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A concise management scheme is discussed for the best outcome in patients with chest pain.
Assuntos
Dor no Peito/terapia , Angina Instável/diagnóstico , Dor no Peito/etiologia , Cuidados Críticos , Diagnóstico Tardio , Diagnóstico Precoce , Eletrocardiografia , Serviço Hospitalar de Emergência , Humanos , Infarto do Miocárdio/diagnóstico , Equipe de Assistência ao Paciente , Medição de RiscoRESUMO
BACKGROUND: Activation of systemic innate immunity is critical in the chain of events leading to restenosis. LABR-312 is a novel compound that transiently modulates circulating monocytes, reducing accumulation of these cells at vascular injury sites and around stent struts. The purpose of the study was to examine the safety and efficacy of a single intravenous bolus of LABR-312 in reducing restenosis in patients treated for coronary narrowing. Patient response was examined in light of differential inflammatory states as evidenced by baseline circulating monocyte levels, diabetes mellitus, and acute coronary syndrome. METHODS: BLAST is a Phase II prospective, randomized, multicenter, double-blind, placebo-controlled trial that assessed the safety and efficacy of LABR-312. Patients were randomized to receive LABR-312 at 2 dose levels or placebo as an intravenous infusion during percutaneous coronary intervention and bare metal stent implantation. The primary end point was mean angiographic in-stent late loss at 6 months. RESULTS: Patients (N = 225) were enrolled at 12 centers. There were no safety concerns associated with the study drug. For the overall cohort, there were no differences between the groups in the primary efficacy end point (in-stent late loss of 0.86 ± 0.60 mm, 0.83 ± 0.57 mm, and 0.81 ± 0.68 mm for the placebo, low-dose, and high-dose group, respectively; P = not significant for all comparisons). In the prespecified subgroups of patients with a baseline proinflammatory state, patients with diabetes mellitus, and patients with high baseline monocyte count, there was a significant treatment effect. CONCLUSIONS: Intravenous administration of LABR-312 to patients undergoing percutaneous coronary intervention is safe and effectively modulates monocyte behavior. The average late loss did not differ between the treatment and placebo groups. However, in the inflammatory patient group with baseline monocyte count higher than the median value, there was a significant reduction in late loss with LABR-312.
Assuntos
Alendronato/administração & dosagem , Reestenose Coronária/terapia , Stents , Administração Intravenosa , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/cirurgia , Intervenção Coronária Percutânea , Estudos Prospectivos , Resultado do TratamentoRESUMO
1) The first evidence of the beneficial impact of Long-Term-Heat-Acclimation (LTHA) on cardio-vascular compliance was the positive inotropic response and improved left ventricular (LV) compliance noted when isolated hearts from LTHA rats were studied. Human echo study demonstrates that passive HA affects the right ventricle and the atria as well. 2) There is a cross-talk between vascular and cardiac compliance. Vascular compliance per se is defined by central venous pressure-Blood volume relationship-Global Vascular Compliance (GVC). It is determined by the sum of the vascular compliance of the vessels in every organ in any physiological state, varies with LTHA and thus influences cardiac performance. LTHA improves endothelial function, increases NO (nitric oxide) production, in-turn stimulating alterations in ECM (extracellular matrix) via the TGF ß1-SMAD pathway. 3) LTHA is associated with transformation from fast to slow myosin, heat acclimation ischemic/hypoxic cross-tolerance and alterations in the extracellular matrix. 4) A human translational study demonstrated improved LV compliance following bypass surgery in LTHA subjects compared to controls. 5) Diastolic dysfunction and the impact of comorbidities with vascular and non- vascular origins are major contributors to the syndrome of heart failure with preserved ejection function (HFPEF). Unfortunately, there is a paucity of treatment modalities that improve diastolic dysfunction. 6) In the current mini-review we suggest that LTHA may be beneficial to HFPEF patients by remodeling cardiac compliance and vascular response.
RESUMO
The release of cardiomyocyte components, i.e. biomarkers, into the bloodstream in higher than usual quantities indicates an ongoing pathological process. Thus, detection of elevated concentrations of cardiac biomarkers in blood is a sign of cardiac injury which could be due to supply-demand imbalance, toxic effects, or haemodynamic stress. It is up to the clinician to determine the most probable aetiology, the proper therapeutic measures, and the subsequent risk implied by the process. For this reason, the measurement of biomarkers always must be applied in relation to the clinical context and never in isolation. There are a large number of cardiac biomarkers, but they can be subdivided into four broad categories, those related to necrosis, inflammation, haemodynamic stress, and/or thrombosis. Their usefulness is dependent on the accuracy and reproducibility of the measurements, the discriminatory limits separating pathology from physiology, and their sensitivity and specificity for specific organ damage and/or disease processes. In recent years, cardiac biomarkers have become important adjuncts to the delivery of acute cardiac care. Therefore, the Working Group on Acute Cardiac Care of the European Society of Cardiology established a committee to deal with ongoing and newly developing issues related to cardiac biomarkers. The intention of the group is to outline the principles for the application of various biomarkers by clinicians in the setting of acute cardiac care in a series of expert consensus documents. The first of these will focus on cardiac troponin, a pivotal marker of cardiac injury/necrosis.
Assuntos
Infarto do Miocárdio/diagnóstico , Troponina/sangue , Bioensaio/normas , Biomarcadores/sangue , Humanos , Valores de Referência , Sensibilidade e EspecificidadeAssuntos
Fator Natriurético Atrial/sangue , Cardiopatias/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Síndrome Coronariana Aguda/diagnóstico , Doença Aguda , Biomarcadores/sangue , Cuidados Críticos , Dispneia/etiologia , Cardiopatias/terapia , Insuficiência Cardíaca/diagnóstico , Humanos , Imunoensaio , Peptídeo Natriurético Encefálico/fisiologia , Guias de Prática Clínica como Assunto , Embolia Pulmonar/diagnóstico , Valores de Referência , Medição de RiscoRESUMO
During the period of 1986-1997 the first 4 publications on the mechanical and metabolic properties of heat acclimated rat's heart were published. The outcome of these studies implied that heat acclimation, sedentary as well as combined with exercise training, confers long lasting protection against ischemic/reperfusion insult. These results promoted a clinical study on patients with coronary artery disease scheduled for elective coronary artery bypass operations aiming to elucidate whether exploitation of environmental stress can be translated into human benefits by improving physiological recovery. During the 1998 study, immediate-post operative chamber stiffness was assessed in patients acclimatized to heat and low intensity training in the desert (spring in the Dead Sea, 17-33°C) vs. patients in colder weather (spring in non-desert areas, 6-19°C) via echocardiogram acquisition simultaneous with left atrial pressure measurement during fast intravascular fluid bolus administration. We showed that patients undergoing "heat acclimatization combined with exercise training" were less susceptible to ischemic injury, therefore expressing less diastolic dysfunction after cardiopulmonary bypass compared to non-acclimatized patients. This was the first clinical translational study on cardiac patients, while exploiting environmental harsh conditions for human benefits. The original experimental data are described and discussed in view of the past as well as the present knowledge of the protective mechanisms induced by Heat Acclimation Mediated Cross-tolerance.
RESUMO
BACKGROUND: Five to 15% of the population have allergy to nickel, chromium, or molybdenum, which is a potential cause for in-stent restenosis. The Titan stent is made of stainless steel and is coated with titanium-nitride oxide (TiNOX), which completely prevents the discharge of metal elements. We performed a real-life multicenter registry to assess the short- and long-term characteristics of the Titan stent. METHODS AND RESULTS: A total of 103 Titan stents was implanted in 100 patients. Patients were 61.4+/-12.6 years old (81 men). Risk factors included hypercholesterolemia (63%), hypertension (53%), diabetes mellitus (DM; 35%), and current smoking (23%). Indications for PCI (percutaneous coronary intervention) were acute coronary syndromes (ACS) in 68% [acute ST elevation myocardial infarction (MI) in 8%], stable AP (angina pectoris) in 25%, and silent ischemia in 7% of the patients. Fifty-two percent of the treated lesions were of Type B2 or C. Lesion length was 14.3+/-2.9 mm and stent diameter was 3.06+/-0.36 mm. Indications for stenting were prevention of restenosis in 66%, residual stenosis in 33%, dissection in 13%, acute MI in 13%, and in-stent restenosis in 7% of the patients. Procedural success was 100%, with no complications. At 30 days, there were no major adverse cardiac events (MACE), including death, MI, and revascularization. At 180 days, only three patients had TVR (target vessel revascularization); two had TLR (target lesion revascularization) (one PCI and one CABG [coronary artery bypass grafting]), and one patient had a new narrowing proximal to the stent and underwent CABG due to multivessel disease. CONCLUSIONS: The Titan stent has a remarkable safety profile in high-risk patients and complex coronary lesions and excellent short- and long-term outcome with a very low clinical TLR rate.
Assuntos
Implante de Prótese Vascular , Materiais Revestidos Biocompatíveis , Avaliação de Resultados em Cuidados de Saúde , Sistema de Registros/estatística & dados numéricos , Stents/estatística & dados numéricos , Titânio , Adulto , Idoso , Idoso de 80 Anos ou mais , Implante de Prótese Vascular/efeitos adversos , Materiais Revestidos Biocompatíveis/efeitos adversos , Feminino , Seguimentos , Oclusão de Enxerto Vascular/prevenção & controle , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Fatores de Risco , Aço Inoxidável , Stents/efeitos adversos , Fatores de Tempo , Titânio/efeitos adversos , Resultado do TratamentoRESUMO
Based on our observations of energy sparing in heat-acclimated (AC) rat hearts, we investigated whether changes in preischemic glycogen level, glycolytic rate, and plasma thyroxine level mediate cardioprotection induced in these hearts during ischemia-reperfusion insults. Control (C) (24 degrees C), AC (34 degrees C, 30 days), acclimated-euthyroid (34 degrees C + 3 ng/ml l-thyroxine), and control hypothyroid (24 degrees C + 0.02% 6-n-propyl-2-thiouracil) groups were studied. Preischemic glycogen was higher in AC than in C hearts [39.0 +/- 8.5 vs. 19.2 +/- 4.2 (SE) micromol glucose/g wet wt; P < 0.0006], and the lactate produced vs. glycogen level during total ischemia ((13)C-NMR spectroscopy) was markedly slower (AC: -0.82x, r = 0.98 vs. C: -4.7x, r = 0.9). Time to onset of ischemic contracture was lengthened, and the fraction of hearts experiencing ischemic contracture was lowered. Pulse pressure recovery was improved in AC compared with C animals before, but not after, absolute sodium iodoacetate-induced glycolysis inhibition. Acclimated-euthyroid hearts exhibited decreased ischemic tolerance, whereas induced hypothyroidism in C improved cardiotolerance. Thus higher preischemic glycogen and slowed glycolysis are associated with hypothyroidism and are likely important mediators of the improved ischemic tolerance exhibited by AC hearts.
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Aclimatação/fisiologia , Glicogênio/metabolismo , Glicólise/fisiologia , Isquemia Miocárdica/metabolismo , Tiroxina/sangue , Animais , Isótopos de Carbono , Glucose/farmacocinética , Temperatura Alta , Hipotireoidismo/metabolismo , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Resistência Física/fisiologia , RatosRESUMO
C-type natriuretic peptide (CNP) and endothelin-1 are paracrine peptides with opposing effects on cardiac myocyte contraction and intracellular cGMP production. Elevated levels of both endothelin-1 and CNP are found in patients with congestive heart failure. These factors may be related to positive and negative regulation of cell apoptosis in the failing heart. To evaluate the effect of CNP and endothelin-1 on apoptosis of cardiac myocytes and the possible mechanisms involved, primary cardiac myocytes were prepared from neonatal Sabra rats. Cardiomyocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Annexin V in situ staining. The TUNEL method was used to measure the apoptotic index. CNP and the cGMP derivative, 8-br-cGMP, induced apoptosis of cardiac myocytes. CNP-induced apoptosis could be blocked by HS 142-1 (a mixture of 20-30 kinds of linear beta-1, 6-glucan esterified by capronic acid, an antagonist of type A and B natriuretic peptide receptors), and KT 5823 (C29H25N3O5), the inhibitor of cGMP-dependent protein kinase). Alpha-difluoromethylornithine (DFMO), the irreversible inhibitor of ornithine decarboxylase, also induced apoptosis to a similar extent. CNP and 8-br-cGMP caused a marked reduction of intracellular ornithine decarboxylase expression, as determined by Western blot analysis and immunohistochemical assay. Preincubation with endothelin-1 attenuated CNP- and 8-br-cGMP-induced cardiomyocyte apoptosis. Endothelin-1 also antagonized the CNP- and 8-br-cGMP-induced reduction of intracellular ornithine decarboxylase expression. These results suggest that CNP has a proapoptotic effect on neonatal rat cardiac myocytes. The effect is mediated via natriuretic peptide receptors and is due to an elevation of intracellular cGMP, which reduces the expression of intracellular ornithine decarboxylase and probably the production of polyamines. Endothelin-1 protects cardiac myocytes against CNP-induced apoptosis by influencing the cGMP-dependent pathway, and this effect is probably mediated through both a reduction of cGMP and antagonism of the CNP-induced reduction of intracellular ornithine decarboxylase expression.
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Apoptose/efeitos dos fármacos , Endotelina-1/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Peptídeo Natriurético Tipo C/farmacologia , Animais , Animais Recém-Nascidos , Western Blotting , Células Cultivadas , Proteínas Quinases Dependentes de GMP Cíclico/biossíntese , Interações Medicamentosas , Eflornitina/farmacologia , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Miócitos Cardíacos/enzimologia , Ornitina Descarboxilase/biossíntese , Polissacarídeos/farmacologia , Ratos , Ratos EndogâmicosRESUMO
BACKGROUND: Little information is available on the clinical practice and implementation of guidelines for treating acute myocardial infarction patients in Israel. OBJECTIVE: To assess patient characteristics, hospital course, management, and 30 day clinical outcome of all AMI patients hospitalized in Israel during a 2 month period in 2000. METHOD: We conducted a prospective 2 month survey of consecutive AMI patients admitted to 82 of 96 internal medicine departments and all 26 cardiac departments operating in Israel in 2000. Data were collected uniformly by means of a hospital and 30 day follow-up form. RESULTS: During the survey 1,683 consecutive patients with a discharge diagnosis of AMI were included. Their mean age was 66 years; 73% were male. The electrocardiographic pattern on admission revealed ST elevation, non-ST elevation and an undetermined ECG in 63%, 34% and 4% of patients respectively. Aspirin and heparin were given to 95% of patients. Beta-blockers and angiotensin-converting enzyme inhibitors were given to 76% and 65% of patients respectively. Among hospital survivors, 45% received lipid-lowering drugs. Thrombolytic therapy was administered in 28% of patients, coronary angiography was used in 45%, and 7% of patients underwent primary percutaneous coronary intervention. The 7 and 30 day mortality rates were 7% and 11% respectively. CONCLUSIONS: This nationwide survey shows that one-third of the AMI patients in Israel are elderly (> or = 75 years). The survey suggests that clinical guidelines for the management of patients with AMI are partially implemented in the community. Data from large surveys representing the "real world" practice are of utmost importance for the evaluation of clinical guidelines, research and educational purposes.
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Infarto do Miocárdio/terapia , Idoso , Eletrocardiografia , Feminino , Fidelidade a Diretrizes , Pesquisas sobre Atenção à Saúde , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Sistema de Registros , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: The aim of the current study was to describe the role of corin, an enzyme that cleaves pro-atrial natriuretic peptide and pro-brain natriuretic peptide into their active peptides, in patients with acute coronary syndrome (ACS). METHODS: Serum corin level was studied in patients with non-ST-elevation ACS who underwent percutaneous coronary intervention (n=152) and in control volunteers (n=103). RESULTS: The corin level was lower in acute coronary syndrome patients (798±288 pg/ml) than in the controls (1165±613 pg/ml, p<0.0001). Those acute coronary syndrome patients who developed major adverse cardiovascular events (MACE; 60.9%) within 3 years of discharge had lower corin levels than the patients who did not experience major adverse cardiovascular events (698.16±233.67 vs. 952.1±297.81 pg/ml, p<0.0001). Using a multiple logistic regression model, corin level was a significant predictor of post-ACS MACE: p=0.0004 for 50 pg/ml steps, AUC 0.791, while p<0.0001, and AUC 0.804 using corin and brain natriuretic peptide as predictors. CONCLUSIONS: Patients with non-ST-elevation ACS have lower serum corin levels than controls. Corin levels are lower in ACS patients who later experience MACE and thus might be predictor for MACE. This new putative biomarker may be useful, either alone or in combination with other biomarkers, for cardiovascular risk stratification assessment and outcome prediction in ACS patients.
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Síndrome Coronariana Aguda/sangue , Serina Endopeptidases/metabolismo , Síndrome Coronariana Aguda/terapia , Área Sob a Curva , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Análise de Regressão , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Efficiency of percutaneous revascularization and the utility of levosimendan for advanced ischemic heart failure (HF) is unclear. We examined the efficacy of revascularization and levosimendan on left ventricular ejection fraction (LVEF) and mortality of patients admitted with acute decompensated HF and severe left ventricular dysfunction. METHODS: A prospective case control study that enrolled 84 patients with ischemic decompensated HF with LVEF <35% and preserved LV wall thickness. Group A: 42 patients whose LVEF improved post percutaneous coronary intervention (PCI). Group B1: 22 patients whose LVEF did not improve post-PCI alone but improved after levosimendan. Group B2: 20 patients whose LVEF did not improve neither post-PCI nor post levosimendan. RESULTS: LVEF increased in group A from 22 ± 5 to 29 ± 5% post PCI and continued to improve at the 6 month follow-up (36 ± 4%). In group B1 LVEF did not improve after PCI, but increased after levosimendan from 23 ± 4% to 32 ± 4% and remained constant at 6 months. In group B2 LVEF 26 ± 4% did not change following both interventions. Reverse remodeling with a decrease in end-diastolic and end-systolic diameters was observed only in groups A and B1. Group B2 had a dismal prognosis with 36% in-hospital and 43% six month mortality. Groups A and B1 had a lower in hospital (4.7%, 4.5%) and mid term (11%, 11%) mortality. CONCLUSION: Improvement of LV size and function with better prognosis can be expected in the majority of patients undergoing PCI for decompensated ischemic HF. Levosimendan enhanced the recovery of LV function post PCI.
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Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/cirurgia , Hidrazonas/administração & dosagem , Intervenção Coronária Percutânea , Piridazinas/administração & dosagem , Recuperação de Função Fisiológica/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , Idoso de 80 Anos ou mais , Cardiotônicos/administração & dosagem , Estudos de Casos e Controles , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/tendências , Estudos Prospectivos , Recuperação de Função Fisiológica/efeitos dos fármacos , Simendana , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
OBJECTIVE: Anemia is an independent predictor of poor prognosis in acute coronary syndrome. Endothelial progenitor cells are bone marrow-derived cells that are mobilized into the circulation in response to ischemia. The number of circulating endothelial progenitor cells increases within days of acute coronary syndrome. There is no confirmation regarding the correlation between the occurrence of anemia and the deficiency in endothelial progenitor cells in patients with acute coronary syndrome. The correlation between chronic anemia and endothelial progenitor cells in patients with acute coronary syndrome was investigated. METHODS: Endothelial progenitor cells were examined in 26 patients with acute coronary syndrome. Fifteen patients had chronic nonprogressive anemia, and 11 patients had a normal blood count. Blood samples were drawn on the first day of admission and 4 to 7 days later. Mononuclear cells were separated and cultured on fibronectin-coated plates with EndoCult medium (StemCell Technologies, Vancouver, BC, Canada) for 5 days. Colony forming unit count and a migration assay were performed at each time point. RESULTS: Baseline colony forming unit in the non-anemic group was higher than in the anemic group (P<.0001). There was a highly significant correlation between admission hemoglobin and colony forming unit count (R=0.83, P<.0001). Colony forming units increased in both groups on the second measurement but to a lower extent in the anemic group (P = .0004). The migration assay in the non-anemic group was higher than in the anemic group at baseline (P = .017) and 4 to 7 days later (P = .0054). CONCLUSION: Patients with acute coronary syndrome with anemia demonstrate a reduced number of peripheral endothelial progenitor cells with impaired function, possibly representing a lower capacity for vascular healing. These phenomena may partly explain the poor prognosis observed in patients with acute coronary syndrome and anemia.