Showing papers by "Steven E. Lipshultz published in 2007"

Epidemiology and Cause-Specific Outcome of Hypertrophic Cardiomyopathy in Children Findings From the Pediatric Cardiomyopathy Registry

Abstract: Background— Current information on the epidemiology and outcomes of hypertrophic cardiomyopathy (HCM) in children is limited by disease diversity and small case series. Methods and Results— The Pediatric Cardiomyopathy Registry has collected prospective and retrospective data on children diagnosed with HCM since 1990. We identified the various causes of HCM in childhood and determined the relationship between outcomes, cause, and age at presentation. Of 855 patients <18 years of age with HCM, 8.7% (n=74) had inborn errors of metabolism, 9.0% (n=77) had malformation syndromes, 7.5% (n=64) had neuromuscular disorders, and 74.2% (n=634) had idiopathic HCM. Children with HCM associated with inborn errors of metabolism and malformation syndromes have significantly worse survival than the other 2 groups. Patients with idiopathic HCM diagnosed before 1 year of age (n=227) had worse survival from the time of diagnosis than those diagnosed after 1 year of age (n=407). Patients with idiopathic HCM who survived to a...

Anthracycline associated cardiotoxicity in survivors of childhood cancer

Abstract: The development of effective antineoplastic therapies for childhood cancer is a great success in modern medicine. Five year survival rates of children diagnosed with cancer in the USA and Western Europe in excess of 70% make long term survivors of childhood cancer a steadily increasing population. Although there is much to celebrate, new challenges lie ahead in treating the systemic sequelae of chemotherapy.1 Results from the Childhood Cancer Survivor Study (CCSS) showed that 30 years after treatment, the cumulative incidence of chronic health conditions in long term survivors reaches 73%, with a cumulative incidence of 42% for severe, disabling, or life threatening conditions or death.2 Severe conditions, that are significantly more common in childhood cancer survivors than in their siblings, include: major joint replacement (relative risk (RR) 54.0), congestive heart failure (RR 15.1), second malignant neoplasm (RR 14.8), severe cognitive dysfunction (RR 10.5), coronary artery disease (RR 10.4), cerebrovascular accident (RR 9.3), and renal failure (RR 8.9).2 Previous CCSS results found that patients who had survived at least 5 years after diagnosis had 10.8-fold increased rates of all cause mortality.3 The standardised mortality ratio for cardiac causes was 8.2 times higher than expected and the cumulative probability of cardiac death increased 15–25 years after cancer diagnosis. A similar study in a large Nordic cohort documented a standardised mortality ratio of 5.8 for cardiac death and elevated rates of sudden, presumed arrhythmic, deaths.4 Chief among adverse late effects is the cardiovascular toxicity of anthracyclines.5–11 Unfortunately, despite well documented dose related toxicity, the superior disease-free survival rates of regimens including anthracyclines leave limited viable treatment alternatives and the majority of long term paediatric cancer survivors in the Pediatric Oncology Group received an anthracycline during treatment.12 ### Mechanism of cardiotoxicity Several cytotoxic biochemical changes follow anthracycline exposure in …

Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management

Abstract: Although effective anti-neoplastic agents, anthracyclines are limited by their well recognized and pervasive cardiotoxic effects. The incidence of late progressive cardiovascular disease in long-term survivors of cancer is established and may contribute to heart failure and death. To maximize the benefits of these drugs, a high-risk population has been identified and new strategies have been investigated to minimize toxic effects, including limiting the cumulative dose, controlling the rate of administration and using liposomal preparations and novel anthracycline analogues. Dexrazoxane also shows promise as a cardioprotectant during treatment. This paper reviews these strategies, as well as medications used to manage anthracycline-induced cardiotoxicity, and functional and biochemical means of monitoring cardiotoxicity, including echocardiography, radionuclide scans and biomarker analysis. The treatment of adult cancer survivors who have had anthracycline-related cardiotoxicity has not been systematically studied. Empirically, anthracycline-associated cardiac dysfunction is treated very similarly to other forms of heart failure. These treatments include avoiding additional cardiotoxic regimens, controlling hypertension, lifestyle changes, medications and heart transplantation.

Long-term effects of treatments for childhood cancers.

Abstract: Purpose of reviewThe late effects of current treatments for childhood cancer increase the risk of morbidity and mortality and diminish the quality of life in long-term survivors. We selectively review the negative late cardiac, endocrine, and neurological effects of childhood cancer and its treatmen

Anthracycline cardiotoxicity in long-term survivors of childhood cancer

Abstract: Anthracycline chemotherapy is a widely-used and effective treatment for a wide spectrum of childhood cancers. Its use is limited by associated progressive and clinically significant cardiotoxic effects. Onset can be acute, early, or late. While acute onset is rare, long-term survivors have significantly elevated rates of cardiac morbidity and mortality. Major complications include cardiomyopathy, coronary artery disease, and atherosclerosis. Means of prevention and treatment continue to be explored including limiting cumulative anthracycline dose, controlling the rate of administration, and using liposomal preparations and novel anthracycline analogues. Dexrazoxane prior to anthracycline chemotherapy has been shown to significantly lower rates of elevated serum cardiac troponin levels, a marker of myocyte injury, indicating a cardioprotective effect. Pilot studies indicate that exercise interventions may also be beneficial in long-term survivors with cardiac damage. Support and study of this population to decrease the morbidity and morality associated with anthracycline-induced cardiotoxicity is indicated in a time sensitive fashion.

Longitudinal Studies With Outcome-Dependent Follow-up: Models and Bayesian Regression.

Abstract: We propose Bayesian parametric and semiparametric partially linear regression methods to analyze the outcome-dependent follow-up data when the random time of a follow-up measurement of an individual depends on the history of both observed longitudinal outcomes and previous measurement times. We begin with the investigation of the simplifying assumptions of Lipsitz, Fitzmaurice, Ibrahim, Gelber, and Lipshultz, and present a new model for analyzing such data by allowing subject-specific correlations for the longitudinal response and by introducing a subject-specific latent variable to accommodate the association between the longitudinal measurements and the follow-up times. An extensive simulation study shows that our Bayesian partially linear regression method facilitates accurate estimation of the true regression line and the regression parameters. We illustrate our new methodology using data from a longitudinal observational study.

Dexrazoxane-associated risk for secondary malignancies in pediatric Hodgkin's disease: a claim without compelling evidence.

Abstract: TO THEEDITOR: The title of a recent article by Tebbi et al 1 claims that dexrazoxane poses a risk, and that it is responsible for a higher incidence of secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and other second malignant neoplasms (SMNs) in children with Hodgkin’s disease (HD) treated with dexrazoxane plus doxorubicin, bleomycin, vincristine, and etoposide (ABVE) or dose-intensified ABVE with prednisone and cyclophosphamide (ABVE-PC) as well as radiotherapy (POG 9426 [low-stage HD] and 9425 [advanced-stage HD]). This claim is based on 10 SMNs (including eight AML/MDS) in 478 patients. Differences in the incidence of SMNs between children randomly assigned to receive dexrazoxane versus no dexrazoxane concomitantly with chemotherapy to evaluate its efficacy as a cardiopulmonary protectant show no statistical significance by simple Fisher’s exact tests (of 239 patients, eight [3.35%] v two [0.84%] with SMNs, respectively, and P .11; six [2.51%] v two [0.84%] with AML/ MDS, respectively, and P .24), nor by the more conventional and appropriate time-to-event analysis used by the authors (P .06 for SMNs;P .16 for AML/MDS). Only after adjusting for race, age, and sex in a different analysis using a Poisson regression model were the authors able to achieve aP value below .05 for any type of SMN (P .02 for SMNs; P .10 for AML/MDS), even though the authors demonstrated no imbalance between arms for race, age, or sex. We would regard this as scant statistical evidence, particularly in a trial that, as the authors observe, was not “designed for statistical comparison of leukemia and SMN risk.” 1 Dexrazoxane is a US Food and Drug Administration–approved, established protectant against doxorubicin-induced cardiotoxicity in patients with breast cancer 2 and is also cardioprotective in acute lymphoblastic leukemia of childhood, 3 as well as with other malignancies. 4 No evidence shows that this protection has impaired the effectiveness (survival) of doxorubicin-treated patients or that it has caused any new or clinically relevant sequelae (infection, hemorrhage, deaths, or necessity for change of dosage). Some 16 clinical trials in seven different countries over the past 10 years involving more than 500 patients have not reported a single case of AML as a result of combining dexrazoxane with doxorubicin plus fluorouracil and cyclophosphamide (the FAC regime). 4

Heart failure in childhood cancer survivors.

Abstract: BACKGROUND Survival rates of children with cancer have improved, in part because of the introduction of anthracyclines. This has led to an increase in the number of adult survivors of childhood cancer, but, unfortunately, anthracycline therapy is cardiotoxic, so these individuals have a risk of clinically significant cardio toxicity during or after therapy. Late clinical heart failure and asymptomatic cardiac dysfunction have been reported. Previous studies of anthra cyclineinduced clinical heart failure (A-CHF) have been small, subgroup-based and performed over a short follow-up period; further study is, therefore, required.

Late effects of therapy for Hodgkin’s lymphoma

Abstract: Hodgkin’s lymphoma exemplifies a malignancy in which the benefits and risks of therapy are strikingly obvious: although 70% to 95% of patients survive (depending on disease stage), the late adverse health effects of therapy compromise quality of life and can be fatal. We review the broad range of these potential effects. Although secondary malignancies and cardiovascular disease are the most life-threatening sequelae, pulmonary, endocrine, and reproductive effects can also substantially compromise quality of life. Specific sequelae are not distributed evenly among survivors but depend on characteristics of the patient and treatment. Recent risk-adapted treatment protocols have eliminated or reduced the use of therapies most associated with adverse effects, such as alkylating agents, anthracyclines, and radiotherapy. Early studies suggest that these strategies reduce the frequency and severity of adverse effects, but additional follow-up of patients is necessary to confirm improved outcomes. Recognition of adverse effects has also led to recommendations for screening.

The cardiovascular manifestations of HIV infections

Abstract: Cardiovascular illness is common in patients with human immunodeficiency virus (HIV) infection, particularly late in the disease course. As better therapy improves longevity for patients with HIV infection, symptomatic heart failure and related cardiovascular morbidity and mortality are becoming important global health concerns. The incidence of symptomatic heart failure among HIV-infected people followed for 2 to 5 years is 8% to 10%, suggesting that there may be about 3 million prevalent cases of symptomatic HIV-related heart failure. There are many different manifestations of cardiac disease in HIV-infected individuals, including left ventricular systolic dysfunction or cardiomyopathy, pericardial effusion, infective endocarditis cardiovascular malignancy, vasculitis, atherosclerosis, and autonomic dysfunction. Cardiac disease may result from HIV itself, other infectious etiologies, or may be accelerated by the effects of the antiretroviral agents used to treat HIV infection. In this paper, we will examine the various cardiovascular manifestations of HIV disease and its treatment, review the prevalence, pathogenesis, and treatment options, and discuss preventive measures and monitoring to identify preclinical cardiac disease early on in its course.

Agreement Between Two Ratings with Different Ordinal Scales

Abstract: Agreement studies, where several observers may be rating the same subject for some characteristic measured on an ordinal scale, provide important information. The weighted Kappa coefficient is a popular measure of agreement for ordinal ratings. However, in some studies, the raters use scales with different numbers of categories. For example, a patient quality of life questionnaire may ask ‘How do you feel today?’ with possible answers ranging from 1 (worst) to 7 (best). At the same visit, the doctor reports his impression of the patient’s health status as very poor, poor, fair, good, or very good. The weighted Kappa coefficient is not applicable here because the two scales have a different number of categories. In this paper, we discuss Kappa coefficients to measure agreement between such ratings. In particular, with R categories of one rating, and C categories of another, by dichotomizing the two ratings at all possible cutpoints, there are (R−1)(C−1) possible (2×2) tables. For each of these (2×2) tables, we estimate the Kappa coefficient for dichotomous ratings. The largest estimated Kappa coefficients suggest the cutpoints for the two ratings where agreement is the highest and where categories can be combined for further analysis.

Abstract 2556: A Comparative Analysis of Outcomes for Pediatric Patients with Biopsy-Proven Myocarditis, Clinically-Diagnosed Myocarditis and Idiopathic Dilated Cardiomyopathy.

Abstract: 2556: A Comparative Analysis of Outcomes for Pediatric Patients with BiopsyProven Myocarditis, Clinically-Diagnosed Myocarditis and Idiopathic Dilated Cardiomyopathy Susan Foerster1; Charles Canter1; Amy Carey2; Lynn A Sleeper2; John L Jefferies3; Paul Kantor4; Jacqueline Lamour5; Renee Margossian6; Jane Messere6; Elfriede Pahl7; Paolo Rusconi8; Robert Shaddy9; Steven Webber10; Jeffrey Towbin11; Steven Lipshultz12 1 Washington Univ at St Louis, Saint Louis, MO 2 New England Rsch Institutes, Inc, Watertown, MA 3 Baylor College of Medicine, Houston, TX 4 Hosp for Sick Children, Toronto, Canada 5 Columbia Univ, New York, NY 6 Children’s Hosp Boston, Boston, MA 7 Northwestern Univ, Chicago, IL 8 Univ of Miami, Miami, FL 9 Univ of Utah, Salt Lake City, UT 10 Children’s Hosp of Pittsburgh, Pittsburgh, PA 11 Baylor College of Medicine, Houston, TX 12 Univ of Miami, Miami, FL Background: Data on outcomes in children with myocarditis is sparse and challenging to interpret given no ``gold standard" for diagnosis The NHLBI Pediatric Cardiomyopathy Registry provides a large, multi-center cohort with clinical and echocardiographic follow-up of up to 16 years Methods/Results: We compared cases of biopsy-confirmed myocarditis (BCM, N=119) and clinicallySearch: Advanced Search Go Circulation Home Subscriptions Archives Feedback Authors Help AHA Journals Home « Previous Article | Table of

Abstract 2343: Outcomes in Children with Noonan Syndrome and Cardiomyopathy

Abstract: OBJECTIVE: The presence of cardiomyopathy in some children with Noonan syndrome (NS) has been well described. The objective of this analysis was to determine the survival experience of these childr...

Erratum: Heart failure in childhood cancer survivors (Nature Clinical Practice Oncology (2007) vol. 4 (334-335) doi:10.1038/ncponc0818)

Abstract: Nature Clinical Practice Oncology (2007) 4: 334–335 [doi:10.1038/ncponc0818] In the June 2007 issue, in the Practice Point by Steven E Lipshultz that was based on the original article by van Dalen EC et al. (2006) Eur J Cancer 42: 3191–3198, there was an error in the objective section of the synopsis.