Influência da Espironolactona na Metaloproteinase de Matriz 2 na Insuficiência Cadíaca Aguda Descompensada

Matrix metalloproteinases (MMPs) are a family of enzymes important for the resorption of extracellular matrices, control of vascular remodeling and repair. Increased activity of MMP2 has been demonstrated in heart failure, and in acutely decompensated heart failure (ADHF) a decrease in circulating MMPs has been demonstrated along with successful treatment.As metaloproteinases de matriz (MMPs) constituem uma família de enzimas importantes para a reabsorção da matriz extracelular e controle do remodelamento e da reparação vasculares. Demonstrou-se aumento da atividade de MMP2 na insuficiência cardíaca, e, na insuficiência cardíaca agudamente descompensada (ICAD), demonstrou-se uma diminuição nas MMPs circulantes juntamente com o tratamento bem-sucedidoThis study was partially funded by Johnson & Johnso

High-Sensitivity Troponin T: A Biomarker for Diuretic Response in Decompensated Heart Failure Patients

Background. Patients presenting with acutely decompensated heart failure (ADHF) and positive circulating cardiac troponins were found to be a high-risk cohort. The advent of high-sensitive troponins resulted in a detection of positive troponins in a great proportion of heart failure patients. However, the pathophysiological significance of this phenomenon is not completely clear. Objectives. The aim of this study is to determine the early evolution and clinical significance of high-sensitivity troponin T (hsTnT) in ADHF. Methods. Retrospective, secondary analysis of a prospective study including 100 patients with ADHF. Results. Globally, high-sensitivity troponin T decreased from day 1 to day 3 (P = 0,039). However, in the subgroup of patients who remained decompensated no significant differences in hsTnT from day 1 to day 3 were observed (P = 0,955), whereas in successfully compensated patients a significant reduction in hsTnT levels was observed (P = 0,025). High-sensitivity troponin T decrease was correlated with NTproBNP reduction (P = 0,007). Patients with hsTnT increase had longer length of stay (P = 0,033). Conclusions. Episodes of ADHF are associated with transient increases in the blood levels of hsTnT that are reduced with effective acute episode treatment. The decrease in hsTnT can translate less myocardial damage along with favourable ADHF treatment

Dynamics of growth differentiation factor 15 in acute heart failure

Aims: Risk stratification in acute heart failure (HF) patients can help to decide therapies and time for discharge. The potential of growth differentiation factor 15 (GDF-15) in HF has been previously shown. We aimed to study the importance of GDF-15-level variations in acute HF patients. Methods and results: We retrospectively evaluated a cohort of patients hospitalized due to acute HF. GDF-15 was measured both at admission and on the discharge day. Patients were followed-up during a 3 year period. The endpoint under analysis was all-cause mortality. GDF-15 variation is equal to [(admission GDF-15 - discharge GDF-15)∕admission GDF-15] × 100. Variation was categorized in levels of increase or decrease of GDF-15. Patients were cross-classified according to admission and discharge GDF-15 cut-off points. A Cox regression analysis was used to assess the prognostic impact of GDF-15 variation and the impact of both admission and discharge GDF-15 according to the cross-classification. We studied a group of 249 patients with high co-morbidity burden. Eighty-one patients died at 1 year and 147 within 3 years. There was a modest decrease in GDF-15 during hospitalization from a median value of 4087 to 3671 ng/mL (P = 0.02). No association existed between GDF-15 variation and mortality. In multivariate analysis, patients with admission GDF-15 ≥ 3500 ng/mL and discharge GDF-15 ≥ 3000 ng/mL had a significantly higher 1 year death risk when compared with the remaining-hazard ratio = 2.59 (95% confidence interval: 1.41-4.76)-and a 3 year 1.76 (95% confidence interval: 1.08-2.87) higher death risk compared with those with both values below the cut-off. Conclusions: Growth differentiation factor 15 decreased during an acute HF hospitalization, but its variation had no prognostic implications. The knowledge of both admission and discharge GDF-15 added meaningful information to patients' risk stratification

Left-sided infective endocarditis: analysis of in-hospital and medium-term outcome and predictors of mortality

Abstract Introduction: Despite diagnostic and therapeutic advances, infective endocarditis (IE) remains a challenging and potentially lethal disease. The prognosis of IE remains poor; in the last 30 years, its incidence and mortality have only been marginally reduced. Early identification of high-risk patients can change the course of the disease and improve outcomes. Objectives and methods: To describe and investigate predictors of mortality during hospital stay and in the six months after discharge in a cohort of left-sided IE patients in two tertiary centers. All patients diagnosed with IE (ICD9 code 133) were registered in a uniform database. Results: One hundred and forty-seven consecutive case patients with left-sided IE were included in this study. Thirty-five patients (23.8%) died during hospital stay. The variables significantly associated with increased mortality in univariate analysis were Charlson index ≥5, use of immunosuppressants, sepsis (severe sepsis and/or septic shock), cardiogenic shock and inappropriate use of antibiotic therapy. Conversely, surgical therapy and hospital length of stay ≥30 days were significantly associated with lower mortality. In multivariate analysis the most important predictors of in-hospital mortality were sepsis (severe and/or shock), use of immunosuppressants and inappropriate use of antibiotic therapy. There was a significant relation between the use of immunosuppressants and the occurrence of sepsis. The presence of significant valve disease after IE significantly increased the risk of heart failure. Conclusions: Our results may help to identify IE patients at increased risk for in-hospital mortality and medium-term disability. These findings can help to identify candidates for earlier and more aggressive management

Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms.

The aim of the present study was to develop novel daptomycin-loaded poly-epsilon-caprolactone (PCL) microparticles with enhanced antibiofilm activity against mature biofilms of clinically relevant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and polysaccharide intercellular adhesin-positive Staphylococcus epidermidis. Daptomycin was encapsulated into PCL microparticles by a double emulsion-solvent evaporation method. For comparison purposes, formulations containing vancomycin were also prepared. Particle morphology, size distribution, encapsulation efficiency, surface charge, thermal behavior, and in vitro release were assessed. All formulations exhibited a spherical morphology, micrometer size, and negative surface charge. From a very early time stage, the released concentrations of daptomycin and vancomycin were higher than the minimal inhibitory concentration and continued so up to 72 hours. Daptomycin presented a sustained release profile with increasing concentrations of the drug being released up to 72 hours, whereas the release of vancomycin stabilized at 24 hours. The antibacterial activity of the microparticles was assessed by isothermal microcalorimetry against planktonic and sessile MRSA and S. epidermidis. Regarding planktonic bacteria, daptomycin-loaded PCL microparticles presented the highest antibacterial activity against both strains. Isothermal microcalorimetry also revealed that lower concentrations of daptomycin-loaded microparticles were required to completely inhibit the recovery of mature MRSA and S. epidermidis biofilms. Further characterization of the effect of daptomycin-loaded PCL microparticles on mature biofilms was performed by fluorescence in situ hybridization. Fluorescence in situ hybridization showed an important reduction in MRSA biofilm, whereas S. epidermidis biofilms, although inhibited, were not eradicated. In addition, an important attachment of the microparticles to MRSA and S. epidermidis biofilms was observed. Finally, all formulations proved to be biocompatible with both ISO compliant L929 fibroblasts and human MG63 osteoblast-like cells

Noninvasive anatomical and functional assessment of coronary artery disease.

INTRODUCTION AND OBJECTIVE: In suspected coronary artery disease (CAD), invasive coronary angiography (ICA) is traditionally the diagnostic tool of choice. However, patients often have no significant disease. Moreover, assessment of fractional flow reserve (FFR) has been shown to have prognostic implications. Recently, coronary computed tomography angiography (CTA) and cardiac magnetic resonance (CMR) myocardial perfusion imaging (CMR-Perf) have gained increasing attention through their accurate anatomical and functional assessment, respectively. We studied the added value of integrating these tests (CT+CMRint) in the diagnosis of CAD, with FFR as the reference standard. METHODS: We included 101 patients consecutively referred for outpatient assessment of CAD who underwent CTA and CMR-Perf prior to ICA with FFR assessment. Lesions were considered positive by CT+CMRint only if positive in the two tests alone. The mean follow-up was 2.9±0.6 years. RESULTS: All patients completed the study protocol without adverse effects. Forty-four patients had CAD by FFR. CTA had excellent sensitivity and negative predictive value (100%) but, as expected, its specificity and positive predictive value were lower (61% and 67%, respectively). Diagnostic accuracy by FFR was 78% for CTA, 88% for CMR-Perf and 92% for CT+CMRint. Regarding diagnostic accuracy, CT+CMRint showed statistically significant superiority (AUC=0.917, 95% CI 0.845-0.963) compared with CTA (AUC=0.807, 95% CI 0.716-0.879, p=0.0057) or CMR-Perf (AUC=0.882, 95% CI 0.802-0.938, p=0.0398) alone. Regarding prediction of revascularization, the integrated protocol maintained its superior performance. CONCLUSIONS: CT+CMRint showed superior diagnostic accuracy and could thus lead to a considerable reduction in invasive procedures for CAD diagnosis, with less risk and greater patient comfort

Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing

Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity. We performed whole-exome sequencing in a discovery sample of four age at onset-concordant and four discordant first-degree relative pairs of Azorean patients, to identify candidate variants which genotypes differed for each discordant pair but were shared in each concordant pair. Variants identified by this approach were then tested in an independent multi-origin cohort of 282 MJD patients. Whole-exome sequencing identified 233 candidate variants, from which 82 variants in 53 genes were prioritized for downstream analysis. Eighteen disease-modifying pathways were identified; two of the most enriched pathways were relevant for the nervous system, namely the neuregulin signaling and the agrin interactions at neuromuscular junction. Variants at PARD3, NFKB1, CHD5, ACTG1, CFAP57, DLGAP2, ITGB1, DIDO1 and CERS4 modulate age at onset in MJD, with those identified in CFAP57, ACTG1 and DIDO1 showing consistent effects across cohorts of different geographical origins. Network analyses of the nine novel MJD modifiers highlighted several important molecular interactions, including genes/proteins previously related with MJD pathogenesis, namely between ACTG1/APOE and VCP/ITGB1. We describe novel pathways, modifiers, and their interaction partners, providing a broad molecular portrait of age at onset modulation to be further exploited as new disease-modifying targets for MJD and related diseases

Consensus Document on Coding of Cardiac Magnetic Resonance Examinations in Portugal

Um dos obstáculos a uma utilização mais frequente e apropriada da ressonância magnética cardíaca (RMC) em Portugal tem sido a ausência de códigos específicos que descrevam adequadamente os exames tal como são efetuados actualmente. Este documento de consenso fornece recomendações para a atualização e uniformização dos códigos empregues na RMC. São igualmente feitas recomendações quanto às técnicas e códigos a utilizar nas indicações clínicas mais frequentes