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1.
J Cardiovasc Magn Reson ; 22(1): 64, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32892749

RESUMO

BACKGROUND: Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO2) is associated with impaired cardiac reserve (defined as the increase in cardiac function from rest to peak exercise) and heart failure risk, but it is unclear whether this relationship exists in pediatric cancer survivors. This study sought to investigate the presence of reduced peak VO2 in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac haemodynamics and systolic function during exercise. METHODS: Twenty pediatric cancer survivors (8-24 years; 10 male) treated with anthracycline chemotherapy ± radiation underwent cardiopulmonary exercise testing to quantify peak VO2, with a value < 85% of predicted defined as impaired peak VO2. Resting cardiac function was assessed using 2- and 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate, stroke volume index (SVI) and cardiac index (CI) using exercise cardiovascular magnetic resonance (CMR). RESULTS: Twelve of 20 survivors (60%) had reduced peak VO2 (70 ± 16% vs. 97 ± 14% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired peak VO2. However, those with reduced peak VO2 had diminished cardiac reserve, with a lesser increase in CI and SVI during exercise (Interaction P < 0.01 for both), whilst the heart rate response was similar (P = 0.71). CONCLUSIONS: Whilst exercise intolerance is common among pediatric cancer survivors, it is poorly explained by resting measures of cardiac function. In contrast, impaired exercise capacity is associated with impaired haemodynamics and systolic functional reserve measured during exercise. Consequently, measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure.


Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Aptidão Cardiorrespiratória , Teste de Esforço , Tolerância ao Exercício , Cardiopatias/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Lesões por Radiação/diagnóstico por imagem , Adolescente , Fatores Etários , Cardiotoxicidade , Criança , Feminino , Nível de Saúde , Cardiopatias/induzido quimicamente , Cardiopatias/fisiopatologia , Hemodinâmica , Humanos , Masculino , Consumo de Oxigênio , Valor Preditivo dos Testes , Lesões por Radiação/etiologia , Lesões por Radiação/fisiopatologia , Radioterapia/efeitos adversos , Fatores de Risco , Adulto Jovem
2.
Elife ; 92020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32639233

RESUMO

Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy. Bayesian regression models were fitted to survival outcomes and electrocardiograph QRS durations from 302 prospectively studied French patients who had taken intentional chloroquine overdoses, of whom 33 died (11%), and 16 healthy volunteers who took 620 mg base chloroquine single doses. Whole blood concentrations of 13.5 µmol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarization is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity.


Assuntos
Cloroquina/envenenamento , Overdose de Drogas/mortalidade , Tentativa de Suicídio , Suicídio , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/envenenamento , Antimaláricos/uso terapêutico , Biotransformação , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Cloroquina/análogos & derivados , Cloroquina/sangue , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Relação Dose-Resposta a Droga , Reposicionamento de Medicamentos , Eletrocardiografia , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/mortalidade , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/envenenamento , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Malária/tratamento farmacológico , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Medição de Risco
3.
PLoS One ; 15(7): e0232507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645007

RESUMO

Sex-related differences in cardiovascular diseases are highly complex in humans and model-dependent in experimental laboratory animals. The objective of this work was to comprehensively investigate key sex differences in the response to acute and prolonged adrenergic stimulation in C57Bl/6NCrl mice. Cardiac function was assessed by trans-thoracic echocardiography before and after acute adrenergic stimulation (a single sub-cutaneous dose of isoproterenol 10 mg/kg) in 15 weeks old male and female C57Bl/6NCrl mice. Thereafter, prolonged adrenergic stimulation was achieved by sub-cutaneous injections of isoproterenol 10 mg/kg/day for 14 days in male and female mice. Cardiac function and morphometry were assessed by trans-thoracic echocardiography on the 15th day. Thereafter, the mice were euthanized, and the hearts were collected. Histopathological analysis of myocardial tissue was performed after staining with hematoxylin & eosin, Masson's trichrome and MAC-2 antibody. Gene expression of remodeling and fibrotic markers was assessed by real-time PCR. Cardiac function and morphometry were also measured before and after isoproterenol 10 mg/kg/day for 14 days in groups of gonadectomized male and female mice and sham-operated controls. In the current work, there were no statistically significant differences in the positive inotropic and chronotropic effects of isoproterenol between male and female C57Bl/6NCrl. After prolonged adrenergic stimulation, there was similar degree of cardiac dysfunction, cardiac hypertrophy, and myocardial fibrosis in male and female mice. Similarly, prolonged isoproterenol administration induced hypertrophic and fibrotic genes in hearts of male and female mice to the same extent. Intriguingly, gonadectomy of male and female mice did not have a significant impact on isoproterenol-induced cardiac dysfunction as compared to sham-operated animals. The current work demonstrated lack of significant sex-related differences in isoproterenol-induced cardiac hypertrophy, dysfunction, and fibrosis in C57Bl/6NCrl mice. This study suggests that female sex may not be sufficient to protect the heart in this model of isoproterenol-induced cardiac dysfunction and underscores the notion that sexual dimorphism in cardiovascular diseases is highly model-dependent.


Assuntos
Cardiopatias/fisiopatologia , Caracteres Sexuais , Animais , Biomarcadores/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Ecocardiografia , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Isoproterenol/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia
4.
J Cardiovasc Transl Res ; 13(3): 431-450, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32642841

RESUMO

In the field of cardio-oncology, it is well recognised that despite the benefits of chemotherapy in treating and possibly curing cancer, it can cause catastrophic damage to bystander tissues resulting in a range of potentially of life-threatening cardiovascular toxicities, and leading to a number of damaging side effects including heart failure and myocardial infarction. Cardiotoxicity is responsible for significant morbidity and mortality in the long-term in oncology patients, specifically due to left ventricular dysfunction. There is increasing emphasis on the early use of biomarkers in order to detect the cardiotoxicity at a stage before it becomes irreversible. The most important markers of cardiac injury are cardiac troponin and natriuretic peptides, whilst markers of inflammation such as interleukin-6, C-reactive protein, myeloperoxidase, Galectin-3, growth differentiation factor-15 are under investigation for their use in detecting cardiotoxicity early. In addition, microRNAs, genome-wide association studies and proteomics are being studied as novel markers of cardiovascular injury or inflammation. The aim of this literature review is to discuss the evidence base behind the use of these biomarkers for the detection of cardiotoxicity.


Assuntos
Antineoplásicos/efeitos adversos , Biomarcadores/metabolismo , Sobreviventes de Câncer , Cardiologia , Cardiopatias/induzido quimicamente , Oncologia , Miócitos Cardíacos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Biomarcadores/sangue , Cardiotoxicidade , Cardiopatias/diagnóstico , Cardiopatias/metabolismo , Cardiopatias/terapia , Humanos , Miócitos Cardíacos/metabolismo , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
5.
Adv Rheumatol ; 60(1): 32, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: covidwho-591986

RESUMO

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.


Assuntos
Antimaláricos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Cloroquina/farmacologia , Hidroxicloroquina/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/imunologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Infecções por Coronavirus/tratamento farmacológico , Erupção por Droga/etiologia , Interações Medicamentosas , Feminino , Glucose/metabolismo , Cardiopatias/induzido quimicamente , Humanos , Lipídeos/sangue , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pandemias , Agregação Plaquetária/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Gravidez , Insuficiência Renal/prevenção & controle , Doenças Retinianas/induzido quimicamente , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/imunologia
6.
Adv Rheumatol ; 60(1): 32, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517786

RESUMO

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.


Assuntos
Antimaláricos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Cloroquina/farmacologia , Hidroxicloroquina/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/imunologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Infecções por Coronavirus/tratamento farmacológico , Erupção por Droga/etiologia , Interações Medicamentosas , Feminino , Glucose/metabolismo , Cardiopatias/induzido quimicamente , Humanos , Lipídeos/sangue , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pandemias , Agregação Plaquetária/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Gravidez , Insuficiência Renal/prevenção & controle , Doenças Retinianas/induzido quimicamente , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/imunologia
8.
Toxicol Lett ; 332: 181-191, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32473956

RESUMO

Trans-1233zd was developed as a refrigerant and propellant in consumer products; its toxicity has been studied extensively. The scope of this assessment is to apply the confirmed NOAEC to conduct Benchmark Dose Modeling (BMD) and determine the Point of Departure (POD). In a previously published 13-week inhalation study, a NOAEC was identified at 4000 ppm. Due to uncertainty concerning the cardiac lesion, an external pathology peer review of heart tissues was undertaken using published best practices and consistent nomenclature and diagnostic criteria. The cardiac lesion observed at 4000 ppm was considered to be spontaneous based on lesion location and microscopic features. BMD was applied to derive the BMDL05 and BMDL10; the more conservative BMDL05 was used as the POD for risk assessment to calculate the Reference Exposure Levels (RELs). The 2-Box Air Dispersion Model was used to calculate the exposure to consumer products. Both the acute and chronic exposure concentrations calculated were compared to the acute and chronic RELs. The acute and chronic exposure to trans-1233zd in the assessed consumer products are below the RELs and deemed safe for their intended uses.


Assuntos
Clorofluorcarbonetos de Metano/toxicidade , Clorofluorcarbonetos/toxicidade , Administração por Inalação , Animais , Benchmarking , Relação Dose-Resposta a Droga , Exposição Ambiental , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Exposição por Inalação , Masculino , Modelos Biológicos , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley , Medição de Risco
9.
Proc Natl Acad Sci U S A ; 117(26): 15182-15192, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32554494

RESUMO

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. It is unclear whether these side effects are coupled to the chemotherapeutic efficacy. Doxo, Daun, Epi, and Ida execute two cellular activities: DNA damage, causing double-strand breaks (DSBs) following poisoning of topoisomerase II (Topo II), and chromatin damage, mediated through histone eviction at selected sites in the genome. Here we report that anthracycline-induced cardiotoxicity requires the combination of both cellular activities. Topo II poisons with either one of the activities fail to induce cardiotoxicity in mice and human cardiac microtissues, as observed for aclarubicin (Acla) and etoposide (Etop). Further, we show that Doxo can be detoxified by chemically separating these two activities. Anthracycline variants that induce chromatin damage without causing DSBs maintain similar anticancer potency in cell lines, mice, and human acute myeloid leukemia patients, implying that chromatin damage constitutes a major cytotoxic mechanism of anthracyclines. With these anthracyclines abstained from cardiotoxicity and therapy-related tumors, we thus uncoupled the side effects from anticancer efficacy. These results suggest that anthracycline variants acting primarily via chromatin damage may allow prolonged treatment of cancer patients and will improve the quality of life of cancer survivors.


Assuntos
Antineoplásicos/efeitos adversos , Cromatina/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/efeitos adversos , Animais , Linhagem Celular , Doxorrubicina/análogos & derivados , Doxorrubicina/síntese química , Doxorrubicina/metabolismo , Doxorrubicina/uso terapêutico , Cardiopatias/induzido quimicamente , Histonas , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos
11.
J Cardiovasc Transl Res ; 13(3): 490-494, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32583314

RESUMO

Cancer therapy-related cardiovascular events are widely recognized as a global problem, and cardio-oncology has been proposed as a new approach to coordinate preventive strategies in oncologic patients. Cardiac imaging plays a critical role in this process. This article summarizes current practices and future needs in cardiac imaging to improve the cardiovascular surveillance of cancer patients.


Assuntos
Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Técnicas de Imagem Cardíaca , Cardiologia , Assistência Integral à Saúde , Cardiopatias/diagnóstico por imagem , Oncologia , Neoplasias/tratamento farmacológico , Cardiotoxicidade , Europa (Continente) , Cardiopatias/induzido quimicamente , Humanos , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
13.
Therapie ; 75(4): 371-379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32418730

RESUMO

INTRODUCTION: COVID-19 is an unprecedented challenge for physicians and scientists. Several publicized drugs are being used with not much evidence of their efficacy such as hydroxychloroquine, azithromycin or lopinavir-ritonavir. Yet, the cardiac safety of these drugs in COVID-19 deserves scrutiny as they are known to foster cardiac adverse ADRs, notably QTc interval prolongation on the electrocardiogram and its arrhythmogenic consequences. METHODS: Since March 27th, 2020, the French Pharmacovigilance Network directed all cardiac adverse drug reactions associated with "off-label" use of hydroxychloroquine, azithromycin and lopinavir-ritonavir in COVID-19 to the Nice Regional Center of Pharmacovigilance. Each Regional Center of Pharmacovigilance first assessed causality of drugs. We performed a specific analysis of these cardiac adverse drug reactions amidst an array of risk factors, reassessed the electrocardiograms and estimated their incidence in coronavirus disease 2019. RESULTS: In one month, 120 reports of cardiac adverse drug reactions have been notified, 103 of which associated with hydroxychloroquine alone (86%), or associated with azithromycin (60%). Their estimated incidence is 0.77% to 1.54% of all patients, notwithstanding strong underreporting. Lopinavir-ritonavir came third with 17 reports (14%) and chloroquine fourth with 3 reports (2.5%). There were 8 sudden, unexplained or aborted deaths (7%), 8 ventricular arrhythmias (7%), 90 reports of prolonged QTc (75%) most of them "serious" (64%), 48 of which proved ≥ 500ms, 20 reports of severe conduction disorders (17%) and 5 reports of other cardiac causes (4%). Six reports derived from automedication. DISCUSSION AND CONCLUSION: "Off-label" use of treatments in COVID-19 increases the risk of cardiac ADRs, some of them avoidable. Even if these drugs are perceived as familiar, they are used in patients with added risk factors caused by infection. Precautions should be taken to mitigate the risk, even if they will be proven efficacious.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Cardiopatias/induzido quimicamente , Uso Off-Label , Farmacovigilância , Pneumonia Viral/tratamento farmacológico , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Idoso , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Combinação de Medicamentos , Eletrocardiografia , Feminino , França/epidemiologia , Cardiopatias/epidemiologia , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
14.
J Cardiovasc Transl Res ; 13(3): 495-505, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32444945

RESUMO

The burgeoning field of cardio-oncology (C-O) is now necessary for the delivery of excellent care for patients with cancer. Many factors have contributed to this increasing population of cancer survivors or those being treated with novel and targeted cancer therapies. There is a tremendous need to provide outstanding cardiovascular (CV) care for these patients; however, current medical literature actually provides a paucity of guidance. C-O therefore provides a novel opportunity for clinical, translational, and basic research to advance patient care. This review aims to be a primer for cardio-oncologists on how to develop a vibrant and comprehensive C-O program, use practical tools to assist in the construction of C-O services, and to proactively incorporate translational and clinical research into the training of future leaders as well as enhance clinical care.


Assuntos
Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Cardiologia/organização & administração , Assistência Integral à Saúde/organização & administração , Prestação Integrada de Cuidados de Saúde/organização & administração , Cardiopatias/diagnóstico por imagem , Oncologia/organização & administração , Neoplasias/tratamento farmacológico , Técnicas de Imagem Cardíaca , Cardiotoxicidade , Cardiopatias/induzido quimicamente , Humanos , Valor Preditivo dos Testes , Prognóstico , Indicadores de Qualidade em Assistência à Saúde/organização & administração , Medição de Risco , Fatores de Risco
15.
J Cardiovasc Transl Res ; 13(3): 478-489, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32458402

RESUMO

We investigated time trends and factors associated with the use of cardiac imaging among women with early-stage breast cancer prior to the initiation of treatment. Of 11,732 women ages 24-64, diagnosed with stage I-III breast cancer in 2006-2011, 2550 (22%) received anthracycline-based chemotherapy. Baseline cardiac imaging was used in 79% of patients receiving anthracyclines and increased over time. Of 2277 (20%) women who received non-anthracycline therapy, 16% received cardiac imaging. Women receiving cardiac imaging in non-anthracycline therapy group were more likely to have higher cardiovascular risk, as well as higher cancer stage and worse histological tumor grade suggesting that results of imaging might have influenced the choice of cancer therapy. Our findings indicate the need for cardio-oncology collaboration in identification and treatment of women at high risk for adverse oncology and cardiovascular outcomes.


Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Técnicas de Imagem Cardíaca , Cardiopatias/diagnóstico por imagem , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Cardiotoxicidade , Quimioterapia Adjuvante , Bases de Dados Factuais , Diagnóstico Precoce , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/epidemiologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
16.
Acta Cir Bras ; 35(2): e202000202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267288

RESUMO

PURPOSE: To investigate the effects of adalimumab pretreatment on the lipopolysaccharide-mediated myocardial injury. METHODS: Twenty-eight Wistar rats were randomized into four groups (n=7). Control (C) group animals were injected once a day with intraperitoneal (i.p) 0.9 % saline for two days. In the Adalimumab (Ada) group, adalimumab was injected at a dose of 10 mg/kg/ day (i.p) for two days. Lipopolysaccharide (Lps) group rats were injected with a dose of 5 mg/kg (i.p) lipopolysaccharide. Lipopolysaccharide + Adalimumab (Lps+Ada) group rats received adalimumab before the administration of lipopolysaccharide. The animals were sacrificed 24 h after the last injection and blood samples were obtained for determination of biochemical cardiac injury markers and circulating levels of TNF-α and interleukin-6 (IL-6). Hearts were harvested for histological examination. RESULTS: Endotoxin exposure resulted in significant increases in serum cardiac injury markers, serum cytokines and histological myocardial injury scores in the Lps group. The levels of circulating cytokines, cardiac injury markers and histological injury scores for myocardial necrosis, perivascular cell infiltration, and inflammation were significantly reduced in Lps+Ada as compared to Lps group (p<0.05). CONCLUSIONS: Adalimumab pretreatment reduces endotoxin-induced myocardial damage in rats. This beneficial effect is thought to be related to the reduction of cytokine release.


Assuntos
Adalimumab/administração & dosagem , Cardiopatias/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Endotoxinas , Feminino , Cardiopatias/induzido quimicamente , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/biossíntese
17.
Minerva Med ; 111(2): 173-180, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32338843

RESUMO

INTRODUCTION: Clinical data on short mandatory dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy, compared with prolonged DAPT in patients undergoing percutaneous coronary intervention (PCI) are insufficient. We aim to evaluate the effectiveness and safety of P2Y12 inhibitor monotherapy and prolonged DAPT after short mandatory DAPT on cardiovascular events in patients undergoing PCI. EVIDENCE ACQUISITION: A systematic literature search was performed in seven medical databases from building the database until July 2019. Three studies with randomized controlled trial (RCTs), totaling 21,970 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager v. 5.3 software. EVIDENCE SYNTHESIS: Our result of pooled analysis showed that there was noninferior rates of in major adverse cardiac and cerebrovascular events (MACCE), stroke, myocardial infarction and cardiac death between short mandatory DAPT followed by P2Y12 inhibitor monotherapy and prolonged DAPT in patients undergoing PCI. Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5 (OR=0.47, 95% CI: 0.31-0.70, P=0.002), compared with prolonged DAPT in patients undergoing PCI. However, Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy was not associated with BARC type 3-5, compared with prolonged DAPT. CONCLUSIONS: This meta-analysis demonstrated that short mandatory DAPT followed by P2Y12 inhibitor monotherapy compared with prolonged DAPT resulted in noninferior rates of MACCE, all-cause mortality, cardiac death, stroke, myocardial infarction and stent thrombosis. Furthermore, short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5.


Assuntos
Aspirina/efeitos adversos , Cardiopatias/mortalidade , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Acidente Vascular Cerebral/mortalidade , Aspirina/uso terapêutico , Causas de Morte , Cardiopatias/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Trombose/induzido quimicamente , Trombose/mortalidade
18.
J Cardiovasc Transl Res ; 13(3): 367-376, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32248349

RESUMO

Animal models of chemotherapy-induced cardiotoxicity have been instrumental in understanding the underlying mechanisms of the disease. The use of cardiac magnetic resonance (CMR) imaging and nuclear magnetic resonance (NMR) imaging in preclinical models allows the non-invasive study of subclinical pathophysiological processes that influence cardiac function and establish imaging parameters that can be adopted into clinical practice to predict cardiovascular outcomes. Given the rising population of cancer survivors and the current lack of effective therapies for the management of cardiotoxicity, research combining clinically relevant animal models and non-invasive cardiac imaging remains essential to improve methods to monitor, predict, and treat cardiovascular adverse events. This comprehensive review summarizes the lessons learned from animal models of cardiotoxicity employing CMR and tissue characterization techniques and discusses the ongoing challenges and hopes for the future.


Assuntos
Antineoplásicos , Cardiopatias/diagnóstico por imagem , Imagem por Ressonância Magnética , Animais , Cardiotoxicidade , Modelos Animais de Doenças , Cardiopatias/induzido quimicamente , Cardiopatias/fisiopatologia , Humanos , Valor Preditivo dos Testes
19.
J Cardiovasc Transl Res ; 13(3): 402-416, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32253744

RESUMO

Cancer therapies have been evolving from conventional chemotherapeutics to targeted agents. This has fulfilled the hope of greater efficacy but unfortunately not of greater safety. In fact, a broad spectrum of toxicities can be seen with targeted therapies, including cardiovascular toxicities. Among these, cardiomyopathy and heart failure have received greatest attention, given their profound implications for continuation of cancer therapies and cardiovascular morbidity and mortality. Prediction of risk has always posed a challenge and even more so with the newer targeted agents. The merits of accurate risk prediction, however, are very evident, e.g. facilitating treatment decisions even before the first dose is given. This is important for agents with a long half-life and high potential to induced life-threatening cardiac complications, such as myocarditis with immune checkpoint inhibitors. An opportunity to address these needs in the field of cardio-oncology is provided by the expanding repertoire of "-omics" and other tools in precision medicine and their integration in a systems biology approach. This may allow for new insights into patho-mechanisms and the creation of more precise and cost-effective risk prediction tools with the ultimate goals of improved therapy decisions and prevention of cardiovascular complications. Herein, we explore this topic as a future approach to translating the complexity of cardio-oncology to the reality of patient care.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Sobreviventes de Câncer , Cardiologia , Cardiopatias/induzido quimicamente , Oncologia , Neoplasias/tratamento farmacológico , Medicina de Precisão , Inibidores de Proteínas Quinases/efeitos adversos , Biologia de Sistemas , Animais , Cardiotoxicidade , Cardiopatias/genética , Cardiopatias/metabolismo , Humanos , Terapia de Alvo Molecular , Neoplasias/enzimologia , Neoplasias/imunologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Medição de Risco , Fatores de Risco
20.
Medicine (Baltimore) ; 99(5): e18701, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000374

RESUMO

INTRODUCTION: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in the treatment of cancer. Immunosuppressive therapy can control the cancer well and is suitable for the moderate to severe diseases. However, according to clinical observation, immune-related cardiac adverse events against PD-1or/and PD-L1 are inevitable, but generally reversible. Understanding the cardiac adverse events of PD-1 or/and PD-L1 inhibitors is crucial to improve the anti-cancer efficacy and ensure the life safety of patients. The variability of cardiac adverse events between different immunosuppressants and different cancers is not clear. METHODS AND ANALYSIS: This protocol established in this study has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search the following electronic bibliographic databases: PubMed, Cochrane Library, EMBASE databases and ClinicalTrials.gov from their inception to December 2019. We will use a combination of Medical Subject Heading, and free-text terms with various synonyms to search based on the Eligibility criteria. We will include RCTs on PD-1 or/and PD-L1 inhibitors therapy to analyze. In addition, our study will include some clinical trials. All relevant RCTs will be included, such as early phase I/II, phase III experimental trials, prospective and retrospective observational studies. According to the inclusion and exclusion criteria outlined above, the full texts of each eligible study will be retrieved for further identification by one reviewer. Two authors will screen the titles and abstracts of all records retrieved in above electronic databases independently to find potentially eligible reviews. Data will be extracted by 2 reviewers independently using a pre-designed data extraction form. The other reviewer will validate data. I-square (I) test, substantial heterogeneity, sensitivity analysis and publication bias assessment will be performed accordingly. For our network meta-analysis, we will use Stata 15.0 and WinBUGS 1.4.3. ETHICS AND DISSEMINATION: Ethics approval and patient consent would be not required because the data of this network meta-analysis mainly are obtained from existing resources. This network meta-analysis will be published in a peer-reviewed journal. PROSPERO NUMBER: CRD42019142865.


Assuntos
Antineoplásicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Cardiopatias/induzido quimicamente , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
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