Medico.ru2

Clinical Features and Outcomes of Childhood
Results From a National Population-Based Study
Piers E.F. Daubeney, MBBS; Alan W. Nugent, MBBS; Patty Chondros, MSc; John B. Carlin, PhD; Steven D. Colan, MD; Michael Cheung, MB, ChB; Andrew M. Davis, MD; C.W. Chow, MD; Robert G. Weintraub, MBBS; on behalf of the National Australian Childhood Cardiomyopathy Study Background—Despite considerable mortality, population-based prognostic factors for childhood dilated cardiomyopathy
are lacking.
Methods and Results—A population-based cohort study was undertaken of all children in Australia who presented with
cardiomyopathy at age 0 to 10 years between January 1, 1987, and December 31, 1996. A single cardiologist analyzedall cardiac investigations, and a single pathologist analyzed histopathological material. There were 184 subjects withdilated cardiomyopathy. Positive viral identification or lymphocytic myocarditis was found in 30 (68.2%) of 44 caseswith available early histology and 8 of 9 cases presenting with sudden death. Freedom from death or transplantation was72% (95% CI, 65% to 78%) 1 year after presentation and 63% (95% CI, 55% to 70%) at 5 years. By proportionalhazards regression analysis, risk factors for death or transplantation comprised age ⬎5 years at presentation (hazard ratio5.6, 95% CI, 2.6 to 12.0), familial dilated cardiomyopathy (hazard ratio, 2.9; 95% CI, 1.5 to 5.6), lower initial fractionalshortening z score (hazard ratio per z-score unit, 0.75; 95% CI, 0.65 to 0.87), and failure to increase fractional shorteningz score during follow-up (hazard ratio per unit increase, 0.68; 95% CI, 0.58 to 0.79). At follow-up, 78 (44.6%) of 175cases diagnosed during life have no symptoms and are not taking any cardiac medication.
Conclusions—Early mortality is high in childhood dilated cardiomyopathy, but the clinical status of long-term survivors
is good. This population-based study identifies children at risk of adverse events. (Circulation. 2006;114:2671-2678.)
Key Words cardiomyopathy 䡲 heart failure 䡲 myocarditis 䡲 pediatrics
Clinical Perspective p 2678
myopathy1,2 and is associated with considerable morbidity and mortality.3–10 International registry data indicate that dilated cardio- therapies.12,13 The present study examines the clinical char- myopathy accounts for ⬎50% of all cardiac transplantations per- acteristics and risk factors for death and transplantation formed in patients between 1 and 10 years of age.11 among children with dilated cardiomyopathy enrolled in the Reported outcomes for childhood dilated cardiomyopathy National Australian Childhood Cardiomyopathy Study.
vary widely and have usually been based on institutional reviews3,4,6–8 or limited geographic regions.9 Institutional The National Australian Childhood Cardiomyopathy Study is a reviews may not detect children who die soon after presen- population-based cohort study of all children in Australia who tation, and prognostic variables derived from population- presented with cardiomyopathy at 0 to 10 years of age between based studies are presently lacking. Some studies have January 1, 1987, and December 31, 1996. Cases were recruited examined outcomes only in relation to patient characteristics during a series of site visits undertaken in 1997 to 2000 by the same3 investigators, who visited all 9 pediatric cardiac centers and an at the time of initial evaluation. A better understanding of the additional 12 hospitals caring for children with heart problems.
spectrum and outcomes of childhood dilated cardiomyopathy Cases were also recruited from rural pediatricians, cardiac transplant would facilitate patient care and permit evaluation of newer centers, and cardiologists caring primarily for adults. In each Received April 20, 2006; revision received September 17, 2006; accepted October 11, 2006.
From the Departments of Cardiology (P.E.F.D., A.W.N., M.C., A.M.D., R.G.W.) and Anatomic Pathology (C.W.C.), Royal Children's Hospital, Melbourne, Australia; Clinical Epidemiology and Biostatistics Unit (P.C., J.B.C.), Murdoch Children's Research Institute, Melbourne, Australia;Departments of General Practice (P.C.) and Paediatrics (J.B.C., C.W.C.), University of Melbourne, Melbourne, Australia; and Department of Cardiology,Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass (S.D.C.).
The online-only Data Supplement, which includes the medical institutions and physicians participating in the National Australian Childhood Cardio-
myopathy Study, is available with this article at http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.106.635128/DC1.
Guest Editor for this article was Robyn J. Barst, MD.
Correspondence to Dr Robert Weintraub, Department of Cardiology, Royal Children's Hospital, Flemington Rd, Parkville, VIC 3052, Australia. E-mail 2006 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
December 12, 2006
location, study subjects were identified from multiple sources, excluded 9 subjects whose initial manifestation was sudden death.
including cardiology and medical record databases and echocardi- Important prognostic factors from the univariate analysis (P⬍0.10) ography logbooks. Children with cardiac dysfunction associated with were included in a multivariable Cox proportional hazards model.
progressive neuromuscular disorders or inborn errors of metabolism Lymphocytic myocarditis on endomyocardial biopsy was predictive with multiple organ involvement were excluded. The methodology of survival on univariate analysis but was not entered into the and epidemiological findings have been described previously.1 multivariable model because cardiac histology was not available in Ethics committee approval was obtained from each participating all subjects. Because echocardiographic measurements were highly interrelated, only fractional shortening z score at presentation and Cardiomyopathies were categorized according to the current change in fractional shortening z score on subsequent examinations World Health Organization cardiomyopathy classification by a were entered into the multivariable model (as continuous predictors, single pediatric cardiologist after review of relevant investigations, with the latter a time-dependent covariate defined by the most recent including direct visualization and reinterpretation of all available available echocardiographic value). Survival curves were plotted cardiac imaging.14 The presence of congestive heart failure was with Kaplan-Meier survival estimates, with accompanying 95% based on signs and symptoms recorded by the attending physician.
Greenwood confidence bands.
The diagnostic criteria for dilated cardiomyopathy were (1) reduced Follow-up data were available at least 2 years after presentation in left ventricular systolic function on any form of cardiac imaging in ⬎90% of surviving subjects. The Wilcoxon rank-sum test was used subjects with symptoms or a family history of dilated cardiomyop- to compare the distribution of time from diagnosis between subjects athy, (2) a measured left ventricular ejection fraction ⬍45% or a with and without lymphocytic myocarditis in those with available fractional shortening ⱕ20% in children without symptoms or a myocardial histology. The Fisher exact test was used to examine the positive family history, or (3) pathological evidence of dilated association between inotropic support at presentation and the pres- cardiomyopathy at autopsy. Although most subjects had left ventric- ence or absence of lymphocytic myocarditis in the same subjects.
ular dilatation, this was not required for study inclusion, because Analysis was undertaken with Stata software.19 Ninety-five per- some subjects with rapidly progressive symptoms had normal left cent CIs are given for estimated hazard ratios, and all reported ventricular size at presentation. Subjects with lymphocytic myocar- probability values are 2-sided.
ditis and associated left ventricular systolic dysfunction were in- The authors had full access to the data and take full responsibility cluded because their clinical and echocardiographic findings were for the integrity of the data. All authors have read and agreed to the frequently indistinguishable from those of other study subjects. A manuscript as written.
single pediatric pathologist who was unaware of clinical patientdetails examined all available pathological specimens, includingcardiac histology.
Autopsy records were obtained from a computerized index kept by The study population included all Australian children diag- the Australian Bureau of Statistics that used the same diagnostic nosed with dilated cardiomyopathy during the study period, codes as for hospital records. In this way, information was obtained as well as additional subjects identified at autopsy. Table 1 about subjects who had never had contact with a physician. Prospec- summarizes the characteristics of the study population. The tive clinical and echocardiographic follow-up was arranged forsurviving subjects, particularly those not seen within the preceding majority of subjects had both left ventricular dilatation and systolic dysfunction at diagnosis.
Specifically designed data forms were used to ascertain and record uniform clinical and epidemiological retrospective information for Presenting Symptoms and Initial Therapy
each enrolled subject from all available hospital and outpatient case Congestive heart failure was the presenting symptom in 165 records, including the results of all relevant investigations. Datarecorded during prospective follow-up were recorded in the same (89.7%) of 184 patients, sudden death in 9 (4.9%), and other way. Prognostic factors sought included clinical features at presen- symptoms (exercise intolerance or arrhythmias) in 4 (2.2%), tation and results of relevant investigations (see Appendix in the whereas 6 cases (3.3%) were detected solely on routine online Data Supplement). The earliest available ECG within 7 days screening of family members. The median age of the 9 cases of presentation was read by a single observer, and measurementswere converted to age-appropriate z scores.15 Serial echocardio- whose initial symptom was sudden death was 2 months graphic measurements of left ventricular dimensions, wall thickness, (range 8 days to 11 months). Of the 175 patients who were and fractional shortening (in those without regional wall-motion diagnosed during life, 154 (88%) were hospitalized, and 79 abnormalities), were expressed as z scores based on body surface (45.1%) were admitted to an intensive care unit. Established area (or age, in the case of fractional shortening).16,17 These renal failure that required dialysis or specific supportive echocardiographic parameters were selected because they wereroutinely quantified in all subjects who underwent echocardiography measures was present in 18 patients (10.3%) at diagnosis, and and were usually available at presentation, after 3, 6, 12, and 24 rhabdomyolysis was present in 2 (1.1%). Assisted mechanical months, and at latest follow-up. Among subjects with serial echo- ventilation was administered in 62 patients (35.4%) and cardiograms available from the time of presentation, the change in inotropic support in 70 (40%). The frequency with which fractional shortening (and fractional shortening z score) at eachsubsequent occasion of measurement was calculated by subtracting inotropic support was administered at presentation was sim- the initial fractional shortening (fractional shortening z score) from ilar among children with lymphocytic myocarditis (9 of 25 the subsequent value.
cases, 36%) compared with those with nonspecific histolog- Familial cardiomyopathy was considered to be present when there ical findings (18 of 45 cases, 40%; P⫽0.80). Long-term was an affected first- or second-degree relative with primary dilatedcardiomyopathy identified from the case notes or from prospective medical therapy for congestive heart failure, including diuret- screening of other family members. Definite lymphocytic myocar- ics, digoxin, an afterload-reducing agent (usually an angio- ditis was classified according to the Dallas criteria.18 Routine genetic tensin-converting enzyme inhibitor), an aldosterone antago- testing for mutations known to cause dilated cardiomyopathy was not nist, or a ␤-blocker, was initiated at some point in 134 available during the study period.
subjects (76.6%), and systemic anticoagulation was adminis- tered in 24 (13.7%). Immune modulating therapy (cyclospor- Standard methods of survival analysis were used for the combined ine, steroids, or ␥-globulin) was used in 11 of 13 children end point of death or transplantation. Analysis of prognostic factors with lymphocytic myocarditis on endomyocardial biopsy.
Daubeney et al
Childhood Dilated Cardiomyopathy
Demographic Characteristics of the Patients
logical findings for lymphocytic myocarditis (Table 2; P⫽0.009). Although viral identification from endomyocardi-al biopsy was not routinely undertaken during the study period, 8 cases had both lymphocytic myocarditis and posi- Proportion of total cases in NACCS (n⫽314) tive viral identification from at least 1 source. When micro- Male/female, n (%) biological and histological investigations were considered Age at presentation, n (%) together, a potential viral contribution was identified in 58 (31.5%) of 184 cases, including 30 (68.2%) of 44 cases who ⬎4 wk and ⱕ1 y underwent cardiac histological examination within 7 days of ⬎1 y and ⱕ5 y presentation and 6 (66.7%) of 9 whose initial manifestation was sudden death.
Familial cardiomyopathy, n (%) Familial Cardiomyopathy, Metabolic Conditions, and
Lymphocytic myocarditis, No. of cases with available histology (%) Familial dilated cardiomyopathy was identified in 27 subjects Presence of metabolic disease, n (%) (14.7%), 8 of whom did not have symptoms at diagnosis.
Death or transplantation, n (%) Three (11.1%) of 27 children with familial cardiomyopathy Years of follow-up from presentation for all showed genetic anticipation, with a prior affected family patients (n⫽175*) member having onset of cardiomyopathy during adult life. A metabolic or mitochondrial disease (Barth syndrome, carni- Interquartile range tine transport defect, fatty acid oxidation defect, or respira- Years of follow-up from presentation for surviving tory chain complex deficiency) with predominant cardiac patients (n⫽109) manifestations was diagnosed in 12 (8.9%) of 135 cases who underwent at least 1 metabolic investigation, 8 of whompresented at age Interquartile range ⬍12 months. Parental consanguinity was present in 14 (8.8%) of 160 cases in which this variable could LV end-systolic dimension z score at presentation be ascertained, including 3 with familial cardiomyopathy.
Interquartile range A total of 75 patients (40.8%) have died or undergone LV end-diastolic z score at presentation (N⫽150†) transplantation. These included 9 subjects who presented with sudden death and 24 who died during their initial hospital- Interquartile range ization at a median of 2 (range, 0 to 18) days after Fractional shortening at presentation (n⫽150†) At latest follow-up, 78 of 184 subjects are taking no regular Interquartile range medication, whereas 31 (16.8%) are receiving long-termmedical therapy. Of the 103 patients with known symptom- Fractional shortening z score at presentation(n⫽150†) atic status, 94 (91.3%) are without cardiac symptoms.
Interquartile range ⫺12.1 to ⫺8.7 Actuarial freedom from death or transplantation was 72% NACCS indicates National Australian Childhood Cardiomyopathy Study; LV, (95% CI, 65% to 78%) 1 year after presentation and 63% left ventricular.
(95% CI, 55% to 70%) at 5 years (Figure, panel A). Risk n denotes the total number of patients with any form of cardiomyopathy factors showing at least weak evidence (P⬍0.1) of associa- over the 10-year ascertainment period in Australia.
tion with risk of death or transplantation are shown in Table *Total excludes 9 subjects whose first manifestation was sudden death.
†Twenty-five subjects did not have a suitable echocardiogram for analysis at 3. There was a clear difference in survival according to age at presentation (P⫽0.001), mainly due to much worse outcomesamong children aged ⬎5 years at diagnosis (Table 3; Figure, panel B). There was also some indication that survival was Viral Identification and Lymphocytic Myocarditis
lower among infants aged 0 to 1 month and those aged 1 to In 41 (22.3%) of 184 subjects, a potentially cardiotoxic virus 12 months than among those aged 12 months to 5 years at (most commonly coxsackievirus or adenovirus) was identi- diagnosis (post hoc 3-group comparison P⫽0.11). Given the fied from urine, stools, or upper-airway secretions at presen- weak evidence for differences between the 3 youngest age tation with polymerase chain reaction or viral culture. Lym- groups, presenting age was dichotomized at 5 years for entry phocytic myocarditis was present in 25 (35.7%) of 70 cases in the multivariable proportional hazards model. In this with available cardiac histology from any source (endomyo- model, factors that showed evidence of independent predic- cardial biopsy, explantation, or autopsy). There was an tive associations included age ⬎5 years at presentation inverse relationship between the time from diagnosis to (Figure, panel B), familial dilated cardiomyopathy (Figure, histological examination and the presence of positive histo- panel C), a lower fractional shortening z score at presentation, December 12, 2006
Frequency of Lymphocytic Myocarditis Among Subjects With Available
Cardiac Histology, According to Time Between Diagnosis and Examination of
Histological Findings (nⴝ70)
Time From Presentation ⬎1–4 Weeks ⬎4–8 Weeks ⬎8 Weeks Total Lymphocytic myocarditis Nonspecific histological findings P⫽0.009, Wilcoxon rank-sum test.
and failure to increase fractional shortening z score from number of subjects who died before recognition of their condition was substantially underestimated. In particular, the At 2 years after presentation, 24 (13.7%) of the 175 number of cases diagnosed from autopsy after sudden unex- patients who were diagnosed during life had a measured pected death has highlighted the significant early mortality in fractional shortening below 20%. Outcomes for this group childhood dilated cardiomyopathy.
were poor. Eleven (45.8%) of the 24 died or underwenttransplantation, and all of the remaining subjects continue to Symptoms and Causes
have impaired left ventricular function.
Symptoms were present in most subjects at presentation andwere usually severe. Congestive heart failure was the initial Lymphocytic Myocarditis
Of 25 children with lymphocytic myocarditis, 12 (48%) were
symptom in almost 90% of patients, half of whom were diagnosed at autopsy. Six (24%) of these presented with admitted to an intensive care unit. Sudden death was the first sudden death, and the other 6 (24%) died within 3 days of manifestation of dilated cardiomyopathy in nearly 5%, and a presentation. The remaining cases were diagnosed from further 13% died during their initial hospitalization.
endomyocardial biopsy. Among 39 children who underwent Lymphocytic myocarditis among adults with left ventric- endomyocardial biopsy, survival among the 13 cases with ular dysfunction occurs in ⬇10% of cases22 and may be due lymphocytic myocarditis was significantly better than among to a variety of viral and autoimmune causes.23 In children the 26 who had nonspecific histological findings (Table 2; with dilated cardiomyopathy, lymphocytic myocarditis is Figure, panel D). At latest follow-up in children with lym- found more frequently5 and more commonly reflects a viral phocytic myocarditis diagnosed from endomyocardial biopsy, origin.24–26 The results of viral identification from tracheal the mean (interquartile range) left ventricular end-diastolic aspirate by polymerase chain reaction have been shown to dimension and fractional shortening z scores were 0.4 correlate well with those obtained from myocardium and the (⫺0.65, 0.7) and ⫺0.5 (⫺1.2, 0.8), respectively.
lower respiratory tract.25 In the present study, positive viralidentification or lymphocytic myocarditis was present in 68% of subjects with early available myocardial histology, includ- Population-based studies have provided unique insights into ing 6 of 9 subjects presenting with sudden death. The disease severity and outcomes among adults with cardiomy- diagnosis of postviral cardiomyopathy remains problematic, opathy.20 The National Australian Childhood Cardiomyopa- and these findings are open to a number of interpretations.
thy study is the largest population-based study of childhood Low ascertainment of viral illness may be due to collection of cardiomyopathy1 and therefore provides useful reference specimens well after the viremic phase of the initial illness, data. Consistency of case classification was maintained by low utilization of early endomyocardial biopsy, and lack of having the same observers examine all available cardiac direct viral testing on myocardial samples, whereas overas- investigations and histopathological material. Although the certainment may be due to spurious association with systemic number of cases with mild unrecognized dilated cardiomy- viral illnesses. The present study demonstrates a potential opathy remains unknown, case ascertainment for children viral contribution in a high proportion of cases, however. This already diagnosed is likely to have been effectively complete unexpectedly high prevalence may reflect the inclusion of for the following reason: The majority of children who arediagnosed with dilated cardiomyopathy come to early medi- autopsy cases and subjects who would otherwise not have cal attention because of severe symptoms.21 Centralization of come to attention in an institutional review. The inverse tertiary services within Australia enabled cases to be recruited relation between the prevalence of myocarditis and increasing from multiple sources, which included all pediatric cardiac time since presentation is consistent with animal models in centers and cardiologists, as well as from rural pediatricians which myocardial inflammation disappears within 6 weeks of and physicians caring primarily for adults. Finally, the inci- viral inoculation.27 dence of dilated cardiomyopathy in the present study was Other potential causes, such as familial dilated cardiomy- similar to that of a recent North American study,1,2 which opathy, a metabolic disease, and parental consanguinity (as a indicates that case ascertainment was likely to be high.
marker for a recessively inherited condition), were each Because Australian law requires autopsies to be performed in documented in 8.8% to 14.7% of study subjects. Familial cases of sudden or unexplained death, it is unlikely that the cardiomyopathy and mitochondrial diseases may well have

Daubeney et al
Childhood Dilated Cardiomyopathy
Survival to death or transplantation from time of presentation: overall, with 95% CI (A); with patients grouped by age at presentation(B); with patients grouped by presence or absence of familial cardiomyopathy (C); and with patients grouped by presence or absenceof lymphocytic myocarditis on endomyocardial biopsy (D).
been underrecognized, because not all subjects and families ed.30 Few pediatric studies have examined late survival in were systematically screened.28 relation to serial assessment of left ventricular function.
In the present study, independent risk factors for death or transplantation comprised older age at presentation, familial Reported outcomes and prognostic factors for childhood dilated cardiomyopathy, lower initial fractional shortening z dilated cardiomyopathy have varied considerably. Five-year score, and failure to increase fractional shortening z score survival rates of 20% to 84% have been described from during follow-up. Younger patients had a nonsignificant trend institutional reviews.3,6,8,10 In 1 study of 24 children pres- to worse survival, which suggests the possibility of a bimodal enting at ⬍2 years of age,4 absence of lymphocytic myocar- age distribution for poor outcomes in childhood dilated ditis, a spherical left ventricular shape, and more depressed cardiomyopathy. The impact of each established risk factor left ventricular function at presentation were associated with was considerable. For example, an increase in fractional worse outcomes. Another review of 25 children aged ⬎2 shortening z score over the baseline value measured at years at presentation reported a 3-year survival of only 20%.6 presentation was associated with a 32% reduction in hazard Some studies have found no relation between late survival ratio per unit z score. Improvement in left ventricular function and age3,7 or severity of cardiac dysfunction3,6–8 at presenta- among surviving subjects may have been due to supportive tion. Other proposed adverse risk factors include the magni- medical therapy and, in some cases, resolution of postviral tude of diastolic dysfunction at cardiac catheterization3 or by cardiomyopathy. The clinical status of long-term survivors echocardiography (in adults).29 A single previous national was good, with nearly half of all study subjects having no study30 of 62 cases who were diagnosed between 1980 and symptoms and no longer receiving cardiological medications.
1991 reported that right ventricular failure at presentation and Despite a high initial mortality, subjects with lymphocytic requirement for anticoagulant therapy were associated with myocarditis diagnosed during life had a better survival than worse outcomes. The study selection criteria differed from those with nonspecific histological findings. This may reflect the present study, however, in that subjects with myocarditis the rapid evolution of pediatric lymphocytic myocarditis, and those with self-limiting cardiomyopathies were exclud- selection of less critically ill patients for biopsy, a more December 12, 2006
Survival Analysis of Predictors of Death or Transplantation (nⴝ175)
Multivariable Survival Analysis Univariable Survival Analysis Age at presentation (4 groups) ⬎4 wk and ⱕ1 y 0.73 (0.39–1.4) ⬎1 y and ⱕ5 y 0.44 (0.20–0.95) 2.26 (1.07–4.8) Age at presentation (2 groups) ⬎5 y 3.27 (1.77–6.0) Familial cardiomyopathy 2.35 (1.35–4.1) Biopsy myocarditis* QRS duration z score 1.38 (1.02–1.9) Fractional shortening at presentation‡ 0.92 (0.87–0.97) Change in fractional shortening from presentation‡ 0.83 (0.78–0.89) Fractional shortening z score at presentation‡ 0.85 (0.75–0.96) 0.75 (0.65–0.87) Change in fractional shortening z score from presentation‡ 0.66 (0.57–0.77) 0.68 (0.58–0.79) Excludes 9 subjects whose first manifestation was sudden death. Measured QRS duration was from the earliest available ECG. For the 3 youngest age groups, presenting age was dichotomized at 5 years for entry in the multivariable proportional hazards regression model.
Only variables that achieved a P value ⬍0.10 are included in the table; other variables examined are listed in the Appendix.
*The finding of myocarditis on biopsy was significantly predictive of survival, but a hazard ratio could not be calculated because all patients with this characteristic were free from death or transplant; P value calculated with log-rank test.
†P values from Wald tests in Cox proportional hazards regression, with 3 degrees of freedom in case of 4-group comparison and 1 degree of freedom otherwise.
‡Per unit (percent fractional shortening or unit z score).
favorable natural history of this condition, or the benefits of tation and the lack of sufficient young donors justify the the various therapies employed. Among adults with lympho- continuing search for better medical therapy.
cytic myocarditis, fulminant onset is associated with im-proved outcomes,31 although there is no evidence that immu- nosuppressive therapy modifies the natural history.22 The Dallas criteria are of limited utility in the diagnosis of However, there exist numerous reports of favorable outcomes postviral cardiomyopathy and are subject to considerable after treatment among both children5,32–34 and subgroups of interobserver variability.38 The latter was minimized by adults with lymphocytic myocarditis.23,31,35 A separate trial of having a single pediatric pathologist examine all available immune-modulating therapy in children appears warranted to myocardial histology. Retrospective data collection, variable address this issue.
diagnostic protocols, and limitations in existing knowledgealso restricted the proportion of study subjects with cardio- myopathy of known origin. By comparison with other pedi- The present study took place during a period of rapidly atric studies, however, the proportion of subjects with a changing medical therapy for subjects with dilated cardiomy- known or probable cause remains high. Routine genetic opathy. The data supporting the efficacy of medical therapy testing for dilated cardiomyopathy was not available during in children with dilated cardiomyopathy are less robust than the study period, and the results of the present study cannot be in adult subjects, and the present study was not designed to extrapolated to children who have not yet developed left draw conclusions about the benefits of any specific treatment.
ventricular dysfunction. A more global measure of left In adult patients with left ventricular dysfunction, carvedilol ventricular systolic function and routine measurement of reduces mortality36 and modifies prognostic factors.37 Retro- diastolic parameters may further increase the predictive value spective studies in children suggest that ␤-blockers improve of echocardiography. These were not serially available on all ventricular performance,12 and a prospective multicenter trial subjects during the study period. The observation that infants is presently under way. Although mortality and requirement may also be at increased risk for worse outcome may be for eventual cardiac transplantation may be reduced by confirmed with a larger study cohort.
aggressive use of newer medical therapies in children, theirimpact in the youngest of patients has yet to be defined. The present study identifies children at greatest risk for death or Congestive heart failure is severe among children with dilated transplantation, who might therefore benefit most from effec- cardiomyopathy, and lymphocytic myocarditis is an impor- tive early treatment.10 The long-term limitations of transplan- tant cause. Although early mortality is high, the clinical status Daubeney et al
Childhood Dilated Cardiomyopathy
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Pediatric cardiomyopathies are characterized by heterogenous origins with varied outcomes. Childhood dilated cardiomy-opathy is most common during the first year of life and is associated with significant morbidity and mortality. Mostavailable information is from institutional reviews, which may not detect children who die early and those who do notrequire hospitalization. Population-based studies of cardiomyopathy in adults have provided valuable insights into diseaseseverity and outcomes. The National Australian Childhood Cardiomyopathy study is a longitudinal cohort study of allchildren in Australia aged 0 to 10 years who were diagnosed with cardiomyopathy between 1987 and 1996. There were184 subjects with dilated cardiomyopathy. At presentation, 90% of cases had signs and symptoms of congestive heartfailure, and sudden death was the presenting symptom in 4%. Familial cardiomyopathy was identified in 14.7% of subjects,a metabolic or mitochondrial disease in 8.9%, and parental consanguinity, consistent with autosomal recessive inheritance,in 8.8% of cases. A potential viral contribution (lymphocytic myocarditis or positive viral identification) was identified in68.2% of case subjects who underwent early cardiac histological examination. By multivariate analysis, independent riskfactors for death or cardiac transplantation included age ⬎5 years at presentation, familial dilated cardiomyopathy, a lowerfractional shortening z score at presentation, and failure to increase fractional shortening z score from presentation. At latestfollow-up, 78 of 109 surviving cases had no symptoms and were not taking any cardiac medication. Early mortality is highin childhood dilated cardiomyopathy, and the clinical status of long-term survivors is good. The present population-basedstudy identifies children at risk of adverse outcomes.

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