Pediatric heart transplantation

Heart transplantation is now a treatment option with good outcome for infants and children with end-stage heart failure or complex, inoperable congenital cardiac defects. One-year and 5-year actuarial survival rates are high, approximately 75% and 65%, respectively, with overall patient survival half-life greater than 10 years. To date, survival has been improving as a result of reducing early mortality. Further reductions in late mortality, in part because of graft coronary artery disease and rejection, will allow achievement of the goal of decades-long survival. Quality of life in surviving children, as judged by activity, is usually "normal." Somatic growth is usually at the low normal range but linear growth can be reduced. Of infant recipients, 85% evaluated at 6 years of age or older were in an age-appropriate grade level. Long-term management of childhood heart recipients requires the collaboration of transplant physicians, given the increasing number of immunosuppressive agents and the balance between rejection and infection. Currently, recipients are maintained on immunosuppressive medications that target calcineurin (eg, cyclosporine, tacrolimus), lymphocyte proliferation (eg, azathioprine, mycophenolate mofetil [MMF], sirolimus) and, in some instances antiinflammatory corticosteroids. Emerging evidence now suggests a favorable immunologic opportunity for transplantation in childhood and, conversely, a higher mortality rate in children who have had prior cardiac surgery. Further studies are needed to define age-dependent factors that are likely to play a role in graft survival and possible graft-specific tolerance (eg, optimal conditions for tolerance induction and how immunosuppressive regimens should be changed with maturation of the immune system). As late outcomes continue to improve, the need for donor organs likely will increase, as transplantation affords a better quality and duration of life for children with complex congenital heart disease, otherwise facing a future of multiple palliative operations and chronic heart failure.     

Poor outcome of very low birthweight babies with serious congenital heart disease

OBJECTIVE: To evaluate incidence and mortality of congenital heart disease in very low birthweight babies. METHOD: Retrospective analysis of a 12 year period. RESULTS: Forty seven babies were diagnosed with severe congenital heart disease. The most common lesions were ventricular septal defect and coarctation of the aorta. Mortality attributed to congenital heart disease was 32%. Coarctation of the aorta, the second most common lesion, was fatal in 62% of cases. Closure of a patent ductus arteriosus with indomethacin proved to be detrimental in babies with undiagnosed coarctation, causing rapid deterioration in some. CONCLUSION: Very low birthweight neonates with severe congenital heart disease have a higher mortality than babies with higher birth weight. A contributing factor is closure of a patent ductus arteriosus if an underlying lesion has not been recognised. This could be of significance if the use of prophylactic treatment with indomethacin becomes more common.     

Neurological complications of congenital heart disease

Neurological complications contribute significantly to mortality and morbidity from congenital heart disease with serious long-term consequences. Congenital heart disease has also been shown to adversely influence the neuro-developmental outcome of children. In developing countries such as India, majority of congenital heart defects remains uncorrected and major neurological complications are frequently encountered. Stroke and brain abscess are the commonest neurological complications of unoperated congenital heart disease. In developed countries the focus has now shifted to neurological complications of cardiac surgery in the very young as a result of cardiopulmonary bypass and total hypothermic circulatory arrest. A variety of neurological disturbances are now being increasingly recognized and are currently the subject of intense investigations. In this review the neurological complications of uncorrected congenital heart disease and the common neurological complications that result from operations for congenital heart disease will be discussed.     

Hypoalbuminemia and poor growth predict worse outcomes in pediatric heart transplant recipients

Children with end‐stage cardiac failure are at risk of HA and PG. The effects of these factors on post‐transplant outcome are not well defined. Using the PHTS database, albumin and growth data from pediatric heart transplant patients from 12/1999 to 12/2009 were analyzed for effect on mortality. Covariables were examined to determine whether HA and PG were risk factors for mortality at listing and transplant. HA patients had higher waitlist mortality (15.81% vs. 10.59%, p = 0.015) with an OR of 1.59 (95% CI 1.09–2.30). Survival was worse for patients with HA at listing and transplant (p ≤ 0.01 and p = 0.026). Infants and patients with congenital heart disease did worse if they were HA at time of transplant (p = 0.020 and p = 0.028). Growth was poor while waiting with PG as risk factor for mortality in multivariate analysis (p = 0.008). HA and PG are risk factors for mortality. Survival was worse in infants and patients with congenital heart disease. PG was a risk factor for mortality in multivariate analysis. These results suggest that an opportunity may exist to improve outcomes for these patients by employing strategies to mitigate these risk factors.     

Outcomes and Risk Factors for Mortality in Premature Neonates With Critical Congenital Heart Disease

We sought to describe contemporary outcomes and identify risk factors for hospital mortality in premature neonates with critical congenital heart disease who were referred for early intervention. Neonates who were born before 37 weeks’ gestation with critical congenital heart disease and admitted to our institution from 2002 to 2008 were included in this retrospective cohort study. Critical congenital heart disease was defined as a defect requiring surgical or transcatheter cardiac intervention or a defect resulting in death within the first 28 days of life. Logistic regression analyses were performed to identify risk factors for mortality before hospital discharge. The study included 180 premature neonates, of whom 37 (21%) died during their initial hospitalization, including 6 (4%) before cardiac intervention and 31 (17%) after cardiac intervention. For the 174 patients undergoing cardiac intervention, independent risk factors for mortality were a 5 min Apgar score ≤7, need for preintervention mechanical ventilation, and Risk Adjustment in Congenital Heart Surgery category ≥4 or not assignable. Mortality for premature infants with critical congenital heart disease who are referred for early intervention remains high. Patients with lower Apgar scores who receive preintervention mechanical ventilation and undergo more complex procedures are at greatest risk.     

What is new in pediatric cardiology

Enormous advances in the diagnosis and management of heart disease in pediatric patient have taken place during the last-four decades. In this review the authors will concentrate on the developments within the last five to ten years. It will deal with what may be called medical advances. Recent advances in molecular genetics and defining the familial patterns have led to finding that certain genetic and molecular factors are linked to congenital heart disease and arrythmia, thus providing opportunity for improved genetic counseling and future gene therapy. Medical treatment of congenital heart disease targets not only the augmentation of ventricular contractility (positive inotropy) but also addresses the neuro-humoral derangement associated with it. The ultrasound technology for the evaluation of the heart has come a long way from the early A — mode and M-mode capabilities to color Doppler, 2-dimentional and 3-dimentional capabilities.     

Mortalidad de las cardiopatías congénitas en España durante 10 años (2003-2012)

Introduction and objectives

Congenital heart disease is a major cause of infant mortality in developed countries. In Spain, there are no publications at national level on mortality due to congenital heart disease. The aim of this study is to analyse mortality in infants with congenital heart disease, lethality of different types of congenital heart disease, and their variation over a ten-year period.

Nongenetic Risk Factors and Congenital Heart Defects

Advances have been made in identifying genetic etiologies of congenital heart defects. Through this knowledge, preventive strategies have been designed and instituted, and prospective parents are counseled regarding their risk of having an affected child. Great strides have been made in genetic variant identification, and genetic susceptibility to environmental exposures has been hypothesized as an etiology for congenital heart defects. Unfortunately, similar advances in understanding have not been made regarding strategies to prevent nongenetic risk factors. Less information is available regarding the potential adverse effect of modifiable risk factors on the fetal heart. This review summarizes the available literature on these modifiable exposures that may alter the risk for congenital heart disease. Information regarding paternal characteristics and conditions, maternal therapeutic drug exposures, parental nontherapeutic drug exposures, and parental environmental exposures are presented. Factors are presented in terms of risk for congenital heart defects as a group. These factors also are broken down by specific defect type. Although additional investigations are needed in this area, many of the discussed risk factors present an opportunity for prevention of potential disease.     

Persistent pulmonary hypertension of the newborn: Historical perspectives

For many decades, persistent pulmonary hypertension of the newborn (PPHN) remained a baffling disorder, often confused with cyanotic congenital heart disease, with a very high mortality. Originally described as a condition characterized by clear lung fields and profound hypoxemia, modern diagnostic techniques and novel therapeutics have improved the outcomes of affected newborns. This paper will review the historical aspects of PPHN and enable the reader to see how far we have come but also how far we have to go in conquering this unique disorder.     

Death in infancy from unrecognised congenital heart disease

This study was undertaken to identify all congenital heart disease in infancy, including deaths before diagnosis, to provide a truer picture of the spectrum of congenital heart disease and to assess the 'treatability' of those dying before diagnosis. All births, infant deaths, and surviving babies with congenital heart disease in one health region in 1985-90 were identified and were classified as 'complex', 'significant', or 'minor'. Of the 1074 infants diagnosed in infancy, 185 died and 56 of these (30%) died undiagnosed. Severe non-cardiac malformations were present in 29 of the 56 while 27 were otherwise normal. Cardiovascular abnormalities in the latter group were complex in 13/27 and significant in 14/27. Identification of undiagnosed cardiovascular anomalies will improve epidemiological evaluation of congenital heart disease and, more importantly, earlier recognition of treatable abnormalities may reduce mortality.     

Death in infancy from unrecognised congenital heart disease.

This study was undertaken to identify all congenital heart disease in infancy, including deaths before diagnosis, to provide a truer picture of the spectrum of congenital heart disease and to assess the 'treatability' of those dying before diagnosis. All births, infant deaths, and surviving babies with congenital heart disease in one health region in 1985-90 were identified and were classified as 'complex', 'significant', or 'minor'. Of the 1074 infants diagnosed in infancy, 185 died and 56 of these (30%) died undiagnosed. Severe non-cardiac malformations were present in 29 of the 56 while 27 were otherwise normal. Cardiovascular abnormalities in the latter group were complex in 13/27 and significant in 14/27. Identification of undiagnosed cardiovascular anomalies will improve epidemiological evaluation of congenital heart disease and, more importantly, earlier recognition of treatable abnormalities may reduce mortality.     

Impact of mechanical circulatory support on survival in pediatric heart transplantation

Evidence on the impact of MCS on pediatric heart transplant survival is still scarce related to congenital heart disease patients including univentricular physiology as well as the risk factors for complications. We performed a retrospective review of all urgent pediatric (aged ≤16 years) HT from 2004 to 2014 in the Spanish Pediatric Heart Transplant Registry Group. Patients were stratified into two groups: urgent 0 (MCS at HT) and urgent 1 (non‐MCS at HT). The primary outcome measure was post‐transplant survival; secondary outcome measures were complications and absence of infections and rejection during the first post‐transplant year. One hundred twenty‐one pediatric patients underwent urgent HT, 58 (47.9%) urgent 0 and 63 (52%) urgent 1. There were 30 (24.8%) deaths: 12 in the urgent 0 group and 18 in the urgent 1 group, P = n.s. Regarding the type of MCS, patients on ECMO had the highest rate of complications (80%) and mortality (40%). Patients in the urgent 1 group showed a higher risk of hospital re‐admission for infection during the first year after transplantation (OR 2.31 [1.1‐4.82]), P = .025. We did not identify a risk factor for mortality. MCS does not impact negatively on survival after HT. However, there is a significant increase in 30‐day and 1‐year mortality and complications in ECMO patients compared with VAD patients. Infants, congenital heart disease, and PediMACS were not found to be risk factors for mortality.     

Neurologic and cognitive outcomes in children with congenital heart disease.

Advances in congenital heart surgery have resulted in the increased survival of infants born with complex congenital heart disease. Questions remain, however, about how these patients will develop and whether they will have normal, productive lives. To date, studies have shown that although the vast majority of children with congenital heart disease have normal outcomes, as a group they generally have higher rates of neurodevelopmental problems. The developmental sequelae include mild problems in cognition, attention, and neuromotor functioning. The etiology of neurologic deficits in this population appears to be multifactorial with preoperative, operative, and postoperative factors all contributing to outcome. Continued research and attempts to minimize neurologic injury and associated sequelae are of primary importance. Recent data suggest that advances in care already may be improving outcome after congenital heart surgery. Ongoing documentation of the long-term outcome in this population needs to be mandated, as does the implementation of environmental enrichment programs to help ameliorate the long-term consequences of congenital heart disease.     

Balloon dilation catheters

Catheter therapy has gained an important role in the treatment of congenital heart disease. The cumulative experience with vascular and valvular balloon dilations has demonstrated low mortality and morbidity with short-term results similar to surgery. Currently, balloon dilation is an accepted treatment for valvular pulmonary stenosis, distal pulmonary artery stenosis, recurrent coarctation, rheumatic mitral stenosis, congenital valvular aortic stenosis, and intra-atrial baffle obstruction. Except for patients at high surgical risk, balloon dilation of native coarctation is considered investigational at most institutions but accepted at others. No conclusive evaluation is yet possible for dilation of bioprosthetic valves and membranous subaortic stenosis. Individual pulmonary veins appear undilatable. Various devices are available for closure of extra- and intracardiac communications. Transcatheter closure of aortopulmonary collaterals and arteriovenous malformations is now well established at some centers. In selected patients, therapeutic embolization of surgical shunts can replace surgery. Transcatheter closure of the patent ductus arteriosus has become routine at some centers. Nonsurgical closure of atrial and ventricular septal defects has entered clinical trials, and preliminary results appear very promising. Blade atrioseptostomy and foreign body retrieval are well established. Improvement of existing procedures and implementation of new concepts will consolidate the role of catheter therapy in congenital and acquired heart disease.     

A Decade of Staged Norwood Palliation in Hypoplastic Left Heart Syndrome in a Midsized Cardiosurgical Center

Hypoplastic left heart syndrome (HLHS) is a challenge for the pediatric cardiologist and the surgeon. It is generally assumed that the postoperative outcome after surgery for congenital heart disease is influenced by the institutional size. We present the results of 43 patients with true HLHS (situs solitus and atrioventricular and ventriculoarterial concordance) referred for operation between 1992 and 2002 in our center. Two children had atrioseptostomy: one died soon after the operation, and the other one was transplanted successfully but died at the age of 6 months following acute rejection. The remaining 41 underwent Norwood I palliation, 21 stage II palliation, and 10 stage III palliation. Early mortality was 29% after stage I operation, 4.7% after stage II palliation, and 0% after stage III operation. Overall mortality was 39% after stage I, 9.5% after stage II, and 10% after stage III operation. Low birth weight was associated with a higher mortality (p < 0.05). Mortality declined with increasing experience, comparable to the results of very large cardiosurgical centers with many more patients. The quality of surgery and perioperative management in smaller pediatric cardiosurgical centers can reach the level of very large centers. T. Krasemann, H. Fenge, this authors are equal in terms of first authorship.     

Clinical and basic laboratory assessment of children for possible congenital heart disease

Accurate and cost-effective detection of congenital heart disease is a priority for the primary care physician, but there are many diagnostic modalities and strategies available. Within the past year, investigators have reported factors that contribute to the failure to diagnose congenital heart disease before autopsy. Recent research also highlights the strengths and weaknesses of the clinical evaluation by the primary care physician. An examination by a pediatric cardiologist is a more specific discriminator between heart disease and innocent murmur and can, in many instances, eliminate the expense of relying on echocardiography for diagnosis. Current reports document substantial limitations of diagnostic utility of electrocardiography and chest roentgenography. Suspicions that echocardiography can be misleading when performed in laboratories without expertise in congenital heart disease are confirmed in recent organized comparisons of accuracy. High-quality, well-designed tele-echocardiography programs are shown to be effective solutions when maldistribution of pediatric cardiology services hampers diagnostic efficiency.     

可降解封堵器治疗先天性心脏病的研究进展

应用封堵器经皮介入治疗已经成为大部分常见先天性心脏病如房间隔缺损、室间隔缺损、动脉导管未闭等的首选根治疗法。目前临床使用的封堵器大多为镍钛合金金属封堵器,被植入人体后将永久存在,并有机体慢性炎症、心脏穿孔及高度传导阻滞等严重并发症风险。可降解封堵器植入体内后可逐渐被自身组织替代。研究者不断探索使用不同可降解材料研制可降解封堵器,其中由张智伟教授团队主持研制的Absnow™完全可降解房间隔封堵系统已于2018年获得广东省药品监督管理局(GDMPA)批准进入临床试验阶段,成为全球首款进入临床试验阶段的完全生物可降解房间隔缺损封堵装置。人体预试验结果显示,该封堵器应用于人体具有初步的安全性和有效性,但尚需多中心临床试验进行评估验证。选择合适的可降解材料研制新型可降解封堵器以及封堵器的有效性及安全性研究,仍然是目前可降解封堵器治疗先天性心脏病相关研究的焦点和发展趋势。     

Hypoplastic left heart syndrome: Prognosis and management options

Few congenital heart malformations have raised as many surgical, ethical, social and economic issues as the therapy for infants diagnosed with hypoplastic left heart syndrome. Before the 1980s, this complex malformation was associated with 95% mortality within the first month of life. In the past two decades, palliative surgery and cardiac transplantation have become management options, in addition to comfort care for the infant. These innovations have forced parents and physicians to make difficult decisions because the long term results of the additional treatment options are not known. This article describes the current risk factors, diagnosis, treatment and outcome of infants with hypoplastic left heart syndrome. Prenatal diagnosis provides families with time for counselling and for becoming more informed about management options. Surgical therapy provides hope for the survival of these infants, but their long term outcomes are not well defined. Comfort care in either the home or hospital remains an acceptable management option. More investigations to determine the long term outcome following palliative surgery and transplantation are needed before they become the standards of care.     

先天性心脏病婴幼儿体外循环时动脉血氧分压与脑损伤的关系

脑损伤是先天性心脏病婴幼儿围术期的常见并发症之一,病因较成人心脏病复杂,存在于整个围术期过程中,并有其独特的临床特点.其发病机制至今尚未完全明了,有学者认为进行心脏纠正手术体外循环时的再氧合损伤起重要作用.现将近年来关于先天性心脏病婴幼儿体外循环时动脉血氧分压与脑损伤的关系进行综述.     

先天性心脏病术后的镇痛治疗研究进展

疼痛是与组织损伤关联的主观感觉和情感体验.外科手术会造成疼痛.疼痛会使交感神经系统兴奋,产生应激反应,对循环、呼吸、神经内分泌等系统造成影响,使心率加快、血压增高、氧耗量增加.疼痛不利于患儿咳嗽,会导致气道分泌物聚集引起肺不张及低氧血症.疼痛的以上影响对于先天性心脏病术后合并低心排血量综合征的患儿是非常不利的.另外,先天性心脏病由于手术创伤较大及应用体外循环,本身应激反应较大,因此其术后疼痛问题更应引起重视.