Primary restrictive cardiomyopathy in childhood

Restrictive cardiomyopathy is one of the rarest forms of cardiomyopathy in childhood and is associated with very poor prognosis (median transplant-free survival approximately 2 years). Little progress has been made in our understanding of the etiology of this condition, and most cases are considered ‘idiopathic’ in nature. No strong predictors of outcome have been identified and sudden death is common, even among those with few symptoms. Disappointingly, no effective therapies have emerged other than heart transplantation. Studies of familial cases suggest genetic and phenotypic overlap with other forms of cardiomyopathy, especially hypertrophic cardiomyopathy. Future research priorities include more careful delineation of phenotype(s), search for genetic etiologies and molecular mechanisms of disease, and studies to identify prognostic factors. Given the rarity of this condition, future studies will require collaboration among large numbers of centers following the models developed by the US Pediatric Cardiomyopathy Registry and the National Australian Childhood Cardiomyopathy Study.     

Epidemiological and outcomes research in children with pediatric cardiomyopathy: Discussions from the international workshop on primary and idiopathic cardiomyopathies in children

This report summarizes the roundtable discussion held at the first International Workshop on Primary and Idiopathic Cardiomyopathies in Children which focused on future directions for research on the epidemiology, etiology and outcomes for children with cardiomyopathy. Areas identified as important for future research included: 1) developing a standardized approach to the assessment and follow-up of children with myocarditis; 2) investigating the epidemiology of sudden death in children with dilated cardiomyopathy; 3) identification of biomarkers to serve as surrogate endpoints for important clinical outcomes; 4) the continuation of observational studies like the National Heart, Lung, and Blood Institute-sponsored Pediatric Cardiomyopathy Registry; and 5) conducting randomized clinical trials of pharmacological and behavioral interventions. It was concluded that optimal research strategies should employ a multidisciplinary research team including pediatric cardiologists, epidemiologists, biostatisticians, geneticists, patient care staff and advocacy groups. Further, adequately powered clinical trials may be facilitated by the establishment of a pediatric cardiomyopathy clinical trials network.     

儿童心力衰竭的诊断与治疗进展

心力衰竭是心脏失去有效泵血或接纳足量静脉回流功能的复杂的临床综合征,从而引起一系列症状,在儿童中的临床表现因年龄而不同。儿童心力衰竭的原因主要是先天性心脏病和心肌病。药物应用在儿童心力衰竭中的治疗进展迅猛,沙库巴曲/缬沙坦于2019年10月由美国食品药品监督管理局(FDA)批准其用于≥1岁儿童伴有症状性左心室收缩功能障碍,标志着儿童心力衰竭药物治疗的新起点。植入型心律转复除颤器和心脏再同步化治疗适用于部分具有指征的患者。机械循环支持是心肺衰竭患者不可缺失的治疗手段,包括体外膜肺氧合和心室辅助装置,作为短期循环辅助-移植等待的重要过渡。儿童心脏移植是心力衰竭终末的治疗方案。     

Cardiac dysrhythmias in children with idiopathic dilated or hypertrophic cardiomyopathy

To assess the incidence and prognostic significance of cardiac dysrhythmias in children with idiopathic dilated or hypertrophic cardiomyopathy, the clinical course of 59 patients was retrospectively reviewed over a period of 27 years. Dilated cardiomyopathy (DCM) was diagnosed in 28 patients and hypertrophic cardiomyopathy (HCM) in 31 patients. The mean age at the time of diagnosis was 2.8±0.7 years in DCM patients and 6.7±0.8 years in HCM patients. Mean follow-up time after diagnosis of cardiomyopathy was 4.1±1.0 years in DCM patients and 6.6±0.8 years in HCM patients. Clinically significant cardiac dysrhythmias were found in 17 of 59 patients (29%): 7 of 28 patients (25%) with DCM and 10 of 31 patients (32%) with HCM. The initial diagnosis of a cardiac dysrhythmia was made by standard electrocardiography in 12 of 17 patients (71%) and by 24-hour Holter monitoring in 5 of 17 patients (29%). Ventricular dysrhythmias were present in 5 of 7 patients with dilated cardiomyopathy and in 5 of 10 patients with hypertrophic cardiomyopathy. During the follow-up time, death occurred in 18 of 59 patients (31%): 8 of 59 patients (14%) died from congestive heart failure and 10 of 59 patients (17%) died suddenly. Among the sudden deaths were 4 of 28 patients (14%) with dilated cardiomyopathy and 6 of 31 patients (19%) with hypertrophic cardiomyopathy. Cardiac dysrhythmias had been documented in 6 of the 10 patients dying suddenly (3 of 4 patients with DCM and 3 of 6 patients with HCM). It is concluded that (1) cardiac dysrhythmias are not a rare finding in children with idiopathic dilated or hypertrophic cardiomyopathy, and (2) their occurrence is not a predictor for sudden death.     

Hypocalcemic cardiomyopathy as initial presentation of primary hypoparathyroidism

Cardiomyopathy is a rare but life‐threatening condition in children. Myocarditis is the leading cause of dilated cardiomyopathy (DCM) and prognosis is generally poor without heart transplantation. We report a rare case of hypocalcemic DCM due to primary hypoparathyroidism in a male infant. In our patient, aggressive management of hypoparathyroidism significantly improved the manifestations of DCM. He is currently 10 years old and has no symptoms of exercise intolerance. Latest echocardiogram revealed near‐normal cardiac function. Our case emphasizes that early diagnosis of this treatable cause of cardiomyopathy prevents serious sequelae.     

Clinical signs of heart failure are associated with increased levels of natriuretic peptide types B and A in children with congenital heart defects or cardiomyopathy

AIM: To study whether natriuretic peptide types B (BNP) and A (ANP) reflect clinical signs of heart failure (CSHF) in children with congenital heart defects or cardiomyopathy resulting in different types of haemodynamic situations, such as pressure overload in coarctation of the aorta (CoA), volume overload in ventricular septal defect (VSD) or systolic dysfunction in dilated cardiomyopathy (DCM). METHODS: Blood samples for plasma P-BNP and P-ANP were taken before procedures during regular investigation from 26 children (9 CoA, 11 VSD and 6 DCM). The ordinary paediatric cardiologist performed the cardiac evaluation and the data were retrieved from medical charts. CSHF was considered positive if two of the following criteria were fulfilled: reduced physical capacity, feeding disorders, dyspnoea, tachypnoea, hepatomegaly and oedema. The statistical methods were non-parametric. RESULTS: 0/9 children with CoA, 5/11 with VSD and 6/6 with DCM had CSHF. In children with CSHF, P-BNP and P-ANP were higher, 263 ng l(-1) (range 47.5-1300) and 303 ng l(-1) (range 168-466), than in those without CSHF, 12.3 ng l(-1) (range 4.8-30.8) and 42.9 ng l(-1) (range 13.7-189), respectively (p < 0.001, Mann-Whitney U-test), irrespective of the diagnosis. The same relationship was also found in the group of children with VSD. CONCLUSION: Plasma levels of ANP and BNP increase in children with CSHF. This increase is seen irrespective of whether it is due to systolic dysfunction, as in children with DCM, or to a volume overload with a normal systolic function, as in children with VSD.     

Genetics of familial dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by ventricular dilatation and impaired systolic function. DCM is the most common form of cardiomyopathy, and is also the commonest cause for heart failure and cardiac transplantation in adults and children. The frequency of familial occurrence of DCM had been significantly underestimated in the past, but extensive family studies showed that 35–45% of cases are familial. This recognition led to molecular genetic investigations that have further enhanced the understanding of the molecular pathogenesis of DCM. In this review, we discuss these new insights into the genetics of DCM which will have important implications for the diagnosis, risk stratification and treatment of DCM.     

Pediatric cardiomyopathy as a chronic disease: A perspective on comprehensive care programs

Substantial numbers of children with cardiomyopathy are now surviving into adulthood, making it essentially a chronic disease. As a chronic condition, it may be best treated through comprehensive, multidisciplinary treatment programs. Such programs have improved health outcomes and reduced costs in managing other pediatric chronic diseases and heart failure in adults, but the treatment and cost implications of programs for managing pediatric cardiomyopathy are unknown. We investigated the treatment and cost implications of establishing such programs by reviewing cost-effectiveness studies of similar programs, estimating the current inpatient costs of this diagnosis, and interviewing experts in the field about the need and desirability of these programs. According to our findings, comprehensive pediatric heart failure programs do exist, but they have not been evaluated or even described in the literature. Consensus among experts in the field is that comprehensive chronic care programs are highly desirable, and similar programs have reported tremendous cost savings through early and intensive management: the return on investment has been as high as 22 to 1. Another study reported that mean length of stay decreased from 83.9 to 10.6 days, mean annual admissions decreased from 2796 to 1622, and median hospital charges decreased from $26.1 million to $14.6 million. In conclusion, limited experience and strong circumstantial evidence suggest that, despite substantial costs, comprehensive multidisciplinary pediatric heart failure programs would be cost-effective and beneficial to patients, families, and institutions alike.     

The highest mortality rates in childhood dilated cardiomyopathy occur during the first year after diagnosis

Aim

The aim of the study was to assess the incidence, mortality and morbidity of dilated cardiomyopathy (DCM) and noncompaction of the left ventricle (LVNC) in Swedish children.

Methods

We reviewed hospital records of all children with dilated cardiomyopathy (DCM) or left ventricular noncompaction cardiomyopathy (LVNC) up to the age of 18 in the healthcare region of western Sweden from 1991 to 2015.

Results

In total, 69 cases (61% males) were identified. The combined incidence of DCM and LVNC was 0.77 (95% CI 0.59‐0.96) per 100 000 person years. Children were divided into six groups, and their outcomes were analysed depending on their aetiology. Idiopathic DCM was reported in 43%, and familial dilated and left ventricular noncompaction aetiology was present in 32%. DCM due to various diseases occurred in 8%. DCM associated with neuromuscular diseases was present in 16%. The overall risk of death or receiving transplants in children with idiopathic and familial DCM was 30% over the study period, and 21% died in the first year after diagnosis.

Conclusion

The combined incidence of DCM and LVNC was similar to previous reports. Most children with idiopathic DCM presented during infancy, and mortality was highest during the first year after diagnosis.     

小儿扩张型心肌病并心力衰竭红细胞分布宽度与心功能关系研究

目的 观察扩张型心肌病（DCM）并发心力衰竭患儿红细胞分布宽度（RDW）水平的变化,并探讨其与常用心功能评价指标的相关性。方法 收集武汉市妇女儿童医疗保健中心2012年1月至2014年12月收治的并发心力衰竭的DCM患儿68例, 按改良Ross评分法, 将其分为轻度、 中度、 重度心力衰竭组, 选取健康体检儿童50名作为对照组, 比较各组间RDW水平的差异, 并将DCM患儿RDW与血浆N-端脑利钠肽前体（NT-proBNP）、 左室射血分数（LVEF）进行相关性分析。结果 DCM合并心力衰竭组RDW水平较对照组明显升高,差异有统计学意义（P＜0.01）。心力衰竭轻度、中度、重度患儿间NT-proBNP水平逐级升高,LVEF逐级下降,差异有统计学意义（P均＜0.01）,而心力衰竭各组间RDW水平差异无统计学意义。RDW与NT-proBNP、LVEF均无显著相关性（r分别为0.144、-0.158,P均＞0.05）。结论 RDW升高有助于小儿DCM合并心力衰竭的诊断,但其能否作为小儿心力衰竭严重程度的判断指标尚不能明确。     

小儿肥厚型心肌病病因学研究现状

小儿肥厚型心肌病系一组多病因疾病,以不能解释的心室肥厚为特征。由于不同病因的肥厚型心脏病危重程度及治疗方法不尽相同,故能否早期做出正确诊断对患儿预后和生存率有很大影响。该文就小儿肥厚型心肌病的病因分类及特点进行综述。     

儿童扩张型心肌病心脏无创性检查及其在鉴别诊断中的价值

目的　明确心脏无创性检查在儿童扩张型心肌病 (DCM )的变化及其在DCM与肥厚型心肌病 (HCM )、心内膜弹力纤维增生症 (EFE)鉴别中的价值。方法　对 14 6例DCM、4 1例HCM、5 9例EFE患儿 ,用心电图(EKG)、多普勒超声心动图 (ECHO)、彩色多普勒组织显像 (DTI)检查 ,并与 6 117名正常儿童EKG、2 86名正常儿童多普勒ECHO、14 3名正常儿童DTI检查对比。结果　EKG左室面电压增高者HCM、EFE显著多于DCM。多普勒ECHO检查 :DCM患儿心腔增大 ,左心室后壁 (LVPW )、室间隔 (IVS)不增厚 ;HCM患儿心腔不增大 ,LVPW、IVS增厚 ;EFE患儿心腔扩大 ,LVPW、IVS增厚。多普勒ECHO检查 :DCM和EFE患儿心脏收缩功能降低大于HCM患儿 ;DCM、HCM、EFE患儿心脏舒张功能下降差异无显著性。DTI检查 :HCM、DCM、EFE三者差异无显著性 ,DCM患儿心脏舒张功能降低重于收缩功能降低。DCM患儿MVRDeV <4cm/s者 ,预后极差。结论　EKG、多普勒ECHO、DTI对DCM的诊断和DCM与HCM、EFE的鉴别有重要价值。DTI对估计DCM预后有重要价值。     

Prospective Single-Arm Protocol of Carvedilol in Children with Ventricular Dysfunction

The objective of this study was to evaluate the safety and efficacy of carvedilol in pediatric patients with stable moderate heart failure. We performed a single-arm prospective drug trial at three academic medical centers and the results were compared to historical controls. Patients were 3 months to 17 years old with an ejection fraction <40% in the systemic ventricle for at least 3 months on maximal medical therapy including ACE inhibitors. Treated patients were started on 0.1 mg/kg/day and uptitrated to 0.8 mg/kg/day or the maximal tolerated dose. Echocardiographic parameters of function were prospectively measured at entry and at 6 months. Two composite endpoints were recorded: severe decline in status and significant clinical change. Adverse events were reviewed by a safety committee. Data were also collected from untreated controls with dilated cardiomyopathy meeting entry criteria, assessed over a similar time frame. Twenty patients [12 dilated cardiomyopathy (DCM) and 8 congenital] with a median age of 8.4 years (range, 8 months to 17.8 years) were treated with carvedilol. Three patients discontinued the drug during the study. At entry, there was no statistical difference in age, weight, or ejection fraction between the treated group and controls. The ejection fraction of the treated DCM group improved significantly from entry to 6 months (median, 31 to 40%, p = 0.04), with no significant change in ejection fraction in the control group [median, 29 to 27%, p = not significant (NS)]. The median increase in ejection fraction was larger for the treated DCM group than for the untreated DCM controls (7 vs 0%, p = 0.05). By Kaplan–Meier analysis, time to death or transplant tended to be longer in treated patients (p = 0.07). The difference in the proportion of patients with severe decline in status or significant clinical change in the treated group was not significant compared to the controls (5 vs 12%, p = NS). We conclude that in this prospective protocol of pediatric patients, the use of adjunct carvedilol in the DCM group improved ejection fraction compared to untreated controls and trended toward delaying time to transplant or death.     

Current applications and Future Needs for Biomarkers in Pediatric Cardiomyopathy and Heart Failure: Summary From The Second International Conference On Pediatric Cardiomyopathy

Biomarkers have established an important role in the diagnosis and prognosis of heart failure in adults, with early indications being that their sensitivity and specificity will be similar in the pediatric population. Since early detection of remodeling is vital to preemptive management in cardiomyopathy and in heart disease arising from congenital lesions, biomarkers may offer a means of identifying high risk patients before they develop symptoms. Although in current use, natriuretic peptides high sensitivity troponins, and C-reactive protein need to have their applications more clearly defined in pediatrics, by evidence based guidelines. Exploratory work should meanwhile continue to define the risk of disease progression in patients with dilated cardiomyopathy, and of sudden death in hypertrophic cardiomyopathy based on biomarker profiles. Further research into the interaction of the genetic basis of disease and proteomic biomarkers will be a valuable means of assessing the importance of different pathways of disease related ventricular remodeling.     

Intracoronary administration of autologous bone marrow-derived progenitor cells in a critically ill two-yr-old child with dilated cardiomyopathy

Abstract:  DCM is the most common cardiomyopathy in childhood. Effectiveness of anticongestive therapy is limited in most cases and about one-third of children diagnosed with DCM die or receive heart transplantation within the first year after diagnosis. Cardiac stem cell transplantation has become a promising therapy to treat heart failure in adult patients. Based on these promising results, the cardiac stem cell therapy might also represent a new therapeutic option particularly in young children. The present case documents for the first time intracoronary administration of autologous bone marrow-derived progenitor cells in a critically ill two-yr-old child with severe heart failure caused by DCM. Because of progressive worsening of the clinical condition despite maximal anticongestive treatment, the decision to perform autologous stem cell therapy was made. Cardiac stem cell therapy proved to be technically feasible, was associated with improvement in cardiac function, and might represent an option before heart transplantation in children with severe heart failure.     

The Heart in Friedreich's Ataxia: Basic Findings and Clinical Implications

The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) was established by the Joint Council on Congenital Heart Disease to dramatically improve the outcomes of care for children with congenital heart disease (CHD) through a national collaborative network of multidisciplinary clinical teams and families, working together to collect longitudinal data, use improvement science methods and conduct research intended to accelerate the development and translation of new knowledge into practice. The initial project selected for this learning network is focused on care processes and outcomes of the initial interstage period for infants with hypoplastic left heart syndrome. A practice-based registry is being used to understand variation in care and outcomes of infants and children with complex CHD. The NPC-QIC has effectively recruited and engaged a large number of U.S. centers caring for infants with complex CHD and provides the infrastructure needed to support the implementation of practice changes across the collaborative that will ultimately improve outcomes in this high-risk group of patients. We describe here the development and early years of NPC-QIC as well as the challenges this collaborative faces moving forward.     

儿童肥厚型梗阻性心肌病的外科治疗

肥厚型心肌病（HCM）是影响儿童和青少年的第二种常见心肌病,是年轻运动员猝死的主要原因。HCM的病因在儿科人群中包括先天代谢异常、神经肌肉疾病和畸形综合征等。然而,大多数儿童期特发性HCM的病例是由心脏肌节蛋白基因突变引起的。对药物治疗无效的肥厚型梗阻性心肌病（HOCM）患儿并不少见;对于此类患儿,手术治疗往往是惟一解决方案。既往常规的外科手术方式包括改良Konno手术,改良扩大Morrow手术,对于儿科患儿行介入酒精消融或射频消融的手术治疗,目前鲜有相关报道和大规模的临床经验。     

Cardiomyopathy in children in Ahmedabad

A clinical study and follow up of 20 children with cardiomyopathies upto age of 16 years are presented. The DCM was most common variety followed by RCM and HCM in pediatric age group. SHMD presenting with cardiomyopathy were common in infancy and early childhood. Cardiomyopathies presented most frequently between 2–5 years and 10–16 years age group with DCM having almost equal distribution. Clinical presentation of various types is described, despite of vigorous decongestive and vasodilator treatment in advanced cases, course was rapidly downhill and prognosis is poor in general.     

Cardiac allograft vasculopathy in children — treatment challenges

Cardiomyopathy in children accounts for greater than 50% of the cases of end-stage cardiac disease leading to heart transplantation in children. While early survival is excellent, late survival is limited with an average graft half-life of approximately 15 years in children. Cardiac allograft vasculopathy is a not uncommon complication of transplantation and is the leading cause of late graft loss and retransplantation in pediatric populations. Studies of the United Network of Organ Sharing database and the Pediatric Heart Transplant Study group report rates of coronary vasculopathy that increase from 5% at 2 years to 35% at 10 years. Coronary artery vasculopathy is a complex process caused by both immune mediated endothelial dysfunction and vascular changes as well as typical cardiovascular risk factors. Unfortunately, despite vigilant surveillance protocols, new onset graft dysfunction and sudden cardiac death can be the presenting symptoms of new disease. In recent years multiple medical and adjuvant therapies have been studied in relation to potential management to minimize this disease process. Further research and collaborative multi-center trials will be the most effective means of developing strategies for the prevention and treatment of coronary vasculopathy in pediatric heart transplant patients.     

《中国儿童肥厚型心肌病诊断的专家共识》诊断价值国内多中心研究

目的　比较《中国儿童肥厚型心肌病诊断的专家共识》（简称国内共识）与《2020年AHA/ACC肥厚型心肌病诊断及治疗指南》（简称AHA/ACC指南）对儿童肥厚型心肌病（HCM）的诊断价值。方法　回顾性分析2015年1月至2019年12月国内32家医院收治的466例心肌肥厚患儿的临床资料,以超声心动图最终随访结果和基因检测结果为金标准,分别按国内共识及AHA/ACC指南制定的诊断流程进行诊断,其诊断结果分为确诊和排除,比较国内共识和AHA/ACC指南对儿童HCM诊断的敏感度、特异度和准确度。结果　466例心肌肥厚患儿超声心动图检查以室间隔和左室后壁肥厚者最多（57.08%）,其次为室间隔肥厚（31.33%）,第3位为左室后壁肥厚（9.23%）,心尖部肥厚患儿最少（2.36%）。93例患儿行基因检测,其中32例存在致病性变异,27例为可能致病性变异。按照金标准,全组病例中396例确诊为HCM,排除70例;按照国内共识确诊370例,排除96例;按照AHA/ACC指南确诊346例,排除120例。国内共识和AHA/ACC指南对所有病例的诊断特异度均为100%;对于全组病例、＞1岁病例和未行基因检测病例,国内共识诊断的敏感度和准确度均高于AHA/ACC指南,且国内共识的Youden指数高于AHA/ACC指南（P＜0.01）;对于≤1岁病例,AHA/ACC指南的诊断敏感度和准确度稍高于国内共识,但二者 Youden指数差异无统计学意义（P＞0.05）。结论　国内共识和AHA/ACC指南均可准确诊断儿童HCM,但国内共识更加适合于我国儿童HCM的精准诊断。