Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 84 year-old woman presenting with evolving breast cancer was admitted in the intensive care unit for malaise. Profound hyponatremia in the context of symptomatic heart failure was documented. Intravenous infusion of NaCl 0.9% was unsuccessful. Treatment with oral urea was begun and sodium level returned to nearly normal values 5 days later.
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PMID:Correction of hyponatremia by urea in a patient with heart failure. 1639 21

Letrozole is a highly selective, nonsteroidal, third-generation aromatase inhibitor approved for first-line and extended adjuvant therapy in postmenopausal women with hormone-responsive, early-stage breast cancer. Binding of letrozole to the haeme component of the cytochrome P450 subunit of aromatase inhibits estrogen biosynthesis throughout the body. As first-line adjuvant therapy in approximate, equals 8000 postmenopausal women with hormone-responsive, early-stage breast cancer, once-daily letrozole 2.5mg significantly prolonged disease-free survival (DFS; primary endpoint) and reduced the risk of relapse at distant sites relative to once-daily tamoxifen 20mg in the ongoing Breast International Group 1-98, double-blind, multinational trial. The median duration of follow-up for this primary core analysis was 25.8 months. Extended adjuvant therapy with once-daily letrozole 2.5mg significantly prolonged DFS relative to placebo treatment at a median follow-up of 30 months (primary endpoint) in the MA-17 trial in approximate, equals 5000 postmenopausal women who were disease free after 4.5-6 years of tamoxifen therapy for hormone-responsive, early-stage breast cancer. Letrozole treatment for up to 5 years was generally well tolerated in this clinical setting. As first-line treatment, relative to tamoxifen, letrozole was associated with a significantly lower incidence of venous thromboembolitic events, vaginal bleeding, hot flushes and night sweating, whereas the incidence of cardiac failure, bone fractures and arthralgia was higher in letrozole recipients.
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PMID:Letrozole : in postmenopausal hormone-responsive early-stage breast cancer. 1652 26

Circulating apoptotic proteins are increased in patients with heart failure. We evaluated whether circulating soluble (s) apoptosis-related proteins and inflammation markers are increased in long-term disease free breast cancer survivors and associated with cardiotoxicity, and if subgroups could be identified based on the applied treatments. Circulating tumour necrosis factor (TNF) alpha, sTNF-receptor (sTNF-R) 1 and 2, sFas, sFas ligand, sTNF-related apoptosis inducing ligand (sTRAIL) and serum HER2 were measured with immunoassay. High-sensitivity C-reactive protein (HS-CRP), fibrinogen, plasma B-type and N-terminal atrial natriuretic peptide (NT-ANP and BNP) were also determined. Thirty-four patients with median 6.0 years follow-up and 12 healthy age-matched women were enrolled. Chemotherapy, consisting of five cycles fluorouracil, epirubicin (90 mg/m(2)), cyclophosphamide (FEC) (n=14) or four cycles FEC followed by myeloablation with high-dose carboplatin, cyclophosphamide, thiotepa (n=20), preceded irradiation and tamoxifen. Circulating apoptosis markers were higher in patients than in controls. No associations with cardiac dysfunction were observed. sFas ligand and sTRAIL were higher in the high-dose than in the standard-dose group. In conclusion, we observed increased circulating apoptotic protein levels in long-term disease-free breast cancer survivors, treated with adjuvant chemoradiotherapy, particularly after myeloablative chemotherapy. The potential relation with late cardiotoxicity of antineoplastic therapy deserves further study.
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PMID:Circulating apoptotic proteins are increased in long-term disease-free breast cancer survivors. 1654 63

(1) There is no consensus on the optimal chemotherapy for metastatic breast cancer. Patients who have never previously received chemotherapy are generally given an anthracycline-based combination of cytotoxic agents. Options for patients who have already received an anthracycline include a taxane such as paclitaxel or docetaxel. The median survival time with these treatments is only about 2 to 2.5 years. (2) Trastuzumab is a monoclonal antibody directed against HER-2, a protein overexpressed by certain tumours, including about 25% of breast tumours. In 2000, the approved indications included first-line treatment of metastatic breast cancer in combination with paclitaxel. One clinical trial had shown, albeit with a low level of evidence, a median increase in survival of about 4 to 5 months. Trastuzumab is now approved for first-line treatment of metastatic breast cancer, in combination with docetaxel. (3) Evaluation data include the results of an open-label trial comparing docetaxel + trastuzumab with docetaxel monotherapy in 186 patients. The median survival time was significantly longer with the combination (31.2 versus 22.7 months). There are no relevant comparisons with other widely used cytotoxic drugs. Indirect comparison suggests that survival is similar with docetaxel + trastuzumab and paclitaxel + trastuzumab. (4) Data on the trastuzumab-docetaxel combination confirm the known adverse effects of trastuzumab, which include heart failure and diarrhea. Trastuzumab increases the frequency of docetaxel-induced neutropenia, which carries a risk of infections. (5) In summary, the results of clinical trials show that median survival time is increased by a few months when trastuzumab is added to a cytotoxic drug. However, the best cytotoxic agent is not known, and adverse effects are poorly documented. (6) In practice, trastuzumab has only been shown to benefit a minority of women with breast cancer, namely those whose tumours overexpress HER-2. Trastuzumab therapy is an option for metastatic breast cancer treatment, provided patients are enrolled in studies designed to answer the many outstanding questions.
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PMID:Trastuzumab: new indication. Metastatic breast cancer, in combination with docetaxel: promising, but more evaluation is needed. 1654 94

In order to downstage locally advanced breast cancer, neoadjuvant chemotherapy consisting of intravenous vinorelbine 25 mg/m plus epirubicin 75 mg/m given on day 1 and oral vinorelbine 60 mg/m on day 8 was administered every 3 weeks for four courses. On day 2, all patients received a single subcutaneous injection of pegfilgrastim (6 mg). From March 2004 to June 2005, 22 patients were enrolled. Patients characteristics were: median age, 53 years (range: 39-70 years); postmenopausal, 7/22; clinical TNM stage, T2 (n=14), T3 (n=8), N0 (n=17) and N1 (n=5). The median number of courses was four (range: two to six courses) with full dose intensity. National Cancer Institute grade 3 haematological toxicities observed were neutropenia in 9% of patients, anaemia in 13% of patients and thrombocytopenia in 9% of patients; no toxicity grade 4 occurred. Two patients (9%) registered grade 2 polyneuropathy; no cardiac failure was observed. Conservative surgery was performed in 14 patients (63%). All patients were evaluable for response: complete pathological response was documented in three patients (13.6%); three patients (13.6%) obtained more than 75% of tumour size reduction; 11 other patients (50%) had 50% of tumour size reduction; stable disease was observed in five patients (22.7%). The present findings indicate that vinorelbine in combination with epirubicin is an effective and safe treatment in locally advanced breast cancer: this regimen obtained more than 50% of tumour size reduction in 77% of patients; the use of pegfilgrastim allowed full dose intensity. Oral vinorelbine on day 8 offers greater convenience to the patient by reducing the need for intravenous injection and the time spent in hospital.
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PMID:Alternating intravenous and oral vinorelbine plus epirubicin with pegfilgrastim as neoadjuvant treatment of locally advanced breast cancer. 1700 Nov 82

Trastuzumab (Herceptin), currently prescribed for metastatic breast cancer, has recently been shown to be effective as adjuvant therapy in early receptor 2 (HER2)-positive breast cancer. Cardiotoxicity is a serious adverse effect. A decrease in left ventricular ejection fraction (LVEF) occurs in as many as 27% of women treated with trastuzumab when combined with standard chemotherapy. The pathophysiology of this effect, which differs from the cardiotoxicity of anthracyclines, remains poorly understood. While overt heart failure is reversed with standard therapy, the longer-term consequences of asymptomatic declines in LVEF remain unknown. Monitoring 3-monthly for 5-10% changes in LVEF, the criteria for cessation of trastuzumab therapy in the clinical trials, is not possible for the population of women who might benefit from trastuzumab for early breast cancer. Extension of this therapy to an older and less fit population than those enrolled in the trials, with less rigorous cardiac screening, may result in significantly more cardiotoxicity.
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PMID:Monitoring the introduction of new drugs--Herceptin to cardiotoxicity. 1734 85

Increased serum level of troponin-T and myoglobin has been recently reported to be related to cumulative anthracycline exposure. Left ventricular ejection fraction seems accurate in monitoring systolic function according to the latest version of Toxicity Criteria by chemotherapeutics 3.0. From January 2002, 20 patients with untreated advanced breast cancer received epirubicin (25 mg/m/week) and paclitaxel (80 mg/m/week) for 24 weeks. Troponin-T, myoglobin and biochemical serum enzymes circulating levels were measured immediately before and 4 h after epirubicin administration every week. Patients underwent electrocardiography and echocardiography at weeks 0, 8, 16 and 24. The number of courses administered was 352 (median 18, range 4-24). Epirubicin median dose administered was 600 mg/m and paclitaxel median dose administered was 1760 mg/m. Troponin-T never overcame the upper normal limit; one patient experienced troponin-T elevation without any clinical or instrumental sign of cardiac failure. Myoglobin never significantly increased with the exception of a patient who underwent several abdominal fluid drainages. Creatine kinase MB and C-reactive protein never moved outside the upper normal limit. No symptomatic cardiac event was recorded. In 55 performed echocardiograms at weeks 0, 8, 16 and 24, neither left ventricular ejection fraction nor early peak flow/atrial flow velocity registered any significant decrease. No troponin-T or myoglobin serum elevations and Left ventricular ejection fraction/early peak flow/atrial flow velocity changes were registered in our series of nonsymptomatic women during epirubicin/paclitaxel weekly chemotherapy in the absence of clinical cardiac toxicity. Longer follow-up is needed, however, to understand whether the troponin-T or myoglobin circulating level measurement is able to detect subclinical, early-stage doxorubicin-induced cardiotoxicity.
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PMID:Troponin-T and myoglobin plus echocardiographic evaluation for monitoring early cardiotoxicity of weekly epirubicin-paclitaxel in metastatic breast cancer patients. 1715 9

Anthracyclines are among the most active chemotherapeutic agents in cancer treatment. Although infrequent, cumulative dose-dependent cardiotoxicity is nevertheless a significant side effect of this therapy resulting in reduced cardiac reserve or even frank cardiac failure. Although used in several types of malignancy, anthracyclines are most commonly used in breast cancer treatment. Importantly, recent advances have also seen the increasing use of another cardiotoxic agent, the monoclonal antibody trastuzumab, both in the metastatic as well as in the adjuvant breast cancer setting. This review discusses the relationship of cardiotoxicity and anthracycline use, particularly in the breast cancer setting, and explores available treatment options for the anthracycline-treated patients based on evidence from recent Phase III trials.
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PMID:Managing cardiotoxicity in anthracycline-treated breast cancers. 1748 Jan 80

Axillary surgery for breast cancer partially obstructs lymph outflow from the arm, chronically raising the lymphatic smooth muscle afterload. This may lead to pump failure, as in hypertensive cardiac failure, and could explain features of breast cancer treatment-related lymphoedema (BCRL) such as its delayed onset. A new method was developed to measure human lymphatic contractility non-invasively and test the hypothesis of contractile impairment. 99mTc-human IgG (Tc-HIG), injected into the hand dermis, drained into the arm lymphatic system which was imaged using a gamma-camera. Lymph transit time from hand to axilla, ttransit, was 9.6+/-7.2 min (mean+/-s.d.) (velocity 8.9 cm min(-1)) in seven normal subjects. To assess lymphatic contractility, a sphygmomanometer cuff around the upper arm was inflated to 60 mmHg (Pcuff) before 99mTc-HIG injection and maintained for>>ttransit. When Pcuff exceeded the maximum pressure generated by the lymphatic pump (Ppump), radiolabelled lymph was held up at the distal cuff border. Pcuff was then lowered in 10 mmHg steps until 99mTc-HIG began to flow under the cuff to the axilla, indicating Ppump>or=Pcuff. In 16 normal subjects Ppump was 39+/-14 mmHg. Ppump was 38% lower in 16 women with BCRL, namely 24+/-19 mmHg (P=0.014, Student's unpaired t test), and correlated negatively with the degree of swelling (12-56%). Blood radiolabel accumulation proved an unreliable measure of lymphatic pump function. Lymphatic congestion lymphoscintigraphy thus provided a quantitative measure of human lymphatic contractility without surgical cut-down, and the results supported the hypothesis of lymphatic pump failure in BCRL.
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PMID:Human lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy. 1756 39

Since the discovery that neuregulin-1 (NRG-1)/ErbB signaling is indispensable in cardiac development, evidence has shown that this system also plays a crucial role in the adult heart. In patients, an inhibitory ErbB2 antibody, trastuzumab, used in the treatment of mammary carcinomas, increases the risk for the development of cardiotoxic cardiomyopathy. Postnatal disruption of NRG-1/ErbB signaling by gene targeting in mice leads to dilated cardiomyopathy. Initially, the search for the mechanisms behind these observations focused mainly on the effects of NRG-1 on cardiomyocyte growth and survival and revealed that NRG-1 has Akt-dependent antiapoptotic effects in cultured cardiomyocytes. In vivo studies, however, did not uniformly reinforce a role for apoptosis in the development of cardiomyopathy induced by impaired NRG-1/ErbB signaling. More recent studies have revealed that NRG-1 is involved in the regulation of cardiac sympathovagal balances by counterbalancing adrenergic stimulation of the adult myocardium and through an obligatory interaction with the muscarinic cholinergic system. NRG-1 is synthesized and released by the endocardial and cardiac microvascular endothelium, dynamically controlled by neurohormonal and biomechanical stimuli. The physiology of the cardiac NRG-1/ErbB system has implications for the treatment of both cancer and heart failure. Clinical studies in breast cancer with novel ErbB inhibitors are currently underway. Novel oncological indications for ErbB inhibition are emerging; cardiovascular side effects need to be carefully monitored. On the other hand, pharmacological activation of ErbB signaling is likely an unrecognized and beneficial effect of currently used drugs in heart failure and a promising therapeutic approach to prevent or reverse myocardial dysfunction.
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PMID:Role of neuregulin-1/ErbB signaling in cardiovascular physiology and disease: implications for therapy of heart failure. 1770 50


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