Cardiac Transplantation In Infants Research Articles

How We Would Treat Our Own Hypoplastic Left Heart Syndrome Neonate for Stage 1 Surgery

ALTHOUGH NO LONGER UNIFORMLY fatal, hypoplastic left heart syndrome (HLHS) continues to significantly challenge providers across pediatric specialties. This is especially true in the neonatal period when patients with HLHS undergo stage 1 palliative surgery. Despite advances in medical and surgical management, in-hospital and 1-year mortality remain high. 1 Ohye RG Sleeper LA Mahony L et al. Comparison of shunt types in the Norwood procedure for single-ventricle lesions. N Engl J Med. 2010; 362: 1980-1992 Crossref PubMed Scopus (686) Google Scholar , 2 Mahle WT Spray TL Wernovsky G et al. Survival after reconstructive surgery for hypoplastic left heart syndrome: A 15-year experience from a single institution. Circulation. 2000; 102: III136-III141 Crossref PubMed Google Scholar , 3 Forbess JM Cook N Roth SJ et al. Ten-year institutional experience with palliative surgery for hypoplastic left heart syndrome. Risk factors related to stage I mortality. Circulation. 1995; 92: II262-II266 Crossref PubMed Google Scholar , 4 Stasik CN Gelehrter S Goldberg CS et al. Current outcomes and risk factors for the Norwood procedure. J Thorac Cardiovasc Surg. 2006; 131: 412-417 Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar , 5 Hirsch JC Copeland G Donohue JE et al. Population-based analysis of survival for hypoplastic left heart syndrome. J Pediatr. 2011; 159: 57-63 Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar , 6 Tweddell JS Sleeper LA Ohye RG et al. Intermediate-term mortality and cardiac transplantation in infants with single-ventricle lesions: Risk factors and their interaction with shunt type. J Thorac Cardiovasc Surg. 2012; 144: 152-159 Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar , 7 Best KE Miller N Draper E et al. The improved prognosis of hypoplastic left heart: A population-based register study of 343 cases in England and Wales. Front Pediatr. 2021; 9635776 Crossref Scopus (10) Google Scholar , 8 Piber N Ono M Palm J et al. Influence of shunt type on survival and right heart function after the Norwood procedure for aortic atresia. Semin Thorac Cardiovasc Surg. 2022; 34: 1300-1310 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar , 9 Karamlou T Diggs BS Ungerleider RM et al. Evolution of treatment options and outcomes for hypoplastic left heart syndrome over an 18-year period. J Thorac Cardiovasc Surg. 2010; 139: 119-126 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar , 10 Azakie T Merklinger SL McCrindle BW et al. Evolving strategies and improving outcomes of the modified Norwood procedure: A 10-year single-institution experience. Ann Thorac Surg. 2001; 72: 1349-1353 Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar , 11 Newburger JW Sleeper LA Gaynor JW et al. Transplant-free survival and interventions at 6 Years in the SVR trial. Circulation. 2018; 137: 2246-2253 Crossref PubMed Scopus (133) Google Scholar At present, there is limited evidence-based society guidance on the perioperative management of neonates with HLHS undergoing stage 1 palliation. 12 Donofrio MT Moon-Grady AJ Hornberger LK et al. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation. 2014; 129: 2183-2242 Crossref PubMed Scopus (694) Google Scholar Extracorporeal Membrane Oxygenation for Stage 1 Palliation: Early bridge to recovery rather than a late act of pure despairJournal of Cardiothoracic and Vascular AnesthesiaPreviewWe appreciate the article by Zaleski et al. as it describes in detail the challenging management of a patient with hypoplastic left heart syndrome (HLHS) undergoing stage I palliation (S1P) - one of the most demanding tasks in cardiac surgery and anesthesiology for congenital heart disease [1]. The course of the young patient presented in their article was uneventful. Nonetheless, internationally reported premature mortality is high at up to 14.3% and remains at 8-11% even in high-volume North American centers, and even after establishing specialized "single-ventricle” teams [2;3]. Full-Text PDF

Ethical and practical dilemmas in cardiac transplantation in infants: a literature review.

The waiting time in infants for a cardiac transplant remains high, due to the scarcity of donors. Consequently, waiting list morbidity and mortality are higher than those in other age groups. Therefore, the decision to list a small infant for cardiac transplantation is seen as an ethical dilemma by most physicians. This review aims to describe outcomes, limitations, and ethical considerations in infant heart transplantation. We used Medline and Embase as data sources. We searched for publications on infant (< 1 year) heart transplantation, bridge-to-transplant and long-term outcomes, and waiting list characteristics from January 2009 to March 2021. Outcome after cardiac transplant in infants is better than that in older children (1-year survival 88%), and complications are less frequent (25% CAV, 10% PTLD). The bridge-to-transplant period in infants is associated with increased mortality (32%) and decreased transplantation rate (43%). This is mainly due to MCS complications or the limited MCS options (with 51% mortality in infancy). Outcomes are worse for infants with CHD or in need of ECMO-support.Conclusion: Infants listed for cardiac transplantation have a high morbidity and mortality, especially in the period between diagnosis and transplantation. For those who receive cardiac transplant, the outlook is encouraging. Unfortunately, despite growing experience in VAD, mortality in children < 10 kg and children with CHD remains high. After transplantation, patients carry a psychological burden and there is a probability of re-transplantation later in life, with decreased outcomes compared to primary transplantation. These considerations are seen as an important ethical dilemma in many centers, when considering cardiac transplantation in infants (< 1 year). What is Known: • For infants, waitlist mortality remains high. In the pediatric population, MCS reduces the waiting list mortality. What is New: • Outcomes after infant cardiac transplantation are better than other age groups; however, MCS options remain limited, with persistently high waiting list mortality. • Future developments in MCS and alternative options to reduce waiting list mortality such as ABO-incompatible transplantation and pulmonary artery banding are encouraging and will improve ethical decision-making when an infant is in need of a cardiac transplant.

Pushing the boundaries: The current status of ABO-incompatible cardiac transplantation

Since the introduction of intentional ABO-incompatible (ABOi) cardiac transplantation in infants in the late 1990's, the number of patients listed for and undergoing ABOi transplants has increased. This practice has been shown to lead to a reduction in waiting list mortality and increased utilisation of donor organs with equivalent outcomes to ABO-compatible transplants. Differences in the infant immune system provide a window of opportunity for ABOi transplantation. However it is increasingly clear that older patients and those with significant amounts of blood group antibody specific isohaemagglutinins may also benefit. Newer research is now focussing on longer term outcomes of ABOi transplants - in particular the development of graft accommodation or tolerance. This review assesses the current status of ABO-incompatible cardiac transplantation both in infants and in sensitized and older patients.

Intermediate-term mortality and cardiac transplantation in infants with single-ventricle lesions: Risk factors and their interaction with shunt type

The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor the modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt. We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors. Data from 549 subjects (follow-up, 2.7 ± 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated with death included lower socioeconomic status (P = .01), obstructed pulmonary venous return (P < .001), smaller ascending aorta (P = .02), and anatomic subtype. Constant phase factors associated with death included genetic syndrome (P < .001) and lower gestational age (P < .001). The right ventricle-to-pulmonary artery shunt demonstrated better survival in the 51% of subjects who were full term with aortic atresia (P < .001). The modified Blalock-Taussig shunt was better among the 4% of subjects who were preterm with a patent aortic valve (P = .003). Lower pre-Norwood right ventricular fractional area change, pre-Norwood surgery, and anatomy other than hypoplastic left heart syndrome were independently associated with transplantation (all P < .03), but shunt type was not (P = .43). Independent risk factors for intermediate-term mortality include lower socioeconomic status, anatomy, genetic syndrome, and lower gestational age. Term infants with aortic atresia benefited from a right ventricle-to-pulmonary artery shunt, and preterm infants with a patent aortic valve benefited from a modified Blalock-Taussig shunt. Right ventricular function and anatomy, but not shunt type, were associated with transplantation.

Influence of size disparity of transplanted hearts on cardiac growth in infants and children

We aimed to evaluate the influence of size disparity of the transplanted heart on cardiac growth in infant and child recipients by comparing donor body surface area (BSA) and cardiac dimensions during transplantation to the corresponding parameters of the recipient over a period of time. A retrospective review of medical and echocardiographic records of 147 children (5.3 ± 4.0; median, 4.1; range, 1 month-15 years) who underwent orthotopic heart transplantation was done. The patients were divided into age groups as follows: less than 1 year (n=23), 1 to 2 years (n=26), more than 2 to 5 years (n=18), more than 5 to 10 years (n=27), and more than 10 to 15 years (n=53). Donor/recipient BSA ratio was determined during transplantation. Cardiac dimensions were measured 30 days after transplantation and compared at 1 year, 2 to 5 years, and 5 to 10 years after transplantation. There were no significant differences in the ventricular end-diastolic diameter, volumes, and mass among those with a donor/recipient BSA ratio of less than 0.80, 0.8 to 1.2, and more than 1.2 (P=.80, .44, and .48, respectively). In all the cardiac dimensions and volumes measured, donor-recipient mismatch did not influence the continuous growth of the heart, as indicated by the measured parameters, in accordance with the recipients' increase in BSA over time. All calculated Z-scores at 1 year, 2 to 5 years, and 6 to 10 years after transplantation were normal when indexed to BSA. This study demonstrates that despite size disparity of a transplanted heart, it undergoes normal growth in diastolic dimensions, volumes, and myocardial mass over time as appropriate for body growth after cardiac transplantation in infants and children.

Late donor cardiectomy after paediatric heterotopic cardiac transplantation

Cardiac transplantation is a life-saving procedure in infants and children with advanced cardiomyopathy. However, it is greatly limited by shortage of paediatric donors and the complications of long-term immunosuppression, including post-transplant lymphoproliferative disorder (PTLD). We report the management of an infant who had heterotopic cardiac transplantation for advanced cardiomyopathy with secondary pulmonary hypertension who developed seemingly incurable PTLD. An 8-month-old girl presented in 1994 with signs of severe heart failure, secondary to dilated cardiomyopathy. At age 11 months, the patient underwent a heterotopic cardiac transplantation. The patient developed many episodes of PTLD associated with Epstein-Barr virus infection that were resistant to several therapies, including reduction of immunosuppression. Native heart recovery enabled removal of the donor heart 10.5 years after the original operation to allow complete cessation of immunosuppression. Her postoperative course was uncomplicated and the outcome was excellent. 3.5 years after surgery, the patient remains well, in complete remission from her PTLD, and has normal cardiac function. This case shows several issues relating to the use of heterotopic cardiac transplantation in infants and the capacity of the heart to recover. It also provides new insights into the interaction between the immune system with several aspects of modern management of post-transplantation PTLD. None.

Effacing of the T Cell Compartment by Cardiac Transplantation in Infancy

For cardiac transplantation in infants, T cells are depleted and the thymus is removed. These manipulations should cause profound defects in the T cell compartment. To test this concept, 20 subjects who underwent cardiac transplantation in infancy and healthy age-matched subjects were studied. The number of T cells in the blood was nearly normal in all subjects 1-10 years after surgery. However, newly generated T cells were undetectable in 10 recipients and 10-fold less than controls in 10, suggesting absence of thymic function. TCRbeta chain diversity, measured by a novel technique, was approximately 100-fold lower than controls. T cell function, deduced from levels of human herpesvirus 7 and response to hepatitis B immunization, were notably impaired. Yet cardiac transplant recipients were generally free of opportunistic infections. Our findings demonstrate a novel approach to measuring lymphocyte diversity and suggest that understanding how these subjects resist infection could yield important insights into immune fitness.

Renal growth after cardiac transplantation in infants

Renal growth after cardiac transplantation in infants

10 years of cardiac transplantation in newborns and infants - a review of the past and an outlook to the future

715 From June 1988 to December 1998 49 heart transplantations were performed in newborns and infants below 1 year of age in our clinic. Diagnosis included hypoplastic left heart syndrom (n = 38), endocardial fibroelastosis (n = 4), cardio- myopathy (n = 5) and other complex congenital heart defects (n = 2). We divided the patients into two groups according to the time of surgery. The first group (n = 11) was transplanted between 1988 and 1992. The second group (n = 38) was transplanted from 1993 to 1998. We noticed a significant change of survival between these groups. While in the first group the survival rate was about 45 %, the total survival in the second group was about 92 % and the one year survival rate of this group is about 93 %. The reasons for death have been right ventricular failure (n = 3), acute rejection (n = 4), viral infection (n = 1) and multi organ failure (n = 1). Only one patient died later than one month after transplantation. During the first month after surgery 69 % of all rejections occured. We found 58 rejection episodes in 36 patients. Until today we could not find any signs of coronary heart desease or malignomas in the transplanted children. The qualitiy of life of our patients is excellent and the somatic development is normal. The infants and babies live at home and beside the immune supressive therapy life of the transplanted children does not differ from those of children of similar age. Our conclusions are, that cardiac transplantation in infants and newborns is a reasonable therapeutic concept of severe and treatment of complex cardiac abnormalities and offers excellent survival rates in experienced Heart-centers.

Neonatal mechanical bridging to total orthotopic heart transplantation

Background. Until recently, newborns with medically intractable cardiac failure caused by congenital malformations were mostly doomed to death because of the severity of the disease, which precludes a palliative operation, or because of fatal deterioration before availability of a suitable donor heart. Methods. The recently developed paracorporeal pneumatically driven Medos HIA ventricular assist device offers a therapeutic option for these small infants because it is manufactured in various sizes and is even suitable for cardiac assistance in neonates with a body surface area less than 0.3 m 2. Results. We report our initial experience with this device, which we used for univentricular bridging to total orthotopic cardiac transplantation in 3 infants. The device was inserted to support the left ventricle in two instances and to support the right heart in one. Successful bridging to transplantation was achieved in 2 infants for periods of 2 and 7 weeks. Conclusions. Our experience demonstrates the feasibility of univentricular mechanical support followed by successful cardiac transplantation in infants and newborns.

Survival and risk factors for death after cardiac transplantation in infants. A multi-institutional study. The Pediatric Heart Transplant Study.

Despite the increasing application of cardiac transplantation in infants, reported survival rates vary, and risk factors for death are poorly understood. 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. 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.

Editorial: Cardiac transplantation for auxiliary circulatory support

In this issue, Khaghani and associates report their experience with heterotopic cardiac transplantation in infants and children. This study is a welcome addition to the literature from the group at Harefield, which has assembled an extensive experience with this procedure. The concept of using the transplanted heart as an auxiliary pump was introduced in 1964.1Reemtsma K The heart as a test organ in transplantation studies.Ann NY Acad Sci. 1964; 120: 778-785PubMed Google Scholar, 2McGough EC Brewer PL Reemtsma K The parallel heart: studies of intrathoracic auxiliary cardiac transplants.Surgery. 1966; 60: 153-158Google Scholar These studies demonstrated that the auxiliary heart, placed in parallel with the animal's own heart, could sustain the circulation when the native heart was nonfunctional. This concept of assisted circulation now has been widely applied in the use of mechanical support, such as ventricular assist devices. It has been applied sporadically in clinical cardiac transplantation, and this report summarizes the experience in infants and children. The authors report that in a total of 1278 cardiac transplants, 104 (8.1% of the total experience) were placed in the intrathoracic, heterotopic position. This report focuses on 12 infants and children, nine of whom survive. The indications that the authors cite are (1) presence of fixed high pulmonary vascular resistance, (2) availability of undersized donors, and (3) the expectation of a degree of recipient heart recovery. It is encouraging that all patients showed a decrease in pulmonary artery pressure and all showed a normal growth pattern. It seems probable that the application of auxiliary cardiac support, both with transplants and with mechanical devices, will continue. The use of this approach for transplantation into patients with high, fixed pulmonary vascular resistance seems established. The further development of ventricular assist devices similarly will usually use this approach in preference to in situ replacement of the heart. Its usefulness in treating patients with reversible myocardial disease is intriguing but not yet established. The increasingly severe shortage of donor hearts has resulted in the use of marginally acceptable organs, and the use of such transplants as auxiliary pumps has certain advantages. Similarly, as cardiac xenografts approach clinical use, the auxiliary position rather than in situ replacement has appeal in this experimental area with uncertain outcome. Finally, a comment about nomenclature: The term heterotopic is nonspecific and refers to placement of the heart in any abnormal position. In the literature of experimental cardiac transplantation, heterotopic often refers to cervical or abdominal placement of the heart. The term piggyback is flippant and should be discarded. I recommend the terms auxiliary and parallel, as used in the original publications of this technique. These terms appropriately describe the function of the transplant, which supplements cardiac function by working in parallel with the native heart.

Heterotopic cardiac transplantation in infants and children

Background: Children with advanced heart failure, particularly those with elevated pulmonary vascular resistance, pose a difficult management problem because the normal donor right ventricle cannot cope with the high pulmonary resistance and because of the relative shortage of donor organs of an appropriate size for this age group. Methods: In an attempt to address these issues and evaluate the role of heterotopic transplantation in this context, we operated on 12 children, six boys and six girls, in the period between January 1, 1991, and March 31, 1996. Their ages ranged from 11 months to 15.2 years (mean 81.6 ± 62.8 months) and their mean weight was 23.3 kg (range 7.6 to 56.8 kg). Eight patients (66.6%) had significant elevation of pulmonary artery pressure (pulmonary artery systolic pressure = 66 ± 9.4 mm Hg, mean transpulmonary gradient = 22.3 ± 3.4 mm Hg). In all patients the donor pulmonary artery was anastomosed to the recipient right atrium without the use of any prosthetic material. Ischemic times varied between 135 and 255 minutes (mean 182.1 ± 30.7 minutes). The immunosuppression regimen included cyclosporine and azathioprine. Steroids were not routinely used. Results: One patient died in the hospital of acute rejection on postoperative day 16. Three patients had lobe collapse within 1 week and all were treated successfully. Two late deaths (18.2%) occurred as a result of cardiac rejection 3 months and 2 years after the operations. Nine survivors (75%) are alive, active, and growing normally at a mean follow-up of 2.2 years (range 11 months to 4.75 years). Repeated cardiac catheterization performed in seven patients with preoperative pulmonary hypertension showed a slow progressive drop in mean pulmonary artery pressure. No significant change was observed in the function of the recipient hearts. Conclusion: We conclude that heterotopic heart transplantation is feasible for a selected group of children with good medium-term results, notably regression of pulmonary artery pressure, normal growth, and lack of long-term chest complications. (J Torac Cardiovasc Surg 1997;113:1042-9)

Pediatric Cardiac Surgery

This text, now in its second edition, contains up-to-date details of recent advances in paediatric cardiac surgery, including improved coverage of myocardial protection, operations, thoracic transplantation, intraoperative echocardiography and transcatheter therapeutic interventions. The chapters in the book discuss embryology, circulatory physiology, diagnostic evaluation, interventional cardiology, anaesthetic management, perioperative care and the role of the nurse practitioner. The remainder is devoted to individual chapters covering all current procedures, including heart, heart-lung and lung transplantation. New to this edition are sections on: cardiac transplantation for infants with hypoplastic left heart syndrome; the fenestrated Fontan procedure; one-stage repair of interrupted aortic arch with ventricular septal defect; the arterial switch operation; and approach to neonates with pulmonary stenosis/atresia with intact ventricular septum.

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

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

Cardiac transplantation for infants with hypoplastic left heart syndrome

Orthotopic cardiac transplantation (OCT) has been our preferred treatment for infants with hypoplastic left heart syndrome (HLHS). This therapy was initially based on years of successful animal studies and later on continued as the results of transplantation proved encouraging. Infants with HLHS awaiting transplantation are maintained on prostaglandin E 1. Ductal stent placement may be necessary in some patients to maintain systemic perfusion. Others may require closed or open atrial septostomy. Shortage of donor organs accounts for 25% pretransplant mortality in our series. Over the last 10 years, 137 infants with HLHS underwent OCT. The operative mortality is 10%, and there have been 20 late deaths mostly due to rejection. The actuarial survival at 1 and 7 years following OCT is 84% and 72%, respectively. Three survivors required retransplantation at 1 month, 2 years and 7 years after initial OCT. Eight recipients developed moderate or severe graft coronary vasculopathy and only one patient was diagnosed with a neoplasm. In spite of few limitations, OCT is an effective therapy for HLHS with acceptable intermediate-term results.

Cardiac transplantation in infants and children

Cardiac transplantation has become a more frequently used therapeutic modality for select cardiac pathology in infants and children. Since June 1986, 30 pediatric patients (19 male and 11 female) ranging in age from 4 days to 15 years (11 ≤ 1 month old) have undergone orthotopic cardiac transplantation at our institution. Indications included idiopathic cardiomyopathy (n = 8), hypoplastic left heart syndrome (n = 13), and other forms of complex congenital heart disease (n = 9). There have been four operative and three late deaths only in the groups with hypoplastic left heart syndrome and other forms of complex congenital heart disease. Cumulative survival is 77% after a mean follow-up of 30 months (range, 6 to 77 months). Three operative deaths were attributable to pulmonary hypertension, and the other was due to pulmonary hemorrhage. Two late deaths were secondary to allograft rejection, and the third was due to infection. There has been uniform survival in the group with idiopathic cardiomyopathy, and intermediate-term survival rates are 78% and 62% in the groups with complex congenital heart diseases and hypoplastic left heart syndrome, respectively ( p = 0.15). Although longer-term results are necessary, orthotopic cardiac transplantation appears to be an acceptable mode of therapy for end-stage heart disease in the pediatric age group and technically can be performed despite complex malformations of the great arteries or atria.

Cardiac transplantation for infants with hypoplastic left-heart syndrome

Cardiac transplantation for infants with hypoplastic left-heart syndrome

Update on cardiac transplantation in infants and children.

Update on cardiac transplantation in infants and children.

Brief report: stenting of the ductus arteriosus as a bridge to cardiac transplantation in infants with the hypoplastic left-heart syndrome.

The hypoplastic left-heart syndrome is a complex congenital cardiac malformation1–3 that accounts for 7 to 8 percent of all cardiac lesions presenting in the first year of life; in addition, it is known to be the most common cause of death due to cardiac causes during the first week of life3–5. The prognosis has changed substantially since the development of the Norwood procedure in 19803,6–11 and the introduction of neonatal heart transplantation in 19853,12–14. When transplantation is considered, however, patency of the ductus arteriosus must be maintained until a suitable donor organ . . .