Mark M. Boucek

The registry of the international society for heart and lung transplantation: eighteenth official report—2001

In this last report of the Registry’s current administration, it is appropriate to review the changes and growth of the Registry during our 7-year stewardship. The total number of thoracic transplant recipients listed in the Registry has grown from 35,972 to more than 73,000 (see Table I). In addition to the increase in sheer volume of data, the breadth and sophistication of the analyses increased, from descriptive and univariate survival analyses to complex multivariate, risk-stratified data that investigate mortality as well as morbidity end-points. In 1993, the number of slides showing thoracic transplant data offered as a service to the members of the International Society for Heart and Lung Transplantation (ISHLT) was in the mid-30s. This year’s slide set offered free as a PowerPointTM file on the ISHLT website will contain 65 data slides. The health of the Registry will continue with a smooth transition to the new directorship.

The Registry of the International Society for Heart and Lung Transplantation: Seventeenth Official Report—2000

The Registry of the International Society for Heart and Lung Transplantation has grown substantially during the past 5 years, from a little more than 43,000 registered procedures at the end of 1994 to almost 70,000 registered procedures by the end of 1999 (see Table I). The substantial increase during this 5-year period occurred despite overall annual transplant numbers that were flat or that declined. We attribute this increase to obtaining more complete data from national and multinational registries, from capturing new centers that did not previously report, and finally, from direct Internetbased data reporting by individual centers. During this same 5-year period, excluding the annual reports, the Registry has peer reviewed 23 publications, reviews, and book chapters. J Heart Lung Transplant 2000;19:909.

Pediatric heart transplantation after declaration of cardiocirculatory death.

In three infants awaiting orthotopic cardiac transplantation, transplantation was successfully performed with the use of organs from donors who had died from cardiocirculatory causes. The three recipients had blood group O and were in the highest-risk waiting-list category. The mean age of donors was 3.7 days, and the mean time to death after withdrawal from life support was 18.3 minutes. The 6-month survival rate was 100% for the 3 transplant recipients and 84% for 17 control infants who received transplants procured through standard organ donation. The mean number of rejection episodes among the three infants during the first 6 months after surgery was 0.3 per patient, as compared with 0.4 per patient among the controls. Echocardiographic measures of ventricular size and function at 6 months were similar among the three infants and the controls (left ventricular shortening fraction, 43.6% and 44.9%, respectively; P=0.73). No late deaths (within 3.5 years) have occurred in the three infants, and they have had functional and immunologic outcomes similar to those of controls. Mortality while awaiting a transplant is an order of magnitude higher in infants than in adults, and donors who died from cardiocirculatory causes offer an opportunity to decrease this waiting-list mortality.

The Registry of the International Society for Heart and Lung Transplantation: Fifteenth Official Report—1998

Over the past 12 months, The Registry of the International Society for Heart and Lung Transplantation added 20 new transplantation programs and a total of 7073 additional thoracic organ recipients. All of the national and multinational registries are now fully integrated into our registry, and electronic data submission via the Internet will be instituted by mid 1998 for those centers not participating in larger registries. For the first time, the entire data set was used to calculate multivariate risks rather than the U.S. data set alone, and we have continued to extend the time frame for both univariate and multivariate analyses. For this report, risk factors for 5-year outcome and morbidity at 3 years are presented.

The registry of the international society for heart and lung transplantation: twentieth official adult heart transplant report—2003

Although only a small number of lung and heart– lung transplantation procedures were performed between 1963 and 1973, the current eras of heart–lung and lung transplantation, which began in 1981 and 1983, respectively, are now entering their third decades. The optimism of the considerable success of these modalities has been tempered by limitations, such as the shortage of donor organs, and by problems, such as chronic allograft dysfunction. This portion of the Twentieth Official Report summarizes the current status of adult heart–lung and lung transplantation from data submitted to the Registry from centers around the world. The Registry now contains information on more than 2000 adult heart–lung recipients and almost 14,000 adult lung recipients, and provides a robust database for analysis.

α-Myosin Heavy Chain A Sarcomeric Gene Associated With Dilated and Hypertrophic Phenotypes of Cardiomyopathy

Background—Mutations in the β-myosin heavy-chain (βMyHC) gene cause hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human hearts, downregulation of αMyHC mRNA or protein has been correlated with systolic dysfunction. We hypothesized that mutations in αMyHC could also lead to pleiotropic cardiac phenotypes, including HCM and DCM. Methods and Results—A cohort of 434 subjects, 374 (134 affected, 214 unaffected, 26 unknown) belonging to 69 DCM families and 60 (29 affected, 30 unaffected, 1 unknown) in 21 HCM families, was screened for αMyHC gene (MYH6) mutations. Three heterozygous MYH6 missense mutations were identified in DCM probands (P830L, A1004S, and E1457K; 4.3% of probands). A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring. All MYH6 mutations were distributed in highly conserved residues, were predicted to change the structure or chemical bonds of αMyHC, and were absent in at least 300 control chromosomes from an ethnically similar population. The DCM carrier phenotype was characterized by late onset, whereas the HCM phenotype was characterized by progression toward dilation, left ventricular dysfunction, and refractory heart failure. Conclusions—This study suggests that mutations in MYH6 may cause a spectrum of phenotypes ranging from DCM to HCM.

Prevalence of Desmin Mutations in Dilated Cardiomyopathy

Background— Desmin-related myofibrillar myopathy (DRM) is a cardiac and skeletal muscle disease caused by mutations in the desmin (DES) gene. Mutations in the central 2B domain of DES cause skeletal muscle disease that typically precedes cardiac involvement. However, the prevalence of DES mutations in dilated cardiomyopathy (DCM) without skeletal muscle disease is not known. Methods and Results— Denaturing high-performance liquid chromatography was used to screen DES for mutations in 116 DCM families from the Familial Dilated Cardiomyopathy Registry and in 309 subjects with DCM from the Beta-Blocker Evaluation of Survival Trial (BEST). DES mutations were transfected into SW13 and human smooth muscle cells and neonatal rat cardiac myocytes, and the effects on cytoskeletal desmin network architecture were analyzed with confocal microscopy. Five novel missense DES mutations, including the first localized to the highly conserved 1A domain, were detected in 6 subjects (1.4%). Transfection of DES mutations in the 2B domain severely disrupted the fine intracytoplasmic staining of desmin, causing clumping of the desmin protein. A tail domain mutation (Val459Ile) showed milder effects on desmin cytoplasmic network formation and appears to be a low-penetrant mutation restricted to black subjects. Conclusions— The prevalence of DES mutations in DCM is between 1% and 2%, and mutations in the 1A helical domain, as well as the 2B rod domain, are capable of causing a DCM phenotype. The lack of severe disruption of cytoskeletal desmin network formation seen with mutations in the 1A and tail domains suggests that dysfunction of seemingly intact desmin networks is sufficient to cause DCM.

Survival and risk factors for death after cardiac transplantation in infants: A multi-institutional study

BACKGROUND Despite the increasing application of cardiac transplantation in infants, reported survival rates vary, and risk factors for death are poorly understood. METHODS AND RESULTS To examine early survival and risk factors for death in infants (< 1 year of age) undergoing cardiac transplantation, 141 infants (36 < 1 months of age) underwent primary cardiac transplantation between January 1, 1993, and January 1, 1995, at 23 centers in the Pediatric Heart Transplant Study (PHTS). Diagnoses were hypoplastic left heart syndrome (66%), other congenital heart disease (17%), cardiomyopathy (14%), and other (3%). Actuarial survival after cardiac transplantation was 84% at 1 month, 70% at 1 year, and 69% at 2 years, with the greatest hazard for death within the first 3 months. The principal cause of death was early graft failure in 20 patients (52% of deaths), infection in 10 (26% of deaths), and rejection in 4 (10%). On the basis of multivariate analysis, risk factors for early mortality were history of previous sternotomy (P = .0003), nonidentical blood type donor (P = .01), recipient non-blood group A (P = .02), and donor cause of death other than closed head trauma (P = .04). Diagnosis at listing, waiting time (mean, 1.3 months), graft ischemic time (mean, 228 minutes; range, 68 to 479 minutes), and recipient ventilatory or inotropic support at listing were not predictive for mortality after transplant. CONCLUSIONS The higher mortality rate observed with infant heart transplantation is due to a higher mortality within the first month after transplantation as a result of early graft failure. Strategies to improve donor heart function at implantation would have the greatest impact on survival after infant cardiac transplantation.

Preliminary Experience With Cardiac Reconstruction Using Decellularized Porcine Extracellular Matrix Scaffold Human Applications in Congenital Heart Disease

An ideal material for repair of congenitally malformed hearts would encourage tissue regeneration with growth potential. Decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) promotes tissue regeneration in animal models and noncardiac human applications. This retrospective review evaluates SIS-ECM for reconstruction of congenital heart defects. From June 2007 to May 2009, SIS-ECM patches were used in 43 operations on 40 patients aged 2 days to 13 years. In 16 cases, the SIS-ECM was used for pericardial closure. The SIS-ECM was used for cardiac or great vessel repair in 37 cases: atrial septal defect repair in 11, pulmonary arterioplasty in 10, right ventricular outflow tract patch in 6, pulmonary monocusp valve creation in 5, superior vena cava patch in 2 and aortoplasty in 2, valve leaflet augmentation in 2, and repair of unroofed coronary sinus in 1. Follow-up was complete. There were 5 deaths, all unrelated to the SIS-ECM. Mean follow-up was 7.85 months (0.5-24 months). No pericardial effusions or intracardiac or intravascular thromboses occurred related to the SIS-ECM. The patches did not shrink or calcify. Four of 5 monocusp valves were competent and none were stenotic. One patient who underwent tricuspid valve anterior leaflet augmentation with SIS-ECM required tricuspid valve replacement 4 months later for severe regurgitation following a catheter-based procedure. Explanted tissue showed resorption of the SIS-ECM, replacement with organized collagen, and re-endothelialization. Repair of congenital heart defects using SIS-ECM is feasible and safe. In valve reconstruction, this procedure shows potential for replacement by autologous tissue. Longer-term follow-up is required to assess the potential for growth.

The Registry of the International Society for Heart and Lung Transplantation: Fifth Official Pediatric Report-2001 to 2002.

Pediatric thoracic organ transplant recipients are an important and biologically unique component of the overall experience in thoracic organ transplantation. Issues of immunologic naivete, growth and development make the pediatric recipient an important biologic model to aid in our understanding of overall thoracic organ transplantation. This report documents stability in the number of pediatric recipients and notes the continued trend of markedly improved survival for heart recipients in the most recent years. Despite improved survival, the overall number of reported pediatric recipients has remained stable, underlining the rate-limiting step of donor organ availability. Compared with previous years, this report offers an expanded analysis of donor and recipient characteristics. Risk factor analysis for mortality is expanded to include parameters important for 5-year survival. A more thorough description of immunosuppressive medication usage and actuarial freedom from morbidity curves represent new analyses of the pediatric data. These data are intended to analyze our experience to date and also to highlight areas where our experience and knowledge base need expansion in the future. HEART TRANSPLANTION Transplant Volumes and Indications