PubMed Health⌕ Search

Biomedical subjects

Jean-Bernard Durand

Publications and source records attributed to Jean-Bernard Durand.

11 recordsLinked to original sources
PubMed2007

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.

Acute Disease↗
PubMed2006

Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience.

PURPOSE: To evaluate the cardiac safety of long-term trastuzumab therapy in patients with human epidermal growth receptor 2 (HER2) -overexpressing metastatic breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX). PATIENTS AND METHODS: Among 218 MBC patients treated with trastuzumab-based therapy for at least 1 year, 173 patients were assessable for cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20 percentage points in LVEF compared with the baseline; or signs or symptoms of congestive heart failure (CHF). RESULTS: The median cumulative time for trastuzumab administration was 21.3 months. The median follow-up was 32.6 months (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points, 27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%) experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There was one cardiac-related death (0.5%). Baseline LVEF was significantly associated with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking concomitant taxanes was higher early in the follow-up period but declined during the course of follow-up. CONCLUSION: The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function.

Adult↗
PubMed2006

Cardiotoxicity of the cancer therapeutic agent imatinib mesylate.

Imatinib mesylate (Gleevec) is a small-molecule inhibitor of the fusion protein Bcr-Abl, the causal agent in chronic myelogenous leukemia. Here we report ten individuals who developed severe congestive heart failure while on imatinib and we show that imatinib-treated mice develop left ventricular contractile dysfunction. Transmission electron micrographs from humans and mice treated with imatinib show mitochondrial abnormalities and accumulation of membrane whorls in both vacuoles and the sarco- (endo-) plasmic reticulum, findings suggestive of a toxic myopathy. With imatinib treatment, cardiomyocytes in culture show activation of the endoplasmic reticulum (ER) stress response, collapse of the mitochondrial membrane potential, release of cytochrome c into the cytosol, reduction in cellular ATP content and cell death. Retroviral gene transfer of an imatinib-resistant mutant of c-Abl, alleviation of ER stress or inhibition of Jun amino-terminal kinases, which are activated as a consequence of ER stress, largely rescues cardiomyocytes from imatinib-induced death. Thus, cardiotoxicity is an unanticipated side effect of inhibition of c-Abl by imatinib.

Adenosine Triphosphatases↗
PubMed2006

Culture-positive and culture-negative endocarditis in patients with cancer: a retrospective observational study, 1994-2004.

Endocarditis is uncommon in patients with cancer. The characteristics of culture-positive (CPE) and culture-negative endocarditis (CNE) in high-risk cancer patients are not known; therefore we sought to evaluate the disease characteristics in patients with endocarditis at a comprehensive cancer center. We retrospectively reviewed the transthoracic (TTE) and transesophageal (TEE) echocardiograms obtained from 654 consecutive cancer patients in whom endocarditis was suspected between 1994 and 2004. Endocarditis was confirmed in 45 (7%) of 654 patients using modified Duke University criteria based on information obtained from hospital records and computerized data systems. In 21 (95%) of 22 cases, TEE examinations were diagnostic, and 16 (42%) of 38 patients with initially nondiagnostic TTE studies had the diagnosis confirmed by TEE study; this difference between diagnostic TEE and initial nondiagnostic TTE was significant (p < 0.0001). Among the 26 (58%) patients with CPE, Staphylococcus aureus (35%) was the most common organism isolated, followed by coagulase-negative Staphylococcus species (23%). Eighteen (78%) of 23 patients with a central venous catheter had CPE, whereas only 8 (36%) of 22 patients without a central venous catheter had CPE (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.69-23.53; p < 0.006). Vegetations were larger in patients with CPE than in patients with CNE (median +/- standard deviation, 10 +/- 8.8 vs. 8.7 +/- 3.9 mm). Fifteen patients (58%) with CPE and 10 (53%) with CNE had embolic complications. We note that cutaneous and septic pulmonary emboli were more common in patients with CPE than in patients with CNE (31% vs. 11% and 15% vs. 0%, respectively), whereas embolic cerebrovascular and fatal embolic coronary events were more common in patients with CNE than in those with CPE (37% vs. 12% and 21% vs. 0%, respectively; p = 0.026). The 4-week endocarditis-attributable death rate did not differ significantly between the groups (CPE, 15% vs. CNE, 32%; p = 0.28). On stepwise multivariate regression analysis, patients with neutropenia (OR, 22.52; 95% CI, 2.25-225.48; p < 0.008) and those with embolic cerebrovascular events (OR, 17.07; 95% CI, 1.63-178.45; p < 0.01) had an increased probability of death due to endocarditis. The clinical spectrums of CPE and CNE differed in these patients with cancer. In patients with CNE, embolic cerebrovascular and fatal myocardial infarction were relatively common.

Adolescent↗
PubMed2005

Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment.

PURPOSE: Trastuzumab is an important biologic agent with significant activity in breast cancers that overexpress the HER2/neu marker. However, trastuzumab is associated with cardiotoxicity that has not yet been fully explored. We present our experience with patients who developed trastuzumab-related cardiotoxicity. PATIENTS AND METHODS: Over a 4-year period, 38 patients with HER2/neu-positive breast cancer were referred for suspected trastuzumab-related cardiotoxicity. All patients had previously received anthracycline-based chemotherapy. Results After doxorubicin but before trastuzumab, the mean (+/- standard deviation) left ventricular ejection fraction (LVEF) was 0.61 +/- 0.13, and the LVEF decreased to 0.43 +/- 0.16 after trastuzumab (P < .0001). After withdrawal of trastuzumab, the LVEF increased to 0.56 +/- 0.11. Mean time to recovery of LVEF was 1.5 months and was temporally associated with medical treatment in 32 (84%) of the 38 patients but occurred without treatment in six patients (16%). Increases in LVEF were noted in 37 of the 38 patients. Twenty-five of these patients were re-treated with trastuzumab; three patients had recurrent left ventricular dysfunction, but 22 patients (88%) did not. All re-treatment patients continued on their therapeutic regimen for heart failure when rechallenged with trastuzumab. Nine patients underwent endomyocardial biopsy. Ultrastructural changes were not seen. CONCLUSION: Patients who develop cardiotoxicity while receiving trastuzumab therapy generally improve on removal of the agent. The mechanism of trastuzumab-related cardiac dysfunction is different from that of anthracycline cardiotoxicity, in part, demonstrated by the absence of anthracycline-like ultrastructural changes. Reintroducing trastuzumab may be appropriate for some individuals who previously have experienced trastuzumab-related cardiac dysfunction.

Adult↗
PubMed2004

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.

Anthracyclines↗
PubMed2004

The update on the rationale, use and selection of beta-blockers in heart failure.

PURPOSE OF REVIEW: The purpose of this review was to describe important developments in the selection of beta-blockers in heart failure. RECENT FINDINGS: The superiority of carvedilol over metoprolol tartrate in one clinical trial is demonstrated, and multiple studies investigated the potential mechanisms of benefit. Current practice patterns still demonstrate the importance of understanding barriers to the effective use of beta-blocking agents. SUMMARY: There are continued refinements in the choice of beta-blockers in heart failure, but clearly an important remaining challenge is to modify health care delivery in an effort to maximize adherence to guidelines.

Adrenergic beta-Antagonists↗
PubMed2004

Heart failure management in African Americans: meeting the challenge.

Heart failure affects 3% of African Americans. The etiology of disease and prognosis for these patients differs substantially from those for non-African Americans. A history of hypertension is associated with development of heart failure more often in African Americans than in non-African Americans and it also appears that target organ involvement is more severe in African Americans with hypertension than in other patient subgroups. Reviewing the results from large-scale clinical end point studies suggests that optimal treatment for heart failure in African Americans may differ from that of their non-African American counterparts. More importantly, concomitant use of beta blockers and angiotensin-converting enzyme inhibitors may be as effective in African Americans as in non-African Americans. Utilizing angiotensin-converting enzyme inhibitors alone may not represent ideal therapy. Of the drugs studied, especially among the beta blockers, carvedilol may be the most effective to use for this population.

Adrenergic beta-Antagonists↗
PubMed2002

Current guidelines in heart failure management.

1. ACE inhibitors are indicated for Class I-IV HF due to LVSD. 2. ARBs are recommended for HF patients with contra-indications or intolerance to ACE inhibitors. 3. Spironolactone provides additional benefit for Class IV HF patients. 4. Beta-blockers (carvedilol or long-acting metoprolol) are indicated as additive treatment to an ACE inhibitor or ARB for Class II or III HF. 5. The beta-blocker carvedilol has been found to be safe and effective in patients with severe HF and appears to improve clinical outcomes in patients with LVSD post-MI.

Adult↗