RESUMO
Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the frequently inconclusive biochemical and genetic test results that do not correlate with clinical course. We sought to identify potential biomarkers of FD to better understand the underlying pathophysiology and clinical phenotypes. We compared the plasma proteomes of 50 FD patients and 50 matched healthy controls using DDA and SWATH-MS. The >30 proteins that were differentially expressed between the 2 groups included proteins implicated in processes such as inflammation, heme and haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose and lipid metabolism, and glycocalyx formation. Stratification by sex revealed that certain proteins were differentially expressed in a sex-dependent manner. Apolipoprotein A-IV was upregulated in FD patients with complications, especially those with chronic kidney disease, and apolipoprotein C-III and fetuin-A were identified as possible markers of FD with left ventricular hypertrophy. All these proteins had a greater capacity to identify the presence of complications in FD patients than lyso-GB3, with apolipoprotein A-IV standing out as being more sensitive and effective in differentiating the presence and absence of chronic kidney disease in FD patients than renal markers such as creatinine, glomerular filtration rate and microalbuminuria. Identification of these potential biomarkers can help further our understanding of the pathophysiological processes that underlie the heterogeneous clinical manifestations associated with FD.
Assuntos
Biomarcadores , Doença de Fabry , Fenótipo , Proteômica , Humanos , Doença de Fabry/sangue , Masculino , Feminino , Biomarcadores/sangue , Adulto , Pessoa de Meia-Idade , Estudos de Casos e Controles , Caracteres Sexuais , Adulto Jovem , Proteoma/metabolismoRESUMO
Background: Primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) improves the survival of patients; nevertheless, some patients develop left ventricular adverse remodeling (LVAR) a few months after the intervention. The main objective of this study was to characterize the role of pro-inflammatory cell populations, related cytokines, and microRNAs (miRNAs) released after PPCI as reliable prognostic biomarkers for LVAR in patients with STEMI. Methods: We evaluated the level of pro-inflammatory subsets, before and after revascularization, 1 and 6 months after PPCI, using flow cytometry. We also performed a miRNA microarray in isolated peripheral blood mononuclear cells (PBMCs) and examined the levels of 27 cytokines in patients' serum of patients by multiplex ELISA. Results: We observed that the levels of classical and intermediate monocytes increased 6 h after PPCI in patients who developed LVAR later. Multivariate regression analysis and ROC curves indicated that intermediate monocytes, after PPCI, were the best monocyte subset that correlated with LVAR. Within the 27 evaluated cytokines evaluated, we found that the increase in the level of vascular endothelial growth factor (VEGF) correlated with LVAR. Furthermore, the microarray analysis of PBMCs determined that up to 1,209 miRNAs were differentially expressed 6 h after PPCI in LVAR patients, compared with those who did not develop LVAR. Using RT-qPCR we confirmed a significant increase in miR-16, miR-21-5p, and miR-29a-3p, suggested to modulate the expression of different cytokines, 6 h post-PPCI in LVAR patients. Interestingly, we determined that the combined analysis of the levels of the intermediate monocyte subpopulation, VEGF, and miRNAs gave a better association with LVAR appearance. Similarly, combined ROC analysis provided high accurate specificity and sensibility to identify STEMI patients who will develop LVAR. Conclusion: Our data suggest that the combined analysis of intermediate monocytes, VEGF, and miRNAs predicts LVAR in STEMI patients.
RESUMO
BACKGROUND AND OBJECTIVE: Atrial fibrillation and anticoagulation decrease the quality of life of patients. The aim of this study is to assess the quality of life and the degree of satisfaction after changing from VKA to edoxaban anticoagulants. MATERIAL AND METHODS: Prospective, multicentre study, including 105 patients in dicumarinic anticoagulant treatment replaced by edoxaban. Their quality of life was evaluated before and after using the EQ-5D questionnaire, and the degree of satisfaction with CRES-4 scale. RESULTS: Average 75 years, CHA2DS2VASC3,5 and HASBLED2,1; thromboembolic events and clinically relevant bleeding during follow-up <1%. EQ-5D showed a significant overall improvement in the mobility and anxiety parameters (P=.023, 95%CI: .0175-.23; P=.019, 95%CI:=.028-.31). The CRES-4 questionnaire showed satisfaction with the therapist of 95%, a positive impact on life of 73% and a negative impact of 3.8%. The emotional state attributed to the change in treatment improved (41% vs 69.5%, P=.0001). The final score of the CRES-4 weakly correlated with the emotional situation of the EQ-5D questionnaire. CONCLUSIONS: The change of anticoagulant for edoxaban improves the quality of life and the degree of patient satisfaction, and the EQ-5D and CRES-4 quality of life questionnaires can be used complementarily.
Assuntos
Satisfação Pessoal , Qualidade de Vida , Humanos , Satisfação do Paciente , Estudos Prospectivos , Piridinas , Inquéritos e Questionários , TiazóisAssuntos
Desfibriladores Implantáveis/efeitos adversos , Traumatismos por Eletricidade/diagnóstico , Traumatismos por Eletricidade/etiologia , Falha de Equipamento , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/prevenção & controle , Adulto , Diagnóstico Diferencial , Traumatismos por Eletricidade/prevenção & controle , Eletrocardiografia/métodos , Feminino , Insuficiência Cardíaca/diagnóstico , HumanosRESUMO
Restoration of epicardial coronary blood flow, achieved by early reperfusion with primary percutaneous coronary intervention (PPCI), is the guideline recommended to treat patients with ST-segment-elevation myocardial infarction (STEMI). However, despite successful blood restoration, increasing numbers of patients develop left ventricular adverse remodelling (LVAR) and heart failure. Therefore, reliable prognostic biomarkers for LVAR in STEMI are urgently needed. Our aim was to investigate the role of circulating microRNAs (miRNAs) and their association with LVAR in STEMI patients following the PPCI procedure. We analysed the expression of circulating miRNAs in blood samples of 56 patients collected at admission and after revascularization (at 3, 6, 12 and 24 h). The associations between miRNAs and left ventricular end diastolic volumes at 6 months were estimated to detect LVAR. miRNAs were also analysed in samples isolated from peripheral blood mononuclear cells (PBMCs) and human myocardium of failing hearts. Kinetic analysis of miRNAs showed a fast time-dependent increase in miR-133a, miR-133b, miR-193b, miR-499, and miR-320a in STEMI patients compared to controls. Moreover, the expression of miR-29a, miR-29b, miR-324, miR-208, miR-423, miR-522, and miR-545 was differentially expressed even before PPCI in STEMI. Furthermore, the increase in circulating miR-320a and the decrease in its expression in PBMCs were significantly associated with LVAR and correlated with the expression of miR-320a in human failing myocardium from ischaemic origin. In conclusion, we determined the time course expression of new circulating miRNAs in patients with STEMI treated with PPCI and we showed that miR-320a was positively associated with LVAR.
RESUMO
Acute contrast-induced thrombocytopenia is a rare event with the use of modern low osmolarity iodinated contrast media. The pathophysiological mechanism that causes platelet counts to drop has not been identified, but an immunological mechanism is suspected due to cytotoxicity after previous exposure to contrast. We report the case of a 47-year-old male patient with acute severe thrombocytopenia due to iodinated contrast media exposure. His platelet count after the procedure with the highest amount of contrast was zero, which is the lowest reported platelet count to date. Percutaneous coronary revascularization under both intravascular ultrasound and gadolinium contrast guidance was performed without complications. The most feared complication after the use of gadolinium is nephrogenic systemic fibrosis, especially in patients on hemodialysis.
Assuntos
Meios de Contraste/efeitos adversos , Angiografia Coronária , Compostos Heterocíclicos , Compostos de Iodo/efeitos adversos , Ácido Ioxáglico/efeitos adversos , Compostos Organometálicos , Intervenção Coronária Percutânea/métodos , Cirurgia Assistida por Computador , Trombocitopenia/induzido quimicamente , Ultrassonografia de Intervenção , Gadolínio , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Idiopathic paroxysmal atrioventricular (AV) block poses a true diagnostic challenge. What is clear about this entity is the confusion about its definition and consequently about its etiology. According to certain sources, the diagnosis of this block requires the lack of a structural cardiac pathology that justifies the observed manifestations and an absence of electrocardiographic disorders prior to an episode. The clinical presentation of idiopathic paroxysmal AV block does not differ from that of another cardiogenic syncope or of a vasovagal syncope with a significant cardioinhibitory component. With respect to the mechanism that explains this block, it has been postulated that patients with low basal adenosine levels exhibit hyperaffinity of the A2 receptors of the AV node. Variations in plasma adenosine levels may favor episodes of paroxysmal AV block. The diagnosis of this block is complex and can require years to determine. Routine electrophysiological examination of these patients is not cost effective due to the low sensitivity and specificity of this approach. Numerous groups have supported the use of an implantable loop recorder to substantiate AV block paroxysms and assess their clinical correlations. Permanent stimulation devices are utilized to reduce syncopal recurrence.
RESUMO
BACKGROUND AND OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP) correlates with burden of arrhythmia in atrial fibrillation (AF) patients. Our objective is to validate the usefulness of the measurement of NT-pro-BNP to determine the success of AF ablation in a long term follow up. PATIENTS AND METHODS: Prospective observational study in which 75 patients with preserved systolic function (81% men; mean age (SD) 52 (9) years; 58.7% paroxysmal) underwent circumferential pulmonary vein isolation. Determination of NT-proBNP baseline and one year after the procedure was performed. The relation between NT-proBNP levels and the success of the procedure is analyzed. RESULTS: In the follow up 53 (70.7%) patients remained free of recurrences. A>30% decrease of NT-proBNP levels identified success with a sensitivity of 79.2%, specificity 81.8%, positive predictive value 91.3% and negative 62% (area under ROC curve 0.84, 95% confidence interval 73-95.6). This reduction was associated with a decrease in left atrial volume and pressure and the presence of diastolic dysfunction (all P<.05). CONCLUSIONS: The decrease of NT-proBNP levels in patients undergoing AF ablation is useful as a marker of success in the follow up and is associated with hemodynamic improvement.