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BACKGROUND: Aortic valve stenosis (AS) is the most prevalent valvular heart disease and is associated with a significant increase in mortality. AS has been shown to be linked with numerous coagulation system abnormalities, including increased fibrin deposition on the stenotic aortic valves. Transcatheter aortic valve implantation (TAVI) is the primary treatment method for patients at high surgical risk. OBJECTIVES: The aim of the study was to assess the impact of treating severe AS with TAVI on thrombin generation and clot lysis time (CLT). METHODS: We studied 135 symptomatic AS patients recommended for TAVI by the local Heart Team. All measurements were performed before and 5-7 days after TAVI. Alongside clinical assessment and echocardiographic analysis, we assessed clot lysis time (CLT) and thrombin generation parameters, including lag time, peak thrombin generation, time to peak thrombin generation (ttPeak), and endogenous thrombin potential (ETP). RESULTS: 70 patients were included in the final analysis. After TAVI, there was a significant 9% reduction in CLT despite a 12% increase in fibrinogen concentration. We observed significant increase in lag time and ttPeak (20% and 12%, respectively), and 13% decrease in peak thrombin concentration compared to pre-procedural levels. Multivariable linear regression analysis demonstrated that baseline CLT and C-reactive protein (CRP) levels were independent predictors of significant reduction in mean aortic gradient, defined as TAVI procedure success. CONCLUSIONS: CLT and peak thrombin concentration decreased, while Lag time and ttPeak increased significantly after TAVI. Multivariable linear regression analysis demonstrated CLT and CRP levels as independent predictors of achieving a reduction in mean aortic gradient, defining TAVI procedure success.
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Patients with takotsubo syndrome (TTS) may present coronary slow flow (CSF) in angiography performed in the acute myocardial infarction (MI). However, the detailed clinical relevance and its long-term impact remain poorly understood. Among 7771 MI patients hospitalized between 2012 and 2019, TTS was identified in 82 (1.1%) subjects. The epicardial blood flow was assessed with thrombolysis in myocardial infarction (TIMI) scale and corrected TIMI frame count (TFC), whereas myocardial perfusion with TIMI myocardial perfusion grade (TMPG). CSF was defined as TIMI-2 or corrected TFC > 27 frames in at least one epicardial vessel. CSF was identified in 33 (40.2%) TTS patients. In the CSF-TTS versus normal-flow-TTS group, lower values of left ventricular ejection fraction on admission (33.5 (25-40) vs. 40 (35-45)%, p = 0.019), more frequent midventricular TTS (27.3 vs. 8.2%, p = 0.020) and the coexistence of both physical and emotional triggers (9.1 vs. 0%, p = 0.032) were noted. Within a median observation of 55 months, higher all-cause mortality was found in CSF-TTS compared with normal-flow TTS (30.3 vs. 10.2%, p = 0.024). CSF was identified as an independent predictor of long-term mortality (hazard ratio 10.09, 95% confidence interval 2.12-48.00, p = 0.004). CSF identified in two-fifths of TTS patients was associated with unfavorable long-term outcomes.
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Infarto do Miocárdio , Fenômeno de não Refluxo , Cardiomiopatia de Takotsubo , Humanos , Cardiomiopatia de Takotsubo/epidemiologia , Prognóstico , Volume Sistólico , Fenômeno de não Refluxo/complicações , Prevalência , Função Ventricular Esquerda , Infarto do Miocárdio/complicações , Angiografia Coronária , Circulação Coronária/fisiologiaRESUMO
Heart failure (HF) is a clinical syndrome that is divided into 3 subtypes based on the left ventricular ejection fraction. Every subtype has specific clinical characteristics and concomitant diseases, substantially increasing risk of thromboembolic complications, such as stroke, peripheral embolism and pulmonary embolism. Despite the annual prevalence of 1% and devastating clinical consequences, thromboembolic complications are not typically recognized as the leading problem in patients with HF, representing an underappreciated clinical challenge. Although the currently available data do not support routine anticoagulation in patients with HF and sinus rhythm, initial reports suggest that such strategy might be beneficial in a subset of patients at especially high thromboembolic risk. Considering the existing evidence gap, we aimed to review the currently available data regarding coagulation disorders in acute and chronic HF based on the insight from preclinical and clinical studies, to summarize the evidence regarding anticoagulation in HF in special-case scenarios and to outline future research directions so as to establish the optimal patient-tailored strategies for antiplatelet and anticoagulant therapy in HF. In summary, we highlight the top 10 pearls in the management of patients with HF and no other specific indications for oral anticoagulation therapy. Further studies are urgently needed to shed light on the pathophysiological role of platelet activation in HF and to evaluate whether antiplatelet or antithrombotic therapy could be beneficial in patients with HF. LAY SUMMARY: Heart failure (HF) is a clinical syndrome divided into 3 subtypes on the basis of the left ventricular systolic function. Every subtype has specific clinical characteristics and concomitant diseases, substantially increasing the risk of thromboembolic complications, such as stroke, peripheral embolism and pulmonary embolism. Despite the annual prevalence of 1% and devastating clinical consequences, thromboembolic complications are not typically recognized as the leading problem in patients with HF, representing an underappreciated clinical challenge. Although the currently available data do not support routine anticoagulation in patients with HF and no atrial arrhythmia, initial reports suggest that such a strategy might be beneficial in a subset of patients at especially high risk of thrombotic complications. Considering the existing evidence gap, we aimed to review the currently available data regarding coagulation problems in stable and unstable patients with HF based on the insight from preclinical and clinical studies, to summarize the evidence regarding anticoagulation in HF in specific patient groups and to outline future research directions to establish the optimal strategies for antiplatelet and anticoagulant therapy in HF, tailored to the needs of an individual patient. In summary, we highlight the top 10 pearls in the management of patients with HF and no other specific indications for oral anticoagulation therapy.
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Fibrilação Atrial , Transtornos da Coagulação Sanguínea , Insuficiência Cardíaca , Embolia Pulmonar , Acidente Vascular Cerebral , Tromboembolia , Humanos , Volume Sistólico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Função Ventricular Esquerda , Anticoagulantes/uso terapêutico , Tromboembolia/tratamento farmacológico , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Acidente Vascular Cerebral/etiologia , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Arritmias Cardíacas , Fibrilação Atrial/complicaçõesRESUMO
BACKGROUND AND AIMS: There is no prior research on the usefulness that popular nutrition-related mobile applications would have in assessing fatty acids intake. In this study, we examine these applications through their utilization in the assessment of consumption of saturated (SFAs) and polyunsaturated (PUFAs) fatty acids against the Polish reference method (RM, Dieta 6.0). This report does also include the information about monounsaturated fatty acids and cholesterol intake. METHODS AND RESULTS: SFAs and PUFAs intake was assessed using two-day dietary recalls obtained from 120 individuals by 3 selected mobile applications (App1 = Yazio, App2 = MyFitnessPal, App3 = Fitatu) and compared with RM. Despite strong (SFAs by App1 and App3) and moderate (SFAs by App2 and PUFAs by App1, App2, App3) correlations with RM, Bland-Altman analyses showed relevant biases and wide range between limits of agreement. Considering SFAs and MUFAs intake, App1 had the best agreement. App1 had high sensitivity (94.6%) in recognition of subjects with SFAs intake >10% with moderate specificity (67.9%), while App2 had poor sensitivity (27.2%) and high specificity (100%). App3 showed moderate sensitivity and specificity (77.2% and 75%, respectively). CONCLUSIONS: Mobile applications are not accurate tools in SFAs and PUFAs assessment when compared to the RM. Nonetheless, their ability to recognize SFAs intake >10% energy intake may suggest that further development of mobile applications could potentially become an attractive tool in clinical practice.
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Doenças Cardiovasculares , Aplicativos Móveis , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Colesterol , Gorduras na Dieta , Ácidos Graxos , Ácidos Graxos Monoinsaturados , Ácidos Graxos Insaturados , HumanosRESUMO
Prostacyclin (PGI2) analogues (epoprostenol, treprostonil, iloprost) are the cornerstone of pulmonary arterial hypertension (PAH) treatment. PGI2 analogues inhibit platelet reactivity, but their impact on coagulation and fibrinolysis parameters has not been elucidated. We compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in patients with PAH treated with PGI2 analogues (n = 20) and those not receiving PGI2 analogues (n = 20). Platelet reactivity was lower in patients treated with PGI2 analogues, compared to the control group, as evaluated with arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor-activating peptide-6 (TRAP) tests (p = .009, p = .02, p = .007, respectively). In the subgroup analysis, both treprostinil and epoprostenol decreased platelet reactivity to the similar extent. There were no differences regarding thrombin generation, clot permeation, and lysis parameters in patients receiving and not receiving PGI2 analogues (p ≥ .60 for all). In the subgroup analysis, there were no differences regarding coagulation and fibrinolysis parameters between treprostinil, epoprostenol, and no PGI2 analogues. To conclude, patients with PAH treated with PGI2 analogues have reduced platelet reactivity, but similar clot formation and lysis parameters, compared to patients not receiving PGI2 analogues. Further randomized clinical trials are required to confirm these findings.
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Carica , Coagulantes , Hipertensão Arterial Pulmonar , Coagulantes/farmacologia , Epoprostenol/farmacologia , Epoprostenol/uso terapêutico , Fibrina , Fibrinólise , Humanos , Agregação Plaquetária , Prostaglandinas I/farmacologia , Trombina/farmacologiaRESUMO
BACKGROUND: Little is known about factors that affect the composition of contracted blood clots in specific diseases. We investigated the content of polyhedral erythrocytes (polyhedrocytes) formed in blood clots and its determinants in type 2 diabetes (T2D) patients. METHODS: In 97 patients with long-standing T2D [median HbA1c, 6.4% (interquartile range 5.9-7.8)], we measured in vitro the composition of blood clots, including a clot area covered by polyhedrocytes using scanning electron microscopy and the erythrocyte compression index (ECI), defined as a ratio of the mean polyhedrocyte area to the mean native erythrocyte area. Moreover, plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, oxidative stress [total protein carbonyl (total PC), total antioxidant capacity and thiobarbituric acid reactive substances (TBARS)], and platelet activation markers were determined. The impact of glucose concentration on polyhedrocytes formation was assessed in vitro. RESULTS: Polyhedrocytes content in contracted clots was positively correlated with glucose (r = 0.24, p = 0.028), glycated hemoglobin (r = 0.40, p = 0.024), total cholesterol (r = 0.22, p = 0.044), TBARS (r = 0.60, p = 0.0027), P-selectin (r = 0.54, p = 0.0078) and platelet factor-4, PF4 (r = 0.59, p = 0.0032), but not with thrombin generation, platelet count, Ks or CLT. Patients who formed more polyhedrocytes (≥ 10th percentile) (n = 83, 85.6%) had higher glucose (+ 15.7%, p = 0.018), fibrinogen (+ 16.6%, p = 0.004), lower red blood cell distribution width (RDW, - 8.8%, p = 0.034), reduced plasma clot density (- 21.8% Ks, p = 0.011) and impaired fibrinolysis (+ 6.5% CLT, p = 0.037) when compared to patients with lesser amount of polyhedrocytes (< 10th percentile). ECI and the content of polyhedrocytes were strongly associated with total PC (r = 0.79, p = 0.036 and r = 0.67, p = 0.0004, respectively). In vitro an increase of glucose concentration by 10 mmol/L was associated with 94% higher polyhedrocytes content (p = 0.033) when compared to the baseline (7.1 mM). After adjustment for age, sex and fibrinogen, multiple regression analysis showed that RDW was the only independent predictor of polyhedrocytes content in T2D (OR = 0.61, 95% CI 0.39-0.92). CONCLUSIONS: Poor glycemic control, together with enhanced platelet activation and oxidative stress, increase the content of polyhedrocytes in blood clots generated in T2D patients.
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Coagulação Sanguínea , Glicemia/metabolismo , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Eritrócitos/metabolismo , Estresse Oxidativo , Ativação Plaquetária , Tromboembolia/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Eritrócitos/ultraestrutura , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Tromboembolia/diagnóstico , Tromboembolia/etiologiaRESUMO
BACKGROUND: There are inconsistent data about the role of serum phospholipid fatty acid composition in patients with type 2 diabetes (T2DM) and atherosclerotic cardiovascular disease (ASCVD). The aim of the study was to investigate the relationship between serum phospholipid fatty acid composition, systemic low-grade inflammation, and glycemic control in high-risk T2DM patients. METHODS: Seventy-four patients (26% women, mean age 65.6 ± 6.8 years) with T2DM (median diabetes duration 10 years) and documented ASCVD (74 with coronary artery disease, 26 with peripheral arterial disease) were enrolled in the study. Baseline HbA1c was estimated using turbidimetric inhibition immunoassay. According to the median value of HbA1c the patients were grouped into those with HbA1c < 7.0% (< 53 mmol/mol) (n = 38) and those with HbA1c ≥ 7.0% (≥ 53 mmol/mol) (n = 36). Serum phospholipid fatty acids were measured with gas chromatography. RESULTS: Patients with HbA1c ≥ 7.0%, compared with those with HbA1c < 7.0% had similar composition of saturated and monounsaturated fatty acids in serum phospholipids, but had higher concentrations of linoleic acid (LA) and higher n-6/n-3 polyunsaturated fatty acid (PUFA) ratio as well as lower levels of eicosapentaenoic acid (EPA), total n-3 PUFAs, and the EPA/arachidonic acid ratio. We found that LA (r = 0.25; p = 0.03) and n-6/n-3 PUFA ratio (r = 0.28; p = 0.02) were positively correlated with HbA1c. Multivariate logistic regression analysis showed that n-6/n-3 PUFA ratio, hsCRP and T2DM duration were independent predictors of worse glycemic control in patients with T2DM and ASCVD. CONCLUSIONS: This study showed that glycemic control in high-risk T2DM patients with ASCVD was significantly associated with unfavorable serum phospholipid n-6/n-3 PUFA ratio and greater systemic inflammation.
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Glicemia/metabolismo , Doença da Artéria Coronariana/sangue , Diabetes Mellitus Tipo 2/sangue , Ácidos Graxos Insaturados/sangue , Mediadores da Inflamação/sangue , Inflamação/sangue , Doença Arterial Periférica/sangue , Fosfolipídeos/sangue , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Doença da Artéria Coronariana/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnósticoRESUMO
BACKGROUND: Despite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in patients with type 2 diabetes (DM2) and established atherosclerosis. PURPOSE: To investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function, coagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients with atherosclerotic vascular disease and DM2 who receive optimal medical therapy. METHODS: We conducted a prospective, double-blind, placebo-controlled, randomized, double-center study, in which thrombin generation (plasma thrombogenic potential from automated thrombogram), fibrin clot properties (plasma fibrin clot permeability; lysis time), platelet aggregation (light transmission aggregometry with adenosine diphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid profiles, leptin and adiponectin levels, as well as markers of systemic inflammation (i.e., hsCRP, IL-6, TNF-α, ICAM-1, VCAM-1, and myeloperoxidase) were determined at baseline and at 3 months after treatment with 2 g/day of n-3 PUFAs (n = 36) or placebo (n = 38). Moreover, we assessed serum fatty acids of the phospholipid fraction by gas chromatography both at baseline and at the end of the study. RESULTS: Majority of patients were treated with optimal medical therapy and achieved recommended treatment targets. Despite higher serum levels of eicosapentaenoic acid (EPA) (by 204%; p < 0.001) and docosahexaenoic acid (DHA) (by 62%; p < 0.0001) in n-3 PUFA group at the end of treatment no changes in platelet aggregation, thrombin generation, fibrin clot properties or markers of systemic inflammation were observed. No intergroup differences in the insulin, HbA1c and lipid levels were found at the end of the study. There was no change in adiponectin and leptin in interventional group, however leptin increased in control group (p = 0.01), therefore after study period leptin levels were lower in the interventional group (p = 0.01). Additionally, resolvin D1 did not differ between interventional and control group. CONCLUSIONS: In conclusion, our study demonstrated that in patients with long-standing, well-controlled DM2 and atherosclerotic disease the treatment with a high dose of n-3 PUFAs (namely, 1 g/day of EPA and 1 g/day of DHA for 3 months) does not improve coagulation, metabolic, and inflammatory status when measured with the specified tests. The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014.
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Aterosclerose/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Mediadores da Inflamação/sangue , Inflamação/tratamento farmacológico , Adiponectina/sangue , Idoso , Aterosclerose/sangue , Aterosclerose/diagnóstico , Biomarcadores/sangue , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/efeitos adversos , Método Duplo-Cego , Ácido Eicosapentaenoico/efeitos adversos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Insulina/sangue , Leptina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Polônia , Estudos Prospectivos , Trombina/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
Acute myocardial infarction is a very rare, life-threatening complication of blunt chest trauma. A 27-year-old man with no previous medical history was admitted to the emergency department due to multiple trauma following a car accident. After 48h following the accident, the patient's condition rapidly deteriorated, with severe dyspnea at rest, tachycardia, and increasing chest pain. A 12-lead ECG showed a sinus tachycardia at 120bpm with significant ST-segment elevation in leads V1 to V5, pathologic Q wave in I, aVL, and QS complex in leads V1 to V4. Bedside echocardiography disclosed akinesis of the anterior and lateral walls, apex, and anterior septum with severely decreased left ventricular ejection fraction of 30%. Urgent coronary angiography revealed an occlusive dissection of the proximal left anterior descending coronary artery. Primary percutaneous coronary intervention with a Biolimus A9™-eluting stent implantation were successfully performed. The further course was uneventful. At 12-month follow-up, the patient has remained asymptomatic with no recurrence of cardiovascular symptoms.
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Vasos Coronários/diagnóstico por imagem , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/cirurgia , Traumatismos Torácicos/complicações , Ferimentos não Penetrantes/complicações , Acidentes de Trânsito , Adulto , Dor no Peito/etiologia , Angiografia Coronária , Stents Farmacológicos , Ecocardiografia , Eletrocardiografia , Humanos , Masculino , Infarto do Miocárdio/etiologia , Intervenção Coronária PercutâneaRESUMO
BACKGROUND: There is a strong link between coronary artery disease (CAD), type 2 diabetes (T2D) on one hand, and altered fibrin clot properties, including increased clot density, and unfavorable fibrin clot structure on the other. T2D-related changes in fibrin clots can increase cardiovascular (CV) disease risk, including future CV events. We aimed to assess fibrin clot properties, thrombin generation, and platelet activation in CAD patients with prediabetes (PD) or T2D, compared to CAD patients without glycemic disorders. METHODS: We allocated patients to three groups: 1) Those with angiographically established CAD but without glycemic abnormalities (CAD group); 2) individuals with PD and established CAD (CAD+PD group); and 3) patients with T2D and CAD (CAD+T2D group). We conducted comparisons across these groups for thrombin generation, fibrin clot permeability, fibrin clot lysis, and platelet activation. RESULTS: The final analysis included 116 eligible patients: 1) CAD group (n = 31); 2) CAD+PD (n = 42); and 3) CAD+T2D (n = 43). The CAD+T2D patients enrolled had well-controlled T2D (median HbA1c level of 5.90%; IQR: 5.7%-6.3%). We found no significant differences in thrombin generation, fibrin clot properties, or platelet activation markers across the three analyzed groups (all P-values >0.20). However, elevated interleukin-6 (IL-6) levels were noted in both the highest and lowest glucose concentration quartiles. Additionally, a substantial increase in endogenous thrombin potential (ETP) was observed in patients in the highest glycated hemoglobin quintile. CONCLUSIONS: Individuals with established CAD and concomitant PD or well-controlled T2D exhibited comparable fibrin clot phenotypes, thrombin generation potential, and platelet activation when compared to CAD patients without dysglycemia.
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Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Ativação Plaquetária , Trombina , Humanos , Feminino , Masculino , Trombina/metabolismo , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Doença da Artéria Coronariana/sangue , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Coagulação Sanguínea , Aterosclerose/sangueRESUMO
INTRODUCTION: Intricate management of heart failure (HF), especially in the context of reduced ejection fraction, is further complicated by an elevated risk of thromboembolic events. Studies published so far offer inconclusive insight into the interplay between mitral regurgitation (MR) and the coagulation system. OBJECTIVES: This study aimed to investigate the impact of transcatheter edgetoedge repair (TEER) on specific coagulation parameters in HF patients. PATIENTS AND METHODS: A cohort of 31 HF patients with severe MR treated with TEER underwent a systematic evaluation at 3 visits (V1, V2, and V3). Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability, and clot lysis time (CLT) were assessed (n = 27 at V2; n = 25 at V3). RESULTS: TEER induced changes in fibrinogen levels (P = 0.01; V3 vs V2) and improved fibrin clot properties over 50day followup (P = 0.01; V3 vs V2). No significant differences were observed between time points in the analyzed blood clot parameters. Correlation analysis showed that baseline CLT was associated with ΔNterminal pro-Btype natriuretic peptide (NTproBNP) level (P = 0.049; r = 0.4). Multivariable analysis identified baseline CLT as an independent predictor of early postTEER NTproBNP change (R2 = 0.55; P = 0.02). CONCLUSIONS: We found decreased level of fibrinogen and increased permeation coefficient over a median 50 (interquartile range, 32.5-75.5)-day postTEER followup, as compared with early postprocedural assessments. Other blood coagulation parameters remained unchanged from baseline at both followup time points after TEER. Finally, CLT was an independent predictor of early NTproBNP increase, emphasizing its role as an indicator of hemodynamic response to TEER.
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Fibrina , Insuficiência da Valva Mitral , Trombina , Humanos , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Mitral/sangue , Feminino , Masculino , Idoso , Trombina/metabolismo , Fibrina/metabolismo , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Fibrinogênio/análise , Fibrinogênio/metabolismo , Tempo de Lise do Coágulo de Fibrina , Coagulação SanguíneaRESUMO
Heart failure with preserved ejection fraction (HFpEF) is associated with multiple cardiovascular and noncardiovascular comorbidities and risk factors which increase the risk of thrombotic complications, such as atrial fibrillation, chronic kidney disease, arterial hypertension and type 2 diabetes mellitus. Subsequently, thromboembolic risk stratification in this population poses a great challenge. Since date from the large randomized clinical trials mostly include both patients with truly preserved EF, and those with heart failure with mildly reduced ejection fraction, there is an unmet need to characterize the patients with truly preserved EF. Considering the significant evidence gap in this area, we sought to describe the coagulation disorders and thrombotic complications in patients with HFpEF and discuss the specific thromboembolic risk factors in patients with HFpEF, with the goal to tailor risk stratification to an individual patient.
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Transtornos da Coagulação Sanguínea , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Tromboembolia , Trombose , Humanos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Diabetes Mellitus Tipo 2/epidemiologia , Comorbidade , Trombose/epidemiologia , Trombose/etiologia , Transtornos da Coagulação Sanguínea/epidemiologia , PrognósticoRESUMO
BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) may play an important role in the development of atherosclerotic cardiovascular disease (ASCVD). Increased plasma levels of Lp-PLA2 may predict future cardiovascular (CV) events in type 2 diabetes (T2D). The potential beneficial effects of polyunsaturated fatty acids (PUFA) on ASCVD have been widely investigated. However, the impact of different PUFA concentrations on Lp-PLA2 remains uncertain. OBJECTIVES: We sought to determine the intergender differences in a population of patients with both T2D and ASCVD regarding Lp-PLA2 mass and the association between Lp-PLA2 mass and plasma levels of PUFA. MATERIAL AND METHODS: In this cross-sectional study, we measured the Lp-PLA2 mass, PUFA concentrations and inflammatory markers in 74 patients (49 males and 25 females) with T2D and ASCVD. RESULTS: In this very high-risk population, males had, on average, 33.6% higher levels of Lp-PLA2 than females. The Lp-PLA2 mass was positively associated with interleukin 6 (IL-6) (r = 0.27, p = 0.019), creatinine (r = 0.29, p = 0.03) and triglyceride levels (r = 0.41, p = 0.002). Additionally, male gender and higher levels of triglycerides, leptin, oxidized low-density lipoprotein (oxLDL), and intercellular adhesion molecule 1 (ICAM-1) were independent predictors for an increased Lp-PLA2. Moreover, arachidonic acid (AA) negatively correlated with Lp-PLA2 (r = -0.26, p = 0.024), which was especially apparent in the female subgroup. CONCLUSIONS: In the population of patients with ASCVD and T2D, males present with higher plasma levels of Lp-PLA2 than females. Additionally, higher plasma levels of AA were associated with lower Lp-PLA2 levels. Our findings support the utilization of Lp-PLA2 as a novel biomarker in ASCVD risk assessment in a very high CV risk population.
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INTRODUCTION: Adiposity has a few phenotypes associated with various levels of risk for diabetes mellitus (DM), but their exact predictive value is not well understood. OBJECTIVES: We aimed to assess the predictive value of anthropometric parameters, vascular ultrasound indexes, and fat depots for longterm cardiometabolic risk. PATIENTS AND METHODS: A total of 150 patients with chronic coronary syndrome (CCS) scheduled for elective coronary angiography were enrolled and a comprehensive clinical and ultrasound assessment of adiposity was performed (2012-2013). Of them, 143 individuals were followed for 8 years for insulin resistance (IR) and / or DM development. RESULTS: At baseline, DM and prediabetes were found in 22% and 8% of the patients, respectively. It was established that 11.7% of the participants died during the followup. The rate of DM increased to 46% with a decrease in the prediabetes rate (3.5%). Significant correlations with the Homeostatic Model Assessment of Insulin Resistance and glycated hemoglobin were observed for major anthropometric and ultrasound variables. In the multivariable analysis, independent predictors of IR were preperitoneal fat thickness (PreFT) (per 10mm increase: odds ratio [OR], 1.63; 95% CI, 1.22-2.33; P = 0.003) and body surface area (per 0.1m2 increase: OR, 1.59; 95% CI, 1.11-2.39; P = 0.02). DM was independently predicted by the highdensity lipoprotein cholesterol concentration (OR, 0.93; 95% CI, 0.87-0.97; P = 0.005) and body fat mass (OR, 1.09; 95% CI, 1.03-1.17; P = 0.003). CONCLUSIONS: A complex assessment of the adipose tissue in patients with CCS is a valuable method for improving metabolic risk stratification. Some anthropometric and ultrasound parameters, such as PreFT or body surface area, were associated with IR and DM development.
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Doenças Cardiovasculares , Diabetes Mellitus , Resistência à Insulina , Estado Pré-Diabético , Humanos , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/metabolismo , Estudos Prospectivos , Estado Pré-Diabético/diagnóstico por imagem , Fatores de Risco , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/metabolismo , Obesidade , Fatores de Risco de Doenças Cardíacas , Índice de Massa CorporalRESUMO
Patients with abdominal aortic aneurysm (AAA) have a higher risk of cardiovascular (CV) events, which seems to be associated with disturbed platelet (PLT) function. Endovascular aneurysm repair (EVAR) is an emerging, less-invasive treatment alternative to surgical AAA repair. Both platelet function abnormalities in patients with AAA and the effect of EVAR on platelet function are poorly understood. In this review, we aim to fill the gap regarding the effect of EVAR on PLT function in AAA patients by discussing PLT function disturbances in patients with AAA, PLT function changes after EVAR, evidence from clinical studies regarding PLT function before and after EVAR, and antiplatelet or and antithrombotic treatment in patients undergoing EVAR. The goal of our review is to summarize the contemporary knowledge and initiate further studies to better understand PLT function changes in patients undergoing EVAR, optimize the pharmacotherapy before and after EVAR and further improve outcomes in this group of patients.
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In the late 1970s, a lower incidence of myocardial infarction and favorable hemostatic alterations were reported in Greenland Inuits. This observation prompted investigators worldwide to continue research on the role of a specific diet in this population and sparked an ongoing discussion about the potential use of polyunsaturated fatty acids (PUFAs) in the primary prevention of cardiovascular disease (VITAL), and the secondary prevention of primarily coronary artery disease (JELIS, REDUCEIT, OMEMI). However, the current evidence to support the preventive value of PUFAs is inconsistent. Seminal clinical trials such as the GISSIPrevenzione, JELIS, PREDIMED, or ASCEND differed in their approach to the assessment of cardiovascular effects of n-3 PUFAs and reported divergent results. The questions remain whether eicosapentaenoic acid is the only PUFA offering cardiovascular benefits, what is the importance of PUFA dosing, and, finally, who should receive n-3 PUFA treatment. This article discusses the latest insights into n-3 PUFA use in cardiovascular disease prevention.
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Doenças Cardiovasculares , Ácidos Graxos Ômega-3 , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Dieta , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Insaturados , Humanos , IncertezaRESUMO
ß-Carotene (ß-Crt) can be dispersed in hydrophobic regions of the membrane of red blood cells (RBC). Its location, orientation and distribution strongly depend on carotenoid concentration. In the present pilot trial (six human subjects involved), it is demonstrated that incubation of RBCs with ß-Crt (1.8 × 107 ß-Crt molecules per RBC, 50 µmol/L) results in expansion of the membrane of RBCs and slight elongation of the cell. The changes are of statistical significance, as verified by the Wilcoxon test at p < 0.05. They indicate (i) a highly random orientation and location of ß-Crt inside the membrane and (ii) a tendency for its interaction with membrane skeleton proteins. The accompanying effect of decreased RBC resistance to lysis is possibly a result of the incorrect functioning of ion channels due to their modification/disruption. At higher ß-Crt concentrations, its clustering inside membranes may occur, leading to further alterations in the shape and size of RBCs, with the most pronounced changes observed at 1.8 × 108 ß-Crt molecules per RBC (500 µmol/L). Due to the reduced permeability of ions, such membranes exhibit increased resistance to haemolysis. Finally, we show that interactions of ß-Crt with the membrane of RBCs lead to an alteration in haemoglobin-oxygen affinity, shifting the oxyhaemoglobin dissociation curve toward higher oxygen partial pressures. If the impact of ß-Crt on a curve course is confirmed in vivo, one may consider its role in the fine tuning of O2 transportation to tissues. Hence, at low concentrations, providing unchanged elastic and functional properties of RBCs, it could serve as a beneficial agent in optimising heart performance and cardiovascular load.
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INTRODUCTION: Coronary artery disease is associated with impaired clot structure. The aim of this study was to investigate acute phase myocardial infarction (AMI) and provide detailed quantitative analysis of clot ultrastructure. MATERIALS AND METHODS: Clot formation and breakdown, pore size, fiber density, fiber radius and protofibril packing were investigated in plasma clots from AMI patients. These data were compared to those from healthy controls. RESULTS: Analysis on clot formation using turbidity showed increased lag time, suggesting changes in protofibril packing and increased fiber size for AMI patients compared to healthy controls. Additionally, increased average rate of clotting and decreased time to maximum absorbance in AMI patients suggest that clots formed more quickly. Moreover, we observed increased time from max OD to max rate of lysis. Increased fibrinogen and decreased plasminogen in AMI patients were accounted for in represented significant differences. AMI samples showed increased time to 25% and 50% lysis, but no change in 75% lysis, representative of delayed lysis onset, but expediated lysis once initiated. These data suggest that AMI patients formed less porous clots made from more densely packed fibers with decreased numbers of protofibrils, which was confirmed using decreased permeation and increased fiber density, and decreased turbidimetry. CONCLUSIONS: AMI plasma formed clots that were denser, less permeable, and lysed more slowly than healthy controls. These findings were confirmed by detailed analysis of clot ultrastructure, fiber size, and protofibril packing. Dense clot structures that are resistant to lysis may contribute to a prothrombotic milieu in AMI.
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Infarto do Miocárdio , Trombose , Coagulação Sanguínea , Fibrina , Tempo de Lise do Coágulo de Fibrina , Fibrinólise , Humanos , Rádio (Anatomia)RESUMO
INTRODUCTION: The expression of glucagonlike peptide receptors (GLPRs) in epicardial fat (EF) and pericardial fat (PF) depots might be involved in the pathogenesis of cardiovascular diseases. OBJECTIVES: We sought to evaluate the messenger RNA (mRNA) expressions of GLP1R and GLP2R in EF and PF and their associations with the reninangiotensinaldosterone system (RAAS) in patients with multivessel coronary artery disease (CAD). PATIENTS AND METHODS: Consecutive stable patients with multivessel CAD requiring elective coronary artery bypass grafting were enrolled. Clinical data, anthropometric parameters, and the quantity of fat depots (assessed by cardiovascular magnetic resonance and abdominal ultrasound) were obtained. Fat samples (EF, PF, subcutaneous fat) were taken from patients during cardiac surgery. Relative mRNA expression of GLP1R, GLP2R, and RAAS components (angiotensin II receptor type 1, angiotensinogen, angiotensin I-converting enzyme 1, and angiotensinI-converting enzyme 2) were assessed in those fat depots. RESULTS: Fiftythree patients (64.7 [7.4] years) were included in the final analysis. We found that only the relative expression of GLP2R was lower in PF compared with subcutaneous fat (reference). Ultrasound abdominal fat depots were associated with both GLP1R and GLP2R in PF. GLP1R and GLP2R showed significant correlations with RAAS components in both EF and PF. CONCLUSIONS: In stable patients with MVD, the relative mRNA expression for both GLP receptors revealed significant associations with majority of analysed RAAS components.
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Doença da Artéria Coronariana , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 2/metabolismo , Sistema Renina-Angiotensina , Tecido Adiposo , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/genética , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Receptor do Peptídeo Semelhante ao Glucagon 2/genética , Humanos , Pericárdio , Sistema Renina-Angiotensina/genéticaRESUMO
Scanning Electron Microscopy (SEM) is a powerful, high-resolution imaging technique widely used to analyze the structure of fibrin networks. Currently, structural features, such as fiber diameter, length, density, and porosity, are mostly analyzed manually, which is tedious and may introduce user bias. A reliable, automated structural image analysis method would mitigate these drawbacks. We evaluated the performance of DiameterJ (an ImageJ plug-in) for analyzing fibrin fiber diameter by comparing automated DiameterJ outputs with manual diameter measurements in four SEM data sets with different imaging parameters. We also investigated correlations between biophysical fibrin clot properties and diameter, and between clot permeability and DiameterJ-determined clot porosity. Several of the 24 DiameterJ algorithms returned diameter values that highly correlated with and closely matched the values of the manual measurements. However, optimal performance was dependent on the pixel size of the images-best results were obtained for images with a pixel size of 8-10 nm (13-16 pixels/fiber). Larger or smaller pixels resulted in an over- or underestimation of diameter values, respectively. The correlation between clot permeability and DiameterJ-determined clot porosity was modest, likely because it is difficult to establish the correct image depth of field in this analysis. In conclusion, several DiameterJ algorithms (M6, M5, T3) perform well for diameter determination from SEM images, given the appropriate imaging conditions (13-16 pixels/fiber). Determining fibrin clot porosity via DiameterJ is challenging.