Myocardial perfusion imaging and cardiovascular outcomes in a cancer population.

Myocardial perfusion imaging can predict outcomes in cardiac patients. However, limited data exist regarding its prediction of cardiovascular outcomes in cancer patients. We sought to determine whether myocardial perfusion imaging predicts long-term cardiovascular outcomes in cancer patients.We performed a retrospective review of 787 consecutive patients at our institution who underwent myocardial perfusion imaging from January 2001 through March 2003. The Cox proportional hazard model was applied, and total cardiac events, cardiac death, and all-cause death were determined for 3 years. We considered P <0.05 to be statistically significant.Patients with abnormal myocardial perfusion imaging results were more likely to be male and older, with heart disease, more vascular risk factors, and lower left ventricular ejection fraction (0.52 +/- 0.14 vs 0.63 +/- 0.11; P <0.001) than patients with normal myocardial perfusion imaging results. Multivariate predictors of total cardiac events included age (P = 0.023), hyperlipidemia (P = 0.0021), pharmacologic myocardial perfusion imaging (P <0.01), left ventricular ejection fraction (P <0.001), and abnormal myocardial perfusion imaging (P = 0.012). Multivariate predictors of cardiac death included age (P = 0.026) and left ventricular ejection fraction (P = 0.0001). Multivariate predictors of all-cause death were age (P = 0.0001), atrial fibrillation (P = 0.0012), and smoking (P <0.001). Overall survival was improved when patients took aspirin (P = 0.0002) and upon each unit increase in left ventricular ejection fraction (P <0.001).Myocardial perfusion imaging in cancer patients can predict 3-year cardiac outcomes. Increasing age, atrial fibrillation, and smoking were associated with worse outcomes, whereas higher left ventricular ejection fraction and the taking of aspirin were protective.

The role of nesiritide in heart failure.

BACKGROUND: Heart failure afflicts > 5 million patients in the US, with about 550,000 new diagnoses a year. Side effects and increased mortality limit heart failure treatment. Nesiritide is the newest addition to therapeutic options for treatment of acute decompensated heart failure (ADHF). It has been used as single in-patient infusions, multiple out-patient infusions, and perioperatively to improve hemodynamics and promote diuresis. Initially well-received, meta-analyses suggesting increased mortality and renal dysfunction after nesiritide use were published 4 - 5 years after its introduction in the US. These reports prompted new recommendations on nesiritide use by an expert panel. OBJECTIVE: Critical review of the studies leading to approval of nesiritide and the current recommendations for its use. METHODS: Medline search and Pubmed search using nesiritide or natrecor for text word searches. CONCLUSION: Nesiritide represents the first drug in a new class designed for treatment of ADHF. In patients with ADHF, nesiritide improves hemodynamic parameters and reduces dyspnea. Questions remain about possible increased mortality and side effects. A continuing study expected to enroll 7000 patients by 2010 has been designed to clarify whether nesiritide reduces mortality, hospital length-of-stay and renal parameters in patients with ADHF.

Phase II trial of the combination of denileukin diftitox and rituximab for relapsed/refractory B-cell non-Hodgkin lymphoma.

Denileukin diftitox plus rituximab was evaluated in relapsed/refractory B-cell non-Hodgkin lymphoma patients. Of the 38 evaluable patients, 30 (80%) were rituximab-refractory. The overall response rate (ORR) was 32%, with six complete responses (CR) and six partial responses (PR). The median time to progression for responders was 8 months (range: 2-36+); two patients with rituximab-refractory follicular lymphoma were in CR at 25 and 36+ months. The ORR was 55% (4 CRs, 2 PRs) in 11/14 patients with rituximab-refractory follicular lymphoma, and 100% in the three patients with rituximab-sensitive tumour. Most toxicities were low grade and transient, and myelotoxicity was uncommon.

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.

Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma.

This phase II study evaluated the safety and efficacy of denileukin diftitox, an interleukin-2-diphtheria toxin fusion protein, in relapsed/refractory T-cell non-Hodgkin lymphoma (T-NHL), excluding cutaneous T-cell lymphoma. Eligible patients received denileukin diftitox 18 microg/kg/d x 5 d every 3 weeks for up to eight cycles. Tumour staging was performed every two cycles and the primary endpoint was the objective response rate [complete response (CR) + partial response (PR)]. For 27 patients enrolled, median age: 55 years (range 26-80 years), 70.4% male, and mean prior therapies: 2.5 (range 1-6). Objective responses (six CRs, seven PRs) were achieved in 13 patients (48.1%), stable disease in eight (29.6%) and six (22.2%) had progressive disease. An objective response was achieved in eight of 13 patients (61.5%) with CD25(+) tumours (four CR/four PR) and five of 11 patients (45.5%) with CD25(-) tumours (two CR/three PR). Median progression-free survival was 6 months (range, 1-38+ months). Most adverse reactions were grade 1/2 and transient. No grade 4-5 toxicities were reported. Denileukin diftitox had significant activity and was well tolerated in relapsed/refractory T-NHL, with responses observed in both CD25(+) and CD25(-) tumours. Further studies of denileukin diftitox in combination with other agents are warranted in previously untreated and relapsed/refractory T-NHL.

Toxic epidermal necrolysis associated with denileukin diftitox (DAB389IL-2) administration in a patient with follicular large cell lymphoma.

Denileukin diftitox (DAB(389)IL-2 or Ontak) is a synthetic fusion protein with demonstrated efficacy in a number of lymphoproliferative disorders, including non-Hodgkin's lymphoma. We report the case of a 45-year-old man with progressive follicular large cell lymphoma following an autologous stem cell transplant treated with denileukin diftitox who developed a fatal skin rash associated with extensive erythema, edema and large bullae involving his entire body. The clinical features and pathology were compatible with toxic epidermal necrolysis. This is the first reported case of toxic epidermal necrolysis in the literature associated with denileukin diftitox.

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.

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.

Transesophageal echocardiography improves risk assessment of thrombolysis of prosthetic valve thrombosis: results of the international PRO-TEE registry.

OBJECTIVES: The goal of this study was to evaluate whether quantitation of thrombus burden with transesophageal echocardiography (TEE) can help risk-stratify patients undergoing thrombolysis of prosthetic valve thrombosis (PVT). BACKGROUND: Thrombolytic therapy of PVT has an unpredictable risk of embolization and complications. METHODS: An international registry of patients with suspected PVT undergoing two-dimensional/Doppler and TEE before thrombolysis was established. All TEE studies were reviewed and quantitated by a single observer blinded to all data. RESULTS: From 1985 to 2001, 107 patients (71 females; age 24 to 86 years) from 14 centers (6 in the U.S.) were identified. The majority of cases involved the mitral valve (79 mitral, 13 aortic, and 15 tricuspid). Hemodynamic success rate was achieved in 85% and was similar across valves. Overall complications were observed in 17.8%, and death in 5.6%. Predictors of complications were: New York Heart Association (NYHA) functional class, presence of shock, sinus tachycardia, hypotension, previous history of stroke, thrombus extension beyond the valve ring, and thrombus area. Multivariate analysis demonstrated that two variables were independent predictors of complications: thrombus area by TEE (odds ratio [OR] 2.41 per 1 cm2 increment, 95% confidence interval [CI] 1.12 to 5.19) and prior history of stroke (OR 4.55, 95% CI 1.35 to 15.38). A thrombus area <0.8 cm2 identified patients at lower risk for complications from thrombolysis, irrespective of NYHA functional class. CONCLUSIONS: In PVT, the thrombus size imaged with TEE is a significant independent predictor of outcome. Transesophageal echocardiography can identify low-risk groups for thrombolysis irrespective of symptom severity and is therefore recommended in the management of prosthetic valve thrombosis.

Transesophageal echocardiography improves risk assessment of thrombolysis prosthetic valve thrombosis: results of the international PRO-TEE registry

The goal of this study was to evaluate whether antitation of thrombus burden with transesophageal echocardiography (TEE) can help risk-stratify patients undergoing thrombolysis of prosthetic valve thrombosis (PVT). BACKGROUND: Thrombolytic therapy of PVT has an unpredictable risk of embolization and complications. METHODS: An international registry of patients with suspected PVT undergoing two-dimensional/Doppler and TEE before thrombolysis was established. All TEE studies were reviewed and quantitated by a single observer blinded to all data. RESULTS: From 1985 to 2001, 107 patients (71 females; age 24 to 86 years) from 14 centers (6 in the U.S.) were identified. The majority of cases involved the mitral valve (79 mitral, 13 aortic, and 15 tricuspid). Hemodynamic success rate was achieved in 85% and was similar across valves. Overall complications were observed in 17.8%, and death in 5.6%.Predictors of complications were: New York Heart Association (NYHA) functional class, presence of shock, sinus tachycardia, hypotension,previous history of stroke, thrombus extension beyond the valve ring, and thrombus area. Multivariate analysis demonstrated that two variables were independent predictors of complications: thrombus area by TEE (odds ratio [OR] 2.41 per 1 cm2 increment, 95% confidence interval [CI] 1.12 to 5.19)and prior history of stroke (OR 4.55, 95% CI 1.35 to 15.38). A thrombus area <0.8 cm2 identified patients at lower risk for complications from thrombolysis, irrespective of NYHA functional class...

Pentostatin in T-non-Hodgkin's lymphomas: efficacy and effect on CD26+ T lymphocytes.

Pentostatin is an adenosine deaminase (ADA) inhibitor with antineoplastic activity. CD26 is a surface glycoprotein with a key role in T cell function as the ADA binding protein. We conducted a phase II study to evaluate pentostatin efficacy in relapsed T-non-Hodgkin's lymphoma (T-NHL) and to correlate response with tumor CD26 expression. We also examined the lymphopenic effect of pentostatin on CD26+ T lymphocytes. Eighteen patients were registered for the study. Pentostatin was administered as intravenous bolus daily over 3 days at an initial dose of 5 mg/m(2)/day, repeated every 4 weeks. CD26 surface expression on tumor cells and T lymphocytes was determined by flow cytometry. Out of 14 patients evaluable for response, there was 1 (7%) complete response (CR) and 6 (43%) partial responses (PR). Median progression-free survival for responders was 6 months (range: 2-15 months); median number of courses was 4 (range: 1-6). Responders included 1 of 2 CD26+ and 5 of 9 CD26- cases. Pentostatin also specifically depleted CD26+ rather than CD26- T lymphocytes, potentially associated with immunosuppression. We therefore conclude that while pentostatin is a safe and active agent for T-NHL regardless of CD26 expression, it may selectively deplete CD26+ T lymphocytes, with potentially significant clinical implications.

Role of echocardiography in the diagnosis and management of infective endocarditis.

Infective endocarditis is a life-threatening disease with significant morbidity and mortality. Accurate and early diagnosis for initiation of effective treatment is essential in improving patient outcome. Echocardiography is currently the primary modality for the detection of vegetations and cardiac complications that result from endocarditis. Technological advances in echocardiography, particularly the development of transesophageal echocardiography (TEE), have revolutionized the diagnosis and management of infective endocarditis. With the enhanced resolution provided by TEE, vegetations and paravalvular complications can be reliably detected. Transthoracic and transesophageal echocardiography provides complementary information for patient management and follow-up, and is best used in conjunction with clinical data. By means of its high sensitivity and negative predictive value, TEE is essential in the evaluation of prosthetic valve endocarditis and the paravalvular complications of IE. All patients with suspected infective endocarditis should undergo transthoracic echocardiography, and most of these patients should also undergo TEE evaluation. The role of new technology such as harmonic and three-dimensional imaging is yet to be determined.