Role of Clinically Indicated Transbronchial Lung Biopsies in the Management of Pediatric Post–Lung Transplant Patients

BACKGROUND Although transbronchial biopsy (TBB) is the definitive method for diagnosing graft dysfunction after pediatric lung transplantation, concern over procedural complications has limited its use. We reviewed our institutional experience with clinically indicated TBB to determine its safety and efficacy with emphasis on how biopsy findings altered management. METHODS A retrospective chart review was done of 61 pediatric lung transplantation patients undergoing 179 TBB procedures. Data were collected on pre-TBB symptoms, pulmonary function testing, and imaging studies. The prebiopsy diagnosis was noted and compared with the findings from TBB to see how frequently treatment changed after biopsy. RESULTS Age at TBB ranged from 2 months to 20 years, with an average of 3 biopsies per patient. There was no procedure-related mortality. The incidence of complications was 9% and included important bleeding with spontaneous resolution in 6% and pneumothorax in 3%. The usual indication for TBB was a change in the chest roentgenogram, frequently accompanied by a decrease in flows on spirometry. The TBB specimens were adequate for pathologic analysis 92% of the time, and a specific pathologic diagnosis could be made in 54% of cases. The findings from TBB altered the clinical management of the patient 64% of the time. CONCLUSIONS In pediatric lung transplant recipients presenting with graft dysfunction, TBB is a low-risk diagnostic procedure that yields clinically useful information in a majority of cases. In our experience, the findings from TBB altered medical treatment in 64% of patients. Treatment was most often changed in the group diagnosed with rejection as the probable cause of graft dysfunction.