Metabolic aspects of myocardial disease and a role for L-carnitine in the treatment of childhood cardiomyopathy.

Published on Jun 1, 2000in Pediatrics5.359
Edward Helton1
Estimated H-index: 1
(UVA: University of Virginia),
Robert K. Darragh7
Estimated H-index: 7
(IU: Indiana University)
+ 8 AuthorsSusan Winter15
Estimated H-index: 15
(Boston Children's Hospital)
Sources
Abstract
Objectives. A multicenter retrospective study was conducted to investigate the possible metabolic causes of pediatric cardiomyopathy and evaluate the outcome of patients treated with l-carnitine. Methods. Seventy-six patients diagnosed with cardiomyopathy were treated with l-carnitine in addition to conventional cardiac treatment, and 145 patients were treated with conventional treatment only. There were 101 males and 120 females between 1 day and 18 years old. Cardiomyopathy diagnoses included dilated (148 patients), hypertrophic (42 patients), restrictive (16 patients), mixed diagnosis (11 patients), and 4 with an unknown type. Of 76 l-carnitine-treated patients, 29 (38%) had evidence to suggest a disorder of metabolism, and of 145 control patients, 15 (10%) were suspected to have a disorder of metabolism. These metabolic disorders were thought to be the cause for the cardiomyopathy of the patients. The duration of l-carnitine treatment ranged from 2 weeks to >1 year. Information was collected on length of survival (time-to-event), clinical outcome, echocardiogram parameters, and clinical assessments. Data were collected at intervals from baseline to study endpoint, death, transplant, or last known follow-up visit. Results. l-Carnitine-treated patients were younger than control patients and had poorer clinical functioning at baseline, yet they demonstrated lower mortality and a level of clinical functioning and clinical severity comparable to control patients on conventional therapy by the end of the study. An analysis of the interaction between clinical outcome and concomitant medications unexpectedly revealed that the population of patients treated with angiotensin-converting enzyme (ACE) inhibitors (40% of patients) had significantly poorer survival (although their greater likelihood for poor survival may possibly have made them more likely to receive ACE inhibitors). Conclusion. Results suggest that l-carnitine provides clinical benefit in treating pediatric cardiomyopathy. There is a need for further exploration of potential explanatory factors for the higher mortality observed in the population of patients treated with ACE inhibitors.
📖 Papers frequently viewed together
197 Citations
57 Citations
52 Citations
References36
Newest
#1Marcy L. Schwartz (Harvard University)H-Index: 12
#2Gerald F. Cox (Harvard University)H-Index: 44
Last. Steven E. Lipshultz (Harvard University)H-Index: 113
view all 7 authors...
Background Cardiomyopathy (CM) remains one of the leading cardiac causes of death in children, although in the majority of cases, the cause is unknown. To have an impact on morbidity and mortality, attention must shift to etiology-specific treatments. The diagnostic evaluation of children with CM of genetic origin is complicated by the large number of rare genetic causes, the broad range of clinical presentations, and the array of specialized diagnostic tests and biochemical assays. Methods and ...
134 CitationsSource
#1Alp Caforio (St George's Hospital)H-Index: 6
#1Alida L.P. Caforio (St George's Hospital)H-Index: 59
47 CitationsSource
#1Hugh Watkins (Brigham and Women's Hospital)H-Index: 134
32 CitationsSource
#1Michael J. Davies (St George's Hospital)H-Index: 54
#2W J McKennaH-Index: 1
6 CitationsSource
#1P. J. Keeling (St George's Hospital)H-Index: 9
#2S TracyH-Index: 1
19 CitationsSource
#1Serenella Servidei (UCSC: Catholic University of the Sacred Heart)H-Index: 50
#2Enrico BertiniH-Index: 111
Last. Salvatore DiMauroH-Index: 136
view all 3 authors...
24 Citations
#1Andrea Schwaiger (University of Innsbruck)H-Index: 2
#2Florian Umlauft (University of Innsbruck)H-Index: 11
Last. Kurt Grünewald (University of Innsbruck)H-Index: 25
view all 8 authors...
Abstract Infection by enteroviruses, especially by Coxsackie B viruses, has been incriminated in pathogenesis of dilated cardiomyopathy. We developed polymerase chain reaction tests for the detection of enteroviral and Coxsackie B3 genomes, respectively, in myocardial biopsies obtained from a homogenous group of 19 patients with idiopathic dilated cardiomyopathy. To determine unambiguously the incidence of enteroviruses and Coxsackie B3 viruses in these patients, we used two primer pairs, one co...
56 CitationsSource
#1Joel Kupfer (VA: United States Department of Veterans Affairs)H-Index: 1
#2Stanley A. RubinH-Index: 10
The clinician’s knowledge and perspective of heart failure has evolved concomitantly with the scientific investigation of the cardiovascular system. This is no accident of coincidence, but rather the purposeful adoption and adaptation by physicians of new information and insight developed through research from the basic and clinical sciences. If a previous clinical era of knowledge about heart failure was characterized by the contemporary information gleaned from research into pathology, and the...
11 CitationsSource
#1Yolanda CamposH-Index: 31
#2Rosa HuertasH-Index: 6
Last. Joaquín ArenasH-Index: 61
view all 8 authors...
Plasma carnitine “insufficiency,” (plasma esterified carnitine to free carnitine ratio above 0.25) was found in 21 48 (43.8%) patients with mitochondrial myopathy, of whom 4 also showed both total and free carnitine deficiencies in plasma. In addition, plasma levels of SCAC and LCAC were higher in patients with mitochondrial myopathy than in controls (P < 0.001 and P <0.01, respectively). Patients diagnosed as having plasma carnitine insufficiency or deficiency were treated with L-carnitine (50–...
85 CitationsSource
#1Jan-Åke LiljeqvistH-Index: 21
#2Tomas BergströmH-Index: 58
Last. Stig JeanssonH-Index: 28
view all 7 authors...
Attempts were made to establish a possible relationship between enterovirus infection and dilated cardiomyopathy (DCM) by use of serology, virus isolation from faecal samples, and detection of enteroviral RNA in endomyocardial biopsies (EMB) by the polymerase chain reaction (PCR). Sera from 63 patients with DCM and matched controls were examined for enterovirus infection by p.-capture IgM and indirect IgG ELISA. Thirty-six patients were further tested for the presence of enterovirus group-specif...
25 CitationsSource
Cited By56
Newest
#1Marta Reyes-Corral (CSIC: Spanish National Research Council)
Last. Patricia Ybot-GonzalezH-Index: 17
view all 5 authors...
Neonatal hypoxia–ischemia (HI) is a brain injury caused by oxygen deprivation to the brain due to birth asphyxia or reduced cerebral blood perfusion, and it often leads to lifelong limiting sequelae such as cerebral palsy, seizures, or mental retardation. HI remains one of the leading causes of neonatal mortality and morbidity worldwide, and current therapies are limited. Hypothermia has been successful in reducing mortality and some disabilities, but it is only applied to a subset of newborns t...
Source
#1Abdulrahman Alghamdi (King Saud bin Abdulaziz University for Health Sciences)H-Index: 3
#2Hani Almalki (King Saud bin Abdulaziz University for Health Sciences)H-Index: 2
Last. Fahad Hakami (King Saud bin Abdulaziz University for Health Sciences)H-Index: 1
view all 5 authors...
Systemic primary carnitine deficiency (SPCD) is an autosomal recessive inborn error of fatty acid metabolism caused by a defect in the transporter responsible for moving carnitine across plasma membrane. The clinical features of SPCD vary widely based on the age of onset and organs involved. During infancy, patients might show episodes of hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia. Skeletal myopathy, elevated creatine kinase, and cardiomyopathy are the mai...
Source
#1Zhong-Yu Wang (JLU: Jilin University)H-Index: 1
#2Ying-Yi Liu (JLU: Jilin University)H-Index: 1
Last. Cui-Ying Mao (JLU: Jilin University)H-Index: 1
view all 5 authors...
Abstract Cardiovascular disease (CVD) is a key cause of deaths worldwide, comprising 15–17% of healthcare expenditure in developed countries. Current records estimate an annual global average of 30 million cardiac dysfunction cases, with a predicted escalation by two-three folds for the next 20–30 years. Although β-blockers and angiotensin-converting-enzymes are commonly prescribed to control CVD risk, hepatotoxicity and hematological changes are frequent adverse events associated with these dru...
35 CitationsSource
#1Thomas J. Ryan (Cincinnati Children's Hospital Medical Center)H-Index: 134
#2Steven J. Kindel (Children's Hospital of Wisconsin)H-Index: 12
Last. Matthew J. O'Connor (Children's Hospital of Philadelphia)H-Index: 12
view all 3 authors...
Abstract Neonatal heart failure is a clinical syndrome caused by cardiovascular and noncardiovascular abnormalities, which results in characteristic signs and symptoms including edema, respiratory distress, and growth failure accompanied by circulatory, neurohormonal, and molecular derangements. The causes of neonatal heart failure are varied and include congenital heart disease, inherited or acquired cardiomyopathy, and systemic diseases. Accurate diagnosis of etiology is key for appropriate th...
Source
Cardiovascular diseases are major health and social problem in the world. Prevention of cardiac complications in extracardial surgical interventions is one of the most urgent problems of modern anesthesiology, surgery and cardiology. Abroad, detailed recommendations are published on optimal diagnostic and therapeutic management in these settings; similar recommendations were issued in Russia. Unfortunately, our country still has no such regulatory documents on the subject. Complications caused b...
Source
view all 5 authors...
Source
#1Lijun Fu (SJTU: Shanghai Jiao Tong University)H-Index: 8
#2Meirong Huang (SJTU: Shanghai Jiao Tong University)H-Index: 8
Last. Shu-bao Chen (SJTU: Shanghai Jiao Tong University)H-Index: 5
view all 3 authors...
Carnitine is essential for the transfer of long-chain fatty acids from the cytosol into mitochondria for subsequent β-oxidation. A lack of carnitine results in impaired energy production from long-chain fatty acids, especially during periods of fasting or stress. Primary carnitine deficiency (PCD) is an autosomal recessive disorder of mitochondrial β-oxidation resulting from defective carnitine transport and is one of the rare treatable etiologies of metabolic cardiomyopathies. Patients affected...
32 CitationsSource
#1Jae Hyeong Park (CNU: Chungnam National University)H-Index: 4
#2Deborah H Kwon (Cleveland Clinic)H-Index: 22
Last. Thomas H. Marwick (Menzies Research Institute)H-Index: 137
view all 4 authors...
Heart failure is a major clinical problem in developed countries with about half of heart failure patients exhibiting decreased left ventricular systolic function. The correct identification and prompt treatment of some specific etiologies can reverse heart failure, and recognition of myocardial recovery may avoid long-term therapy. However, the echocardiographic patterns of patients with a variety of etiologies of heart failure are similar, so the selective use of other imaging techniques is ne...
4 CitationsSource
#1Brian H. WalshH-Index: 17
#2David Broadhurst (U of A: University of Alberta)H-Index: 48
Last. Deirdre M. MurrayH-Index: 30
view all 7 authors...
Background Hypoxic ischaemic encephalopathy (HIE) in newborns can cause significant long-term neurological disability. The insult is a complex injury characterised by energy failure and disruption of cellular homeostasis, leading to mitochondrial damage. The importance of individual metabolic pathways, and their interaction in the disease process is not fully understood. The aim of this study was to describe and quantify the metabolomic profile of umbilical cord blood samples in a carefully defi...
65 CitationsSource
#1Brian H. Walsh (UCC: University College Cork)H-Index: 17
#2David BroadhurstH-Index: 48
Last. Deirdre M. Murray (UCC: University College Cork)H-Index: 30
view all 7 authors...
Background Hypoxic ischaemic encephalopathy (HIE) is associated with the activation of multiple biochemical pathways. The importance of these pathways individually, and that of their interaction, in the disease process is not fully understood. The aim of this study was to describe and quantify the metabolomic profile of umbilical cord blood samples in a carefully defined population of full-term infants with HIE. Methods Full-term infants with perinatal asphyxia (with and without HIE) and healthy...
Source