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1.
Oncologist ; 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064888

RESUMO

Cardiac monitoring is becoming an important part of breast cancer care. Breast cancer and cardiovascular disease (CVD) share many common risk factors, and it is estimated that by the median age of diagnosis, many patients with breast cancer will have established or subclinical CVD. In addition, a number of treatments for metastatic breast cancer are known to have cardiac effects. As such, there is a clear need to prevent, identify, and effectively manage cardiovascular events in patients with breast cancer. Current clinical practice for patients with metastatic breast cancer involves a comprehensive set of assessments to ensure efficacy and safety of treatment. Adding cardiac monitoring to the assessments already required for patients with breast cancer may improve survival and quality of life. Currently, cardiac monitoring is recommended for several breast cancer treatments, and guidelines related to cardiac monitoring are available. Here, we review the risk of CVD in patients with breast cancer, providing an overview of the cardiac events associated with standard therapies for metastatic breast cancer. We also assess the current clinical recommendations relating to cardiac monitoring, and practical management strategies for oncologists. Cardio-oncology is a growing medical subspecialty that promotes the need for effective cancer therapy while minimizing cardiac effects. Integrating cardiac monitoring into routine clinical practice may safeguard patients with metastatic breast cancer against adverse cardiac effects. IMPLICATIONS FOR PRACTICE: This review details the common risk factors associated with cardiovascular disease that are frequently observed in patients with metastatic breast cancer, as well as the adverse cardiac effects of many therapies that are commonly prescribed. The review also provides a rationale for routine and comprehensive cardiovascular assessment of all patients at baseline, and during and after therapy depending on the treatment and presence of risk factors for cardiovascular disease. The medical discipline of cardio-oncology is increasingly being recognized as an important part of clinical practice to ensure effective cancer therapy while maintaining cardiac health.

2.
Expert Rev Anticancer Ther ; 19(5): 359-374, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30916598

RESUMO

INTRODUCTION: Recent breakthroughs in cancer treatment has improved the prospects and life expectancy of cancer patients. Therefore, risk of cardiotoxicity induced by oncologic therapies has become an important determinant of patient's survival and quality of life, independently of the oncologic prognosis. Areas covered: This paper provides an overview of the proposed strategies to mitigate the risk of cardiotoxicity. Limitation of current approaches, the need for early detection and the treatment of cardiotoxicity are also discussed. Possible future research directions are also described. Expert opinion: The most effective approach to minimize cardiotoxicity is early identification and early onset of a prophylactic treatment. However, the current standard of cardiac monitor identifies cardiotoxicity only when a functional impairment has already occurred, precluding any chance of effective prevention. The use of troponins to identify subclinical cardiotoxicity, and early treatment with ACE-inhibitors to prevent cardiac dysfunction and cardiac events have recently emerged, and appear to be an effective tool against this complication.

3.
Lung Cancer ; 123: 155-159, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30089588

RESUMO

BACKGROUND: Acute kidney injury (AKI) frequently occurs in several medical and surgical settings, and it is associated with increased morbidity and mortality. In patients undergoing lung cancer surgery, AKI has not been fully investigated. We prospectively evaluated the incidence, clinical relevance, and risk factors of AKI in patients undergoing lung cancer surgery. Moreover, we estimated the accuracy of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prediction of AKI. METHODS: Patients undergoing lung cancer surgery were included in the study. Plasma NT-proBNP was measured before and soon after surgery. Postoperative AKI was defined according to the Acute Kidney Injury Network (AKIN) classification. RESULTS: A total of 2179 patients were enrolled. Of them, 222 (10%) developed AKI and had a more complicated in-hospital clinical course (overall complication rate: 35% vs. 16%; P < 0.0001), and a longer hospital stay (10 ± 7 vs. 7 ± 4 days; P < 0.0001). The incidence of AKI increased in parallel with the extent of lung resection. Among the independent predictors of AKI, serum creatinine (area under the curve [AUC] 0.70 [95% CI 0.67-0.74]) and NT-proBNP (AUC 0.71 [95% CI 0.67-0.74]) provided the highest predictive accuracy, and their combination further significantly improved AKI prediction (AUC 0.74 [95% CI 0.71-0.77]). No difference in AKI prediction was observed between preoperative and postoperative NT-proBNP (P = 0.84). CONCLUSIONS: Acute kidney injury occurs in 10% of patients undergoing lung cancer surgery, and it is associated with a high incidence of postoperative complications. The risk of AKI can be accurately predicted by the combined evaluation of preoperative serum creatinine and NT-proBNP.

4.
Eur J Cancer ; 94: 126-137, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29567630

RESUMO

BACKGROUND: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit. METHODS: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals. Patients were randomly assigned to two strategies: enalapril in all patients started before chemotherapy (CT; 'prevention' arm), and enalapril started only in patients with an increase in troponin during or after CT ('troponin-triggered' arm). Troponin was assayed locally in 2596 blood samples, before and after each anthracycline-containing CT cycle and at each study visit; electrocardiogram and echocardiogram were done at baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the incidence of troponin elevation above the threshold. FINDINGS: Of the 273 patients, 88% were women, mean age 51 ± 12 years. The majority (76%) had breast cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and doxorubicin were most commonly prescribed, with median cumulative doses of 360 [270-360] and 240 [240-240] mg/m2, respectively. The incidence of troponin elevation was 23% in the prevention and 26% in the troponin-triggered group (p = 0.50). Three patients (1.1%) -two in the prevention, one in the troponin-triggered group-developed cardiotoxicity, defined as 10% point reduction of LV ejection fraction, with values lower than 50%. INTERPRETATION: Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient.

5.
Curr Oncol Rep ; 19(8): 55, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28707189

RESUMO

Over the past 20 years, cancer treatments have become more effective, leading to significant improvements in survival rates. However, anticancer drugs can have several possible cardiovascular side effects; in particular, the development of left ventricular dysfunction with chemoradiation therapy can negatively affect patients' cardiac outcome, and can limit anticancer treatments. This is an ongoing issue that will continue to persist, due to the ongoing development of new antitumor agents with potential cardiotoxic effects, and the prolonged life expectancy of long-term cancer survivors. Thus, the need for cooperation between oncologists and cardiologists in the management of cancer patients has led to the development of a new medical discipline-cardio-oncology-where the issue of cardiotoxicity is a topic of intense interest and research. However, several issues remain-the proper definition and diagnosis of cardiotoxicity, as well as monitoring and treatment strategies. In this review, the current advances in cardio-oncology, limitations of current approaches, and future research fields will be discussed.


Assuntos
Antineoplásicos/uso terapêutico , Metas , Educação em Saúde/métodos , Neoplasias Cardíacas/tratamento farmacológico , Oncologia/educação , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/análise , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Testes de Função Cardíaca/métodos , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/fisiopatologia , Humanos
6.
Expert Rev Mol Diagn ; 17(3): 245-256, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28092472

RESUMO

INTRODUCTION: Cardiotoxicity is a common complication that may compromise the clinical effectiveness of anticancer therapy. The current standard for monitoring cardiac function detects cardiotoxicity only when a functional impairment has already occurred, not allowing for any early preventive strategy. Areas covered: A novel approach, based on the use of biomarkers has recently emerged, resulting in a very effective tool for early, real-time identification, and monitoring of cardiotoxicity. In particular, cardiac troponin elevation during chemotherapy allows to identify patients more prone to develop myocardial dysfunction and cardiac events. In these patients, use of angiotensin-converting enzyme inhibitors, such as enalapril, has shown to be effective in improving clinical outcomes, giving the chance for cardioprotective strategies in a selected population. The authors reviewed the currently available data about the role of biomarkers in this setting. Expert commentary: Early identification of patients at high risk of cardiotoxicity by cardiac biomarkers - in particular troponin - provides a rationale for targeted preventive strategies against cancer therapy-induced left ventricular dysfunction and its associated clinical complications, with the advantage of limiting prophylactic therapy only to a restricted number of patients. Although the major international oncologic societies encourage this approach, some limitations to a routinely use of biomarkers still exist.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antineoplásicos/efeitos adversos , Enalapril/uso terapêutico , Cardiopatias , Neoplasias/tratamento farmacológico , Troponina C/sangue , Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Cardiopatias/sangue , Cardiopatias/induzido quimicamente , Cardiopatias/prevenção & controle , Humanos , Miocárdio/metabolismo , Neoplasias/sangue
7.
Circ Res ; 119(12): 1339-1346, 2016 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-27799252

RESUMO

RATIONALE: In contrast to cardiomyocyte necrosis, which can be quantified by cardiac troponin, functional cardiomyocyte impairment, including mitochondrial dysfunction, has escaped clinical recognition in acute myocardial infarction (AMI) patients. OBJECTIVE: To investigate the diagnostic accuracy for AMI and prognostic prediction of in-hospital mortality of cytochrome c. METHODS AND RESULTS: We prospectively assessed cytochrome c serum levels at hospital presentation in 2 cohorts: a diagnostic cohort of patients presenting with suspected AMI and a prognostic cohort of definite AMI patients. Diagnostic accuracy for AMI was the primary diagnostic end point, and prognostic prediction of in-hospital mortality was the primary prognostic end point. Serum cytochrome c had no diagnostic utility for AMI (area under the receiver-operating characteristics curve 0.51; 95% confidence intervals 0.44-0.58; P=0.76). Among 753 AMI patients in the prognostic cohort, cytochrome c was detectable in 280 (37%) patients. These patients had higher in-hospital mortality than patients with nondetectable cytochrome c (6% versus 1%; P<0.001). This result was mainly driven by the high mortality rate observed in ST-segment-elevation AMI patients with detectable cytochrome c, as compared with those with nondetectable cytochrome c (11% versus 1%; P<0.001). At multivariable analysis, cytochrome c remained a significant independent predictor of in-hospital mortality (odds ratio 3.0; 95% confidence interval 1.9-5.7; P<0.001), even after adjustment for major clinical confounders (odds ratio 4.01; 95% confidence interval 1.20-13.38; P=0.02). CONCLUSIONS: Cytochrome c serum concentrations do not have diagnostic but substantial prognostic utility in AMI.


Assuntos
Citocromos c/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Admissão do Paciente/tendências , Prognóstico , Estudos Prospectivos
9.
J Clin Oncol ; 34(26): 3157-65, 2016 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-27458291

RESUMO

PURPOSE: Patients with metabolic syndrome have a greater risk of cardiovascular disease, although their susceptibility to chemotherapy-induced cardiac disease is not well documented. The aim of this meta-analysis was to assess associations between obesity or being overweight and cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab in patients with breast cancer. METHODS: We performed a random-effects analysis and a network meta-analysis and assessed publication bias. We included 15 studies and 8,745 patients with breast cancers who were treated with anthracyclines and sequential anthracyclines and trastuzumab. RESULTS: Combination of obesity and being overweight was significantly associated with a greater risk of developing cardiotoxicity after anthracyclines and a sequential anthracyclines and trastuzumab regimen in patients with breast cancer. Pooled odds ratio for cardiotoxicity was 1.38 (95% CI, 1.06 to 1.80; I(2) = 43%; N = 8,745) for overweight or obesity (body mass index > 25 kg/m(2)), 1.47 (95% CI, 0.95 to 2.28; I(2) = 47%; n = 2,615) for obesity, and 1.15 (95% CI, 0.83 to 1.58; I(2) = 27%; n = 2,708) for overweight. Associations were independent of study design, year of publication, drug regimen (anthracyclines alone v sequential anthracyclines and trastuzumab), or definitions of cardiotoxicity and of overweight or obesity. There was no evidence of publication bias; however, we could not separate the contributions of obesity-related cardiovascular risk factors, such as diabetes and hypertension, from that of obesity itself in this largely unadjusted analysis. CONCLUSION: Our findings in a largely unadjusted analysis suggest that overweight and obesity are risk factors for cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab.


Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Cardiopatias/induzido quimicamente , Obesidade/complicações , Trastuzumab/efeitos adversos , Índice de Massa Corporal , Neoplasias da Mama/diagnóstico , Cardiotoxicidade , Feminino , Cardiopatias/diagnóstico , Humanos , Obesidade/diagnóstico , Razão de Chances , Medição de Risco , Fatores de Risco
10.
Curr Cardiol Rep ; 18(6): 51, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27108361

RESUMO

Advances in oncologic therapies have led to considerable improvements in prognosis and survival. However, these improvements may ultimately be diminished by the increase of cardiovascular side effects. Typically, both conventional and new antitumoral therapies may induce asymptomatic or symptomatic left ventricular dysfunction. Its development still remains a major deterrent that may compromise clinical effectiveness of cancer treatment, independently of the oncologic prognosis, having a serious impact on the patient's survival and quality of life. Hence, prevention of cardiotoxicity remains a crucial topic both for cardiologists and oncologists. Many strategies to mitigate the risk of cardiotoxicity have been developed, including cardiac function monitoring, limitation of chemotherapy doses, use of anthracycline analogues and cardioprotectants, and early detection of cardiotoxicity by biomarkers, followed by prophylactic intervention in selected high risk patients. We reviewed the currently available approaches which have been demonstrated to be effective in preventing or limiting cancer drug-induced cardiotoxicity.


Assuntos
Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiotoxicidade/diagnóstico , Cardiotoxinas/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Neoplasias/tratamento farmacológico , Disfunção Ventricular Esquerda/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Humanos , Prognóstico , Qualidade de Vida
11.
CA Cancer J Clin ; 66(4): 309-25, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26919165

RESUMO

Answer questions and earn CME/CNE Cancer and heart disease are the leading causes of morbidity and mortality in the industrialized world. Modern treatment strategies have led to an improvement in the chances of surviving a diagnosis of cancer; however, these gains can come at a cost. Patients may experience adverse cardiovascular events related to their cancer treatment or as a result of an exacerbation of underlying cardiovascular disease. With longer periods of survival, late effects of cancer treatment may become clinically evident years or decades after completion of therapy. Current cancer therapy incorporates multiple agents whose deleterious cardiac effects may be additive or synergistic. Cardiac dysfunction may result from agents that can result in myocyte destruction, such as with anthracycline use, or from agents that appear to transiently affect left ventricular contractility. In addition, cancer treatment may be associated with other cardiac events, such as severe treatment-induced hypertension and vasospastic and thromboembolic ischemia, as well as rhythm disturbances, including QTc prolongation, that may be rarely life-threatening. Early and late effects of chest radiation can lead to radiation-induced heart disease, including pericardial disease, myocardial fibrosis, cardiomyopathy, coronary artery disease, valvular disease, and arrhythmias, in the setting of myocardial fibrosis. The discipline of cardio-oncology has developed in response to the combined decision making necessary to optimize the care of cancer patients, whether they are receiving active treatment or are long-term survivors. Strategies to prevent or mitigate cardiovascular damage from cancer treatment are needed to provide the best cancer care. This review will focus on the common cardiovascular issues that may arise during or after cancer therapy, the detection and monitoring of cardiovascular injury, and the best management principles to protect against or minimize cardiotoxicity during the spectrum of cancer treatment strategies. CA Cancer J Clin 2016;66:309-325. © 2016 American Cancer Society.


Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Coração/efeitos dos fármacos , Neoplasias/tratamento farmacológico , American Cancer Society , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/prevenção & controle , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Educação Médica Continuada , Humanos , Hipertensão/induzido quimicamente , Hipertensão/prevenção & controle , Fatores de Risco , Estados Unidos/epidemiologia
12.
Circ Heart Fail ; 9(2): e002843, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26839395

RESUMO

Success with oncologic treatment has allowed cancer patients to experience longer cancer-free survival gains. Unfortunately, this success has been tempered by unintended and often devastating cardiac complications affecting overall patient outcomes. Cardiac toxicity, specifically the association of several cancer therapy agents with the development of left ventricular dysfunction and cardiomyopathy, is an issue of growing concern. Although the pathophysiologic mechanisms behind cardiac toxicity have been characterized, there is currently no evidence-based approach for monitoring and management of these patients. In the first of a 2-part review, we discuss the epidemiologic, pathophysiologic, risk factors, and imaging aspects of cancer therapy-related cardiac dysfunction and heart failure. In this second part, we discuss the prevention and treatment aspects in these patients and conclude with highlighting the evidence gaps and future directions for research in this area.


Assuntos
Antineoplásicos/efeitos adversos , Cardiomiopatias/prevenção & controle , Cardiomiopatias/terapia , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/terapia , Disfunção Ventricular Esquerda/prevenção & controle , Disfunção Ventricular Esquerda/terapia , Algoritmos , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico , Cardiomiopatias/fisiopatologia , Procedimentos Clínicos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Fatores de Risco , Resultado do Tratamento , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos
13.
Front Plant Sci ; 7: 89, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26904061

RESUMO

The highly ordered protein backbone of virus particles makes them attractive candidates for use as enzyme nano-carriers (ENCs). We have previously developed a non-covalent and versatile approach for adhesion of enzymes to virus particles. This approach makes use of z33, a peptide derived from the B-domain of Staphylococcus aureus protein A, which binds to the Fc domain of many immunoglobulins. We have demonstrated that with specific antibodies addressed against the viral capsid proteins (CPs) an 87% coverage of z33-tagged proteins can be achieved on potyvirus particles. 4-coumarate coenzyme A ligase (4CL2) and stilbene synthase (STS) catalyze consecutive steps in the resveratrol synthetic pathway. In this study, these enzymes were modified to carry an N-terminal z33 peptide and a C-terminal 6xHis tag to obtain (z)4CL2(His) and (z)STS(His), respectively. A protein chimera, (z)4CL2::STS(His), with the same modifications was also generated from the genetic fusion of both mono-enzyme encoding genes. All z33 enzymes were biologically active after expression in Escherichia coli as revealed by LC-MS analysis to identify resveratrol and assembled readily into macromolecular complexes with Potato virus A particles and α-PVA CP antibodies. To test simultaneous immobilization-purification, we applied the double antibody sandwich - ELISA protocol to capture active z33-containg mono-enzymes and protein chimera directly from clarified soluble cell lysates onto the virus particle surface. These immobilized enzymes were able to synthesize resveratrol. We present here a bottom up approach to immobilize active enzymes onto virus-based ENCs and discuss the potential to utilize this method in the purification and configuration of nano-devices.

14.
Circ Heart Fail ; 9(1): e002661, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26747861

RESUMO

Advances in cancer therapy have resulted in significant improvement in long-term survival for many types of cancer but have also resulted in untoward side effects associated with treatment. One such complication that has become increasingly recognized is the development of cardiomyopathy and heart failure. Whether a previously healthy person from a cardiovascular perspective develops cancer therapy-related cardiac dysfunction or a high-risk cardiovascular patient requires cancer therapy, the team of oncologists and cardiologists must be better equipped with an evidence-based approach to care for these patients across the spectrum. Although the toxicities associated with various cancer therapies are well recognized, limitations to our understanding of the appropriate course of action remain. In this first of a 2-part review, we discuss the epidemiologic, pathophysiologic, risk factors, and imaging aspects of cancer therapy-related cardiac dysfunction and heart failure. In a subsequent second part, we discuss the prevention and treatment aspects, concluding with a section on evidence gap and future directions. We focus on adult patients in all stages of cancer therapy from pretreatment surveillance, to ongoing therapy, and long-term follow-up.


Assuntos
Antineoplásicos/efeitos adversos , Cardiomiopatias/induzido quimicamente , Diagnóstico por Imagem , Insuficiência Cardíaca/induzido quimicamente , Neoplasias/tratamento farmacológico , Biomarcadores/sangue , Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Cardiomiopatias/fisiopatologia , Comorbidade , Diagnóstico por Imagem/métodos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Neoplasias/radioterapia , Valor Preditivo dos Testes , Prognóstico , Lesões por Radiação/diagnóstico , Lesões por Radiação/epidemiologia , Lesões por Radiação/fisiopatologia , Radioterapia/efeitos adversos , Medição de Risco , Fatores de Risco , Terminologia como Assunto , Fatores de Tempo , Resultado do Tratamento
16.
Ann Surg ; 264(2): 244-51, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26764872

RESUMO

OBJECTIVE: We performed a prospective, randomized clinical study to assess whether prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, reduces the incidence of postoperative atrial fibrillation. BACKGROUND: Postoperative atrial fibrillation is a well recognized complication after lung cancer surgery, with an incidence as high as 30%. Perioperative increase of NT-proBNP has been demonstrated to be a strong independent predictor of postoperative atrial fibrillation in this setting. METHODS: NT-proBNP concentration was measured 24 hours before surgery and soon after surgery in 1116 patients. Three hundred twenty (29%) patients showed a high NT-proBNP value and were enrolled: 108 were assigned to the metoprolol group, 102 to the losartan group, and 110 to the control group. RESULTS: Overall, the incidence of postoperative atrial fibrillation was 20% (n = 64); it was significantly lower in the metoprolol and losartan groups compared with the control group [6%, 12%, and 40%, respectively; relative risk 0.19, 95% confidence intervals (CIs), 0.09-0.37; P < 0.001 in the metoprolol group; and 0.29, 95% CI, 0.16-0.52; P < 0.001 in the losartan group). No significant difference was found when the metoprolol and losartan groups were directly compared (P = 0.21). CONCLUSIONS: A prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with high NT-proBNP levels, significantly reduced the occurrence of postoperative atrial fibrillation.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/prevenção & controle , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/epidemiologia , Feminino , Humanos , Incidência , Losartan/uso terapêutico , Neoplasias Pulmonares/sangue , Masculino , Metoprolol/uso terapêutico , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos
17.
Nat Rev Clin Oncol ; 13(3): 172-84, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26598943

RESUMO

Breast cancer treatments have evolved over the past decades, although several widely used treatments have adverse cardiac effects. Radiotherapy generally improves the survival of women with breast cancer, although its deleterious cardiovascular effects pose competing risks of morbidity and/or mortality. In the past, radiation-associated cardiovascular disease was a phenomenon considered to take more than a decade to manifest, but newer research suggests that this latency is much shorter. Knowledge of coronary anatomy relative to the distribution of the delivered radiation dose has improved over time, and as a result, techniques have enabled this risk to be decreased. Studies continue to be performed to better understand, prevent and mitigate against radiation-associated cardiovascular disease. Treatments such as anthracyclines, which are a mainstay of chemotherapy for breast cancer, and newer targeted agents such as trastuzumab both have established risks of cardiotoxicity, which can limit their effectiveness and result in increased morbidity and/or mortality. Interest in whether ß-blockers, statins and/or angiotensin-converting enzyme (ACE)-inhibitors might have therapeutic and/or preventative effects in these patients is currently increasing. This Review summarizes the incidence, risks and effects of treatment-induced cardiovascular disease in patients with breast cancer and describes strategies that might be used to minimize this risk.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/terapia , Doenças Cardiovasculares/induzido quimicamente , Lesões por Radiação/etiologia , Animais , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Incidência , Prevenção Primária/métodos , Lesões por Radiação/diagnóstico , Lesões por Radiação/mortalidade , Lesões por Radiação/prevenção & controle , Radioterapia/efeitos adversos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
18.
Anesthesiology ; 123(2): 264-71, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26200179

RESUMO

BACKGROUND: N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. METHODS: The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. RESULTS: The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. CONCLUSIONS: Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.


Assuntos
Cardiopatias/sangue , Cardiopatias/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Biomarcadores/sangue , Humanos , Prognóstico
19.
Circulation ; 131(22): 1981-8, 2015 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-25948538

RESUMO

BACKGROUND: Three types of anthracycline-induced cardiotoxicities are currently recognized: acute, early-onset chronic, and late-onset chronic. However, data supporting this classification are lacking. We prospectively evaluated incidence, time of occurrence, clinical correlates, and response to heart failure therapy of cardiotoxicity. METHODS AND RESULTS: We assessed left ventricular ejection fraction (LVEF), at baseline, every 3 months during chemotherapy and for the following year, every 6 months over the following 4 years, and yearly afterward in a heterogeneous cohort of 2625 patients receiving anthracycline-containing therapy. In case of cardiotoxicity (LVEF decrease >10 absolute points, and <50%), heart failure therapy was initiated. Recovery from cardiotoxicity was defined as partial (LVEF increase >5 absolute points and >50%) or full (LVEF increase to the baseline value). The median follow-up was 5.2 (quartile 1 to quartile 3, 2.6-8.0) years. The overall incidence of cardiotoxicity was 9% (n=226). The median time elapsed between the end of chemotherapy and cardiotoxicity development was 3.5 (quartile 1 to quartile 3, 3-6) months. In 98% of cases (n=221), cardiotoxicity occurred within the first year. Twenty-five (11%) patients had full recovery, and 160 (71%) patients had partial recovery. At multivariable analysis, end-chemotherapy LVEF (hazard ratio, 1.37; 95% confidence interval, 1.33-1.42 for each percent unit decrement) and cumulative doxorubicin dose (hazard ratio, 1.09; 95% confidence interval, 1.04-1.15 for each 50 mg/m(2) increment) were independent correlates of cardiotoxicity. CONCLUSIONS: Most cardiotoxicity after anthracycline-containing therapy occurs within the first year and is associated with anthracycline dose and LVEF at the end of treatment. Early detection and prompt therapy of cardiotoxicity appear crucial for substantial recovery of cardiac function.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico , Adulto , Antraciclinas/efeitos adversos , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/terapia , Estudos de Coortes , Diagnóstico Precoce , Feminino , Seguimentos , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia
20.
ACS Nano ; 9(5): 4911-24, 2015 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-25905663

RESUMO

We show herein that electrochemical atomic force microscopy (AFM-SECM), operated in molecule touching (Mt) mode and combined with redox immunomarking, enables the in situ mapping of the distribution of proteins on individual virus particles and makes localization of individual viral proteins possible. Acquisition of a topography image allows isolated virus particles to be identified and structurally characterized, while simultaneous acquisition of a current image allows the sought after protein, marked by redox antibodies, to be selectively located. We concomitantly show that Mt/AFM-SECM, due to its single-particle resolution, can also uniquely reveal the way redox functionalization endowed to viral particles is distributed both statistically among the viruses and spatially over individual virus particles. This possibility makes Mt/AFM-SECM a unique tool for viral nanotechnology.


Assuntos
Proteínas do Capsídeo/metabolismo , Microscopia de Força Atômica/métodos , Potyvirus/metabolismo , Vírion/metabolismo , Eletroquímica , Ouro/química , Microscopia Eletroquímica de Varredura , Nanotecnologia , Oxirredução , Potyvirus/química , Propriedades de Superfície , Vírion/química
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