Cardiotoxicity of cancer chemotherapy: implications for children.

Many children and adolescents with cancer receive chemotherapeutic agents that are cardiotoxic. Thus, while survival rates in this population have improved for some cancers, many survivors may experience acute or chronic cardiovascular complications that can impair their quality of life years after treatment. In addition, cardiac complications of treatment lead to reductions in dose and duration of chemotherapy regimens, potentially compromising clinical efficacy. Anthracyclines are well known for their cardiotoxicity, and alkylating agents, such as cyclophosphamide, ifosfamide, cisplatin, busulfan, and mitomycin, have also been associated with cardiotoxicity. Other agents with cardiac effects include vinca alkaloids, fluorouracil, cytarabine, amsacrine, and asparaginase and the newer agents, paclitaxel, trastuzumab, etoposide, and teniposide. The heart is relatively vulnerable to oxidative injuries from oxygen radicals generated by chemotherapy. The cardiac effects of these drugs include asymptomatic electrocardiographic abnormalities, blood pressure changes, arrhythmias, myocarditis, pericarditis, cardiac tamponade, acute myocardial infarction, cardiac failure, shock, and long-term cardiomyopathy. These effects may occur during or immediately after treatment or may not be apparent until months or years after treatment. Mild myocardiocyte injury from chemotherapy may be of more concern in children than in adults because of the need for subsequent cardiac growth to match somatic growth and because survival is longer in children. Primary prevention is therefore important. Patients should be educated about the cardiotoxic risks of treatment and the need for long-term cardiac monitoring before chemotherapy is begun. Cardiotoxicity may be prevented by screening for risk factors, monitoring for signs and symptoms during chemotherapy, and continuing follow-up that may include electrocardiographic and echocardiographic studies, angiography, and measurements of biochemical markers of myocardial injury. Secondary prevention should aim to minimize progression of left ventricular dysfunction to overt heart failure. Approaches include altering the dose, schedule, or approach to drug delivery; using analogs or new formulations with fewer or milder cardiotoxic effects; using cardioprotectants and agents that reduce oxidative stress during chemotherapy; correcting for metabolic derangements caused by chemotherapy that can potentiate the cardiotoxic effects of the drug; and cardiac monitoring during and after cancer therapy. Avoiding additional cardiotoxic regimens is also important in managing these patients. Treating the adverse cardiac effects of chemotherapy will usually be dependent on symptoms or will depend on the anticipated cardiovascular effects of each regimen. Treatments include diuresis, afterload reduction, beta-adrenoceptor antagonists, and improving myocardial contractility.

Cardiovascular outcomes of pediatric seroreverters perinatally exposed to HAART: design of a longitudinal clinical study.

Seroreverters (uninfected children of HIV-infected mothers) have exhibited left ventricular (LV) dysfunction. Mitochondrial toxicity associated with in utero or postnatal exposure to highly active antiretroviral therapy (HAART) is a possible mechanism. Adult and animal models have demonstrated associations between LV abnormalities, cardiomyopathy, and components of HAART. Yet, outcomes in children are poorly understood. In this study, we explore HAART-associated LV abnormalities in seroreverters exposed to HAART (n = 144) or never exposed (n = 252). Subjects are drawn from the Women and Infants Transmission Study and the Pediatric Pulmonary and Cardiovascular Complications of HIV Study, respectively. Data include (1) echocardiographic studies of LV structure and function and (2) serologic cardiac biomarkers (cardiac troponin, probrain natriuretic peptide, high-sensitivity C reactive protein), both collected during the first month of life, and again at 6, 12, 24, 36, and 48 months postnatally. Planned analyses include several regression models. At this time, we have access to data for all 252 unexposed children, and 53 exposed subjects are enrolled. The cohorts are similar in terms of gender and race and the recruited subjects are representative of all eligible subjects in terms of exposure to HAART. Recruitment will continue into 2006.

Cardiomyopathy Caused by Antineoplastic Therapies.

The goals of care for patients at risk for cardiomyopathy induced by cancer treatment should include prevention, early diagnosis, treatment of subclinical cardiac dysfunction, prevention of disease progression, and prolongation of patient survival. Any strategy aimed to minimize the cardiotoxic effects of cancer treatment should maintain the treatment's antineoplastic efficacy. Successful therapy achieves the highest health-related quality of life that is defined by the balance between maximizing the efficacy of oncologic therapy and minimizing the toxicity of this therapy. Doxorubicin-induced cardiotoxicity can be reduced by limiting the overall cumulative dose. There is no specific treatment for cancer therapy-related cardiomyopathy, and symptomatic patients should receive standard treatments for congestive heart failure such as afterload reduction, beta-blockers, diuresis, and digoxin. Afterload reduction with angiotensin-converting enzyme inhibitors such as enalapril and captopril may be indicated in patients with elevated afterload and asymptomatic left ventricular dysfunction diagnosed by echocardiography. Beta-blockers may improve myocardial systolic dysfunction and may be useful in the treatment of cancer treatment-induced cardiomyopathy. Cardiac transplantation remains a viable option in patients with cancer treatment-induced end-stage heart disease.