Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor.

BACKGROUND: Sunitinib malate is a novel multitargeted receptor tyrosine kinase inhibitor with established efficacy in the treatment of metastatic renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor. This report describes the development of heart failure in cancer patients who received this novel agent. METHODS: A retrospective study was conducted at M. D. Anderson Cancer Center during a 1-year period on patients who received sunitinib and developed heart failure. RESULTS: During 2006, 6 of 224 (2.7%) patients who received sunitinib developed heart failure (HF) that resulted in substantial morbidity and, in some cases, mortality. Symptomatic heart failure occurred soon after initiation of sunitinib (mean onset 22 days after initiation), was associated with decline in cardiac function and elevations in blood pressure, and was not completely reversible in most patients, even after termination of sunitinib therapy. CONCLUSIONS: These observations suggested that sunitinib-associated heart failure may represent a potentially serious toxicity and underscore the need for careful monitoring of cardiac function and aggressive control of hypertension in these patients. Studies to elucidate potential mechanisms of heart failure and left ventricular dysfunction resulting from treatment with sunitinib are necessary to develop strategies for prevention and treatment of this complication.

Adherence to the NASPE guideline for amiodarone monitoring at a medical university.

OBJECTIVE: Amiodarone is an effective antiarrhythmic, but the clinical usefulness of this agent is complicated by its extensive side-effect profile, which necessitates careful patient selection and frequent monitoring. The purpose of this study was to quantify adherence to published recommendations for baseline monitoring when initiating inpatient amiodarone therapy at a university teaching hospital and determine whether appropriate serial monitoring of chronic amiodarone therapy (>or= 6 months) is occurring in the outpatient setting. METHODS: A retrospective review of electronic medical records was conducted for inpatients at the Medical University of South Carolina (MUSC) who received amiodarone between November 1, 2003, and March 31, 2004, and for a subset of outpatients who had received amiodarone therapy for at least 6 months. Their medical records were reviewed for demographic data; reason for, date of initiation of, and duration of amiodarone therapy; and the occurrence of laboratory and diagnostic tests. The amiodarone guideline from the North American Society of Pacing and Electrophysiology (NASPE) was used as the measure of appropriate monitoring for baseline and follow-up chest x-rays (CXRs), liver function tests (LFTs), thyroid function tests (TFTs), and pulmonary function tests (PFTs). RESULTS: Over the 5-month period from November 1, 2003, through March 31, 2004, 277 adult patients received oral amiodarone as inpatients at MUSC. Of these, 45 patients (16%) were initiated on chronic amiodarone therapy during their hospital admission. Baseline assessments of CXRs, LFTs, and TFTs occurred in 82% to 87% of these patients. Baseline assessment of PFTs occurred in 24% of patients, and 55% of these assessments included a diffusion capacity (DLCO). Overall, only 5 (11%) of the 45 patients initiated on amiodarone received all recommended monitoring tests. Twenty patients with available outpatient records in the MUSC system were identified as receiving chronic amiodarone therapy. Baseline assessments of LFTs, TFTs, and CXRs occurred in approximately 75% to 95% of these patients; baseline assessment of PFTs occurred in

Biliary sludge and hyperbilirubinemia associated with ceftriaxone in an adult: case report and review of the literature.

Ceftriaxone is a commonly used third-generation cephalosporin that has antimicrobial activity against many gram-positive and gram-negative organisms. Generally, ceftriaxone is a safe antibiotic; however, symptomatic biliary sludge has been reported in rare instances, most of which have involved children. It is uncommon for ceftriaxone to cause increases in laboratory indexes, such as bilirubin levels. We describe the case of a 53-year-old man who was treated with intravenous ceftriaxone 2 g every 12 hours. After 7 days of therapy, the patient's liver function test results, including total, direct, and indirect bilirubin levels, increased significantly from baseline, and the patient became jaundiced. A right upper quadrant ultrasound examination revealed biliary sludge and cholelithiasis without sonographic evidence of cholecystitis. Ceftriaxone was thought to be the responsible agent, and it was discontinued. The patient's jaundice subsided, and his liver function test results improved, returning to baseline within 14 days. Clinicians need to be aware of the association of ceftriaxone and biliary pseudolithiasis and hyperbilirubinemia, and monitor accordingly.

Efficacy and safety of ibutilide for chemical cardioversion of atrial fibrillation and atrial flutter in cancer patients.

BACKGROUND: Atrial fibrillation and atrial flutter (AF/AFL) are the most common arrhythmias encountered in clinical practice. Rate versus rhythm control remains a difficult decision, especially in the acute setting. Ibutilide is a class III antiarrhythmic indicated for pharmacological cardioversion of recent-onset AF/AFL. At the University of Texas MD Anderson Cancer Center, restoration of sinus rhythm is desirable because many patients have contraindications to anticoagulation. In addition, most are on multiple medications that prolong the QT interval; therefore, the objective of this study was to establish the safety and efficacy of ibutilide. METHODS: This was a retrospective chart review of 81 patients who were identified via the pharmacy database as receiving ibutilide for AF/AFL from January 2002 to May 2006. Outcomes including cardioversion rates and effects on the QT interval were recorded. RESULTS: Ibutilide use was associated with successful cardioversion in 75% of patients. Out of 81 patients, 68 patients (84%) were on at least 1 medication that prolonged the QT interval at the time of ibutilide administration. However, no significant changes in the corrected QT interval pre and post ibutilide cardioversion were noted in any group of patients. CONCLUSIONS: Overall, ibutilide is safe and effective in cancer patients when used for acute cardioversion of AF/AFL. Despite the use of multiple medications that can potentially prolong the QT interval, no patient experienced serious life-threatening rhythm disturbances or significant QT prolongation during ibutilide administration.

Pregnancy in a patient with cancer and heart failure: challenges and complexities.

A 24-year-old African American female (L.R.) with a history of smoking and gestational diabetes was diagnosed with Hodgkin lymphoma. She received multiple chemotherapies, including six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), followed by radiation therapy to left inguinal areas for a total of 30.6 Gy in 17 fractions; she obtained complete remission. Two years later, L.R. had disease relapse in the mediastinum and received two cycles of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) followed by etoposide and ifosfamide. She then received BEAM (carmustine, etoposide, cytarabine, and melphalan) as a conditioning regimen and underwent autologous bone marrow transplant. Her post-transplant course was complicated by cytomegalovirus antigenemia, aspergillus pneumonia, and congestive heart failure with left ventricular ejection fraction (LVEF) of 20%-25%. She was treated with an ACE inhibitor (lisinopril) and a beta-blocker (carvedilol) with improvement of her LVEF to 30%-35%. A follow-up chest x-ray showed an increase in the size of the anterior mediastinal adenopathy suspicious for relapse of lymphoma, and at the same time she was also found to be 5 weeks pregnant. Given her cardiomyopathy, significant obesity, poorly controlled diabetes, and cancer recurrence, L.R. was advised by her gynecologist that the pregnancy was very high risk and might not be viable. The oncologists advised her to terminate the pregnancy within the first trimester, as she needed salvage radiotherapy treatment to the mediastinum and chemotherapy treatments that might endanger the fetus. However, the patient decided to continue with the pregnancy. A multidisciplinary team-which included a cardiologist, oncologist, high-risk obstetrician, pharmacist, and nurse practitioner-was then involved to provide care during the pregnancy. A social worker was also solicited to help with home and financial issues because L.R. was a single mother with a 2-year-old son. L.R. was treated with carvedilol and furosemide, with monthly cardiology clinical follow-up during the first and second trimesters, then every 2 weeks starting with the 28th week, and weekly thereafter until delivery. Between visits, she notified the clinic for symptoms of heart failure exacerbation and was seen as necessary. The possible in utero effects of both medications were discussed with the patient. L.R. had a normal uncomplicated pregnancy and delivered a 6-pound, 10-ounce healthy boy at 39 weeks via vaginal delivery and was discharged home 2 days later. A week after delivery, L.R. presented to the cardiology clinic in good spirits and was excited to show pictures of her newborn baby. She had no cardiac complaints and the repeat echocardiogram showed an unchanged LVEF of 30%-35%.

Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management.

Cancer treatment today employs a combination of chemotherapy, radiotherapy, and surgery to prolong life and provide cure. However, many of these treatments can cause cardiovascular complications such as heart failure, myocardial ischemia/infarction, hypertension, thromboembolism, and arrhythmias. In this article we review the incidence of cardiotoxicity caused by commonly used chemotherapeutic agents as well as discuss the pathogenesis, diagnosis, management, and prevention of these cardiovascular side effects. Cardiotoxicity related to anticancer treatment is important to recognize as it may have a significant impact on the overall prognosis and survival of cancer patients, and it is likely to remain a significant challenge for both cardiologists and oncologists in the future due to an increasing aging population of patients with cancer and the introduction of many new cancer therapies.