Blood cell adhesion to arterial filters analysis by scanning electron microscopy and real-time PCR assay: observational clinical study in cardiac surgery patients.

INTRODUCTION: Arterial filter is the part of the cardiopulmonary bypass circuit where blood cells are exposed to high mechanical stress and where cellular aggregates may fasten in large quantities. The aim of this study was to analyse blood cell adhesiveness in the arterial filter through scanning electron microscopy and real-time PCR assay. METHODS: Prospective, clinical and observational study performed on 28 patients undergoing cardiac surgery with cardiopulmonary bypass. Arterial filters were analysed by scanning electron microscopy. Real-time PCR assay was performed in extracted material from the arterial filters for analysis of platelet GPIb and CD45 leucocyte gene expression. Blood coagulation was analysed during cardiopulmonary bypass. Patients were followed until hospital discharge or 28 days after surgery. RESULTS: All studied arterial filters used in the subject patients showed a degree of adhesion from blood elements at scanning electron microscopy. All studied filters were positive for platelets GPIb gene expression and 15% had CD45 leucocyte gene expression. The GPIb platelet gene expression in blood lowered at the end of cardiopulmonary bypass (p = 0.019). There was negative correlation between blood GPIb platelet gene expression and Clot SR (HEPSCREEN2 ReoRox®) (rho = 0.635; p = 0.027). The filter fields count was correlated to the D-dimer dosage (rho = 0.828; p < 0.001). CONCLUSION: There was adhesion of blood elements, especially nucleated platelets, on all arterial filters studied. Although the arterial filter worked as a safety device, that possibly prevented arterial embolisation, it may also have caused greater hyperfibrinolysis during cardiopulmonary bypass.

Platelet Reactivity and Coagulation Markers in Patients with COVID-19.

INTRODUTION: COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls. METHODS: Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as < 53 AUC), arachidonic acid (MEA-ASPI, low PR < 86 AUC) and thrombin receptor-activating peptide 6 (MEA-TRAP, low PR < 97 AUC) in both groups. RESULTS: The rates of low PR with MEA-ADP were 27.5% in the COVID-19 group and 21.7% in the control group (OR = 1.60, p = 0.20); with MEA-ASPI, the rates were, respectively, 37.5% and 22.5% (OR = 3.67, p < 0.001); and with MEA-TRAP, the incidences were 48.5% and 18.8%, respectively (OR = 9.58, p < 0.001). Levels of D-dimer, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) were higher in the COVID-19 group in comparison with the control group (all p < 0.05). Thromboelastometry was utilized in a subgroup of patients and showed a hypercoagulable state in the COVID-19 group. CONCLUSION: Patients hospitalized with non-severe COVID-19 had lower PR compared to healthy controls, despite having higher levels of D-dimer, fibrinogen, and PAI-1, and hypercoagulability by thromboelastometry. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04447131.

Incidence and outcomes of perioperative myocardial infarction/injury diagnosed by high-sensitivity cardiac troponin I.

BACKGROUND:  Perioperative myocardial infarction/injury (PMI) diagnosed by high-sensitivity troponin (hs-cTn) T is frequent and a prognostically important complication of non-cardiac surgery. We aimed to evaluate the incidence and outcome of PMI diagnosed using hs-cTnI, and compare it to PMI diagnosed using hs-cTnT. METHODS: We prospectively included 2455 patients at high cardiovascular risk undergoing 3111 non-cardiac surgeries, for whom hs-cTnI and hs-cTnT concentrations were measured before surgery and on postoperative days 1 and 2. PMI was defined as a composite of perioperative myocardial infarction (PMIInfarct) and perioperative myocardial injury (PMIInjury), according to the Fourth Universal Definition of Myocardial Infarction. All-cause mortality was the primary endpoint. RESULTS: Using hs-cTnI, the incidence of overall PMI was 9% (95% confidence interval [CI] 8-10%), including PMIInfarct 2.6% (95% CI 2.0-3.2) and PMIInjury 6.1% (95% CI 5.3-6.9%), which was lower versus using hs-cTnT: overall PMI 15% (95% CI 14-16%), PMIInfarct 3.7% (95% CI 3.0-4.4) and PMIInjury 11.3% (95% CI 10.2-12.4%). All-cause mortality occurred in 52 (2%) patients within 30 days and 217 (9%) within 1 year. Using hs-cTnI, both PMIInfarct and PMIInjury were independent predictors of 30-day all-cause mortality (adjusted hazard ratio [aHR] 2.5 [95% CI 1.1-6.0], and aHR 2.8 [95% CI 1.4-5.5], respectively) and, 1-year all-cause mortality (aHR 2.0 [95% CI 1.2-3.3], and aHR 1.8 [95% CI 1.2-2.7], respectively). Overall, the prognostic impact of PMI diagnosed by hs-cTnI was comparable to the prognostic impact of PMI using hs-cTnT. CONCLUSIONS: Using hs-cTnI, PMI is less common versus using hs-cTnT. Using hs-cTnI, both PMIInfarct and PMIInjury remain independent predictors of 30-day and 1-year mortality.

Platelet Reactivity in Patients With Acute Coronary Syndromes Awaiting Surgical Revascularization.

BACKGROUND: Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications. OBJECTIVES: This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding. METHODS: In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y12 receptor inhibitors, were assigned to either control group, P2Y12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units). RESULTS: Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003). CONCLUSIONS: A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267).

Relation of High Lipoprotein (a) Concentrations to Platelet Reactivity in Individuals with and Without Coronary Artery Disease.

INTRODUCTION: Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention. METHODS: Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y12 assay. Platelet reactivity was also induced by arachidonic acid and collagen-epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. RESULTS: Overall, 294 (74.2%) individuals had Lp(a) < 50 mg/dL [median (IQR) 13.2 (5.8-27.9) mg/dL] and 102 (25.8%) had Lp(a) ≥ 50 mg/dL [82.5 (67.6-114.5) mg/dL], P < 0.001. Univariate analysis in the entire population revealed no differences in ADP-induced platelet reactivity between individuals with Lp(a) ≥ 50 mg/dL (249.4 ± 43.8 PRU) versus Lp(a) < 50 mg/dL (243.1 ± 52.2 PRU), P = 0.277. Similar findings were present in individuals with (P = 0.228) and without (P = 0.669) CAD, and regardless of the agonist used or method of analysis (all P > 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99-1.01), P = 0.590]. CONCLUSION: In individuals with or without CAD, Lp(a) ≥ 50 mg/dL was not associated with higher platelet reactivity.

Biomarkers for prediction of mortality in left-sided infective endocarditis.

BACKGROUND: Evidence regarding biomarkers for risk prediction in patients with infective endocarditis (IE) is limited. We aimed to investigate the value of a panel of biomarkers for the prediction of in-hospital mortality in patients with IE. METHODS: Between 2016 and 2018, consecutive IE patients admitted to the emergency department were prospectively included. Blood concentrations of nine biomarkers were measured at admission (D0) and on the seventh day (D7) of antibiotic therapy: C-reactive protein (CRP), sensitive troponin I (s-cTnI), procalcitonin, B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL6), tumor necrosis factor α (TNF-α), proadrenomedullin, alpha-1-acid glycoprotein, and galectin 3. The primary endpoint was in-hospital mortality. RESULTS: Among 97 patients, 56% underwent cardiac surgery, and in-hospital mortality was 27%. At admission, six biomarkers were independent predictors of in-hospital mortality: s-cTnI (OR 3.4; 95%CI 1.8-6.4; P<0.001), BNP (OR 2.7; 95%CI 1.4-5.1; P=0.002), IL-6 (OR 2.06; 95%CI 1.3-3.7; P=0.019), procalcitonin (OR 1.9; 95%CI 1.1-3.2; P=0.018), TNF-α (OR 1.8; 95%CI 1.1-2.9; P=0.019), and CRP (OR 1.8; 95%CI 1.0-3.3; P=0.037). At admission, S-cTnI provided the highest accuracy for predicting mortality (area under the ROC curve: s-cTnI 0.812, BNP 0.727, IL-6 0.734, procalcitonin 0.684, TNF-α 0.675, CRP 0.670). After 7 days of antibiotic therapy, BNP and inflammatory biomarkers improved their performance (s-cTnI 0.814, BNP 0.823, IL-6 0.695, procalcitonin 0.802, TNF-α 0.554, CRP 0.759). CONCLUSION: S-cTnI concentration measured at admission had the highest accuracy for mortality prediction in patients with IE.

Significant association of SYNTAX score on release of cardiac biomarkers in uncomplicated post-revascularization procedures among patients with stable multivessel disease: MASS-V Study group.

This study investigated the relationship between angiographic complexities of coronary artery disease (CAD) assessed by SYNTAX Score synergy between percutaneous coronary intervention with taxus and cardiac surgery score (SYNTAX Score) and cardiac biomarker elevation after revascularization procedures.This is a post-hoc analysis of the medicine, angioplasty or surgery study V study of patients with stable CAD. High-sensitivity troponin 1 (hs-TnI) and creatinine kinase-muscle/brain (CK-MB) were assessed before and after cardiovascular procedures. Baselines SYNTAX Scores (SXScores) were calculated by blinded investigators to patient characteristics.Of the 202 patients studied, the mean SXScore was 21.25 ±â€Š9.24; 40.10 ±â€Š7.09 in the high SXScore group and 19.06 ±â€Š6.61 in low/mid SXscore group (P < .0001). Positive correlations existed between SXScore and median peaks after procedural hs-TnI (r = 0.18, P = .009) and CK-MB (r = 0.24, P = .001) levels. In patients with high SXScores (≥33), the median peaks of post-procedural hs-TnI (P = .034)and CK-MB (P = .004) levels were higher than in low/mid SXScore group (<33).The release of hs-TnI at 6 (P = .002), 12 (P = .008), and 24 hours (P = .039) was higher in high SXScore group than in low/mid SXscore group (<33) as was the release of CK-MB at 6 (P < .0001), 12 (P < .0001), 24 (P = .001), 36 (P = .007), 48 (P = .008), and 72 hours (P = .023). After multivariable analysis, high SXScore was a significant independent predictor of release of CK-MB and hs-TnI peaks higher than the median.The increase in release of cardiac biomarkers was significantly associated with the extent of atherosclerosis identified by the SYNTAX Score.

Platelet function, coagulation and fibrinolysis in patients with previous coronary and cerebrovascular ischemic events

OBJECTIVES: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA. METHODS: A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated. RESULTS: Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group). CONCLUSION: Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.

Comparison of high-sensitivity cardiac troponin I and T for the prediction of cardiac complications after non-cardiac surgery.

BACKGROUND: We aimed to directly compare preoperative high-sensitivity cardiac troponin (hs-cTn) I and T concentration for the prediction of major cardiac complications after non-cardiac surgery. METHODS: We measured hs-cTnI and hs-cTnT preoperatively in a blinded fashion in 1022 patients undergoing non-cardiac surgery. The primary endpoint was a composite of major cardiac complications including cardiac death, cardiac arrest, myocardial infarction, clinically relevant arrhythmias, and acute heart failure within 30 days. We hypothesized that the type of surgery may impact on the predictive accuracy of hs-cTnI/T and stratified all analyses according to the type of surgery. RESULTS: Major cardiac complications occurred in 108 (11%) patients, 58/243 (24%) patients undergoing vascular surgery and 50/779 (6%, P < .001) patients undergoing non-vascular surgery. Using regulatory-approved 99th percentile cut-off concentrations, preoperative hs-cTnI elevations were less than one-fifth as common as preoperative hs-cTnT elevations (P < .001). Among patients undergoing vascular surgery, preoperative hs-cTnI concentrations, but not hs-cTnT, was an independent predictor of cardiac complications (adjusted odds ratio (aOR) 1.5, 95% confidence interval (95% CI) 1.0-2.1). The area under the receiver-operating characteristics curve (AUC) was 0.67 (95% CI, 0.59-0.75) for hs-cTnI versus 0.59 (95% CI 0.51-0.67, P = .012) for hs-cTnT. In contrast, among patients undergoing non-vascular surgery both preoperative hs-cTnI and hs-cTnT were independent predictors of the primary endpoint (aOR 1.6, 95% CI 1.3-2.0, and aOR 3.0, 95% CI 2.0-4.6, respectively) and showed higher predictive accuracy (AUC 0.77, 95% CI, 0.71-0.83, and 0.79, 95% CI 0.73-0.85, P = ns). CONCLUSIONS: Preoperative hs-cTnI and hs-cTnT concentrations predict major cardiac complications after non-vascular surgery, while, in patients undergoing vascular surgery, hs-cTnI may have better accuracy.

Role of P-selectin in thromboembolic events in patients with cancer.

The objective of the present study was to evaluate the role of P-selectin in patients with cancer with suspected thromboembolic events (TEEs). Patients with cancer have a four times greater risk of developing TEEs. P-selectin is a glycoprotein that has the function of facilitating the interaction (adhesion) of leukocytes with the endothelium, or with platelets. There is a well-defined relationship between P-selectin and thrombosis; however, it is likely that the cut-off value of P-selectin for patients with cancer should be considered differently from that of the general population. In the present report, a prospective cross-sectional study was performed with patients of the Cancer Hospital of Barretos who were suspected of having TEEs. Among the 178 study participants, 167 (93.82%) were suspected of having deep vein thrombosis, while 59 of them (35.33%) were confirmed as such; and 11 (6.18%) were suspected of having pulmonary thromboembolism, while 3 of them were confirmed as such (27.69%). The mean results obtained were: P-selectin, 25.37 ng/ml; and D-dimer, 2,181.22 ng/ml. The P-selectin levels averaged 33.60 ng/ml with the confirmed TEE group compared with 20.40 ng/ml with the unconfirmed TEE group, with a standard deviation of 23.35 compared with 6.92 (P<0.001); and the level of D-dimer was 4,615.38 ng/ml compared with 977.52 ng/ml, with a standard deviation of 6,460.54 compared with 2,145.50 (P<0.001). Multiple logistic regression adjusted for distant metastases and the Eastern Cooperative Oncology Group (ECOG) score (2,3 and 4) were constructed. The cut-off value of P-selectin for patients with cancer was identified to be different from that reported in the literature for the general population, and the models using D-dimer and P-selectin therefore have been demonstrated to be a potentially useful tool to be used in a panel of tests to predict TEEs, either independently or in a prediction score.

Quality of Life Score as a Predictor of Death in Dogs with Degenerative Mitral Valve Disease / Escore de Qualidade de Vida como Preditor de Mortalidade em Cães com Doença Degenerativa da Valva Mitral

Abstract Background: The knowledge of the variables predicting mortality is important in clinical practice and for therapeutic monitoring in mitral valve disease. Objectives: To determine whether a quality of life score evaluated with the Functional Evaluation of Cardiac Health questionnaire would predict mortality in dogs with degenerative mitral valve disease (DMVD). Methods: Thirty-six client-owned dogs with mitral valve disease underwent clinical, laboratory, and echocardiographic evaluations at baseline and were monitored for 6 months. Cardiovascular death was the primary outcome. Results: The 36 dogs were classified as survivors or nonsurvivors. Higher values of the following variables were obtained at baseline in the nonsurviving group (12 dogs): amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, plasma norepinephrine, heart rate, quality of life score, diastolic left ventricular internal dimension to aortic root ratio, systolic left ventricular internal dimension to aortic root ratio, and left atrium to aortic root ratio. NT-proBNP levels and quality life score were independently associated with death in the multivariable analysis. Conclusion: The quality life score was an independent variable for cardiac death in dogs with DMVD. This result is encouraging, as this score is easy to apply and does not require any technology, only a veterinarian and an observant owner.

Resumo Fundamento: O conhecimento das variáveis preditoras de mortalidade é importante para a prática clínica e para o acompanhamento terapêutico na doença da valva mitral. Objetivos: Determinar se um escore de qualidade de vida avaliado com o Functional Evaluation of Cardiac Health poderia auxiliar na predição de mortalidade em cães com doença degenerativa da valva mitral (DDVM). Métodos: Trinta e seis cães de estimação com doença valvar mitral foram submetidos a avaliação clínica, laboratorial e ecocardiográfica no início do estudo e monitorizados durante 6 meses. A morte cardiovascular foi o desfecho primário. Resultados: Os 36 cães foram classificados como sobreviventes ou não sobreviventes. Os valores mais elevados das seguintes variáveis foram obtidos no início do estudo no grupo de não sobreviventes (12 cães): fragmento N-terminal do peptídeo natriurético tipo B (NT-proBNP), norepinefrina plasmática, frequência cardíaca, escore de qualidade de vida, razão da dimensão interna diastólica do ventrículo esquerdo e raiz aórtica, razão da dimensão interna sistólica do ventrículo esquerdo e raiz aórtica e a relação da dimensão do átrio esquerdo e a raiz aórtica. Concentrações de NT-proBNP e o escore de qualidade de vida foram independentemente associados com morte na análise multivariada. Conclusão: O escore de qualidade de vida foi uma variável independente para a morte por doença cardíaca em cães com DDVM. Este resultado é encorajador, pois este escore é de fácil aplicação e não requer o emprego de tecnologia, necessitando apenas de um veterinário e um dono observador.

Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes.

Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function.

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome / Mutações gênicas das glicoproteínas plaquetárias e resposta ao tirofiban na síndrome coronariana aguda

CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. DESIGN AND SETTING: Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. METHOD: Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T ), Ib (Thr/Met) , IIb (Ile/Ser ) and IIIa (PIA ) were the mutations selected. RESULTS: Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. CONCLUSIONS: Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction.

RESUMO CONTEXTO E OBJETIVOS: Inibidores da glicoproteína (abciximab, eptifibatide, tirofiban) são utilizados em pacientes com angina instável e infarto do miocárdio sem elevação do segmento ST (IAMSSST) antes da intervenção coronária percutânea. Dentre eles, o tirofiban é o menos eficaz. Nossa hipótese é que a resposta ao tirofiban possa estar associada a mutações no gene da glicoproteína. DESENHO E LOCAL: Estudo prospectivo na Unidade de Emergência do Instituto do Coração (InCor), Universidade de São Paulo (USP). MÉTODOS: Foram analisadas a evolução intra-hospitalar e agregabilidade plaquetária em resposta ao tirofiban de 4 mutações da glicoproteína em 50 pacientes com indicação para intervenção coronária percutânea, 17 (34%) com angina instável e 33 (66%) com IAMSSST. A agregação plaquetária foi analisada pelo método de Born. Amostras de sangue foram obtidas antes e uma hora após infusão do tirofiban. As glicoproteínas Ia (807C/T ), Ib (Thr/Met ), IIb (Ile/Ser ) e IIIa (PIA ) foram as mutações selecionadas. RESULTADOS: Hipertensão, dislipidemia, diabetes, tabagismo, doença coronariana e acidente vascular cerebral prévios foram semelhantes entre os grupos. Observou-se menor agregabilidade plaquetária dos genótipos mutantes da glicoproteína IIIa antes da administração de tirofiban do genótipo selvagem (41% ± 22% versus 56% ± 21%; P = 0,035). Genótipos mutantes da glicoproteína IIIa correlacionaram-se moderadamente com menor inibição plaquetária (r = -0,31; P = 0,030). Após a administração tirofiban, as mutações das glicoproteínas Ia, Ib, IIb, e IIIa não influenciaram o grau de inibição da agregação plaquetária e mortalidade intra-hospitalar. CONCLUSÕES: Mutações das glicoproteínas Ia, Ib, IIb e IIIa não influenciaram a agregação plaquetária em resposta ao tirofiban nos pacientes com angina instável e IAMSSST.

Accuracy of Myocardial Biomarkers in the Diagnosis of Myocardial Infarction After Revascularization as Assessed by Cardiac Resonance: The Medicine, Angioplasty, Surgery Study V (MASS-V) Trial.

BACKGROUND: The lack of a correlation between myocardial necrosis biomarkers and electrocardiographic abnormalities after revascularization procedures has resulted in a change in the myocardial infarction (MI) definition. METHODS: Patients with stable multivessel disease who underwent percutaneous or surgical revascularization were included. Electrocardiograms and concentrations of high-sensitive cardiac troponin I (cTnI) and creatine kinase (CK)-MB were assessed before and after procedures. Cardiac magnetic resonance and late gadolinium enhancement were performed before and after procedures. MI was defined as more than five times the 99th percentile upper reference limit for cTnI and 10 times for CK-MB in percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), respectively, and new late gadolinium enhancement for cardiac magnetic resonance. RESULTS: Of the 202 patients studied, 69 (34.1%) underwent on-pump CABG, 67 (33.2%) off-pump CABG, and 66 (32.7%) PCI. The receiver operating characteristic curve showed the accuracy of cTnI for on-pump CABG, off-pump CABG, and PCI patients was 21.7%, 28.3%, and 52.4% and for CK-MB was 72.5%, 81.2%, and 90.5%, respectively. The specificity of cTnI was 3.6%, 9.4%, and 42.1% and of CK-MB was 73.2%, 86.8%, and 96.4%, respectively. Sensitivity of cTnI was 100%, 100%, and 100% and of CK-MB was 69.2%, 64.3%, and 44.4%, respectively. The best cutoff of cTnI for on-pump CABG, off-pump CABG, and PCI was 6.5 ng/mL, 4.5 ng/mL, and 4.5 ng/mL (162.5, 112.5, and 112.5 times the 99th percentile upper reference limit) and of CK-MB was 37.5 ng/mL, 22.5 ng/mL, and 11.5 ng/mL (8.5, 5.1, and 2.6 times the 99th percentile upper reference limit), respectively. CONCLUSIONS: Compared with cardiac magnetic resonance, CK-MB was more accurate than cTnI for diagnosing MI. These data suggest a higher troponin cutoff for the diagnosis of procedure-related MI.

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome.

CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. DESIGN AND SETTING: Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. METHOD: Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T ), Ib (Thr/Met) , IIb (Ile/Ser ) and IIIa (PIA ) were the mutations selected. RESULTS: Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. CONCLUSIONS: Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction.

Preprocedural statin therapy, inflammation, and myocardial injury in low-risk stable coronary artery disease patients submitted to coronary stent implantation.

OBJECTIVE: Evaluate if statin therapy prior to elective coronary stent implantation (CSI) reduces the plasma levels of markers of inflammation and of myocardial necrosis in low-risk stable coronary artery disease patients (CAD). BACKGROUND: The elevation of markers of inflammation and of myocardial necrosis after percutaneous coronary intervention may interfere with clinical outcome. Among acute coronary syndrome patients, statins improve clinical outcomes when used before CSI-mostly due to reduction of CSI-related myocardial infarction. However, little is known concerning preprocedural statin therapy on the reduction of these markers in stable patients at low-risk. METHODS: In this prospective, observational study, 100 patients (n = 50 on statin therapy vs. n = 50 not on statin) with stable coronary artery disease underwent elective CSI. Inflammatory (C-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor-α and matrix metalloproteinase-9) and myocardial necrosis markers (troponin I and CK-MB) were determined before and 24 hr after CSI. RESULTS: All patients presented a significant increase of CRP and IL-6 after CSI. However, this increase was attenuated in patients on statin therapy prior to CSI than those without statin therapy: 75% vs. 150% (P < 0.001) and 192% vs. 300% (P < 0.01). The other pro-inflammatory markers were similar for both sets of patients. Troponin I and CK-MB did not change after CSI regardless of previous statin therapy or not. CONCLUSIONS: Pretreatment with statin attenuates procedural inflammation, denoted by markedly lower increases of CRP and IL-6 levels, in elective CSI within low-risk stable CAD patients. Periprocedural myocardial injury was irrelevant and was not affected by preprocedural statin therapy in this population.

Correlation between C-Reactive Protein in Peripheral Vein and Coronary Sinus in Stable and Unstable Angina / Correlação entre Proteína C-Reativa em Veia Periférica e Seio Coronário na Angina Estável e Instável

Background: High sensitivity C-reactive protein (hs-CRP) is commonly used in clinical practice to assess cardiovascular risk. However, a correlation has not yet been established between the absolute levels of peripheral and central hs-CRP. Objective: To assess the correlation between serum hs-CRP levels (mg/L) in a peripheral vein in the left forearm (LFPV) with those in the coronary sinus (CS) of patients with coronary artery disease (CAD) and a diagnosis of stable angina (SA) or unstable angina (UA). Methods: This observational, descriptive, and cross-sectional study was conducted at the Instituto do Coração, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, and at the Hospital Beneficência Portuguesa de Sao Paulo, where CAD patients referred to the hospital for coronary angiography were evaluated. Results: Forty patients with CAD (20 with SA and 20 with UA) were included in the study. Blood samples from LFPV and CS were collected before coronary angiography. Furthermore, analysis of the correlation between serum levels of hs-CRP in LFPV versus CS showed a strong linear correlation for both SA (r = 0.993, p < 0.001) and UA (r = 0.976, p < 0.001) and for the entire sample (r = 0.985, p < 0.001). Conclusion: Our data suggest a strong linear correlation between hs-CRP levels in LFPV versus CS in patients with SA and UA. .

Fundamento: A proteína C-reativa de alta sensibilidade (PCR-as) é comumente utilizada na prática clínica para avaliar o risco cardiovascular. Entretanto, a correlação entre os níveis séricos de PCR-as (valores absolutos) periférico versus central ainda não foi feita. Objetivo: Avaliar a correlação entre os níveis séricos de PCR-as (mg/L) em veia periférica do antebraço esquerdo (VPAE) versus seio coronário (SC), em pacientes portadores de doença arterial coronária (DAC) com diagnóstico de angina estável (AE) ou angina instável (AI). Métodos: Estudo observacional, descritivo, transversal, realizado no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e no Hospital Beneficência Portuguesa de São Paulo, onde foram avaliados os pacientes encaminhados ao hospital com DAC para angiografia coronária. Resultados: Quarenta pacientes com DAC (20 AE e 20 AI) foram incluídos no estudo. Amostras de sangue na VPAE e SC foram coletadas simultaneamente antes da angiografia coronária. A análise de correlação entre os níveis séricos de PCR-as em VPAE versus SC mostrou forte correlação linear tanto para AE (r = 0,993, p < 0,001) como para AI (r = 0,976, p < 0,001) e em toda a amostra (r = 0,985, p < 0,001). Conclusão: Nossos dados sugeriram forte correlação linear entre os níveis de PCR-as em VPAE versus SC na AE e AI. .

Lipoprotein (a): Structure, Pathophysiology and Clinical Implications / Lipoproteína (a): Estrutura, Metabolismo, Fisiopatologia e Implicações Clínicas

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.

A partícula de lipoproteína (a) apresenta estrutura semelhante à da LDL, diferenciando-se pela presença da apolipoproteína (a) ligada por uma ponte dissulfeto à apolipoproteína B. Sua síntese ocorre no fígado e sua concentração plasmática varia de < 1 mg a > 1.000 mg/dL, podendo ser dosada de rotina em laboratório clínico por método baseado em anticorpos monoclonais. Acima de 20 a 30 mg/dL o risco de desenvolvimento de doença cardiovascular aumenta em cerca de duas vezes, o que não é válido para os afrodescendentes, que já apresentam normalmente níveis mais altos dessa lipoproteína, do que caucasianos e orientais. Entretanto, o risco para indivíduos negros também deve ser levado em conta. Gênero e idade exercem pouca influência na concentração de lipoproteína (a). A homologia com o plasminogênio, que interfere na cascata fibrinolítica, pode ser um mecanismo da aterogenicidade da lipoproteína (a). Entretanto, a deposição direta na parede da artéria também é um dos mecanismos possíveis, sendo a lipoprotrína (a) mais oxidável do que a LDL. De forma geral estudos prospectivos confirmam a lipoproteína (a) como fator predisponente à aterosclerose. O uso de estatinas não interfere no nível da lipoproteína (a), diferentemente da niacina e da ezetimiba, que promovem sua diminuição, embora essa última dependa de confirmação. Não está demonstrado que a redução de lipoproteína (a) resulte em diminuição de risco de doença arterial coronária. Diante de concentrações mais elevadas de lipoproteína (a) e na falta de medicações mais efetivas e de boa tolerabilidade, deve-se, pelo menos, procurar controlar, de forma mais rigorosa, os outros fatores de risco de doença arterial coronária.

The involvement of multiple thrombogenic and atherogenic markers in premature coronary artery disease

OBJECTIVE: To examine the association of atherogenic and thrombogenic markers and lymphotoxin-alfa gene mutations with the risk of premature coronary disease. METHODS: This cross-sectional, case-control, age-adjusted study was conducted in 336 patients with premature coronary disease (<50 years old) and 189 healthy controls. The control subjects had normal clinical, resting, and exercise stress electrocardiographic assessments. The coronary disease group patients had either angiographically documented disease (>50% luminal reduction) or a previous myocardial infarction. The laboratory data evaluated included thrombogenic factors (fibrinogen, protein C, protein S, and antithrombin III), atherogenic factors (glucose and lipid profiles, lipoprotein(a), and apolipoproteins AI and B), and lymphotoxin-alfa mutations. Genetic variability of lymphotoxin-alfa was determined by polymerase chain reaction analysis. RESULTS: Coronary disease patients exhibited lower concentrations of HDL-cholesterol and higher levels of glucose, lipoprotein(a), and protein S. The frequencies of AA, AG, and GG lymphotoxin-alfa mutation genotypes were 55.0%, 37.6%, and 7.4% for controls and 42.7%, 46.0%, and 11.3% for coronary disease patients (p = 0.02), respectively. Smoking, dyslipidemia, family history, and lipoprotein(a) and lymphotoxin-alfa mutations in men were independent variables associated with coronary disease. The area under the curve (C-statistic) increased from 0.779 to 0.802 (p<0.05) with the inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors. CONCLUSIONS: The inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors showed an additive but small increase in the risk prediction of premature coronary disease. .