natriuretic-peptide--brain and Neoplasms

Cardiac biomarkers are a mainstay in diagnosis of cardiovascular disease but their role in cardio-oncology has not yet been systematically evaluated. This meta-analysis aims to determine whether cardiac troponins and (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) predict cancer therapy-related left ventricular (LV) dysfunction.. Scientific databases were searched for studies that assessed troponins or BNP/NT-proBNP in adult patients undergoing cancer therapy. Data from 61 trials with 5691 patients were included. Cancer therapy was associated with an increase in troponin levels [odds ratio (OR) 14.3, 95% confidence interval (CI) 6.0-34.1; n = 3049]. Patients with elevated troponins receiving chemotherapy or human epidermal growth factor receptor 2 inhibitor therapy were at higher risk for LV dysfunction (OR 11.9, 95% CI 4.4-32.1; n = 2163). Troponin had a negative predictive value of 93%. Mean BNP/NT-proBNP levels were increased in patients post-treatment (standardized mean difference 0.6, 95% CI 0.3-0.9; n = 912), but the available evidence did not consistently indicate prediction of LV dysfunction (OR 1.7, 95% CI 0.7-4.2; n = 197). β-blocker and angiotensin-converting enzyme inhibitor therapy to mitigate cardiotoxicity during cancer therapy was associated with a decline in serum troponins (OR 4.1, 95% CI 1.7-9.8; n = 466).. Elevated troponin levels predict LV dysfunction in patients receiving cancer therapy. Assessment of troponin levels may qualify as a screening test to identify patients who require referral to cardio-oncology units and benefit from preventive strategies. Further evidence is required for both biomarkers.

Topics: Adult; Biomarkers; Cardiotoxicity; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Troponin

Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients.. PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT-proBNP (OR = 7.1; 95% CI = 2.0-25.5; n = 350; P = 0.003). The sensitivity of BNP/NT-proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1-6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5-13.2; n = 179; P = 0.53).. BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

Topics: Anthracyclines; Biomarkers; Cardiotoxicity; Child; Humans; Natriuretic Peptide, Brain; Neoplasms; Ventricular Dysfunction, Left

As the number of cancer survivors increases due to early screening and modern (antineoplastic) treatments, cancer treatment associated cardiotoxicity (CTAC) is becoming an increasing health burden that affects survival and quality of life among cancer survivors. Thus, clinicians need to identify adverse events early, in an effort to take suitable measures before the occurrence of permanent or irreversible cardiac dysfunction.. Cardiac troponin (cTn) and B-type natriuretic peptide (BNP) have been proven to detect subclinical cardiotoxicity during antineoplastic treatment. As such, these cardio-specific biomarkers could predict which patients are at risk of developing CTAC even before the start of therapy. Nevertheless, there are inconsistent data from published studies, and the recommendations regarding the use of these biomarkers and their validity are mostly based on expert consensus opinion. In this review, we summarize available literature that evaluates biomarkers of CTAC, and we encourage strategies that integrate circulating biomarkers and cardiac imaging in identifying cancer patients that are at high risk.

Topics: Antineoplastic Agents; Biomarkers; Cardiotoxicity; Humans; Natriuretic Peptide, Brain; Neoplasms; Troponin

Natriuretic factors are peptidic substances produced by atrial and ventricular myocardium. Primary stimulus to the synthesis of these factors is intramural pressure of atriums by the increase of venous return during intravascular hypervolemia. They may serve as useful cardiac markers in clinical practice. The elevation of N-terminal fragment of atrial natriuretic peptide is characteristic for cardiac failure. Troponin T is a basic component of muscle and is specific for myocardial cell. It is a marker of myocardial damage, specifically of myocardial infarction.. This paper aims to summarize the current knowledge on levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and their associations with cancer. At present, it is well known that natriuretic peptides may be produced by cancer cells without cardiac failure. While small cell lung cancer is a known producer of natriuretic factor, all oncologic diseases may have a potential to produce these substances. ProBNP synthesis may be stimulated by several pro-inflammatory cytokines, including tumour necrosis factor alpha and some interleukins. The production of pro-inflammatory cytokines has been proven in cancer. The influence of natriuretic factors to proto-oncogenes and cancer cells is considered and cross-reacting antibodies increasing NT-proBNP in paraproteinemias were described. Works discussing extreme elevations of NT-proBNP in terminal cancer patients without symptoms of cardiac failure were previously published. NT-proBNP and troponin T are also markers of myocardial damage during cardiotoxic chemotherapy with anthracyclines.. NT-proBNP and troponin T can be valuable markers of the prognosis of oncologic diseases regarding not only cardiac damage during chemotherapy but also prognosis and extension of cancer patient lives.

Topics: Biomarkers, Tumor; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prognosis; Troponin T

To systematically review the literature and assess the diagnostic value of biomarkers in detection of late-onset left ventricular (LV) dysfunction in childhood cancer survivors (CCS) treated with anthracyclines.. We systematically searched the literature for studies that evaluated the use of biomarkers for detection of LV dysfunction in CCS treated with anthracyclines more than 1 year since childhood cancer diagnosis. LV dysfunction definitions were accepted as an ejection fraction <50% or <55% and/or a fractional shortening <28%, <29% or <30%. Contingency tables were created to assess diagnostic accuracies of biomarkers for diagnosing LV dysfunction.. Of 1362 original studies screened, eight heterogeneous studies evaluating four different biomarkers in mostly asymptomatic CCS were included. In four studies, an abnormal N-terminal pro-B-type natriuretic peptide (NT-proBNP, cut-off range 63-125 ng/L) had low sensitivity (maximally 22%) and a specificity of up to 97% for detection of LV dysfunction. For troponin levels, in five studies one patient had an abnormal troponin value as well as LV dysfunction, while in total 127 patients had LV dysfunction without troponin elevations above cut-off values (lowest 0.01 ng/mL). Two studies that evaluated brain natriuretic peptide and nitric oxide were underpowered to draw conclusions.. In individual studies, the diagnostic value of NT-proBNP for detection of LV dysfunction in CCS is limited. Troponins have no role in detecting late-onset LV dysfunction with cut-off values as low as 0.01 ng/mL. Further study on optimal NT-proBNP cut-off values for rule out or rule in of LV dysfunction is warranted.

Topics: Anthracyclines; Antineoplastic Agents; Biomarkers; Cardiac Imaging Techniques; Child; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Reproducibility of Results; Survivors; Troponin; Ventricular Dysfunction, Left

In this article, we review current and emerging approaches to biomarker discovery to facilitate early diagnosis of cancer therapy-associated cardiovascular toxicity.. Although small studies have demonstrated an association between established biomarkers of cardiac injury (troponins and brain natriuretic peptide) and acute or subacute cardiotoxicity, there is insufficient evidence to support their use in routine clinical care. Preclinical studies to define the molecular mechanisms of cardiotoxicity, as well as the use of unbiased "omics" techniques in small patient cohorts, have yielded promising candidate biomarkers that have the potential to enrich current risk stratification algorithms. New biomarkers of cardiotoxicity have the potential to improve patient outcomes in cardio-oncology. Further studies are needed to assess the clinical relevance of molecular mechanisms described in animal models. Similarly, findings from "omics" platforms require validation in large patient cohorts before they can be incorporated into everyday practice.

Topics: Antineoplastic Agents; Biomarkers; Cardiovascular Diseases; Humans; Natriuretic Peptide, Brain; Neoplasms; Troponin

Chemotherapy-related cardiac dysfunction (CRCD) has challenged clinicians to hesitate in using cardiotoxic agents such as anthracycline and several protein kinase inhibitors. As early detection of CRCD and timely cessation of cardiotoxic agents became a strategy to avoid CRCD, cardiac troponin and natriuretic peptide are measured to monitor cardiotoxicity; however, there are inconsistencies in their predictability of CRCD. Alternative biomarkers have been researched extensively for potential use as more sensitive and accurate biomarkers. The mechanisms of CRCD and previous studies on traditional and novel biomarkers for CRCD are examined to enlighten future direction of investigation in this combined biology.

Topics: Antineoplastic Agents; Biomarkers; Early Diagnosis; Heart Diseases; Humans; Natriuretic Peptide, Brain; Neoplasms; Translational Research, Biomedical; Troponin T

Cardiac biomarkers have been extensively investigated as early detectors of cardiac toxicity from cancer therapies. Whereas the role of biomarkers in monitoring anthracycline toxicity is generally well understood, substantial uncertainty remains regarding their role in monitoring newer targeted cancer therapies.. This review article examines all major published studies using cardiac troponins and/or N-terminal pro-B-type natriuretic peptide (NT-proBNP) in monitoring for cardiac toxicity with trastuzumab, tyrosine kinase inhibitors, and mammalian target of rapamycin (mTOR) inhibitors. There is substantial variability among studies regarding biomarker assays used, sensitivity of the assays, and definitions of abnormal results. In general, troponin I predicts early but not late cardiac events when trastuzumab is administered after anthracyclines, but troponin increases likely reflect anthracycline injury rather than trastuzumab injury. NT-proBNP detects cardiac toxicity with tyrosine kinase inhibitors and mTOR inhibitors, but not independently from echocardiography.. Troponin I can serve as a marker for susceptibility to cardiac toxicity during early trastuzumab treatment in patients who have received recent anthracyclines. NT-proBNP can serve as a useful marker of cardiac toxicity in patients treated with tyrosine kinase inhibitors or mTOR inhibitors if echocardiographic screening is not being used.

Topics: Antineoplastic Agents; Biomarkers; Cardiomyopathies; Cardiotoxicity; Humans; Natriuretic Peptide, Brain; Neoplasms; Troponin I

Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.

Topics: Antineoplastic Agents; Arrhythmias, Cardiac; Biomarkers; C-Reactive Protein; Cardiotonic Agents; Cardiotoxicity; Cardiotoxins; Coronary Thrombosis; Early Diagnosis; Echocardiography, Three-Dimensional; Humans; Hypertension; Magnetic Resonance Imaging, Cine; Myocardial Ischemia; Natriuretic Peptide, Brain; Neoplasms; Primary Prevention; Radiotherapy; Risk Factors; Troponin T; Ventricular Dysfunction, Left

Early detection of anticancer drug-induced cardiotoxicity (CTX) has been evaluated by most international scientific cardiology and oncology societies. High expectations have been placed on the use of specific biomarkers. In recent years, conventional biomarkers and molecules of more recent interest have been tested and compared in the context of anticancer drug-related CTX. Encouraging results were obtained from studies on molecules of myocardial damage, such as troponin and markers of myocardial wall stress, including circulating natriuretic peptides, as well as from the assessment of the products of inflammation or circulating levels of free radicals. However, clear guidelines on their sensitivity, specificity, and accuracy are not yet available, and many challenges, such as the optimal time of assessing, optimal schedule for evaluation, optimal cut-off point for positivity with the highest level of specificity, and optimal comparability of different assays for the measurements, remain unresolved. Given the importance of having a reliable and accurate tool for monitoring anticancer drug-induced CTX, this review will focus on the available data on the most effective and widely used biomarkers and the studies that are currently underway that aim to identify the effectiveness of new approaches in this therapeutic setting.

Topics: Antineoplastic Agents; Biomarkers; Cardiotoxicity; Early Diagnosis; Humans; Natriuretic Peptide, Brain; Neoplasms; Sensitivity and Specificity; Troponin

Natriuretic peptide receptor A (NPR-A) is the receptor for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). NPR-A plays critical physiological and pathophysiological roles in several target cell and tissue system processes, such as cell growth, apoptosis, proliferation, and inflammation. Accumulating data demonstrate that NPR-A is involved in immune and inflammatory reactions and is a potential target in inflammation treatment. It is expressed in various cancer cells and is important for tumor growth. A recent study indicated that NPR-A signaling can regulate stem cell recruitment and angiogenesis. This signaling can serve as a model for studying the linkage between inflammation and tumorigenesis. In this review we highlight the mechanisms by which NPR-A affects signaling pathways involved in inflammation and cancer, and we discuss its potential as a novel target in inflammation, cancer, and cancer-related inflammation.

Topics: Apoptosis; Atrial Natriuretic Factor; Carcinogenesis; Cell Proliferation; Humans; Inflammation; Natriuretic Peptide, Brain; Neoplasms; Neovascularization, Pathologic; Receptors, Atrial Natriuretic Factor; Signal Transduction

An ever-increasing array of chemotherapeutic agents is being used in the treatment of solid organ or hematologic malignancies. The success of many of these agents has led to an increasing survival of patients with cancer. However, many of these agents, particularly anthracyclines and trastuzumab, are associated with the development of cardiotoxicity. The current standard for the evaluation of chemotherapy-associated cardiotoxicity typically involves the use of serial measurements of left ventricular (LV) function by echocardiogram (Echo) and radionuclide ventriculogram (MUGA). Unfortunately, this time-honored method offers low sensitivity to the early prediction or detection of cardiac events. Frequently, by the time cardiotoxicity is detected, significant LV dysfunction has occurred and ultimately this may not respond to standard cardioprotective treatment. Cardiac biomarkers, troponin I and B-type natriuretic peptide, may allow a more accurate and timely monitoring strategy. The current data and a summarized understanding of how to utilize cardiac biomarkers for the prevention and early detection of cardiac dysfunction during chemotherapy are presented.

Topics: Anthracyclines; Antineoplastic Agents; Biomarkers; Cardiotoxicity; Echocardiography; Humans; Natriuretic Peptide, Brain; Neoplasms; Stroke Volume; Trastuzumab; Troponin C; Troponin I; Ventricular Dysfunction, Left

Anthracycline-related cardiotoxicity has a substantial negative impact on long-term survivors of childhood cancer. The detection of cardiotoxicity is currently based on echocardiography or radionuclide angiography. However, as they depict only the final outcome of myocardial injury in terms of reduced heart contractility, heart specific biomarkers of myocardial destruction or dysfunction could be advantageous by allowing for an earlier detection of cardiotoxicity. In the present study, the usefulness of cardiac troponins and natriuretic peptides, the most commonly used biomarkers of myocardial destruction and ventricular dysfunction respectively, to detect and to predict the development of anthracycline cardiotoxicity has been reviewed.

Topics: Anthracyclines; Biomarkers; Cardiotoxins; Child; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Humans; Natriuretic Peptide, Brain; Neoplasms; Troponin

Anthracycline-induced cardiotoxicity can cause serious health problems for an increasing number of children surviving childhood malignancies. Early detection of cardiac failure is critically important for the prevention and management of anthracycline-induced cardiotoxicity. The aim of this research was to determine the role of biomarkers in the early detection of anthracycline-induced cardiotoxicity in children. A literature review is presented of studies regarding the use of the biomarkers B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-pro-BNP), cardiac troponin T (cTnT), and cardiac troponin I (cTnI) in relation with anthracycline-induced cardiotoxicity in children. Six of 14 studies in children showed a significant relation between elevated biomarkers BNP, NT-pro-BNP, and cTnT and cardiac dysfunction. Six studies, although small, suggest that BNP, NT-pro-BNP, and cTnT might be useful markers in the early detection of anthracycline-induced cardiotoxicity.

Topics: Anthracyclines; Biomarkers; Child; Early Diagnosis; Heart Diseases; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Troponin I; Troponin T

Cardiac natriuretic peptides consist of a family of six peptide hormones that are synthesised by three separate genes and then stored as three separate prohormones (i.e. 126 amino acid atrial natriuretic peptide (ANP), 108 amino acid B-type natriuretic peptide (BNP) and 103 amino acid C-type natriuretic peptide (CNP) prohormones). The ANP prohormone contains four peptide hormones: long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide and ANP. 2. Currently, the only natriuretic peptide available commercially to treat congestive heart failure (CHF) is BNP (Nesiritide/Natrecor; SCIOS, Sunnyvale, CA, USA), which causes a small increase in the urine volume of 90 38 mL/h compared with 67 27 mL/h and no significant natriuresis, but has beneficial haemodynamic effects in acute CHF individuals. These haemodynamic effects probably contribute to the side-effects of BNP in patients with acute CHF with a 27% incidence of hypotension and possibly to 22% worsening of renal function, defined as an increase in serum creatinine of 0.5 mg/dL, associated with a worse prognosis. A review of clinical trials suggests a twofold increased risk of death at 30 days post-nesiritide treatment, a finding that needs further investigation. 3. The best of the natriuretic peptides for treating chronic CHF is the vessel dilator, which increases urinary flow up to 13-fold and sodium excretion up to fourfold, without the previously mentioned side-effects. The natriuretic and diuretic effects of vessel dilators last 6 h, which would allow them to be used on a four times per day basis in treating chronic CHF. 4. Atrial natriuretic peptide does not cause significant improvement in acute renal failure (ARF) in humans. The only natriuretic peptide that significantly improves ARF is the vessel dilator. Even when ARF has been established for 2 days before treatment in an ischaemic ARF animal model, vessel dilator decreases serum creatinine from 8.2 0.5 to 0.98 0.12 mg/dL in 6 days. At day 6 of ARF, mortality decreases to 14% (from 88%) without the vessel dilator. After 6 days of treatment with the vessel dilator, the proximal and distal tubules regenerate. 5. In cancer, vessel dilator, LANP, kaliuretic peptide and ANP at 1 mmol/L, decrease up to 97% of human breast, pancreatic and prostate adenocarcinoma cells, as well as small cell and squamous cell lung cancer cells within 24 h. In vivo, vessel dilator, LANP and kaliuretic peptide completely stop the growth of human pancreati

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neoplasms; Renal Insufficiency

Chemotherapy is an established approach for several malignancies, but its utility may be hampered by induced cardiac toxicity possibly leading to heart failure, with a negative impact on the patient's quality of life and ultimately survival. Prospective left ventricular systolic function monitoring has demonstrated that cardiotoxicity could be subclinically present for many months or years before its overt manifestation. Although considered irreversible, some reports suggested recovery or delayed progression of cardiac dysfunction by preventive cardioactive therapies. Thus, the identification of earlier instrumental or biochemical markers of cardiac injury able to predict heart failure remains a major task. Diastolic indexes as a primary expression of hemodynamic dysfunction after cardiac damage, analyzed by means of conventional or newer Doppler technologies (tissue Doppler, color M-mode, etc.) are discussed. Moreover, brain natriuretic peptides, troponins and endothelin-1, as possible sensitive/specific markers/predictors of subclinical cardiotoxicity are reviewed in order to update and possibly improve the strategy for the detection and clinical management of chemotherapy-related cardiotoxic effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cardiac Output, Low; Endothelin-1; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Predictive Value of Tests; Primary Prevention; Prognosis; Quality of Life; Sensitivity and Specificity; Severity of Illness Index; Troponin; Ventricular Dysfunction, Left

Several anticancer drugs have been associated with cardiac toxicity, especially the anthracyclines and trastuzumab. The pathogenesis of anthracycline-associated toxicity has been well described, whereas the mechanism of trastuzumab-associated toxicity is unknown. Although routine cardiac imaging studies (e.g. echocardiogram or multiple gated acquisition scans) may identify subclinical evidence of myocardial dysfunction, available data do not support their routine use for monitoring asymptomatic patients undergoing cancer therapy. Other modalities such as nuclear medicine scintigraphy with indium-111-antimyosin antibody and endomyocardial biopsy have been shown to be useful in identifying early cardiac damage, but their routine use is limited by practical considerations such as feasibility and cost. Consequently, there is significant interest in developing simple and reproducible methods for identifying patients at risk for treatment-induced myocardial damage. Available data suggest that circulating markers such as troponins and natriuretic peptides could potentially be useful for this purpose. Measurement of plasma troponin levels are commonly used in clinical practice in order to provide diagnostic and prognostic information in patients with myocardial ischaemia. Elevated levels may likewise correlate with anthracycline-induced cardiac damage, although plasma levels are only minimally elevated (well below that associated with ischaemia), and elevations may persist for weeks or months after anthracycline exposure. Clinical trials are currently evaluating the role of these markers in predicting both early and late, clinical and subclinical damage associated with anthracyclines and trastuzumab.

Topics: Antibiotics, Antineoplastic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Humans; Natriuretic Peptide, Brain; Neoplasms; Trastuzumab; Troponin T

Atrial and brain natriuretic peptides (ANP and BNP) are established diagnostic and prognostic markers in heart failure, but their utility in patients with advanced cancer is unclear.. Our objective was to examine the association between plasma natriuretic peptides and survival in patients with advanced cancer without clinical evidence of heart failure.. This exploratory analysis of a multicenter, randomized clinical trial of cancer patients receiving hospice care assessed the association between elevated plasma ANP, BNP, or Pro-BNP (cutoffs of >77, 100, and 900 pg/mL, respectively) and overall survival. Time-to-event analyses, including multivariate Cox regression, were conducted.. Among 97 patients, the mean age was 67.2 years and the overall survival was 16 days (95% CI, 13-23 days). ANP, BNP, and Pro-BNP were elevated in 29 of 36 (81%), nine of 23 (39%), and 32 of 38 (84%) patients, respectively. Elevated ANP, BNP, or Pro-BNP was associated with worse survival (median 14 vs. 21 days; P = 0.02). BNP or Pro-BNP was inversely associated with overall survival (hazard ratio = 2.27; 95% CI, 1.29-3.97) in univariate Cox regression analysis, and remained significant in multivariate Cox regression analysis (hazard ratio = 3.09; 95% CI, 1.40-6.84) after adjusting for treatment group and known prognostic variables such as performance status, albumin, creatinine, delirium, dyspnea, and anorexia. Elevated ANP alone was not significantly associated with survival (P = 0.17).. Our preliminary findings suggest that BNP or Pro-BNP may be a novel objective prognostic marker in cancer patients without heart failure. Further research is needed to confirm these findings.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Prognosis; Survival Rate

Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death. We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a marker of myocyte stress. Both markers have shown strong association with adverse cardiovascular outcomes. In 519 women with no evidence of cardiovascular disease, we measured circulating concentrations of cardiac troponin T, using a high-sensitivity assay (hsTnT), and the N-terminal fragment of B-type natriuretic peptide (NT-proBNP). We used logistic regression to determine if these behaviors were associated with hsTnT ≥ 3 ng/l or with NT-proBNP in the highest quartile (≥ 127.3 ng/l). The median (Q1 to Q3) NT-proBNP of the cohort was 68.8 ng/l (40.3 to 127.3 ng/l), and 30.8% (160 of 519) of the cohort had circulating hsTnT ≥ 3 ng/l. In adjusted models, women who drank 1 to 6 drinks/week had lower odds of having a hsTnT ≥ 3 ng/l (odds ratio 0.58, 95% confidence interval 0.34 to 0.96) and lower odds of having an elevated NT-proBNP (odds ratio 0.55, 95% confidence interval 0.32 to 0.96). We were subsequently able to validate the results for B-type natriuretic peptide in a large independent cohort. In conclusion, our results suggest that regular alcohol consumption is associated with lower concentrations of hsTnT and NT-proBNP, 2 cardiovascular biomarkers associated with cardiovascular risk, and raise the hypothesis that the beneficial effects of alcohol consumption may be mediated by direct effects on the myocardium.

Topics: Aged; Aspirin; Biomarkers; Cardiovascular Diseases; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Incidence; Massachusetts; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Platelet Aggregation Inhibitors; Prospective Studies; Risk Assessment; Risk Factors; Troponin T; Vitamin E; Vitamins; Women's Health

Although the relationship between malignancies and catecholamine-induced myocardial stunning remains largely speculative, it has been suggested that the presence of cancer may lower the threshold for stress stimuli and/or may aggravate cardiac adrenoreceptor sensitivity. We sought to investigate whether associations exist between a previous or current diagnosis of malignancy, diagnostic parameters during hospitalization and death in takotsubo.. The 154 takotsubo patients were retrospectively identified between May 2008 and December 2014. Previous history of malignancy was identified in 44 patients (28.5%). Cardiac arrest was present at admission in 13 patients (8.4%). Intra-aortic balloon pump was inserted in 16 patients (10.4%). In patients with malignancy, higher B-type natriuretic peptide (BNP), leukocyte and C-reactive protein (CRP) peaks could be observed during the hospital phase. Initial impairment of left ventricular ejection fraction was negatively related to BNP, leukocyte, and CRP peaks. At a median follow-up of 364 days, all-cause death occurred in 41 patients (26.6%) and cardiac death in 12 patients (7.7%). Multivariate Cox regression analysis identified malignancy (hazard ratio 4.77 (1.02-22.17), leukocyte peak and age as independent predictors of cardiac death. Malignancy (2.62 (1.26-5.44), leukocyte peak (1.05 (1.01-1.08) and initial cardiac arrest (6.68 (2.47-18.01) were identified as independent predictors of overall mortality.. In the present takotsubo patients, the prevalence of malignancy was high and may have affected cardiovascular outcomes through the activation of inflammatory and neurohormonal mechanisms. (Circ J 2016; 80: 2192-2198).

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Female; Humans; Leukocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Prevalence; Retrospective Studies; Stroke Volume; Takotsubo Cardiomyopathy

The role that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins T (cTnT) and I (cTnI) play in supplementing imaging to screen for cardiac late effects remains controversial and the impact of high-sensitivity cTnT and troponin-specific autoantibodies (cTnAAbs) remains unexplored. We studied the role of cardiac biomarkers as indicators of the late effects of anthracyclines among childhood cancer survivors.. We measured NT-proBNP, cTnT, high-sensitivity cTnT, cTnI and cTnAAbs in 76 childhood cancer survivors at a median of 9 years after primary diagnosis. The survivors underwent conventional and real-time three-dimensional echocardiography and 62 underwent cardiac magnetic resonance imaging (MRI).. Of the survivors, four (5.3%) without risk factors for cardiotoxicity were cTnAAb-positive with an impaired cardiac function in MRI. Another four (5.3%) had an abnormal NT-proBNP level associated with an abnormal cardiac function and risk factors for cardiotoxicity. None showed measurable cardiac troponins, determined by the three different methods, with even the high-sensitivity cTnT-levels remaining normal.. Elevated plasma NT-proBNP or cTnAAbs indicated that childhood cancer survivors benefitted from being evaluated with modern imaging, despite normal function in conventional echocardiography. However, troponins did not seem to provide additional information on the late cardiotoxicity of anthracyclines.

Topics: Adolescent; Anthracyclines; Antibiotics, Antineoplastic; Autoantibodies; Biomarkers; Cardiomyopathies; Child; Cross-Sectional Studies; Echocardiography; Female; Heart; Humans; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prospective Studies; Sensitivity and Specificity; Survivors; Troponin I; Troponin T; Young Adult

The aim of this study was to evaluate N-terminal probrain natriuretic peptides (NT-pro-BNP), cardiac troponin T, and creatinine kinase, MB isoenzyme (CK-MB) in the determination of subclinical left ventricular (LV) dysfunction by echocardiography in patients treated with doxorubicin. We performed a cross-sectional case study of systolic, diastolic function and tissue Doppler imaging by echocardiography in children with cancer who received a certain cumulative dose of doxorubicin. Blood levels for NT-pro-BNP, cardiac troponin T, and CK-MB were analyzed within 6 hours of the cardiac study. Of 30 patients, 5 (16.7%) had LV dysfunction with an abnormally high NT-pro-BNP level of 363 ± 78 pg/mL, whereas patients with normal LV function had an NT-pro-BNP level of 148 ± 173 pg/mL (P = 0.012). The NT-pro-BNP level not only inversely correlated with fractional shortening (r = -0.43, P = 0.017) and ejection fraction (r = - 0.45, P = 0.013) but also correlated with mitral deceleration time ( r = 0.41, P = 0.021) and a cumulative dose of doxorubicin (r = 0.44, P = 0.014). For tissue Doppler imaging, NT-pro-BNP correlated with a peak systolic velocity at the myocardial segment (Sm) (r = -0.40, P = 0.027). NT-pro-BNP is a sensitive test and has a moderate relationship with the LV systolic and diastolic function, thus making it a useful cardiac marker for the monitoring of early anthracycline cardiotoxicity.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Child; Child, Preschool; Creatine Kinase, MB Form; Cross-Sectional Studies; Diastole; Dose-Response Relationship, Drug; Doxorubicin; Drug Monitoring; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Stroke Volume; Systole; Troponin T; Ventricular Dysfunction, Left

rhuMAb 2C4 (pertuzumab, RO4368451), a human epidermal growth factor receptor-2 (HER2) targeted antibody that binds to an epitope distinct from trastuzumab, blocks ligand-associated heterodimerization of HER2 with other HER receptor family members. This study evaluated the toxicity, pharmacokinetics and anti-tumor activities of pertuzumab in Japanese patients with solid tumors.. Patients with solid tumors refractory to standard therapy were administered pertuzumab 5, 10, 15, 20 and 25 mg/kg intravenously once every 3 weeks. Grade 3 toxicities were considered as dose limiting. The maximum tolerated dose (MTD) was a dose at which two out of six patients had Grade 3 toxicities.. Eighteen patients, aged 38-66 (median 57) years, with solid tumors were enrolled and a total of 32 cycles of pertuzumab were administered. Toxicities were generally acceptable. Grade 3 elevation of gamma-glutamyl transpeptidase was observed in one patient at 25 mg/kg and was considered to be dose limiting. MTD was not reached up to a dose level of 25 mg/kg. The serum concentration of pertuzumab declined slowly (terminal half-life is approximately 3 weeks). The AUC proportionally increased over the dose range tested. There was limited evidence of activity (stable disease 2; progressive disease 13; and not evaluable 3); however, tumor shrinkage and tumor marker decrease were observed in an ovarian cancer and a non-small-cell lung cancer patient, respectively.. Pertuzumab is well tolerated up to 25 mg/kg. Although objective tumor response was not observed, it is worth evaluating as a flat dose and in combination with other cytotoxics and molecular-targeted agents.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Area Under Curve; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Diarrhea; Digestive System Neoplasms; Drug Eruptions; Female; Humans; Hypersensitivity; Lung Neoplasms; Lymphopenia; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms, Unknown Primary; Ovarian Neoplasms; Radiotherapy, Adjuvant; Receptor, ErbB-2

Cancer patients are at risk of suffering from cardiovascular diseases (CVD). Nevertheless, the impact of cardiovascular comorbidity on all-cause mortality (ACM) in large clinical cohorts is not well investigated. In this retrospective cohort study, we collected data from 40,329 patients who were subjected to cardiac catherization from 01/2006 to 12/2017 at University Hospital Heidelberg. The study population included 3666 patients with a diagnosis of cancer prior to catherization and 3666 propensity-score matched non-cancer patients according to age, gender, diabetes and hypertension. 5-year ACM in cancer patients was higher with a reduced left ventricular function (LVEF < 50%; 68.0% vs 50.9%) or cardiac biomarker elevation (high-sensitivity cardiac troponin T (hs-cTnT; 64.6% vs 44.6%) and N-terminal brain natriuretic peptide (NT-proBNP; 62.9% vs 41.4%) compared to cancer patients without cardiac risk. Compared to non-cancer patients, NT-proBNP was found to be significantly higher (median NT-proBNP cancer: 881 ng/L, IQR [254; 3983 ng/L] vs non-cancer: 668 ng/L, IQR [179; 2704 ng/L]; p < 0.001, Wilcoxon-rank sum test) and turned out to predict ACM more accurately than hs-cTnT (NT-proBNP: AUC: 0.74; hs-cTnT: AUC: 0.63; p < 0.001, DeLong's test) in cancer patients. Risk factors for atherosclerosis, such as diabetes and age (> 65 years) were significant predictors for increased ACM in cancer patients in a multivariate analysis (OR diabetes: 1.96 (1.39-2.75); p < 0.001; OR age > 65 years: 2.95 (1.68-5.4); p < 0.001, logistic regression). Our data support the notion, that overall outcome in cancer patients who underwent cardiac catherization depends on cardiovascular comorbidities. Therefore, particularly cancer patients may benefit from standardized cardiac care.

Topics: Aged; Biomarkers; Cohort Studies; Coronary Artery Disease; Diabetes Mellitus; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Retrospective Studies; Troponin T; Ventricular Function, Left

Biological age is an important risk factor for chronic diseases. We examined the associations between five markers of unhealthy ageing; Growth Differentiation Factor-15 (GDF-15), N-terminal pro-brain natriuretic peptide (NT-proBNP), glycated hemoglobin A1c (HbA1C), C-Reactive Protein (CRP) and cystatin-C; with risks of cancer and cardiovascular disease (CVD). We used a case-cohort design embedded in the EPIC-Heidelberg cohort, including a subcohort of 3792 participants along with 4867 incident cases of cancer and CVD. Hazard ratios (HRs) were computed and the strongest associations were used to build weighted multi-marker combinations, and their associations with cancer and CVD risks were tested. After adjusting for common confounders, we observed direct associations of GDF-15 with lung cancer risk, NT-proBNP with breast, prostate and colorectal cancers, HbA1C with lung, colorectal, and breast cancer risks, and CRP with lung and colorectal cancer risks. An inverse association was observed for GDF-15 and prostate cancer risk. We also found direct associations of all 5 markers with myocardial infarction (MI) risk, and of GDF-15, NT-proBNP, CRP and cystatin-C with stroke risk. A combination of the independently-associated markers showed a moderately strong association with the risks of cancer and CVD (HR

Topics: Aging; Biomarkers; Cardiovascular Diseases; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prospective Studies; Risk Factors

Topics: Biomarkers; Clinical Trials as Topic; Growth Differentiation Factor 15; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Troponin T; Venous Thromboembolism

Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction ≥53% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75;

Topics: Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Cancer Survivors; Cardiomyopathies; Cardiomyopathy, Dilated; Case-Control Studies; Child; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Stroke Volume; Ventricular Function, Left

Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage.. This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage.. The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.

Topics: Breast Neoplasms; Cardiotoxicity; Clinical Protocols; Echocardiography; Endothelial Cells; Esophageal Neoplasms; Female; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Male; Myocardial Contraction; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Radiation Dosage; Radiation Injuries; Stroke Volume; Troponin T; Ventricular Dysfunction, Left

Aim    To evaluate clinical features of the course of acute coronary syndrome (ACS) in patients with oncological diseases (OD) and to determine the role of biomarkers GDF-15, NT-proBNP, and hs-CRP in short-term and long-term prognoses.Material and methods    In 88 patients (34 patients with ACS and OD and 54 patients with ACS without OD), complaints and historical, objective, and laboratory and instrumental data were evaluated and blood concentrations of GDF-15, NT-proBNP, and hs-CRP biomarkers were measured on the first day of hospitalization. Incidence of cardiovascular complications (CVC) and outcomes of hospital and long-term (6 months) periods were analyzed. Statistical analysis of results was performed with the Statistica 12.0, MedCalc 19.1.7 software. The level of statistical significance was р<0.05.Results    In the ACS+OD group as compared to the ACS without OD group, the onset of disease was mostly atypical, with shortness of breath and/or general weakness; the ACS+OD patients more frequently had III-IV Killip class acute heart failure (29 and 7 %, р=0.01); mean hemoglobin concentration (125.6±27.9 and 141±16.6 g/l, р=0.003), prothrombin index (76.4±15.2 and 84.9±17.6 %, р=0.003), and left ventricular ejection fraction (47.7±6.1 and 50.7±7.2 %, р=0.02) were lower; and median concentrations of GDF-15 (1.95 [1.3; 2.8] and 1.45 [1.2; 2.0] ng/ml, р=0.03), NT-proBNP (947.3 [517.8; 1598.2], and 491.1 [85.1; 1069.1] pg/ml, р=0.006), and hs-CRP (14.1 [8.15; 36.75] and 7.8 [4.4; 16.2] mg/l, р=0.01) were higher. The presence of OD was associated with development of CVC, including urgent endpoints in the long-term and also increased the probability of fatal outcome within 6 months after discharge from the hospital. To predict the risk of CVC in patients with ACS and OD, two models with high prognostic values (AUC>0.9) were proposed. In the long-term, the value of NT-proBNP (cut-off point >524.5 pg/ml) was a statistically significant predictor for development of endpoints with a high predictive value (AUC>0.8).Conclusion    The features of the clinical course of ACS in patients with OD indicate the importance of isolating such patients into a separate group. Additional use of the developed models, along with a standard risk assessment by the GRACE scale, will allow individualized management of patients with ACS and OD during the hospital and long-term (6 months) periods.

Topics: Acute Coronary Syndrome; Biomarkers; C-Reactive Protein; Growth Differentiation Factor 15; Hospitals; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prognosis; Stroke Volume; Ventricular Function, Left

Topics: Adult; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antigens, Surface; Antineoplastic Agents; Antioxidants; Antiviral Agents; Aporphines; Atherosclerosis; Benzoyl Peroxide; beta Catenin; Biofilms; Biomarkers; Brain; Cannabis; Carcinoma, Squamous Cell; Case-Control Studies; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Child; China; Chlorides; Chlorophyll; Cholesterol, LDL; Coinfection; Corylus; Cross-Sectional Studies; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Developmental Disabilities; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Electroencephalography; Environmental Exposure; Enzyme Inhibitors; Epilepsy, Generalized; Ethnicity; Female; Fertilization in Vitro; Fluorescent Dyes; Follow-Up Studies; Forecasting; Glutamate Carboxypeptidase II; Glycine; Half-Life; Head and Neck Neoplasms; Health Communication; Heart Ventricles; Hepacivirus; Hepatitis C; Heterosexuality; HIV Infections; Humans; Hypercholesterolemia; Immunoassay; Inhalation Exposure; Isocitrate Dehydrogenase; Laryngeal Neoplasms; Ligands; Light; Lipopolysaccharide Receptors; Liver Cirrhosis; Lung; Lung Neoplasms; Magnetic Resonance Imaging, Cine; Male; Maternal Age; Mechanical Phenomena; Mice; Mice, Nude; Mice, SCID; Microglia; MicroRNAs; Microscopy, Fluorescence; Microsomes, Liver; Middle Aged; Minority Groups; Mitochondrial Membrane Transport Proteins; Models, Biological; Molecular Structure; Molecular Weight; Monte Carlo Method; Muscle Hypotonia; Mutagenesis, Site-Directed; Mutation, Missense; Natriuretic Peptide, Brain; Neoplasms; Nickel; Nitric Oxide; Optical Imaging; Oxides; Particle Size; Particulate Matter; PCSK9 Inhibitors; Peptide Fragments; Phenotype; Photochemotherapy; Photosensitizing Agents; Phytochemicals; Piper; Placenta Growth Factor; Plant Extracts; Plant Leaves; Plant Stems; Platinum; Point-of-Care Testing; Population Surveillance; Postpartum Period; Pregnancy; Pregnancy, Twin; Prevalence; Prospective Studies; Prostatic Neoplasms; Pseudomonas aeruginosa; Pyridines; Pyridones; Racial Groups; Rats; Respiratory Physiological Phenomena; Retrospective Studies; Risk Factors; RNA, Long Noncoding; Semiconductors; Sexual and Gender Minorities; Sexual Behavior; Social Media; Sodium; Solubility; Stereoisomerism; Stochastic Processes; Structure-Activity Relationship; Substance-Related Disorders; Sustained Virologic Response; Sweat; Temperature; Time Factors; Tissue Distribution; Titanium; Transplantation, Heterologous; Tumor Cells, Cultured; Tungsten; Tyramine; United States; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Veterans; Xenograft Model Antitumor Assays; Young Adult

This study aimed to examine the correlation between early brain natriuretic peptide (BNP) levels and mortality in cancer patients with septic shock.. A retrospective analysis of 159 cancer patients with septic shock admitted to the intensive care unit (ICU) from Dec. 2012 to Dec. 2019 was performed. BNP levels and other variables, including blood lactate (Lac), procalcitonin (PCT), white blood cell (WBC) counts, acute physiology and chronic health status system II scores (APACHE-II scores) were collected within 24 hours after ICU admission. According to 28-day mortality, patients were divided into a death group (60 cases) and a survival group (99 cases). All variables were compared by univariate analysis, and then a multiple logistic regression analysis was performed on the variables that showed significant differences. Receiver operating characteristic curve (ROC curve) analysis was used to evaluate the predictive value of BNP on mortality in cancer patients with septic shock.. BNP, APACHE-II score, Lac, and PCT in the death group were significantly higher than those in the survival group (P<0.05). Multiple logistic regression analysis of these four variables indicated that BNP, APACHE-II score and Lac were independent risk predictors of mortality in these patients (P<0.05). The BNP level at 899.6 pg/mL predicted mortality with a sensitivity of 76.7% and a specificity of 84.7%. The area under the ROC curve was 0.86±0.03 (P<0.05) for BNP, which was significantly larger than that of the APACHE-II score (P<0.05) and Lac (P<0.05).. BNP was an independent risk factor for mortality in cancer patients with septic shock, and had a higher predictive value than the APACHE-II score and Lac.

Topics: Humans; Natriuretic Peptide, Brain; Neoplasms; Prognosis; Retrospective Studies; Shock, Septic

This article aimed to study the value of brain natriuretic peptide (BNP) and cardiac troponin I(cTnI) for predicting the prognosis in cancer patients with sepsis.. A cohort of 233 cancer patients with sepsis admitted to our ICU from January 2017 to October 2020 was included in this retrospective study. The data of BNP and cTnI on the first day (d1) and the third day(d3) after entering ICU, blood lactate (Lac), procalcitonin (PCT), Leucocyte and Sequential Organ failure assessment (SOFA) scores within 24 hr of entering ICU, the incidence of septic shock, acute kidney injury(AKI), acute respiratory failure (ARF) or sepsis-induced myocardial dysfunction(SIMD) in ICU, fluid balance in 24 hr and 72 hr after entering ICU, time of mechanical ventilation(MV), length of stay, emergency surgery were collected. According to 28-day mortality, patients were divided into survival group (190 cases) and death group (43 cases). All the above variables were compared.. BNP was an independent predictor for the mortality in these patients (P < 0.05).While cTnI was not. BNP on d3 in 681.5 pg/ml predicted the mortality with a sensitivity of 91.5 % and a specificity of 88.7 %. All patients were divided into the new two groups following the cutoff value of BNP on d3(681.5pg/ml), and the survival curve showed a significant difference with Kaplan-Meier analysis (P < 0.05). BNP had statistical differences between four groups based on the comorbidities(septic shock, AKI, ARF or SIMD), but cTnI was not.. BNP was a great predictor for the prognosis of cancer patients with sepsis, while cTnI was not.

Topics: Biomarkers; Cohort Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Predictive Value of Tests; Prognosis; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Sepsis; Survival Analysis; Troponin I

Patients undergoing chemotherapy are extremely vulnerable to cardiotoxicity. Early detection of cardiac dysfunction is of vital importance to optimize the management of these patients.. The aim of this study was to test the effectiveness of non-invasive hemodynamic whole-body bioimpedance (WBI) technology as a modality to detect heart failure in patients undergoing chemotherapy treatment.. This retrospective observational trial included 84 patients treated at the cardio-oncology outpatient clinic of the Rabin Medical Center. Clinical assessments were performed including biomarker testing and measurement of hemodynamic and volume status parameters as measured by WBI.. We included 84 patients with a median age of 64.8 years, and 40.5% were males. Clinical heart failure was detected in 43% of the whole group. Patients were divided into two groups according to baseline NT-proBNP levels with a cut-off of 900 pg/mL. Left ventricular ejection fraction did not differ between the groups. Those with NT-proBNP >900 pg/mL had lower levels of stroke index, cardiac index, and Granov-Goor index (GGI; 25.9 vs. 34.0, 2.0 vs. 2.3, 8.3 vs. 11.4, respectively, with p < 0.001 for all comparisons). The optimal cut-off value for the GGI to detect NT-proBNP >900 pg/mL was 8.3. The area under the curve of a GGI cut-off <8.3 to detect NT-proBNP >900 pg/mL was 0.81 (positive predictive value 95% and negative predictive value 72%), with a 51% sensitivity and 98% specificity.. GGI, a parameter measured by WBI, can reliably correlate to biomarker evidence of heart failure in patients after chemotherapy. Its use as a screening tool for cardiotoxicity in patients with ongoing anticancer therapy is promising.

Topics: Biomarkers; Early Detection of Cancer; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Retrospective Studies; Stroke Volume; Ventricular Function, Left

Topics: Biomarkers; Brain; Cardiotoxicity; Heart Failure; Humans; Natriuretic Peptide, Brain; Neoplasms; Troponin

Anthracycline is used to treat various types of cancer; however, cardiotoxicity negatively affects patient prognosis.. The aim of the present study was to investigate serial changes in levels of cardiac troponin I (TnI) and B-type natriuretic peptide (BNP) in patients treated with anthracycline-containing therapy.. 91 consecutive cancer patients planned for anthracycline treatment were enrolled and followed up for 12 months. All patients underwent echocardiography and blood sampling at baseline, 3, 6, and 12 months.. The patients were divided into two groups based on their TnI level during the follow-up period: the elevated TnI group (TnI ≥0.03 ng/mL; n = 37) and the normal TnI group (n = 54). In the elevated TnI group, the TnI levels increased at 3 and 6 months, but they returned to within normal range at 12 months after anthracycline administration. Unlike TnI, the BNP levels began to increase after 6 months, and remained increased at 12 months. The occurrence of cancer therapeutics-related cardiac dysfunction was higher in the elevated TnI group than in the normal TnI group. When we set the cut-off value of TnI at 0.029 ng/mL, sensitivity and specificity to predict an elevated BNP level of more than 100 pg/mL were 90 and 63%, respectively. Multivariate logistic regression analysis revealed that elevated TnI was an independent predictor of elevated BNP levels.. Elevated TnI was an independent predictor for the development of BNP increase. The different characteristics of TnI and BNP should be considered when managing patients treated with anthracycline-containing therapy.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Cardiotoxicity; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Predictive Value of Tests; Troponin I

Topics: Betacoronavirus; Biomarkers; Child; Coronavirus Infections; COVID-19; Heart Diseases; Heart Failure; Humans; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Neoplasms; Pandemics; Peptide Fragments; Pneumonia, Viral; Renal Insufficiency, Chronic; SARS-CoV-2; Troponin I; Troponin T; Virus Diseases

GDF-15 is an established cardiovascular risk marker but is equally implicated in tumour biology. Elevated levels of GDF-15 have indeed been observed in distinct tumour entities. This study aimed to explore the relation of GDF-15 to other cardiac biomarkers and the general association of GDF-15 on prognosis in an unselected cohort of treatment-naïve cancer patients.. We prospectively enrolled 555 consecutive patients at time of diagnosis of malignant disease prior receiving anticancer therapy. Plasma GDF-15 concentrations were determined alongside other cardiac and routine laboratory markers. All-cause mortality was defined as primary endpoint.. GDF-15 levels were 338 ng/L (IQR:205-534) for the total cohort, and values were comparable for different tumour entities except breast cancer. Metastatic disease was characterized by higher plasma GDF-15 [435 ng/L (IQR:279-614) vs 266 ng/L (IQR:175-427), P < .001]. GDF-15 correlated positively with inflammatory status reflected by CRP, SAA and IL-6 [r = .31, P < .001, r = .23, P < .001 and r = .14, P = .002] and cardiac biomarkers as NT-proBNP, hsTnT, MR-proADM and CT-proET-1 [r = .46; r = .46; r = .59 and r = .50; P < .001 for all]. GDF-15 was significantly associated with all-cause mortality after multivariate adjustment [adj.HR for ln(GDF-15) 1.78, 95%CI:1.47-2.16, P < .001]. There was a significant interaction between solid and haematological malignancies with loss of association of GDF-15 with outcome in myelodysplastic and myeloproliferative disease.. Elevated plasma GDF-15 is associated with progressing disease severity and poor prognosis in solid tumours of treatment-naïve cancer patients. GDF-15 increase is accompanied by worsening systemic inflammation and a subclinical functional impairment of different organs including the heart. GDF-15 represents a promising target for our pathophysiologic understanding in cardio-oncology linking conditions of both cardiac and neoplastic disease.

Topics: Adrenomedullin; Aged; Breast Neoplasms; C-Reactive Protein; Cause of Death; Endothelin-1; Female; Gastrointestinal Neoplasms; Glycopeptides; Growth Differentiation Factor 15; Humans; Interleukin-6; Lung Neoplasms; Male; Middle Aged; Mortality; Myelodysplastic Syndromes; Myeloproliferative Disorders; Natriuretic Peptide, Brain; Neoplasm Metastasis; Neoplasms; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Serum Amyloid A Protein; Troponin T

Severe aortic stenosis (AS) is considered as an independent risk factor for perioperative cardiac complications of non-cardiac surgery. Surgical aortic valve replacement should be considered before non-cardiac surgery in patients with symptomatic severe AS. However, recently, transcatheter aortic valve replacement (TAVR) has emerged as an alternative approach for selected AS patients. We sought to determine the safety and efficacy of TAVR in preparation for major non-cardiac surgery. From our retrospective database, seven patients who underwent TAVR in preparation for major non-cardiac surgery were identified, and their clinical and hemodynamic data were collected. After TAVR, a significant reduction in the mean transaortic pressure gradient from 54.0 (Interquartile range (IQR) 47.5-64.5) to 18.0 (IQR 12.5-19.0) mmHg (p = 0.016) and an increase in the calculated aortic valve area from 0.6 (IQR 0.6-0.7) to 1.3 (IQR 1.1-1.5) cm

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Retrospective Studies; Transcatheter Aortic Valve Replacement

Mean platelet volume (MPV) is a risk factor for cardiovascular and inflammatory diseases.. To evaluate the association between high MPV and 90-day mortality after an episode of venous thromboembolism (VTE).. Retrospective cohort of 594 patients with a median age of 73 years (58% women) with a first episode VTE, included in an institutional Thromboembolic Disease registry between 2014 and 2015. MPV values were obtained from the automated blood cell count measured at the moment of VTE diagnosis. Volumes ≥ 11 fL were classified as high. All patients were followed for 90 days to assess survival.. The main comorbidities were cancer in 221 patients (37%), sepsis in 172 (29%) and coronary artery disease in 107 (18%). Median MPV was 8 fl (8-9), brain natriuretic peptide 2,000 pg/ml (1,025-3,900) and troponin 40 pg/ml (19.5-75). Overall mortality was 20% (121/594) during the 90 days of follow-up. Thirty three deaths occurred within 7 days and 43 within the first month. The loss of patients from follow-up was 5% (28/594) at 90 days. Mortality among patients with high MP was 36% (23/63). The crude mortality hazard ratio (HR) for high MPV was 2.2 (95% confidence intervals (CI) 1.4-3.5). When adjusted for sepsis, oncological disease, heart disease, kidney failure and surgery, the mortality HR of high MPV was 2.4 (CI95% 1.5-3.9) in the VTE group, 2.3 (CI95% 1.5-4.4) in the deep venous thrombosis group, and 2.9 (CI95% 1.6 -5.6) in the pulmonary embolism group.. High MPV is an independent risk factor for mortality following an episode of VTE.

Topics: Acute Disease; Aged; Aged, 80 and over; Blood Platelets; Female; Follow-Up Studies; Humans; Male; Mean Platelet Volume; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prognosis; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Risk Factors; Sepsis; Survival Analysis; Troponin; Venous Thromboembolism; Venous Thrombosis

Elevated BNP is associated with adverse cardiac outcomes after noncardiac surgery. We assessed BNP values as markers of perioperative fluid status and their correlation with major/cardiopulmonary (CP) complications following CRS + HIPEC.. Fluid balance, BNP levels, and morbidity data were collected for all patients undergoing CRS + HIPEC between 6/2014 and 2/2016.. One hundred and twenty-nine patients underwent CRS + HIPEC for appendiceal adenocarcinoma (n = 99), mesothelioma (n = 16), and colon cancer (n = 14). Less than 10% had CP comorbidities. The median PCI was 14 (range 4-39); 89% underwent CC0/1 resection (n = 115). Median blood loss (EBL) was 497 mL (50-2700). Major complications (Clavien III-V) occurred in 16 (12%), CP in 17 (13%), and major/CP in 24 (18%). Thirty-day mortality occurred in 2 (1.5%). Elevated BNP on POD1 correlated with increased risk of major/CP complications (OR 2.2, P = 0.052). This was most pronounced in the 25 patients receiving cisplatin: for each 100 unit increase in POD1 BNP the OR for major/CP complication was 7.4 versus 1.2 for the remaining patients, P = 0.083. Multivariate analysis identified increased EBL (OR 4.1 P = 0.011) and a trend toward increased BNP on POD1 (OR for each 100 unit increase 2.0, P = 0.10) as risk factors for major/CP complications.. Postoperative BNP measurement after CRS + HIPEC may guide postoperative fluid resuscitation and facilitate identification of patients at risk for major and/or cardiopulmonary complications.

Topics: Adenocarcinoma; Adult; Aged; Appendiceal Neoplasms; Brain; Colonic Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Female; Humans; Hyperthermia, Induced; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Predictive Value of Tests; Retrospective Studies; Young Adult

Asymptomatic diastolic dysfunction (DD) with preserved left ventricular ejection fraction (LVEF) is suspected to precede late cardiac events in cancer survivors treated by chemotherapy. We conducted the first multicenter study of early DD induced by chemotherapy. Patients who were candidates for standard dose chemotherapy were screened for the absence of cardiovascular risk factors, LVEF ≥50%, normal-for-age diastolic function at echocardiography (E/A ratio, E wave deceleration time; DT), normal levels of potential DD biomarkers like Nt-proBNP (≤125 pg/mL), and cardiac troponin I (cTnI, ≤0.05 ng/mL). Mitral Doppler (E/E') was left at the investigator's discretion. Chemotherapy-induced DD with preserved LVEF was diagnosed for patients showing LVEF ≥50% and any of the following: Nt-proBNP > 125 pg/mL, cTnI > 0.05 ng/mL, and out-of-range E/A and DT. Eighty patients (68 females, 12 males, median age 49 years) were evaluated at 1 week after chemotherapy (T1) [corrected]. Thirty-three protocol-defined diastolic events were observed (15 Nt-proBNP > 125 pg/mL, 14 grade I DD by E/A and DT, 4 cTnI > 0.05 ng/mL). The events occurred in 29 asymptomatic patients with LVEF ≥50% (36% incidence of DD with preserved LVEF). Interactions occurred between biomarkers and grade I DD. E/E' abnormalities were not observed. Both anthracycline-based and nonanthracycline regimens induced DD. These findings show that biomarkers and echocardiography intercept early DD in otherwise asymptomatic low-risk cancer patients treated by standard dose chemotherapy. These findings therefore call for the adequate cardiac management of cancer patients.

Topics: Adult; Antineoplastic Agents; Biomarkers; Case-Control Studies; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Troponin I; Ventricular Dysfunction, Left

We have reported that cancer patients treated with anthracycline-based or nonanthracycline chemotherapy developed an early impairment of myocardial relaxation at echocardiography or persistent elevations of the cardiac hormone B-type natriuretic peptide (BNP). Post-hoc pharmacologic analyses showed that BNP elevations were induced by impaired relaxation and caused positive lusitropic effects that maintained normal relaxation. High BNP levels and impaired relaxation were therefore characterized as mutually exclusive manifestations of diastolic dysfunction, but high BNP levels resulted in positive chronotropism and inappropriate tachycardia. Some patients developed increased circulating levels of cardiac troponin I isoform (cTnI), a marker of cardiomyocyte necrosis. Here we have characterized whether cTnI elevations correlated with diastolic dysfunction that manifested as impaired relaxation or a high level of BNP. The effects of high BNP levels on cTnI elevations were also characterized. We show that impaired relaxation or high BNP levels were significantly more frequent in patients with cTnI elevations. High BNP levels diminished the plasma peak and area under the curve of cTnI, but this result was accompanied by inappropriate tachycardia. cTnI elevations occurred only in patients treated with anthracyclines; moreover, the association of impaired relaxation or high BNP levels with cTnI elevations was significantly more frequent in doxorubicin-treated patients compared with patients treated with its analog, epirubicin. These findings describe cause-and-effect relations between impaired relaxation and cardiomyocyte necrosis, illuminate the role of anthracycline analogs, denote that the beneficial effects of BNP in relieving impaired relaxation and cardiomyocyte necrosis are counterbalanced by inappropriate tachycardia. Patients showing troponin elevations and impaired relaxation or high BNP levels should be treated with lusitropic drugs that lack a positive chronotropism.

Topics: Adult; Anthracyclines; Biomarkers; Doxorubicin; Epirubicin; Female; Heart; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Necrosis; Neoplasms; Pilot Projects; Troponin I

Natriuretic peptides have been proposed as biomarkers of cardiovascular disease, especially heart failure. Brain natriuretic peptide (BNP) has also been shown to be upregulated at the transcriptional and translational levels by pro-inflammatory cytokines in cardiac myocytes. Although we often measure plasma BNP levels in cancer patients, it remains unknown whether cancer-related inflammation affects the plasma BNP levels. We investigated the relationship between the BNP and human cancers.. We retrospectively studied 2,923 patients in whom the plasma BNP levels and serum C-reactive protein (CRP) were measured and echocardiography was performed. Patients with clinically evident heart failure (NYHA II or higher), heart disease requiring medical treatment or surgery, renal dysfunction, and inflammatory disease were excluded. There were 234 patients in the final analysis. Blood sampling was performed before surgery and chemotherapy. In addition, we evaluated the relationship between the inflammation and plasma BNP levels in mouse models of colon cancer.. Of the 234 patients, 80 were diagnosed with cancer. Both the plasma BNP and serum CRP levels were significantly higher in cancer patients than those without. There were no significant differences in the echocardiographic parameters. There was a significant positive correlation between the plasma BNP and serum CRP levels in cancer patients (r = 0.360, P<0.01) but not in those without. In cancer patients, only the CRP correlated with the BNP independent of the age, creatinine level, hypertension, and body mass index. In addition, in nude mice with subcutaneous colon cancer, the plasma BNP level was elevated compared with that in non-cancer mice, and there was a significant relationship between the plasma BNP and serum levels of the inflammatory markers.. In cancer patients, as well as colon cancer model mice, the plasma BNP levels were elevated, possibly due to cancer-related inflammation. The effect of cancer on the BNP levels should be considered when using BNP as an indicator of heart failure in cancer patients.

Topics: Animals; Body Mass Index; C-Reactive Protein; Creatinine; Disease Models, Animal; Female; Humans; Mice; Natriuretic Peptide, Brain; Neoplasms; Regression Analysis; Retrospective Studies

Drug-induced cardiomyopathy can be life-threatening in patients with cancer. Our objective was to explore early detection of drug-induced cardiomyopathy in children with cancer. We enrolled pediatric outpatients diagnosed with cancer between 2012 and 2013. In addition, we recruited pediatric outpatients in good general condition without cardiac disease or cancer, as controls. We measured the serum levels of biomarkers and performed chest radiography, electrocardiography, and ultrasound cardiography (UCG). We analyzed left ventricular (LV) torsion and torsion-related parameters using 2-dimensional (2D) speckle tracking on UCG. In total, 35 pediatric patients were enrolled. All patients showed negative findings for plasma troponin T, radiography, and electrocardiography. During 2D speckle tracking, 9 patients were excluded due to inappropriate dynamic echo images. We compared UCG findings between 26 patients and 16 controls. Although there was no difference in ejection fraction between patients and controls, peak LV torsion tended to be lower in patients than in controls, and the absolute basal rotation value at the timing of peak LV torsion was significantly lower in patients than in controls. In conclusion, a decrease of basal rotation in 2D speckle tracking might indicate the initial changes leading to myocardial disorder after chemotherapy.

Topics: Adolescent; Anthracyclines; Antineoplastic Agents; Biomarkers; Bone Marrow Transplantation; Cardiomyopathies; Child; Chronic Disease; Cyclophosphamide; Early Diagnosis; Echocardiography; Electrocardiography; Female; Heart Ventricles; Humans; Maintenance Chemotherapy; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Radiography, Thoracic; Rotation; Stroke Volume; Troponin T

To evaluate the feasibility and correlation of 3D echocardiography (echo) and cardiac biomarkers with cardiac MRI, in surveillance of cardiac function for cancer survivors.. Subjects ≥10 years of age who have survived >2 years after completion of cancer treatment from a single center were enrolled. Cardiac MRI and 3D echo images were obtained on the same day when routine echo was obtained. On the same day, along with annual routine blood test, cardiac biomarkers N-terminal pro-B-type natriuretic peptide levels (NT-proBNP) and troponin-I levels were also measured.. Cardiac MRI was feasible in all 50 subjects. Three-dimensional echo and 2D echo images were of poor quality in four subjects. With a median duration of remission of 10 years, there were four subjects with mild LV dysfunction (cardiac MRI LV EF of<53%). None had MRI EF <50%, and nine subjects had LVEF <55%. M-mode echo overestimated EF more than 2D and 3D echo. Two-dimensional and 3D echo methods had much tighter limits of agreement for LV EF. For measurement of LVEF, 3D echo had a lower % error than 2D echo or M-mode echo. One subject had an abnormal troponin-I level and another one had an elevated NT-proBNP.. Three-dimensional echo can be performed in most adolescent cancer survivors, and it correlates well with MRI. Further large-scale research is required in assessing utility of cardiac biomarkers in pediatric cancer survivors.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Echocardiography, Three-Dimensional; Feasibility Studies; Heart; Humans; Infant; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Survivors; Troponin I

Recognizing heart disease is relevant to oncologists because cancer patients are at an increased risk of cardiac mortality due to shared risk factors and the adverse effects of cancer therapy. This study assessed the extent to which the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) aids in the diagnosis of heart disease in addition to a history of coronary artery disease and the presence of atrial fibrillation (composite test). The NT- proBNP cutoff value was 100 pg/ml.. A series of 583 consecutive cancer patients (68.4 ± 11.0 years) who were referred because of cardiac or pulmonary symptoms prospectively underwent a diagnostic work-up. Heart disease was diagnosed if at least one of the following conditions was present: (a) history of coronary artery disease, (b) atrial fibrillation, (c) impaired left ventricular systolic function, (d) significant valvular disease, (e) pulmonary hypertension, or (f) left ventricular hypertrophy.. Except for (a), all 6 conditions were associated with NT-proBNP >100 pg/ml. The sensitivity/specificity values of the composite test were 0.92/0.50 for any heart disease. Several extracardiac covariates were associated with NT-proBNP >100 pg/ml, which contributed to the low test specificity.. The low specificity of NT-proBNP limits its value for the diagnosis of heart disease in cancer patients.

Topics: Adult; Aged; Atrial Fibrillation; Biomarkers; Coronary Artery Disease; Female; Heart Diseases; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Predictive Value of Tests; Research Design; Sensitivity and Specificity; Ventricular Dysfunction, Left

The purpose of this pilot study was to evaluate the usefulness of selected echocardiographic parameters, NT-proBNP and cardiac troponin I (cTnI) in the detection of cardiotoxicity in dogs treated with doxorubicin for various malignancies. Echocardiographic studies and biomarker measurements were performed before each administration of doxorubicin, then 1 and 3 months after completion of therapy. Thirteen dogs were included, with a total cumulative dose of doxorubicin ranging from 30 to 150 mg/m(2). E/A ratio significantly decreased during doxorubicin administration (p=0.047). cTnI level was also significantly affected by treatment (p=0.046), increasing above normal at least at one time point in 11 of 13 dogs. The results of this pilot study suggest that monitoring of left ventricular diastolic function and cTnI level measurement might be useful in the early detection of cardiotoxic signs of doxorubicin therapy in dogs.

Topics: Animals; Antibiotics, Antineoplastic; Biomarkers; Cardiotoxicity; Diastole; Dogs; Doxorubicin; Echocardiography, Doppler; Female; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Pilot Projects; Prospective Studies; Troponin I; Ventricular Function, Left

Anthracycline chemotherapy is associated with an increased risk of developing heart failure (HF). The current standard for detecting HF or cardiotoxicity during chemotherapy involves episodic cardiac imaging typically at prescribed intervals and there are limited studies examining techniques beyond measuring left ventricular (LV) function. This study explores whether cardiac biomarkers troponin I (TnI) and B-type natriuretic peptide (BNP) could be part of a screening strategy for early detection of the development of cardiotoxicity in patients undergoing anthracycline chemotherapy.. Patients were enrolled from a single medical center. Cardiac biomarkers (TnI, BNP) were measured before and within 24 hours after completion of anthracycline administration for each cycle of therapy. Cardiac imaging was obtained at baseline and at completion of chemotherapy (commonly at 6 or 12 months) or based on clinical suspicion of a cardiac event. Of the enrolled 109 patients, 11 (10.1%) experienced cardiac events; all of these patients had at least 1 BNP value >100 pg/mL before the cardiac event. Significant reduction in LV ejection fraction as defined for cardiotoxicity occurred in only 3 of 10 patients (30%) with a cardiac event.. The use of cardiac biomarkers, particularly BNP, may allow early detection of cardiotoxicity related to anthracycline chemotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anthracyclines; Biomarkers; Cardiotoxicity; Feasibility Studies; Female; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Point-of-Care Systems; Troponin I; Young Adult

An increasing awareness of chemotherapy and radiotherapy as preventable causes of cardiac failure among large numbers of patients surviving cancer has contributed to the development of cardio-oncology as a subspecialty. Perhaps the most important driver has been that the aging of the population undergoing cancer therapy has provided an increasing number of patients at risk for the development of heart failure. Cardio-oncology has many unresolved questions. In this article the 6 most important unresolved issues requiring additional research are discussed: (1) the frequency of overt heart failure as a manifestation of cardiotoxicity; (2) the optimal diagnostic approach to cardiotoxicity in the context of large numbers of patients requiring repeated testing; (3) the need for better risk prediction; (4) alternatives to the use of ejection fraction as the cornerstone of evaluation; (5) definition of the best strategy for protection; and (6) the need for evidence-based algorithms to guide late follow-up. When this evidence base is mature, we will have a better understanding of the magnitude of the problem of cardiotoxicity, who best to screen (and how), who justifies the use of cardioprotective therapy, and how all at-risk patients should be followed over the decades following cancer therapy.

Topics: Antineoplastic Agents; Biomarkers; Cardiotonic Agents; Cardiotoxicity; Cardiotoxins; Heart Failure; Humans; Magnetic Resonance Imaging, Cine; Natriuretic Peptide, Brain; Neoplasms; Troponin; Ventricular Dysfunction, Left

Several papers have reported elevated plasma levels of natriuretic peptides in patients with a previous diagnosis of cancer. We have explored whether N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels predict a future diagnosis of cancer in patients with coronary artery disease (CAD).. We studied 699 patients with CAD free of cancer. At baseline, NT-proBNP, galectin-3, monocyte chemoattractant protein-1, soluble tumor necrosis factor-like weak inducer of apoptosis, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin I plasma levels were assessed. The primary outcome was new cancer diagnosis. The secondary outcome was cancer diagnosis, heart failure requiring hospitalization, or death.. After 2.15±0.98 years of follow-up, 24 patients developed cancer. They were older (68.5 [61.5, 75.8] vs 60.0 [52.0, 72.0] years; p=0.011), had higher NT-proBNP (302.0 [134.8, 919.8] vs 165.5 [87.4, 407.5] pg/ml; p=0.040) and high-sensitivity C-reactive protein (3.27 [1.33, 5.94] vs 1.92 [0.83, 4.00] mg/L; p=0.030), and lower triglyceride (92.5 [70.5, 132.8] vs 112.0 [82.0, 157.0] mg/dl; p=0.044) plasma levels than those without cancer. NT-proBNP (Hazard Ratio [HR]=1.030; 95% Confidence Interval [CI]=1.008-1.053; p=0.007) and triglyceride levels (HR=0.987; 95%CI=0.975-0.998; p=0.024) were independent predictors of a new cancer diagnosis (multivariate Cox regression analysis). When patients in whom the suspicion of cancer appeared in the first one-hundred days after blood extraction were excluded, NT-proBNP was the only predictor of cancer (HR=1.061; 95%CI=1.034-1.088; p<0.001). NT-proBNP was an independent predictor of cancer, heart failure, or death (HR=1.038; 95%CI=1.023-1.052; p<0.001) along with age, and use of insulin and acenocumarol.. NT-proBNP is an independent predictor of malignancies in patients with CAD. New studies in large populations are needed to confirm these findings.

Topics: Aged; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Female; Follow-Up Studies; Galectin 3; Heart Failure; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Proportional Hazards Models; Risk Factors; Triglycerides; Troponin I

Topics: Cardiovascular Diseases; Female; Glycopeptides; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Troponin T

Patients with cancer may display elevated levels of B-type natriuretic peptide (BNP) and high-sensitive troponin T (hsTnT) without clinical manifestation of cardiac disease. This study aimed to evaluate circulating cardiovascular hormones and hsTnT and their association with mortality in cancer.. We prospectively enrolled 555 consecutive patients with a primary diagnosis of cancer and without prior cardiotoxic anticancer therapy. N-terminal pro BNP (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), copeptin, hsTnT, proinflammatory markers interleukin 6 (IL-6) and C reactive protein (CRP), and cytokines serum amyloid A (SAA), haptoglobin and fibronectin were measured. All-cause mortality was defined as primary endpoint.. During a median follow-up of 25 (IQR 16-31) months, 186 (34%) patients died. All cardiovascular hormones and hsTnT levels rose with tumour stage progression. All markers were significant predictors of mortality with HRs per IQR of 1.54 (95% CI 1.24 to 1.90, p<0.001) for NT-proBNP, 1.40 (95% CI 1.10 to 1.79, p<0.01) for MR-proANP, 1.31 (95% CI 1.19 to 1.44, p<0.001) for MR-proADM, 1.21 (95% CI 1.14 to 1.30, p<0.001) for CT-proET-1, 1.22 (95% CI 1.04 to 1.42, p=0.014) for copeptin and 1.21 (95% CI 1.13 to 1.32, p<0.001) for hsTnT, independent of age, gender, tumour entity and stage, and presence of cardiac comorbidities. NT-proBNP, MR-proANP, MR-proADM and hsTnT displayed a significant correlation with IL-6 and CRP.. Circulating levels of cardiovascular peptides like NT-proBNP, MR-proANP, MR-proADM, CT-pro-ET-1 and hsTnT were elevated in an unselected population of patients with cancer prior to induction of any cardiotoxic anticancer therapy. The aforementioned markers and copeptin were strongly related to all-cause mortality, suggesting the presence of subclinical functional and morphological myocardial damage directly linked to disease progression.

Topics: Adrenomedullin; Aged; Asymptomatic Diseases; Atrial Natriuretic Factor; Austria; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Endothelin-1; Female; Glycopeptides; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Neoplasms; Peptide Fragments; Prospective Studies; Protein Precursors; Troponin T

Many studies of human subjects have demonstrated the utility of assessing serum levels of endothelin-1 (ET-1) and big ET-1 as clinical biomarkers in cardiopulmonary and neoplastic diseases. In this study we explored the feasibility of using serum big ET-1 as a reliable veterinary marker in dogs with various cardiopulmonary and neoplastic diseases.. Serum big ET-1 levels were measured by ELISA in dogs with cardiopulmonary (n=21) and neoplastic diseases (n=57). Dogs exhibiting cardiopulmonary disease were divided into two groups based on the velocity of tricuspid valve regurgitation (3.0>m/s) measured by ultrasound: without and with pulmonary hypertension. Big ET-1 levels for the dogs with the diseases were compared with levels in normal healthy dogs (n=17).. Dogs with cardiopulmonary disease (4.6±4.6 pmol/l) showed a significantly (P<0.01) higher level of big ET-1 than healthy control dogs (1.1±0.53 pmol/l). Serum levels in the dogs with pulmonary hypertension (6.2±5.3 pmol/l) were significantly (P<0.01) higher than those without pulmonary hypertension (2.0±0.6 pmol/l). Dogs with hemangiosarcoma (5.6±2.2 pmol/l), adenocarcinoma (2.0±1.8 pmol/l), histiocytic sarcoma (3.3±1.9 pmol/l), chondrosarcoma or osteosarcoma (3.0±1.6 pmol/l) and hepatocellular carcinoma (2.7±1.8 pmol/l) showed significantly (P<0.05) higher levels than healthy control dogs.. These findings point to the potential of serum big ET-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs.

Topics: Animals; Biomarkers; Cardiovascular Diseases; Dogs; Endothelin-1; Female; Humans; Lung Diseases; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments

Cardiotoxicity is a dose-limiting side-effect of cancer chemotherapeutics such as anthracyclines. The drug-induced cardiac toxicity is currently monitored with repeated assessments of the left ventricular ejection fraction (LVEF) using multigated equilibrium radionuclide ventriculography (MUGA) or echocardiography. However, the plasma cardiac biomarker B-type natriuretic peptide (BNP) has been suggested for early identification of cardiac dysfunction. The aim of the study was to compare LVEF obtained by MUGA and plasma BNP as predictors of developing congestive heart failure (CHF) or death in a population of anthracycline-treated cancer patients.. We prospectively followed 333 cancer patients referred to our department for routine monitoring of LVEF with MUGA and measurement of BNP, January-December 2004. Study end points were hospitalization for CHF and death during follow-up 2004-2010. Data were obtained from the Danish National Patient Registry.. During follow-up (mean 1,360 days), 21 of the patients were admitted to hospital with a diagnosis of CHF and 194 of the patients died. BNP levels were significantly higher and LVEF lower in the group of patients that developed CHF. Using cut-off points of BNP>100 pg/ml (HR 5.5; CI 1.8-17.2; p = 0.003) and LVEF <50% (HR 7.9; CI 3.0-21.4; p<0.001) both significantly predicted CHF. Using the same cut-off points only BNP (HR 1.9; CI 1.3-2.9; p = 0.002) and not LVEF (HR 1.1; CI 0.7-1.8; p = 0.58) was predictive of overall death. In multivariate Cox analysis both BNP and LVEF were independent predictors of CHF while age remained the only independent predictor of overall death.. In cancer patients treated with cardiotoxic chemotherapy both BNP and LVEF can significantly predict subsequent hospitalization with CHF. In addition, BNP and not LVEF has a prognostic value in detecting overall death. This prospective study based on the hitherto largest study population supports BNP as a clinical relevant method for monitoring chemotherapy-related cardiac failure and death.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Child; Female; Follow-Up Studies; Gated Blood-Pool Imaging; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Prognosis; Proportional Hazards Models; Prospective Studies; Registries; Ventricular Function, Left; Young Adult

Several factors have been associated with mortality in the months after PE. Factors associated with short-term clinical deterioration or need for hospital-based intervention are less well known.. We prospectively enrolled consecutive emergency department patients with PE and recorded clinical, biomarker and radiographic data. We assessed hospitalised patients daily to identify clinical deterioration or need for hospital-based intervention for 5 days after PE. We captured postdischarge events via 5-day and 30-day interviews. We used univariate and multivariable models to assess associations with clinical deterioration, severe clinical deterioration and 30-day all-cause mortality. We also assessed the test characteristics of three published clinical decision rules.. We enrolled 298 patients with PE: mean age 59 (SD±17) years; 152 (51%) male and 268 (90%) white race. 101 (34%) patients clinically deteriorated or required a hospital-based intervention within 5 days, and 197 (66%) did not. 27 (9%) patients suffered severe clinical deterioration and 12 died within 30 days. Factors independently associated with clinical deterioration were hypotension (p=0.001), hypoxia (p<0.001), coronary disease (p=0.004), residual deep vein thrombosis (p=0.006) and right heart strain on echocardiogram (p<0.001). In contrast, factors associated with 30-day all-cause mortality were active malignancy (p<0.001) and congestive heart failure (p=0.009). The sensitivity of clinical decision rules was moderate (39-80%) for 5-day clinical deterioration but higher (67-100%) for 30-day mortality.. Most patients do not clinically deteriorate after PE diagnosis. Several factors are associated with short-term clinical deterioration, but these factors differ from those associated with 30-day mortality.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Coronary Artery Disease; Decision Support Techniques; Disease Progression; Echocardiography; Female; Heart Failure; Humans; Hypotension; Hypoxia; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Oxygen; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Pulmonary Embolism; Radiography; Risk Assessment; Risk Factors; ROC Curve; Time Factors; Venous Thrombosis

To evaluate the relationship between plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) and weaning outcomes, and the ability of NT-proBNP level to predict weaning success, in cancer patients with pulmonary complications undergoing noncardiac major surgeries.. Patients who were mechanically ventilated following postoperative respiratory failure were enrolled. NT-proBNP levels at the end of a 2-h spontaneous breathing trial were measured. Weaning was considered a success in patients who completed the trial and maintained spontaneous breathing following extubation for >48 h.. Out of 29 patients, 22 patients weaned successfully but weaning failed in 7 patients. Plasma NT-proBNP was significantly higher in the weaning failure group than in the weaning success group. For predicting weaning success, the optimal NT-proBNP threshold value at the end of the spontaneous breathing trial was <448 ng/l (receiver operating characteristic analysis; sensitivity 68.18%, specificity 85.71%, positive predictive value 93.7% and negative predictive value 46.2%).. Measuring NT-proBNP at the end of a spontaneous breathing trial may assist in predicting weaning success, as a noninvasive, quantitative and repeatable indicator of cardiac stress in patients with postsurgical respiratory failure.

Topics: Aged; Airway Extubation; Biomarkers; Female; Humans; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Postoperative Complications; Respiration, Artificial; Respiratory Insufficiency; ROC Curve; Treatment Outcome; Ventilator Weaning; Ventilators, Mechanical

Cardiac injury is one of the complications of cancer treatment. This study aimed to investigate the relationships between the types of radiotherapy of the chest (RT), chemotherapy (CT), cancer surgery (CS) and endocrine therapy (ET), and the presence of heart disease, and their associations with the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP).. A consecutive series of 374 patients with cancer who were referred because of symptoms suggestive of heart or lung disease prospectively underwent a diagnostic workup.. The prevalence of heart disease was 36.9%. RT administered before 1995 (n = 19) was associated with both increased odds of heart disease [adjusted odds ratio 10.3, 95% confidence interval 3.1-34.0] and higher ln-transformed NT-proBNP values (p < 0.01) compared to the control group (no RT or RT for right-sided breast cancer from 1995 onwards; n = 311). Anthracycline-treated patients (n = 54) had higher adjusted values for ln(NT-proBNP) compared to the control group (no CT; n = 243; p < 0.01) but no increased odds of heart disease.. While pre-1995 RT and anthracycline-containing CT were associated with cardiac effects, there was no evidence that RT using modern cardioprotective techniques, CT in the absence of anthracyclines, CS or ET had detrimental effects on the heart.

Topics: Aged; Anthracyclines; Antineoplastic Agents; Biomarkers; Echocardiography; Female; Follow-Up Studies; Germany; Heart Diseases; Heart Ventricles; Humans; Lung Diseases; Male; Natriuretic Peptide, Brain; Neoplasms; Odds Ratio; Organs at Risk; Peptide Fragments; Prospective Studies; Radiation Dosage; Radiation Injuries; Risk Assessment; Risk Factors; Sensitivity and Specificity; Time Factors; Tomography, X-Ray Computed; Troponin T

Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24-48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.

Topics: Biomarkers; Cardiac Tamponade; Down-Regulation; Drainage; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Pericardiocentesis; Retrospective Studies; Treatment Outcome; Uremia

We sought to evaluate the associations of high-sensitivity troponin T (Hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high sensitivity C-reactive protein (Hs-CRP) with mortality from any cause, cardiovascular disease (CVD), coronary heart disease (CHD), stroke, cancer, and respiratory disease in the Atherosclerosis Risk in Communities cohort.. We included 11,193 participants aged 54 to 74 years, initially free of the conditions being studied, and who had biomarkers measured. Participants were followed for a mean of 9.9 years.. Hazard ratios (HR), adjusted for multiple risk factors, for mortality in participants in the highest Hs-TnT category compared with those with undetectable levels were: Total 3.42 (95% confidence interval [CI], 2.75-4.26); CVD, 7.34 (95% CI, 4.64-11.6); CHD, 6.06 (95% CI, 2.91-12.6); stroke, 3.31 (95% CI, 1.26-8.66); cancer, 1.60 (95% CI, 1.08-2.38); and respiratory, 3.85 (95% CI, 1.39-10.7). Comparing the highest NT-proBNP quintile with those in the lowest quintile, the adjusted HRs for mortality were: Total, 3.05 (95% CI, 2.46-3.77); CVD, 7.48 (95% CI, 4.67-12.0); CHD, 4.07 (95% CI, 2.07-7.98); and stroke, 10.4 (95% CI, 2.26-47.7). Comparing extreme Hs-CRP quintiles, the adjusted HRs for mortality were: Total, 1.61 (95% CI, 1.32-1.97); CVD, 1.76 (95% CI, 1.19-2.62); and respiratory, 3.36 (95% CI, 1.34-8.45). Having multiple markers elevated simultaneously greatly increased cause-specific mortality risks.. Greater levels of Hs-TnT, NT-proBNP and Hs-CRP are associated with increased risk of death, not just from CVD, but also from some noncardiovascular causes.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Neoplasms; Population Surveillance; Predictive Value of Tests; Prevalence; Proportional Hazards Models; Prospective Studies; Respiration Disorders; Risk Factors; Surveys and Questionnaires; Troponin T

Galectin-3 is involved in fibrosis and inflammation and plays a role in heart failure, renal disease, obesity and cancer. We aimed to establish the relationship between galectin-3 and cardiovascular (CV) risk factors and mortality in the general population.. This study included 7968 subjects from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, with a median follow-up of approximately 10 years. Plasma galectin-3 was measured in baseline samples.. We investigated the relationships between galectin-3 levels, demographic characteristics and risk factors of CV disease. We determined the prognostic value for all-cause, CV and cancer mortality.. The mean age of the population was 50 ± 13 years. Mean blood pressure was 129/74 mmHg, mean cholesterol was 5.7 ± 1.1 mmol L(-1) and median galectin-3 was 10.9 ng mL(-1) [interquartile range (IQR) 9.0-13.1]. Galectin-3 levels correlated with a wide range of risk factors of CV disease, including blood pressure, serum lipids, body mass index, renal function and N-terminal pro-B-type natriuretic peptide (P < 0.0001). We observed a strong association between galectin-3 and age. Furthermore, we found a gender interaction, with female subjects (n = 4001) having higher median galectin-3 levels (11.0 ng mL(-1) , IQR 9.1-13.4 vs. men (n = 3967) 10.7 ng mL(-1) , IQR 8.9-12.8; P < 0.0001), and galectin-3 levels in women more strongly correlated with risk factors of CV disease. After correction for the classical CV risk factors (smoking, blood pressure, cholesterol and diabetes), galectin-3 levels independently predicted all-cause mortality (hazard ratio per SD galectin-3 1.09, 95% CI 1.01-1.19; P = 0.036), but not CV and cancer mortality separately.. Galectin-3 is associated with age and risk factors of CV disease, with a strong gender interaction for these correlations. Galectin-3 predicts all-cause mortality in the general population.

Topics: Adult; Age Factors; Aged; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Confounding Factors, Epidemiologic; Female; Fibrosis; Galectin 3; Humans; Hypertension; Kaplan-Meier Estimate; Kidney; Lipids; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neoplasms; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Sex Factors

To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status.. We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls.. The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons).. Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.

Topics: Adolescent; Adult; Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; C-Reactive Protein; Child; Child, Preschool; Cholesterol; Coronary Artery Disease; Echocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Retrospective Studies; Risk Assessment; Risk Factors; Siblings; Survivors; Time Factors

Light's criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Light's criteria has been reported, especially in the setting of diuretic use in patients with heart failure (HF). The objective of this study was to evaluate the utility of B-type natriuretic peptide (BNP) measurements as a diagnostic tool for determining the cardiac aetiology of pleural effusions.. Patients with pleural effusions attributable to HF (n = 34), hepatic hydrothorax (n = 10), pleural effusions due to cancer (n = 21) and pleural effusions due to tuberculosis (n = 12) were studied. Diagnostic thoracentesis was performed for all 77 patients. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic accuracy of plasma BNP and pleural fluid BNP for the prediction of HF.. The areas under the ROC curves were 0.987 (95% CI 0.93-0.998) for plasma BNP and 0.949 (95% CI 0.874-0.986) for pleural fluid BNP, for distinguishing between patients with pleural effusions caused by HF (n = 34) and those with pleural effusions attributable to other causes (n = 43). The cut-off concentrations with the highest diagnostic accuracy for the diagnosis of HF as the cause of pleural effusion were 132 pg/mL for plasma BNP (sensitivity 97.1%, specificity 97.4%) and 127 pg/mL for pleural fluid BNP (sensitivity 97.1%, specificity 87.8%).. In patients with pleural effusions of suspected cardiac origin, measurements of BNP in plasma and pleural fluid may be useful for the diagnosis of HF as the underlying cause.

Topics: Adult; Aged; Aged, 80 and over; Female; Heart Failure; Humans; Hydrothorax; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Paracentesis; Pleural Effusion; ROC Curve; Sensitivity and Specificity; Stroke Volume; Tuberculosis, Pulmonary

Brain natriuretic peptide (BNP) is considered as a prognostic marker in patients with sepsis, but no data are available on BNP in pediatric cancer patients with febrile neutropenia (FN). Twenty-five pediatric cancer patients with FN were included in this study. Serum BNP level was measured. The mean BNP level was 330.8 ± 765.3 pg/mL (5.9-3806 pg/mL). BNP levels of 12 patients were found over the normal level. High BNP levels were related to some conditions of the patients, and these were statistically significant (P < .05). These conditions were required erythrocyte suspension, had pneumonia, time stayed in hospital, and neutropenia time. When regression test was done, required erythrocyte suspension for anemia and had pneumonia were found to be statistically significant. In conclusion, this is one of the first studies on BNP levels in pediatric cancer patients with FN. However, further studies with large sample sizes are needed to confirm the results and provide new data about this issue.

Topics: Adolescent; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Neutropenia; Prognosis

Risk stratification of patients with PE has gained interest in terms of the identification of patients in whom treatment on an outpatient base can be considered. Previous studies are of limited value due to their focus on adverse clinical events within several months after diagnosis of PE. We developed a prognostic model, based on easily accessible, clinical, and laboratory parameters, to predict adverse events during the first 10 days after the diagnosis of acute PE. We have analyzed the data of 210 outpatients with confirmed PE. Collected data included medical history, pulse rate, blood pressure, NT-proBNP, and D-dimer concentrations. The primary outcome was the occurrence of adverse clinical events in a 10 day follow-up period. Our final prognostic model to predict short-term adverse events consists of NT-proBNP levels, D-dimer concentrations, pulse rate, and the occurrence of active malignancy; the total score ranges from 0 to 37 points. Patients with a low score (no active malignancy, pulse rate <90 bpm, NT-proBNP <500 pg/ml, and D-dimer <3,000 μg/l FEU) have a 10-day adverse event risk <1.5%. This risk increases to over 30% in patients with a maximum score, based on high pulse rate, D-dimer concentrations, and NT-proBNP levels. Our prognostic model, once prospectively validated in an independent sample of patients, can be used in the early risk stratification of PE to estimate the risk of adverse events and to differentiate between candidates for in- or out- hospital treatment.

Topics: Adult; Aged; Cohort Studies; Female; Fibrin Fibrinogen Degradation Products; Heart Rate; Hospitals, Teaching; Humans; Male; Middle Aged; Models, Biological; Natriuretic Peptide, Brain; Neoplasms; Netherlands; Peptide Fragments; Prognosis; Pulmonary Embolism; Retrospective Studies; Risk Assessment

To assess systolic and diastolic function in adult childhood-cancer survivors (CCS) after treatment entailing potential cardiovascular toxicity.. The study cohort consisted of 277 adult CCS (median age 28 [range 18-48]years), who had been treated with anthracyclines, platinum, and/or radiotherapy between 1976 and 1999, along with 130 healthy sibling controls. The assessments included echocardiography, baroreflex sensitivity measurement, and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP). Echocardiography measurements were shortening fraction (SF) (abnormal<29%) for systolic function and tissue velocity imaging of early diastole (TVI Et) (abnormal<8.00)cm/sec for diastolic function; systolic function was also assessed by the wall motion score index (WMSI).. At 18 (5-31)years post-treatment, the prevalence of both impaired SF and abnormal WMSI was increased in CCS compared to controls (p=0.003 and p<0.001, respectively). CCS also had an increased prevalence of diastolic dysfunction compared to the controls (12% versus 1%, p<0.001). Abnormal SF and/or abnormal diastolic function were found in 43% of CCS. NT-proBNP was higher in CCS and was associated to increased WMSI. Baroreflex sensitivity was lower in CCS and was associated with diastolic dysfunction. Systolic as well as diastolic dysfunction was associated with cumulative dose of anthracyclines and mediastinal irradiation.. After treatment with potential cardiovascular toxic therapies, the risk of systolic and diastolic dysfunction in CCS is considerable. Since these abnormalities, in particular diastolic dysfunction, are age related, the observed effects might be considered a sign of precocious cardiac ageing.

Topics: Adolescent; Adult; Anthracyclines; Baroreflex; Biomarkers; Cohort Studies; Diastole; Electrocardiography; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Platinum; Radiotherapy; Survivors; Systole; Ventricular Dysfunction, Left; Young Adult

Current evidence indicates that measurement of pleural fluid N-terminal pro-brain natriuretic peptide (NT-proBNP) levels can aid in distinguishing pleural effusions of cardiac origin from those of noncardiac origin. To date, only one study, to our knowledge, has described simultaneous measurement of pleural fluid brain natriuretic-32 peptide (BNP) and NT-proBNP. The purpose of the present study was to determine pleural fluid BNP and NT-proBNP levels and analyze the relationship between these two measurements. We hypothesized that there would be a positive correlation between pleural fluid NT-proBNP and BNP, whereas NT-proBNP levels would be higher than BNP levels.. Levels of pleural fluid NT-proBNP and BNP were measured by enzyme immunoassay in a total of 80 patients: 20 with congestive heart failure, 20 status post-coronary artery bypass graft, 20 with carcinoma, and 20 with pneumonia.. Comparison of NT-proBNP and BNP concentrations using the Spearman method of statistical analysis revealed a correlation coefficient of 0.572, P < .001. Evaluation of the diagnostic accuracy of BNP and NT-proBNP in patients with pleural effusions of cardiac origin demonstrated an area under the receiver operating characteristic curve of 0.700 (95% CI, 0.569-0.831) and 0.835 (95% CI, 0.721-0.949), respectively.. Although levels of pleural fluid BNP have a statistically significant correlation with those of NT-proBNP, this relationship only explains 32% of the variance in NT-proBNP levels. Furthermore, when compared with BNP, NT-proBNP is a more accurate diagnostic aid in the evaluation of pleural effusions of cardiac origin.

Topics: Biomarkers; Coronary Artery Bypass; Exudates and Transudates; Heart Failure; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Pleural Effusion; Pleural Effusion, Malignant; Pneumonia; ROC Curve; Sensitivity and Specificity; Statistics, Nonparametric

Anthracycline-induced cardiotoxicity can cause serious health problems for an increasing number of survivors of childhood malignancies. The aims of this study were to document plasma concentrations of cardiac troponin T (cTnT) and NT-pro-brain natriuretic peptide (NT-pro-BNP) in a large group of asymptomatic long-term survivors of childhood cancer treated with anthracyclines, and to study the relation of the abnormal biomarker levels with different risk factors for anthracycline-induced cardiotoxicity and conventional echocardiographic parameters.. One hundred twenty-two asymptomatic survivors of childhood cancer underwent a detailed echocardiography. Blood samples were taken to determine the levels of NT-pro-BNP and cTnT.. None of the survivors had abnormal cTnT levels. Thirteen percent of the survivors (n = 16) had abnormal NT-pro-BNP levels. Abnormal NT-pro-BNP levels were significantly related to cumulative anthracycline dosage (P < 0.003). Eleven of 31 survivors (35%) treated with cumulative anthracycline dose of 300 mg/m(2) or more, had abnormal NT-pro-BNP levels which were significantly related to end-diastolic left ventricular internal diameter (LVIDd) indexed for body surface area (BSA) (P < 0.01).. Cardiac TnT does not contribute to the early detection of late onset anthracycline-induced cardiotoxicity. Abnormal levels of NT-pro-BNP were detected in 13% of 122 asymptomatic, long-term survivors of childhood cancer. Follow-up of these survivors is essential to answer the question whether NT-pro-BNP is an early marker for late onset anthracycline-induced cardiotoxicity.

Topics: Adolescent; Adult; Anthracyclines; Antineoplastic Agents; Biomarkers; Child; Child, Preschool; Disease-Free Survival; Dose-Response Relationship, Drug; Echocardiography; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Survivors

Anthracycline therapy is limited by cardiotoxicity. Currently no diagnostic parameter is available allowing ubiquitous and reliable detection of preclinical anthracycline cardiomyopathy and prediction of prognosis.. In 100 consecutive patients receiving anthracycline-based chemotherapy serial measurements of left ventricular systolic and diastolic function, Tei index (a Doppler echocardiographic parameter of global ventricular function), cardiac troponin T (cTnT) and NT-probrain natriuretic peptides (BNP) at baseline and during 1-year follow-up were performed.. Mean ejection fraction (LVEF) significantly decreased immediately after completion of anthracycline therapy (mean dose 226.1 +/- 8.3 mg/m(2)) und further declined during follow-up (65.9 +/- 0.6% Vs. 61.6 +/- 0.7%; P < 0.001), while mean E/A ratio decreased after 6 months (P = 0.05). No patient presented with cardiac symptoms. The Tei index increased after therapy in the majority of patients (78.8%) compared with pre-therapy values indicating myocardial alteration in more patients than previously recognized. cTnT levels did not exceed the upper limit of the normal range in any patient. Seven patients had low-level elevations of cTnT. Only one of these patients developed a concomitant decrease in LVEF. Mean N-terminal-pro-BNP (NT-proBNP) levels did not significantly change after anthracycline administration. However, in 13 patients (15.3%) a marked, transient increase of NT-proBNP was obtained after the first anthracycline cycle without cardiac dysfunction presumably due to altered cardiac loading conditions during chemotherapy.. Low to moderate doses of anthracyclines resulted in subclinical myocardial alteration in more patients than so far noticed. Clinical implications of increased Tei index remain to be determined in long-term. Our results do not support that assessment of cTnT or BNP levels may safely replace serial echocardiographic evaluation of systolic and diastolic function for the monitoring of anthracycline cardiotoxicity.

Topics: Adult; Aged; Anthracyclines; Biomarkers; Cardiomyopathies; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Ventricles; Humans; Immunoassay; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prognosis; Protein Precursors; Time Factors; Troponin T; Ventricular Function, Left

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Respiratory Insufficiency

To assess the accuracy of plasma N-terminal-pro-B-type natriuretic peptide concentrations (NT-proBNP) as a diagnostic tool to recognize acute respiratory failure (ARF) of cardiac origin.. Prospective observational study in 100 medical intensive care unit (ICU) patients. NT-proBNP was measured at ICU admission, and diagnosis of cardiac dysfunction was performed using echocardiography.. Sixteen patients had cardiac ARF, 58 patients had noncardiac ARF, and 26 patients were non-ARF controls. Median (IQR) NT-proBNP was 1,951 (617-9,320) pg/ml and was significantly influenced by the level of renal dysfunction. Patients with noncardiac ARF had higher NT-proBNP [1,912 (704-1,922) pg/ml] than non-ARF patients [1,022 (383-2,613) pg/ml], but lower concentrations than cardiac ARF patients [4,536 (1,568-35,171) pg/ml]. The area under the curve (AUC) was 0.663+/-0.078 (95% confidence interval 0.510-0.815) and was not significantly influenced by the level of renal dysfunction. In addition, using a stepwise logistic regression model, NT-proBNP failed to predict independently the presence of cardiac dysfunction. However, with specificity and negative predictive value of 100%, a NT-proBNP cutoff value of 500 pg/ml seemed useful to rule out cardiac dysfunction. Indeed, none of the 16 patients with cardiac ARF had a NT-proBNP value below 500 pg/ml, whereas it was the case in 8 (30.8%) non-ARF controls and in 12 (20.7%) noncardiac ARF patients.. In cancer patients with ARF, plasma NT-proBNP concentration is not a relevant tool to recognize cardiac dysfunction, but is specific enough to rule out the diagnosis in patients with plasma NT-proBNP concentrations below 500 pg/ml.

Topics: Acute Disease; Adult; Biomarkers; Case-Control Studies; Female; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prospective Studies; Respiratory Insufficiency; Sensitivity and Specificity

Renal impairment (RI) has been shown to be one major risk factor in a number of diseases and is associated with a dismal clinical outcome. However, the influence of milder degrees of renal disease is less well defined, particularly not in patients with malignant diseases.. We analyzed 167 patients with solid tumors and hematological malignancies. Besides disease-specific parameters, serum creatinine, cystatin C and the estimated glomerular filtration rate (eGFR) ['modification of diet in renal disease' equation (MDRD)/Cockcroft-Gault (CG)] were determined. Patients were compared within eGFR, creatinine and cystatin C groups.. The median MDRD, CG, creatinine and cystatin C levels of all patients were 88 ml/min/1.73 m2, 89 ml/min, 1 mg/dl and 0.9 mg/l, respectively. Patients with chronic kidney disease stage 2 still showed normal creatinine and cystatin levels of 1 mg/dl and 1.1 mg/l, respectively, although mild RI was frequent. Those cancer patients with decreased eGFR (MDRD) (<60 ml/min/1.73 m2) had increased odds ratios (ORs) to have more concurrent diagnoses [OR 3.4; 95% confidence interval (CI) 1.5-8.1], a body mass index >24 kg/m2 (OR 2.1; 95% CI 1.0-4.5) and an elevated (> 245 pg/ml) pro-brain natriuretic peptide level (proBNP) (OR 9.2; 95% CI 3.0-28.3).. These observations suggest that grouping cancer patients according to renal function, especially eGFR, may be one way to determine specific risk groups.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Chronic Disease; Creatinine; Cystatin C; Cystatins; Female; Glomerular Filtration Rate; Hematologic Neoplasms; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Monitoring, Physiologic; Natriuretic Peptide, Brain; Neoplasms; Protein Precursors

The overall prognosis of critically ill patients with cancer has improved during the past decade. The aim of this study was to identify early prognostic factors of intensive care unit (ICU) mortality in patients with cancer.. We designed a prospective, consecutive, observational study over a one-year period. Fifty-one cancer patients with septic shock were enrolled.. The ICU mortality rate was 51% (26 deaths). Among the 45 patients who benefited from transthoracic echocardiography evaluation, 17 showed right ventricular dysfunction, 18 showed left ventricular diastolic dysfunction, 18 showed left ventricular systolic dysfunction, and 11 did not show any cardiac dysfunction. During the first three days of ICU course, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were significantly higher in patients presenting cardiac dysfunctions compared to patients without any cardiac dysfunction. Multivariate analysis discriminated early prognostic factors (within the first 24 hours after the septic shock diagnosis). ICU mortality was independently associated with NT-proBNP levels at day 2 (odds ratio, 1.2; 95% confidence interval, 1.004 to 1.32; p = 0.022). An NT-proBNP level of more than 6,624 pg/ml predicted ICU mortality with a sensitivity of 86%, a specificity of 77%, a positive predictive value of 79%, a negative predictive value of 85%, and an accuracy of 81%.. We observed that critically ill cancer patients with septic shock have an approximately 50% chance of survival to ICU discharge. NT-proBNP was independently associated with ICU mortality within the first 24 hours. NT-proBNP could be a useful tool for detecting high-risk cancer patients within the first 24 hours after septic shock diagnosis.

Topics: Aged; Echocardiography; Echocardiography, Doppler; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neoplasms; Prognosis; Prospective Studies; ROC Curve; Shock, Septic; Troponin I

B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) plasma levels are commonly high at the early phase of septic shock and have been suggested to be prognostic markers for this condition. It is uncertain, however, whether this increase reflects sepsis related cardiac dysfunction. In a recent issue of Critical Care, Mokart and coworkers showed the accuracy of NT-proBNP in predicting intensive care unit mortality in cancer patients with septic shock, which could help in identifying high risk cancer patients. Results from repeated transthoracic echocardiographs show that NT-proBNP on day 2 after admission was higher in patients presenting with cardiac dysfunction, whereas NT-proBNP on day 1 did not predict cardiac dysfunction. These data suggest that after an initial overexpression of NT-proBNP in all septic patients, patients with cardiac dysfunction will present persistent high levels of NT-proBNP.

Topics: Aged; Biomarkers; Environmental Monitoring; Hospital Mortality; Humans; Intensive Care Units; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prognosis; Research Design; Shock, Cardiogenic; Shock, Septic

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Diabetes Complications; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Prognosis; Sepsis; Water-Electrolyte Imbalance

The therapeutic potential of anthracycline antibiotics is limited by their cardiotoxicity. Electrocardiography, exercise testing, and two-dimensional echocardiography are non-invasive techniques used in the follow-up of children for cardiotoxicity. Plasma B-type natriuretic peptide (BNP) levels are thought to be useful markers in the early detection of AC induced cardiomyopathy.. We evaluated cardiac status of 34 patients with solid tumors treated with anthracycline antibiotics. All of the patients were asymptomatic and had no evidence of residual malignancy. They were evaluated by electrocardiography, exercise testing, echocardiography, and plasma BNP levels measured before and after the exercise testing.. Electrocardiography revealed only minor abnormalities of little clinical significance. All of the patients completed the exercise testing without complication, and the duration of the exercise for each patient was between normal limits. Cardiac output (CO) and wall stress (WS) were significantly increased in patients, than in controls in echocardiographic evaluation of systolic functions (P < 0.001). Diastolic filling patterns showed various abnormalities; M-E, M-A, T-E, T-A, AT, and IVRT were significantly higher than those of controls. Mean plasma BNP levels of the patients (10.56 +/- 10.22 pg/ml) were significantly higher than BNP levels of the healthy controls (4.09 +/- 2.26 pg/ml) (P < 0.016), before exercise testing. The mean plasma BNP levels of the patients (15.70 +/- 14.06 pg/ml) were higher than resting state after exercise testing, but it was not statistically significant (P > 0.05).. Our findings demonstrated that echocardiographic and biochemical abnormalities could be found even at low cumulative doses of AC antibiotics. The use of serial echocardiographic studies and plasma BNP determinations to identify high-risk patients for cardiotoxicity needs to be verified by additional studies.

Topics: Adolescent; Adult; Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Cardiomyopathies; Case-Control Studies; Child; Child, Preschool; Echocardiography; Electrocardiography; Exercise Test; Female; Heart Function Tests; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Prospective Studies; Sensitivity and Specificity; Statistics, Nonparametric; Turkey

The use of anthracyclines in treatment of cancer is limited by cardiotoxicity of these compounds and may lead to heart failure. Therefore monitoring of cardiac function is necessary during therapy.. We evaluated the value of natriuretic peptides (N-terminal pro-atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP)) for monitoring and predicting anthracycline induced cardiotoxicity using radionuclide left ventricular ejection fraction (EF) measurements as reference.. A total of 107 consecutive patients receiving anthracycline as part of their chemotherapy for malignant disease were studied. Plasma concentrations of the peptides were measured by radioimmunoassay and EF by radionuclide cardiography. For reduced EF values, i.e. below 0.50 a fairly strong correlation was found between N-ANP or BNP and EF. Of 48 patients with serial EF and peptide measurements, 19% showed a significant EF decrease (>0.10) and ended with a final EF value below 0.50. Baseline EF was no predictor of a change in EF during treatment. Neither baseline levels of N-ANP or BNP nor a change in the same variables during therapy were predictive of a change in EF.. In spite of correlations between peptide concentrations and reduced EF values neither baseline values nor serial measurements can safely substitute EF monitoring in patients undergoing anthracycline therapy.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Atrial Natriuretic Factor; Epirubicin; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Predictive Value of Tests; Protein Precursors; Stroke Volume; Ventricular Function, Left

Topics: Anthracyclines; Antibiotics, Antineoplastic; Atrial Natriuretic Factor; Humans; Natriuretic Peptide, Brain; Neoplasms; Predictive Value of Tests; Protein Precursors; Stroke Volume; Ventricular Function, Left

Circulating levels of B-type natriuretic peptide (BNP), a cardiac hormone, reflect the severity of cardiac dysfunction. Because the plasma BNP level changes dramatically during the period after the onset of acute myocardial infarction (AMI), identification of a suitable sampling time is problematic. There have been several reports indicating that the plasma BNP level obtained in the acute phase of AMI can be used as a prognostic marker. We examined whether the plasma BNP level measured 3 to 4 weeks after the onset of AMI represents a reliable prognostic marker for patients with AMI.. We analyzed 145 consecutive patients with AMI. Plasma BNP levels were measured during the 3 to 4 weeks after onset of AMI. Of those patients, 23 experienced fatal cardiac events during this study. The mean follow-up period was 58.6 months. Log BNP, left ventricular end-diastolic pressure, and pulmonary vascular resistance were all significantly higher in the cardiac death group, and there were more men and more patients with a history of heart failure in the cardiac death group. A Cox proportional hazards model analysis showed that log BNP was an independent predictor of cardiac death. The survival rate was significantly higher in patients with log BNP <2.26 (180 pg/mL) than in those with log BNP > or =2.26.. The plasma BNP level obtained 3 to 4 weeks after the onset of AMI can be used as an independent predictor of cardiac death in patients with AMI.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiac Catheterization; Cause of Death; Convalescence; Death, Sudden; Female; Follow-Up Studies; Heart Failure; Hemodynamics; Humans; Life Tables; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Neoplasms; Pneumonia; Proportional Hazards Models; Survival Analysis; Survival Rate

Aldosterone is produced not only in the adrenal gland but also in the extra-adrenal tissues, including failing human heart. This study examined the production of dehydroepiandrosterone (DHEA) in human heart and elucidated the possible physiological significance. Method and Results- Using left ventricular tissues obtained at autopsy, reverse transcription-polymerase chain reaction followed by Southern blot analysis revealed the gene expressions of CYP17. By measuring plasma aldosterone and DHEA levels at the coronary sinuses and aortic roots during cardiac catheterization, we found that DHEA but not aldosterone was secreted from control subjects (P<0.0001 and P=0.74, respectively), whereas aldosterone but not DHEA was secreted from patients with heart failure (P=0.0017 and P=0.67, respectively). To examine the significance of DHEA, we measured myocyte cell sizes and the gene expression of B-type natriuretic peptide (BNP), using a neonatal rat cardiocyte culture system. We found that DHEA (10(-8) mol/L) significantly inhibited the increase in myocyte cell sizes and BNP mRNA levels upregulated by endothelin-1 (P=0.031 and P<0.0001, respectively).. CYP17 gene expression and production of DHEA were demonstrated in human control heart. Also, we found that cardiac production of DHEA was suppressed in failing heart. We postulated that DHEA and/or its metabolites exert a cardioprotective action through antihypertrophic effects.

Topics: Adult; Aged; Aldosterone; Animals; Blotting, Southern; Cardiac Catheterization; Cell Size; Cells, Cultured; Dehydroepiandrosterone; Endothelin-1; Female; Heart Failure; Heart Ventricles; Humans; Hypertrophy; Male; Middle Aged; Myocytes, Cardiac; Natriuretic Peptide, Brain; Neoplasms; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Steroid 11-beta-Hydroxylase; Steroid 17-alpha-Hydroxylase

Although the dehydration-rehydration problem in end-of-life care is one of the most important issues, clinical indications of hydration therapy have not been clarified because the pathophysiology is poorly understood. To explore the physiological changes of fluid status in terminally ill cancer patients, a prospective observational study was performed. We obtained 9 pairs of blood samplings from hospice inpatients with irreversible bowel obstruction who underwent two or more laboratory examinations during the admission periods. The plasma renin activity (PRA) and brain natriuretic peptide (BNP) were measured, in addition to basic laboratory tests performed as clinically required. A chart review evaluated the degree of fluid retention symptoms. In 7 patients receiving intravenous rehydration of 700-2200 ml/day, the mean PRA level significantly increased from 3.5+/-2.5 ng ml(-1) h(-1) to 11+/-8.2 ng ml(-1) x h(-1) ( P=0.047), and the mean BNP level significantly decreased from 52+/-34 pg/ml to 22+/-14 pg/ml ( P=0.047). Edema, ascites, and pleural effusion/pulmonary edema deteriorated in 5, 3, and 5 patients, respectively. In 2 patients without rehydration therapy, peripheral edema deteriorated with increased PRA levels (0.5 to 20 ng ml(-1) x h(-1), 0.4 to 8.7 ng ml(-1) x h(-1), respectively). In conclusion, intravenous volume depletion with fluid retention symptoms was observed in terminally ill cancer patients with intestinal obstruction both receiving and not receiving intravenous hydration. The pathological mechanism hypothesized is the fluid shift from the intravascular compartment to the interstitial spaces.

Topics: Aged; Biomarkers; Dehydration; Edema; Extracellular Space; Female; Fluid Therapy; Humans; Intestinal Obstruction; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Palliative Care; Prospective Studies; Renin; Terminal Care

Anthracyclines are effective anticancer drugs for childhood cancer with dose-limiting cardiotoxicity. Children who have received anthracyclines thus need periodical cardiac evaluation. The plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have been shown to increase in proportion to severity of cardiac dysfunction. We examined whether plasma levels of ANP and BNP, in addition to echocardiographic evaluation, can be used as specific markers for doxorubicin-induced cardiotoxic effects in children.. Consecutively, 34 patients (18 boys and 16 girls) who had previously received doxorubicin-containing chemotherapy were enrolled in this study. Plasma ANP and BNP were assayed simultaneously at the time of first cardiac function evaluation by echocardiography.. Of the 34 patients, 8 (23.5%) had left ventricular dysfunction as assessed by echocardiography. Both ANP and BNP plasma levels in these patients were significantly elevated in comparison with healthy controls (P < 0.01) or patients with normal cardiac function (P < 0.05). It should be also noted that ANP and BNP levels were correlated significantly with cardiac systolic function, but not with diastolic function.. These results suggest that plasma ANP and BNP levels could be markers for doxorubicin-induced cardiotoxicity in children. Measurement of natriuretic peptide levels during treatment may allow earlier-identification of individuals at risk for severe cardiac damage.

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Atrial Natriuretic Factor; Blood Flow Velocity; Blood Pressure; Case-Control Studies; Child; Child, Preschool; Doxorubicin; Echocardiography, Doppler, Pulsed; Female; Humans; Incidence; Infant; Japan; Male; Natriuretic Peptide, Brain; Neoplasms; Stroke Volume; Time Factors; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Diphosphonates; Equipment Reuse; Heart Failure; Humans; Hypercalcemia; Imidazoles; Natriuretic Peptide, Brain; Neoplasms; United States; United States Food and Drug Administration; Zoledronic Acid

Based on cDNA sequence data for human brain natriuretic peptide (BNP) precursor (1), a radioimmunoassay (RIA) system highly specific to human BNP (hBNP) was developed and used to characterize immunoreactive (ir-) hBNP in cardiac atrium. Gel filtration of ir-hBNP in atrium indicated that ir-hBNP was mainly comprised of two molecular forms of 13-15K and 4K. In reverse phase high performance liquid chromatography (HPLC), the low molecular weight (MW) ir-hBNP emerged as a single peak at an elution time identical to that of synthetic hBNP-32. The high MW ir-hBNP was also eluted as a single peak. On the other hand, tissue concentrations of ir-hBNP in cardiac atria were found to be 9.98-593.22 pmol/g in 13 specimens, being about 1/150 the concentration of ir-human atrial natriuretic peptide (hANP). These results demonstrate that hBNP is present as a peptide in human heart, suggesting that hBNP is secreted from heart and functions together with hANP as a hormone.

Topics: Adult; Aged; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Heart Atria; Humans; Male; Middle Aged; Molecular Weight; Myocardium; Natriuretic Peptide, Brain; Neoplasms; Nerve Tissue Proteins; Radioimmunoassay