Ingrid King

Long-Term Outcomes of Dilated Cardiomyopathy Diagnosed During Childhood: Results from a National Population-Based Study of Childhood Cardiomyopathy

Background— Existing studies of childhood dilated cardiomyopathy deal mainly with early survival. This population-based study examines long-term outcomes for children with dilated cardiomyopathy. Methods and Results— The diagnosis of dilated cardiomyopathy was based on clinical, echocardiographic, and pathological findings. The primary study end point included time to the combined outcome of death or cardiac transplantation. There were 175 patients 0 to <10 years of age at the time of diagnosis. Survival free from death or transplantation was 74% (95% confidence interval, 67–80) 1 year after diagnosis, 62% (95% confidence interval, 55–69) at 10 years, and 56% (95% confidence interval, 46–65) at 20 years. In multivariable analysis, age at diagnosis <4 weeks or >5 years, familial cardiomyopathy, and lower baseline left ventricular fractional shortening Z score were associated with increased risk of death or transplantation, as was lower left ventricular fractional shortening Z score during follow-up. At 15 years after diagnosis, echocardiographic normalization had occurred in 69% of surviving study subjects. Normalization was related to higher baseline left ventricular fractional shortening Z score, higher left ventricular fractional shortening Z score during follow-up, and greater improvement in left ventricular fractional shortening Z score. Children with lymphocytic myocarditis had better survival and a higher rate of echocardiographic normalization. At the latest follow-up, 100 of 104 of survivors (96%) were free of cardiac symptoms, and 83 (80%) were no longer receiving pharmacotherapy. Conclusions— Death or transplantation occurred in 26% of patients with childhood dilated cardiomyopathy within 1 year of diagnosis and ~1% per year thereafter. Risk factors for death or transplantation include age at diagnosis, familial cardiomyopathy, and severity of left ventricular dysfunction. The majority of surviving subjects are well and free of cardiac medication.Background— Existing studies of childhood dilated cardiomyopathy deal mainly with early survival. This population-based study examines long-term outcomes for children with dilated cardiomyopathy. Methods and Results— The diagnosis of dilated cardiomyopathy was based on clinical, echocardiographic, and pathological findings. The primary study end point included time to the combined outcome of death or cardiac transplantation. There were 175 patients 0 to 5 years, familial cardiomyopathy, and lower baseline left ventricular fractional shortening Z score were associated with increased risk of death or transplantation, as was lower left ventricular fractional shortening Z score during follow-up. At 15 years after diagnosis, echocardiographic normalization had occurred in 69% of surviving study subjects. Normalization was related to higher baseline left ventricular fractional shortening Z score, higher left ventricular fractional shortening Z score during follow-up, and greater improvement in left ventricular fractional shortening Z score. Children with lymphocytic myocarditis had better survival and a higher rate of echocardiographic normalization. At the latest follow-up, 100 of 104 of survivors (96%) were free of cardiac symptoms, and 83 (80%) were no longer receiving pharmacotherapy. Conclusions— Death or transplantation occurred in 26% of patients with childhood dilated cardiomyopathy within 1 year of diagnosis and ~1% per year thereafter. Risk factors for death or transplantation include age at diagnosis, familial cardiomyopathy, and severity of left ventricular dysfunction. The majority of surviving subjects are well and free of cardiac medication. # Clinical Perspective {#article-title-45}

Sudden Death in Childhood Cardiomyopathy: Results From a Long-Term National Population-Based Study

BACKGROUND Children with cardiomyopathy (CM) are at risk of sudden cardiac death (SCD), but the incidence and risk factors for this outcome are not clear. OBJECTIVES This study sought to determine the incidence and risk factors for SCD in children with varying CM phenotypes from a long-term population-based study of childhood CM. METHODS The NACCS (National Australian Childhood Cardiomyopathy Study) is an ongoing longitudinal cohort study including all children in Australia with primary CM who were diagnosed between January 1, 1987, and December 31, 1996, and were <10 years of age. The cumulative incidence and risk factors for SCD within individual CM phenotypes were explored using survival analysis. RESULTS Of 289 eligible patients, 16 (5.5%) experienced SCD over a median follow-up of 11.9 years (interquartile range: 1.7 to 15.4). The risk of SCD varied according to CM phenotype (p=0.007). The cumulative incidence of SCD at 15 years was 5% for dilated cardiomyopathy (DCM), 6% for hypertrophic cardiomyopathy (HCM), 12% for restrictive cardiomyopathy, and 23% for left ventricular (LV) noncompaction. Older age at diagnosis, positive family history of CM, and severity of LV dysfunction were related to increased risk of SCD in patients with DCM, and a higher posterior wall thickness Z-score was the sole risk factor identified for patients with HCM. CONCLUSIONS Predictors of SCD include CM phenotype, family history of CM (DCM), severity of systolic dysfunction (DCM), and extent of LV hypertrophy (HCM). Continuing follow-up of this cohort into adulthood is likely to reveal an ongoing risk of SCD.

Fertility and pregnancy in the Fontan population

BACKGROUND Women with a Fontan circulation are deemed at significantly increased risk of maternal morbidity and mortality during pregnancy. Publications describe a small number of pregnancies worldwide and a high rate of miscarriage. We compiled the experience of women enrolled in the Australia and New Zealand Fontan (ANZ) Registry with regard to menarche, contraceptive use, pregnancy advice and pregnancy outcomes. METHODS Women within the ANZ Fontan Registry were contacted and asked to consent to receiving sequential questionnaires. RESULTS 156 women ≥ 18 years of age (including 4 deceased individuals) were identified, 101 women consented and 97 completed the initial questionnaire. Women were aged (median) 25 years (23-32); menarche occurred at a median 14 years (13-16). A wide variety of contraceptive methods was reported. 81% of women reported having received advice that pregnancy carried an increased risk or was inadvisable. Pregnancy was reported in a minority (n=27). Miscarriage (42.5%) and termination (7.5%) accounted for half the pregnancy outcomes and the babies were born early (median 31.5 weeks) and small (median 1350 g). Maternal complications of bleeding, arrhythmia and heart failure were reported with no early maternal mortality. CONCLUSIONS In women with a Fontan circulation the fertility onset is delayed and pregnancy has a higher rate of miscarriage. Successful pregnancy resulted in small and premature babies. Significant maternal morbidity occurred. Whether pregnancy with its volume loading has an adverse effect on the long-term outcome of women with a single ventricle remains to be elucidated.

Congenital heart disease-associated pulmonary arterial hypertension: preliminary results from a novel registry.

Background/Aims:  Pulmonary arterial hypertension (PAH) frequently accompanies childhood congenital heart disease (CHD) and may persist into adult life. The advent of specific PAH therapies for PAH prompted formation of a national Australian and New Zealand registry in 2010 to document the incidence, demographics, presentation and outcomes for these patients.

Anticoagulation of cardiomyopathy in children

OBJECTIVES Cardiomyopathy is a common cause of heart failure in children. Thrombosis is a potential significant secondary complication. Thus warfarin is recommended by the American College of Chest Physicians for the treatment of children with cardiomyopathy despite the lack of published evidence to support its use. METHODS A retrospective clinical audit to estimate the rates of major bleeding and incidence of thromboembolism associated with oral anticoagulant therapy (warfarin) for primary thromboprophylaxis in a cohort of children with cardiomyopathy. Relevant outcomes including thrombosis and major haemorrhage were defined a priori according to internationally accepted definitions. RESULTS 36 children (35.9 warfarin years) were examined, with 25% taking warfarin for greater than 1year. Primary reasons for discontinuation of warfarin therapy were cardiac transplantation (n=7), transition to VAD (n=1), improved cardiac function (n=17), transfer of care (n=3), change to aspirin (n=2). The mean age at starting warfarin was 5.4years (range 0.2-15.2). The most common Target Therapeutic Range (TTR) for warfarin therapy was 2.0 - 3.0. TTR achievement was normally distributed and occurred in a mean 48.5% of all INR tests. There were zero warfarin related adverse events, including thrombosis or haemorrhage. CONCLUSION The low rate of TTR achievement is consistent with previously reported TTR achievement rates for infants. In addition the low rate of TTR achievement was likely influenced by the clinical profile of this complicated condition in children. Nonetheless, this data shows that the clinical outcomes for this cohort are acceptable and warfarin therapy can be safe in children with cardiomyopathy.

Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood: Results From a National Population-Based Study

Background: Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy. Methods: The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0–10 years of age) diagnosed with cardiomyopathy between 1987 and 1996. The primary study end point was time to death or cardiac transplantation. Results: There were 80 patients with hypertrophic cardiomyopathy, with a median age at diagnosis of 0.48 (interquartile range, 0.1, 2.5) years. Freedom from death/transplantation was 86% (95% confidence interval [CI], 77.0–92.0) 1 year after presentation, 80% (95% CI, 69.0–87.0) at 10 years, and 78% (95% CI, 67.0–86.0) at 20 years. From multivariable analyses, risk factors for death/transplantation included symmetrical left ventricular hypertrophy at the time of diagnosis (hazard ratio, 4.20; 95% CI, 1.60–11.05; P=0.004), Noonan syndrome (hazard ratio, 2.88; 95% CI, 1.02–8.08; P=0.045), higher posterior wall thickness z score (hazard ratio, 1.45; 95% CI, 1.22–1.73; P<0.001), and lower fractional shortening z score (hazard ratio, 0.84; 95% CI, 0.74–0.95; P=0.005) during follow-up. Nineteen (23%) subjects underwent left ventricular myectomy. At a median of 15.7 years of follow-up, 27 (42%) of 63 survivors were treated with &bgr;-blocker, and 13 (21%) had an implantable cardioverter-defibrillator. Conclusions: The highest risk of death or transplantation for children with hypertrophic cardiomyopathy is within 1 year after diagnosis, with low attrition rates thereafter. Many subjects receive medical, surgical, or device therapy.

“Will she live a long happy life?” Parents' concerns for their children with Fontan circulation

Background Families of children at the worst end of the congenital heart disease endure a significant burden which is often not clearly delineated in the clinical literature. We examined the greatest concerns of parents whose children have a Fontan circulation. Methods Parents (N = 107) of children in the Australian and New Zealand Fontan Registry completed online surveys with open-ended and closed questions. A qualitative method approach incorporating thematic analyses was used. Results The greatest concerns for parents of a child with a Fontan circulation were centered on fear of death for their child and psychosocial well-being, followed by lesser themes around anti-coagulation use, pregnancy and financial burdens. Conclusions Fear of death and the psychological well-being of their children were the main parental concerns. It highlights the need to clearly communicate information on outcomes to families, and the need for family-focused psychological interventions to improve the psychosocial functioning of both parents and young people.

Long-Term Outcomes of Childhood Left Ventricular Non-Compaction Cardiomyopathy: Results from a National Population-Based Study

Background: Long-term outcomes for childhood left ventricular noncompaction (LVNC) are uncertain. We examined late outcomes for children with LVNC enrolled in a national population-based study. Methods: The National Australian Childhood Cardiomyopathy Study includes all children in Australia with primary cardiomyopathy diagnosed before 10 years of age between 1987 and 1996. Outcomes for subjects with LVNC with a dilated phenotype (LVNC-D) were compared with outcomes for those with dilated cardiomyopathy. Propensity-score analysis was used for risk factor adjustment. Results: There were 29 subjects with LVNC (9.2% of all cardiomyopathy subjects), with a mean annual incidence of newly diagnosed cases of 0.11 per 100 000 at-risk individuals. Congestive heart failure was the initial symptom in 24 of 29 subjects (83%), and 27 (93%) had LVNC-D. The median age at diagnosis was 0.3 (interquartile interval, 0.08–1.3) years. The median duration of follow-up was 6.8 (interquartile interval, 0.7–24.0) years for all subjects and 24.7 (interquartile interval, 23.3 – 27.7) years for surviving subjects. Freedom from death or transplantation was 48% (95% confidence interval [CI], 30–65) at 10 years after diagnosis and 45% (95% CI, 27–63) at 15 years. In competing-risk analysis, 21% of subjects with LVNC were alive with normal left ventricular systolic function, and 31% were alive with abnormal function at 15 years. Propensity-score matching between subjects with LVNC-D and those with dilated cardiomyopathy suggested a lower freedom from death/transplantation at 15 years after diagnosis in the subjects with LVNC-D (LVNC-D, 46% [95% CI, 26–66] versus dilated cardiomyopathy, 70% [95% CI, 42–97]; P=0.08). Using propensity-score inverse probability of treatment–weighted Cox regression, we found evidence that LVNC-D was associated with a greater risk of death or transplantation (hazard ratio, 2.3; 95% CI, 1.4–3.8; P=0.0012). Conclusions: Symptomatic children with LVNC usually present in early infancy with a predominant dilated phenotype. Long-term outcomes are worse than for matched children with dilated cardiomyopathy.

LONG-TERM OUTCOMES OF CHILDHOOD LEFT VENTRICULAR NON-COMPACTION: RESULTS FROM A NATIONAL POPULATION-BASED STUDY

Introduction: Long-term outcomes for childhood left ventricular non-compaction (LVNC) are uncertain. We examined this question as part of a national population-based study. Methods: The National Australian Childhood Cardiomyopathy Study includes all children in Australia diagnosed with primary

Long-Term Outcomes of Dilated Cardiomyopathy Diagnosed During ChildhoodClinical Perspective

Background— Existing studies of childhood dilated cardiomyopathy deal mainly with early survival. This population-based study examines long-term outcomes for children with dilated cardiomyopathy. Methods and Results— The diagnosis of dilated cardiomyopathy was based on clinical, echocardiographic, and pathological findings. The primary study end point included time to the combined outcome of death or cardiac transplantation. There were 175 patients 0 to <10 years of age at the time of diagnosis. Survival free from death or transplantation was 74% (95% confidence interval, 67–80) 1 year after diagnosis, 62% (95% confidence interval, 55–69) at 10 years, and 56% (95% confidence interval, 46–65) at 20 years. In multivariable analysis, age at diagnosis <4 weeks or >5 years, familial cardiomyopathy, and lower baseline left ventricular fractional shortening Z score were associated with increased risk of death or transplantation, as was lower left ventricular fractional shortening Z score during follow-up. At 15 years after diagnosis, echocardiographic normalization had occurred in 69% of surviving study subjects. Normalization was related to higher baseline left ventricular fractional shortening Z score, higher left ventricular fractional shortening Z score during follow-up, and greater improvement in left ventricular fractional shortening Z score. Children with lymphocytic myocarditis had better survival and a higher rate of echocardiographic normalization. At the latest follow-up, 100 of 104 of survivors (96%) were free of cardiac symptoms, and 83 (80%) were no longer receiving pharmacotherapy. Conclusions— Death or transplantation occurred in 26% of patients with childhood dilated cardiomyopathy within 1 year of diagnosis and ~1% per year thereafter. Risk factors for death or transplantation include age at diagnosis, familial cardiomyopathy, and severity of left ventricular dysfunction. The majority of surviving subjects are well and free of cardiac medication.Background— Existing studies of childhood dilated cardiomyopathy deal mainly with early survival. This population-based study examines long-term outcomes for children with dilated cardiomyopathy. Methods and Results— The diagnosis of dilated cardiomyopathy was based on clinical, echocardiographic, and pathological findings. The primary study end point included time to the combined outcome of death or cardiac transplantation. There were 175 patients 0 to 5 years, familial cardiomyopathy, and lower baseline left ventricular fractional shortening Z score were associated with increased risk of death or transplantation, as was lower left ventricular fractional shortening Z score during follow-up. At 15 years after diagnosis, echocardiographic normalization had occurred in 69% of surviving study subjects. Normalization was related to higher baseline left ventricular fractional shortening Z score, higher left ventricular fractional shortening Z score during follow-up, and greater improvement in left ventricular fractional shortening Z score. Children with lymphocytic myocarditis had better survival and a higher rate of echocardiographic normalization. At the latest follow-up, 100 of 104 of survivors (96%) were free of cardiac symptoms, and 83 (80%) were no longer receiving pharmacotherapy. Conclusions— Death or transplantation occurred in 26% of patients with childhood dilated cardiomyopathy within 1 year of diagnosis and ~1% per year thereafter. Risk factors for death or transplantation include age at diagnosis, familial cardiomyopathy, and severity of left ventricular dysfunction. The majority of surviving subjects are well and free of cardiac medication. # Clinical Perspective {#article-title-45}