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

The cardiotoxicity of anticancer agents can lead to significant complications that can affect patients being treated for various malignancies. The severity of such toxicity depends on many factors such as the molecular site of action, the immediate and cumulative dose, the method of administration, the presence of any underlying cardiac condition, and the demographics of the patient. Moreover, toxicity can be affected by current or previous treatment with other antineoplastic agents. Cardiotoxic effects can occur immediately during administration of the drug, or they may not manifest themselves until months or years after the patient has been treated. In this article we review commonly used chemotherapy agents, including several recently approved medications, for their propensity to cause cardiotoxicity. Further research will be required to more accurately predict which patients are at risk for developing cardiotoxicity. In addition, management plans, as well as strategies to reduce cardiotoxicity, need to be developed.

Combined intense lifestyle and pharmacologic lipid treatment further reduce coronary events and myocardial perfusion abnormalities compared with usual-care cholesterol-lowering drugs in coronary artery disease.

OBJECTIVES: The purpose of this study was to determine if combined intense lifestyle and pharmacologic lipid treatment reduce myocardial perfusion abnormalities and coronary events in comparison to usual-care cholesterol-lowering drugs and whether perfusion changes predict outcomes. BACKGROUND: Lifestyle and lipid drugs separately benefit patients with coronary artery disease (CAD). METHODS: A total of 409 patients with CAD, who underwent myocardial perfusion imaging by dipyridamole positron emission tomography at baseline and after 2.6 years, had quantitative size/severity of perfusion defects measured objectively by automated software with follow-up for five additional years for coronary artery bypass graft, percutaneous coronary intervention, myocardial infarction, or cardiac death. Patients were categorized blindly according to prospective, predefined criteria as "poor" treatment without diet or lipid drugs, or smoking; "moderate" treatment on American Heart Association diet and lipid-lowering drugs or on strict low-fat diet (<10% of calories) without lipid drugs; and "maximal" treatment with diet <10% of calories as fat, regular exercise, and lipid active drugs dosed to target goals of low-density lipoproteins <2.3 mmol/l (90 mg/dl), high-density lipoproteins >1.2 mmol/l (45 mg/dl), and triglycerides <1.1 mmol/l (100 mg/dl). RESULTS: Over five years, coronary events occurred in 6.6%, 20.3%, and 30.6% of patients on maximal, moderate, and poor treatment, respectively (p = 0.001). Size/severity of perfusion abnormalities significantly decreased for patients receiving maximal treatment and increased for patients undergoing moderate and poor treatment (p = 0.003 and 0.0001, respectively). Combined intense lifestyle change plus lipid active drugs and severity/change of perfusion abnormalities independently predicted cardiac events. CONCLUSIONS: Intense lifestyle and pharmacologic lipid treatment reduce size/severity of myocardial perfusion abnormalities and cardiac events compared with usual-care cholesterol-lowering drugs. Perfusion changes parallel treatment intensity and predict outcomes.

Cardiomyopathy in association with selenium deficiency: a case report.

A 46-year-old man developed "dilated cardiomyopathy" probably caused by selenium deficiency while on total parenteral nutrition (TPN). This development emphasizes the role of considering selenium deficiency as a reversible cause of unexplained cardiomyopathy in impaired nutritional state.

Cancer patients with markedly elevated B-type natriuretic peptide may not have volume overload.

OBJECTIVES: Elevated B-type natriuretic peptide (BNP) levels are established as a marker for volume overload and left ventricular (LV) dysfunction in patients with predominately cardiac diseases. Little is known about markedly elevated BNP values in patients with multiple comorbidities. METHODS: A total of 99 patients, admitted to M. D. Anderson Cancer Center, were identified as having a BNP value >1000 pg/mL during the year 2003. Clinical characteristics, including the presence of volume overload and sepsis, as well as echocardiographic parameters were measured. Principal outcome was defined as 30-day mortality. RESULTS: The median BNP (pg/mL) of the group was 2270 (range, 1010-5000), and there was no association between elevation of the BNP level and the presence of volume overload or LV dysfunction (P = not significant). The large majority of patients (n = 71, 72%) had no volume overload and normal or nearly normal LV function (n = 60, 61%). A majority were also identified as having sepsis (n = 52, 53%). There was no echocardiographic parameter that consistently correlated with BNP levels or volume overload. There was a highly significant association with sepsis and mortality in patients with markedly elevated BNP values, and this conferred a 2.71-fold increased risk of mortality. CONCLUSIONS: In patients admitted with multiple comorbidities and markedly elevated BNP values, there is no significant association with clinical evidence of volume overload or LV dysfunction. An elevated BNP level in patients with sepsis was significantly associated with mortality.

Impact of aspirin therapy in cancer patients with thrombocytopenia and acute coronary syndromes.

BACKGROUND: Patients with cancer who have thrombocytopenia may experience acute coronary syndromes (ACS), and the use of aspirin (ASA) poses an increased risk of bleeding. The purpose of this study was to test the hypothesis that the benefit of ASA therapy in the treatment of ACS would extend to cancer patients with thrombocytopenia and outweigh the risks of severe bleeding. METHODS: The records of all cancer patients diagnosed with an ACS in 2001 and referred for cardiology consultation were reviewed. Patients were divided into 2 groups on the basis of platelet count, >100 cells k/microL and < or = 100 cells k/microL. Data were collected on the use of ASA therapy, bleeding complications, and survival rates. The authors assessed group differences by using the Wilcoxon rank sum test or 2-tailed Fisher exact test, as appropriate. Univariate and multivariate logistic regression models were used to assess factors potentially associated with 7-day survival. RESULTS: In cancer patients with ACS and thrombocytopenia, those who did not receive ASA had a 7-day survival rate of 6% compared with 90% in those who did receive ASA (P < .0001). There were no severe bleeding complications. Patients with a platelet count (>100 cells k/microL) who received ASA had a 7-day survival rate of 88% compared with 45% in those who did not receive ASA (P = .0096). CONCLUSIONS: Therapy with ASA was associated with a significantly improved 7-day survival after ACS in cancer patients, with or without thrombocytopenia, and not associated with more severe bleeding.

The impact of hypogonadism and autonomic dysfunction on fatigue, emotional function, and sexual desire in male patients with advanced cancer: a pilot study.

BACKGROUND: The objective of this study was to determine whether hypogonadism and autonomic dysfunction contribute substantially to cancer-related fatigue, decreased sexual desire, and depression in male patients with advanced, incurable cancer. METHODS: Forty-eight patients who had received no major antineoplastic intervention for at least 2 weeks were tested for autonomic dysfunction by using Ewing tests. Total and free testosterone levels were measured. Multivariate analyses were performed to test the relation of these factors with the Functional Assessment of Cancer Therapy (FACT) (the Functional Assessment of Anorexia/Cachexia Therapy [FAACT] scale and the Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] subscale), the Hospital Anxiety and Depression Scale (HADS), the Edmonton Symptom Assessment Scale, the Sexual Desire Inventory, and sexual function (Cancer Rehabilitation Evaluation System subscale). Common causes for fatigue (anemia, depression, malnutrition, symptom distress, and medications) also were considered. RESULTS: Thirty-eight of 47 patients (81%) had autonomic dysfunction, although it was not associated significantly with the other variables examined. Twenty-nine of 45 patients (64%) had a low level of free testosterone (hypogonadism), which was correlated with the HADS Anxiety score (P = .002), the FACT Emotional Well-Being score (P = .02), and the HADS Depression score (P = .04). Hypogonadal men also had lower scores on the FACT Functional Well-Being scale (P = .01) and the FACIT-F subscale (P = .05). Men who reported symptoms related to weight loss (FAACT scale) had significantly lower levels of free testosterone (r = 0.34; P = .02) but did not differ from the other group in actual weight loss (P = .22). The total testosterone level was not appropriate for screening of hypogonadism unless the patients had values <100 ng/ mL. Logistic regression analysis failed to reveal a distinct multivariate model of autonomic dysfunction or hypogonadism that predicted clinical outcomes. CONCLUSIONS: Hypogonadism is a frequent condition in patients with advanced, incurable cancer and is associated with negative mood, fatigue, and symptoms related to anorexia/cachexia.

Abciximab administration and clinical outcomes after percutaneous intervention for in-stent restenosis.

Abciximab therapy improves clinical outcomes after percutaneous interventions for de novo coronary artery disease. We sought to determine whether clinical outcomes after percutaneous intervention for in-stent restenosis are affected by abciximab administration. Between January 1996 and July 1999, 322 consecutive patients underwent percutaneous intervention for in-stent restenosis; 157 patients received abciximab and 165 patients were treated without abciximab based on operator discretion. Baseline clinical and angiographic variables and type of percutaneous intervention were recorded. Follow-up information was obtained and clinical endpoints were recorded. A multivariate analysis was performed to determine the independent variables associated with adverse clinical outcomes. Baseline clinical and angiographic variables were similar in both groups. Patients who received abciximab were more likely to be treated with rotational atherectomy and less likely to have only balloon angioplasty or repeat stenting. Mean follow-up duration was 19 +/- 12 months. There were no significant differences in the incidence of angina/myocardial infarction (29% vs. 30%; P = 0.9), target vessel revascularization (18% vs. 21%; P = 0.5), death (8% vs. 7%; P = 0.4), or major adverse cardiovascular events (38% vs. 39%; P = 0.9) in both groups. Abciximab administration was not an independent variable associated with adverse outcomes. In this observational study, clinical outcomes after percutaneous intervention for in-stent restenosis did not seem to be affected by abciximab administration. Randomized trials are needed to identify the role of platelet glycoprotein IIb/IIIa inhibitors in the management of in-stent restenosis.