Correlação da Variação dos Níveis de NT-ProBNP com a Modificação da Capacidade Funcional em Doentes com Insuficiência Cardíaca Crónica

OBJECTIVE: We set out to evaluate whether changes in N-terminal pro-brain natriuretic peptide (proBNP) can predict changes in functional capacity, as determined by cardiopulmonary exercise testing (CPET), in patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM). METHODS: We studied 37 patients with CHF due to DCM, 81% non-ischemic, 28 male, who performed symptom-limited treadmill CPET, with the modified Bruce protocol, in two consecutive evaluations, with determination of proBNP after 10 minutes rest prior to CPET. The time between evaluations was 9.6+/-5.5 months, and age at first evaluation was 41.1+/-13.9 years (21 to 67). RESULTS IN THE FIRST AND SECOND EVALUATIONS RESPECTIVELY WERE: NYHA functional class >II 51% and 16% (p<0.001), sinus rhythm 89% and 86.5% (NS), left ventricular ejection fraction 24.9+/-8.9% and 26.6+/-8.6% (NS), creatinine 1.03+/-0.25 and 1.09+/-0.42 mg/dl (NS), taking ACE inhibitors or ARBs 94.5% and 100% (NS), beta-blockers 73% and 97.3% (p<0.001), and spironolactone 89% and 89% (NS). We analyzed the absolute and percentage variation (AV and PV) in peak oxygen uptake (pVO2--ml/kg/min) and proBNP (pg/ml) between the two evaluations. RESULTS: (1) pVO2 AV: -17.4 to 15.2 (1.9+/-5.7); pVO2 PV: -56.1 to 84% (11.0+/-25.2); proBNP AV: -12850 to 5983 (-778.4+/-3332.5); proBNP PV: -99.0 to 379.5% (-8.8+/-86.3); (2) The correlations obtained--r value and p value [r (p)]--are shown in the table below; (3) We considered that a coefficient of variation of pVO2 PV of >10% represented a significant change in functional capacity. On ROC curve analysis, a proBNP PV value of 28% showed 80% sensitivity and 79% specificity for pVO2 PV of >10% (AUC=0.876, p=0.01, 95% CI 0.75 to 0.99). CONCLUSIONS: In patients with CHF due to DCM, changes in proBNP values correlate with variations in pVO2, as assessed by CPET. However, our results suggest that only a proBNP PV of >28% predicts a significant change in functional capacity.

Será que a Definição de Síndroma Metabólica pela International Diabetes Federation Melhora a Capacidade Preditora para Doença Coronária e do Espessamento da Íntima-Média Carotídea?

BACKGROUND: Metabolic syndrome (MS) is associated with increased incidence of diabetes and atherosclerotic complications. The new definition of the International Diabetes Federation (IDF) increases the population with this entity, compared to the NCEP ATP III definition. OBJECTIVES: To study the prevalence of coronary artery disease (CAD) and carotid intima-media thickness (IMT) in patients with and without MS, according to the NCEP ATP III and IDF definitions, and the predictive ability of carotid IMT for CAD. METHODS: We studied 270 consecutive patients admitted for elective coronary angiography due to suspicion of CAD. All patients underwent ultrasound study of the carotid arteries to measure IMT (the highest value between the right and left common carotid arteries was used in the analysis). Coronary stenosis of > or =70% (or 50% for the left main coronary artery) was considered significant. RESULTS: By the ATP III definition, 14% of the patients had MS, and these patients had a higher prevalence of CAD (87% vs. 63%, p = 0.004), but no significant difference was found for carotid IMT (1.03 +/- 0.36 mm vs. 0.95 +/- 0.35 mm, p=NS). With the IDF definition, 61% of the patients had MS; this group was slightly older and included more women. There were no differences in terms of CAD (68% vs. 63%) or carotid IMT (0.97 +/- 0.34 vs. 0.96 +/- 0.39 mm). On multivariate analysis, the ATP III definition of MS predicts CAD (OR 4.76, 95% CI 1.71-13.25, p = 0.003), but the IDF definition does not (OR 1.29, 95% CI 0.74-2.27, p = 0.37). On ROC curve analysis, an IMT of > or = 0.95 mm predicts CAD (AUC 0.66, p < 0.001), with a sensitivity of 52% and specificity of 75%. CONCLUSIONS: The new IDF definition increases the population with MS, decreasing the capacity to predict the presence of CAD. In our population, neither the ATP III nor the IDF definition showed differences in terms of carotid IMT. Carotid IMT can predict CAD, but with only modest sensitivity.

Use of Distress and Depression Thermometers to Measure Psychosocial Morbidity Among Southern European Cancer Patients

GOALS OF WORK: Recent literature has indicated the need for rapid evaluation of psychosocial issues secondary to cancer. Because of the problems of routine use of psychometric instruments, short instruments such as visual analogue scales or one-item 0-10 scales have been developed as valid assessment alternatives. PATIENTS AND METHODS: A study was conducted to examine the role of two 0-10 scales in measuring emotional stress (distress thermometer, DT) and depressed mood (mood thermometer, MT), respectively, in a multicenter study carried out in southern European countries (Italy, Portugal, Spain, and Switzerland). A convenience sample of 312 cancer outpatients completed the DT and MT and the Hospital Anxiety Depression Scale (HADS). MAIN RESULTS: DT was more significantly associated HADS anxiety than HADS depression while MT was related both to HADS anxiety and depression. The correlation of MT with HADS was higher than DT. A cutoff point >4 on the DT maximized sensitivity (65%) and specificity (79%) for general psychosocial morbidity while a cutoff >5 identified more severe "caseness" (sensitivity=70%; specificity=73%). On the MT, sensitivity and specificity for general psychosocial morbidity were 85% and 72% by using the cutoff score >3. A score >4 on the MT was associated with a sensitivity of 78% and a specificity of 77% in detecting more severe caseness. CONCLUSIONS: Two simple instruments, the DT and the MT, were found to have acceptable levels of sensitivity and specificity in detecting psychosocial morbidity. Compared to the HADS, however, the mood MT performed better than the DT.

Operação de Ross - Como Minimizar os Efeitos da Curva de Aprendizagem

The introduction of new procedures in surgery usually implies the costs of the so called learning curve. However patients should not suffer the negative effects of surgeon's learning curves. We report our results with the first 15 Ross procedures, a single surgeon and institution experience, and how it was possible to build a safe learning curve without major consequences for the patients. We emphasize the need for a continuous program of surgical performance assessment throughout the learning curve period, as was demonstrated in our series.

C4d Presence in Kidney Allograft Biopsy: Sensitivity and Specifity of Immunoperoxidase vs Immunofluorescence

OBJECTIVES: Evaluate the sensitivity/specificity of immunoperoxidase method in comparison with the standard immunofluorescence. MATERIAL AND METHODS: Retrospective review of 87 biopsies made for allograft dysfunction. Immunofluorescence (IF) was performed in frozen allograft biopsies using monoclonal antibody anti-C4d from Quidel®. The indirect immunoperoxidase (IP) technique was performed in paraffin-embebbed tissue with polyclonal antiserum from Serotec®. Biopsies were independently evaluated by two nephropathologist according Banff 2007 classification. RESULTS: By IF, peritubular C4d deposition were detected in 60 biopsies and absent in 27 biopsies. The evaluation of biopsy by IP was less precise due to the presence of background and unspecific staining. We find 13.8% (12/87) of false negative and Banff classification concordance in 79.3% (69/87) of cases (table1). The ROC curve study reveal a specificity of 100% and sensitivity of 80.0 % of IP method in relation to the gold standard (area under curve:0.900; 95% Confidence interval :0.817-0.954; p=0.0001). Banff Classification C4d Cases Immunofluorescence Immunoperoxidase n =87 Diffuse Negative 3 (3.4%) Focal Negative 9 (10.3%) Negative Negative 27 (31.0%) Diffuse Diffuse 33 (37.9%) Focal Focal 9 (10.3%) Diffuse Focal 6 (6.9%) CONCLUSION: The IP method presents a good specificity, but lesser sensitivity to C4d detection in allograft dysfunction. The evaluation is more difficult, requiring more experience of the observer than IF method. If frozen tissue is unavailable, the use of IP for C4d detection is acceptable.

C4d Detection in Renal Allograft Biopsies: Immunohistochemistry vs. Immunofluorescence

Introduction. Peritubular capillary complement 4d staining is one of the criteria for the diagnosis of antibody-mediated rejection, and research into this is essential to kidney allograft evaluation. The immunofluorescence technique applied to frozen sections is the present gold-standard method for complement 4d staining and is used routinely in our laboratory. The immunohistochemistry technique applied to paraffin-embedded tissue may be used when no frozen tissue is available. Material and Methods. The aim of this study is to evaluate the sensitivity and specificity of immunohistochemistry compared with immunofluorescence. We describe the advantages and disadvantages of the immunohistochemistry vs. the immunofluorescence technique. For this purpose complement 4d staining was performed retrospectively by the two methods in indication biopsies (n=143) and graded using the Banff 07 classification. Results. There was total classification agreement between methods in 87.4% (125/143) of cases. However, immunohistochemistry staining caused more difficulties in interpretation, due to nonspecific staining in tubular cells and surrounding interstitium. All cases negative by immunofluorescence were also negative by immunohistochemistry. The biopsies were classified as positive in 44.7% (64/143) of cases performed by immunofluorescence vs. 36.4% (52/143) performed by immunohistochemistry. Fewer biopsies were classified as positive diffuse in the immunohistochemistry group(25.1% vs. 31.4%) and more as positive focal (13.2% vs. 11.1%). More cases were classified as negative by immunohistochemistry (63.6% vs. 55.2%). Study by ROC curve showed immunohistochemistry has a specificity of 100% and a sensitivity of 81.2% in relation to immunofluorescence (AUC: 0.906; 95% confidence interval: 0.846-0.949; p=0.0001). Conclusions. The immunohistochemistry method presents an excellent specificity but lower sensitivity to C4d detection in allograft dysfunction. The evaluation is more difficult, requiring a more experienced observer than the immunofluorescence method. Based on these results, we conclude that the immunohistochemistry technique can safely be used when immunofluorescence is not available.

Focal Malignant Liver Lesions: Diagnosis by Dynamic Incremental CT, Early Phase

The purpose of our study was to evaluate the accuracy of dynamic incremental bolus-enhanced conventional CT (DICT) with intravenous contrast administration, early phase, in the diagnosis of malignancy of focal liver lesions. A total of 122 lesions were selected in 74 patients considering the following criteria: lesion diameter 10 mm or more, number of lesions less than six per study, except in multiple angiomatosis and the existence of a valid criteria of definitive diagnosis. Lesions were categorized into seven levels of diagnostic confidence of malignancy compared with the definitive diagnosis for acquisition of a receiver-operator-characteristic (ROC) curve analysis and to determine the sensitivity and specificity of the technique. Forty-six and 70 lesions were correctly diagnosed as malignant and benign, respectively; there were 2 false-positive and 4 false-negative diagnoses of malignancy and the sensitivity and specificity obtained were 92 and 97%. The DICT early phase was confirmed as a highly accurate method in the characterization and diagnosis of malignancy of focal liver lesions, requiring an optimal technical performance and judicious analysis of existing semiological data.

Carotid Intima-Media Thickness and Carotid Plaques Improves Prediction of Obstructive Angiographic Coronary Artery Disease in Women

Does carotid intima-media thickness (cIMT), a surrogate marker of cardiovascular events, have predictive incremental value over established risk factors for stable coronary artery disease (CAD)? Prospective study of 300 patients, with suspected stable CAD, admitted for an elective coronary angiography and carotid ultrasound. The CAD patients had a higher cIMT, which showed a modest predictive accuracy for CAD (area under the receiver-operating characteristic curve 0.638, 95% confidence interval 0.576-0.701, P < .001). The cIMT was an independent predictor of CAD, together with age, gender, and diabetes. C-statistic for CAD prediction by traditional risk factors was not significantly different from a model that included cIMT, carotid plaque presence, or both. However, in women, it was significantly increased by the addition of cIMT or carotid plaque presence. Although cIMT cannot be used as a sole indicator of CAD, it should be considered in the panel of investigations that is requested, particularly in women who are candidates for coronary angiography.

Methacholine Dose-Response Slopes from Maximal Bronchial Challenge Tests in Asthmatic Children: Methodological Aspects

To determine whether the slope of a maximal bronchial challenge test (in which FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single maximal bronchial challenge test with methacholin(dose range: 0.097–30.08 umol) by the dosimeter method. Maximal dose-response curves were included according to the following criteria: (1) at least one more dose beyond a FEV1 ù 20%; and (2) a MFEV1 ù 50%. PD20 FEV1 was calculated, and the slopes of the early part of the dose-response curve (standard dose-response slopes) and of the entire curve (maximal dose-response slopes) were calculated by two methods: the two-point slope (DRR) and the least squares method (LSS) in % FEV1 × umol−1. Maximal dose-response slopes were compared with the corresponding standard dose-response slopes by a paired Student’s t test after logarithmic transformation of the data; the goodness of fit of the LSS was also determined. Maximal dose-response slopes were significantly different (p < 0.0001) from those calculated on the early part of the curve: DRR20% (91.2 ± 2.7 FEV1% z umol−1)was 2.88 times higher than DRR50% (31.6 ± 3.4 DFEV1% z umol−1), and the LSS20% (89.1 ± 2.8% FEV1 z umol−1) was 3.10 times higher than LSS 50% (28.8 ± 1.5%FEV1 z umol−1). The goodness of fit of LSS 50% was significant in all cases, whereas LSS 20% failed to be significant in one. These results suggest that maximal dose-response slopes cannot be predicted from the data of standard bronchial challenge tests.

Optimal Cut-Off Value for Homeostasis Model Assessment (HOMA) Index of Insulin-Resistance in a Population of Patients Admitted Electively in a Portuguese Cardiology Ward

INTRODUCTION: Insulin resistance is the pathophysiological key to explain metabolic syndrome. Although clearly useful, the Homeostasis Model Assessment index (an insulin resistance measurement) hasn't been systematically applied in clinical practice. One of the main reasons is the discrepancy in cut-off values reported in different populations. We sought to evaluate in a Portuguese population the ideal cut-off for Homeostasis Model Assessment index and assess its relationship with metabolic syndrome. MATERIAL AND METHODS: We selected a cohort of individuals admitted electively in a Cardiology ward with a BMI < 25 Kg/m2 and no abnormalities in glucose metabolism (fasting plasma glucose < 100 mg/dL and no diabetes). The 90th percentile of the Homeostasis Model Assessment index distribution was used to obtain the ideal cut-off for insulin resistance. We also selected a validation cohort of 300 individuals (no exclusion criteria applied). RESULTS: From 7 000 individuals, and after the exclusion criteria, there were left 1 784 individuals. The 90th percentile for Homeostasis Model Assessment index was 2.33. In the validation cohort, applying that cut-off, we have 49.3% of individuals with insulin resistance. However, only 69.9% of the metabolic syndrome patients had insulin resistance according to that cut-off. By ROC curve analysis, the ideal cut-off for metabolic syndrome is 2.41. Homeostasis Model Assessment index correlated with BMI (r = 0.371, p < 0.001) and is an independent predictor of the presence of metabolic syndrome (OR 19.4, 95% CI 6.6 - 57.2, p < 0.001). DISCUSSION: Our study showed that in a Portuguese population of patients admitted electively in a Cardiology ward, 2.33 is the Homeostasis Model Assessment index cut-off for insulin resistance and 2.41 for metabolic syndrome. CONCLUSION: Homeostasis Model Assessment index is directly correlated with BMI and is an independent predictor of metabolic syndrome.

Disturbed Correlation Between Arterial Resistance and Pulsatility in Glaucoma Patients

PURPOSE: (i) To investigate whether pulsatility index (PI) and mean flow velocities (MFV) are altered in glaucoma patients. (ii) To evaluate the significance of PI in retrobulbar autoregulation capacity. METHODS: Patients with primary open-angle glaucoma (POAG; n = 49), normal tension glaucoma (NTG; n = 62) and healthy controls (n = 48) underwent colour Doppler imaging measurements of the retrobulbar vasculature. Kruskal-Wallis test was used to compare variables between the three diagnostic groups. Restricted cubic splines were used to determine nonlinearities between the resistive index (RI) and PI correlations. RESULTS: Mean flow velocities (MFV) were lower in both short posterior ciliary arteries (SCPA) and central retinal arteries (CRA) from the two glaucoma groups (p < 0.04 versus healthy controls). No differences were detected in RI or PI in any arteries of the three diagnostic groups (p > 0.08). In healthy individuals, correlations between RI and PI were linear in all arteries. In both POAG and NTG patients, CRA presented a nonlinear curve with a cutpoint at RI 0.77 (p < 0.001) and 0.61 (p = 0.03), respectively, above which the slope increased nearly five- and tenfold (POAG: 1.96 to 10.06; NTG: -0.46-4.06), respectively. A nonlinear correlation in the ophthalmic artery was only observed in NTG patients, with a cutpoint at RI 0.82 (p < 0.001), above which the slope increased from 3.47 to 14.03. CONCLUSIONS: Glaucoma patients do not present the linear relationships between RI and PI observed in healthy individuals. Their nonlinear relations may be indicative of an altered autoregulation and suggest a possible threshold RI could be determined above which autoregulatory disturbances become more relevant.

American Society of Anesthesiologists Score: Still Useful After 60 Years? Results of the EuSOS Study

OBJECTIVE: The European Surgical Outcomes Study described mortality following in-patient surgery. Several factors were identified that were able to predict poor outcomes in a multivariate analysis. These included age, procedure urgency, severity and type and the American Association of Anaesthesia score. This study describes in greater detail the relationship between the American Association of Anaesthesia score and postoperative mortality. METHODS: Patients in this 7-day cohort study were enrolled in April 2011. Consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery with a recorded American Association of Anaesthesia score in 498 hospitals across 28 European nations were included and followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Decision tree analysis with the CHAID (SPSS) system was used to delineate nodes associated with mortality. RESULTS: The study enrolled 46,539 patients. Due to missing values, 873 patients were excluded, resulting in the analysis of 45,666 patients. Increasing American Association of Anaesthesia scores were associated with increased admission rates to intensive care and higher mortality rates. Despite a progressive relationship with mortality, discrimination was poor, with an area under the ROC curve of 0.658 (95% CI 0.642 - 0.6775). Using regression trees (CHAID), we identified four discrete American Association of Anaesthesia nodes associated with mortality, with American Association of Anaesthesia 1 and American Association of Anaesthesia 2 compressed into the same node. CONCLUSION: The American Association of Anaesthesia score can be used to determine higher risk groups of surgical patients, but clinicians cannot use the score to discriminate between grades 1 and 2. Overall, the discriminatory power of the model was less than acceptable for widespread use.

Predição de Pré-Eclâmpsia no Primeiro Trimestre em Gravidezes de Baixo Risco: Determinação do Cut-Off numa Amostra da População Portuguesa

Objective:We aimed to identify the cut-off for risk of pre-eclampsia (PE) in Portuguese population by applying the first trimester prediction model from Fetal Medicine Foundation (FMF) in a prospective enrolled cohort of low risk pregnant women. Population and methods: A prospective cohort of low risk singleton pregnancies underwent routine first-trimester scree - ning from 2011 through 2013. Maternal characteristics, blood pressure, uterine artery Doppler, levels of pregnancy-associated plasma protein-A (PAPP-A) and free b-human chorionic gonadotropin were evaluated. The prediction of PE in first trimester was calculated through software Astraia, the outcome obtained from medical records and the cutoff value was subse quently calculated. Results:Of the 273 enrolled patients, 7 (2.6%) developed PE. In first trimester women who developed PE presented higher uterine arteries resistance, represented by higher values of lowest and mean uterine pulsatility index, p <0.005. There was no statistical significance among the remaining maternal characteristics, body mass index, blood pressure and PAPP-A. Using the FMF first trimester PE algorithm, an ideal cut-off of 0.045 (1/22) would correctly detect 71% women who developed PE for a 12% false positive rate and a likelihood ratio of 12.98 (area under the curve: 0.69; confidence interval 95%: 0.39-0.99). By applying the reported cutoff to our cohort, we would obtain 71.4% true positives, 88.3% true negatives, 11.4% false positives and 28.6% false negatives. Conclusion: By applying a first trimester PE prediction model to low risk pregnancies derived from a Portuguese population, a significant proportion of patients would have been predicted as high risk. New larger studies are required to confirm the present findings.

Validation of Two US Risk Scores for Percutaneous Coronary Intervention in a Single-Center Portuguese Population of Patients with Acute Coronary Syndrome

INTRODUCTION: New scores have been developed and validated in the US for in-hospital mortality risk stratification in patients undergoing coronary angioplasty: the National Cardiovascular Data Registry (NCDR) risk score and the Mayo Clinic Risk Score (MCRS). We sought to validate these scores in a European population with acute coronary syndrome (ACS) and to compare their predictive accuracy with that of the GRACE risk score. METHODS: In a single-center ACS registry of patients undergoing coronary angioplasty, we used the area under the receiver operating characteristic curve (AUC), a graphical representation of observed vs. expected mortality, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analysis to compare the scores. RESULTS: A total of 2148 consecutive patients were included, mean age 63 years (SD 13), 74% male and 71% with ST-segment elevation ACS. In-hospital mortality was 4.5%. The GRACE score showed the best AUC (0.94, 95% CI 0.91-0.96) compared with NCDR (0.87, 95% CI 0.83-0.91, p=0.0003) and MCRS (0.85, 95% CI 0.81-0.90, p=0.0003). In model calibration analysis, GRACE showed the best predictive power. With GRACE, patients were more often correctly classified than with MCRS (NRI 78.7, 95% CI 59.6-97.7; IDI 0.136, 95% CI 0.073-0.199) or NCDR (NRI 79.2, 95% CI 60.2-98.2; IDI 0.148, 95% CI 0.087-0.209). CONCLUSION: The NCDR and Mayo Clinic risk scores are useful for risk stratification of in-hospital mortality in a European population of patients with ACS undergoing coronary angioplasty. However, the GRACE score is still to be preferred.

Baseline Susceptibility of Primary HIV-2 to Entry Inhibitors

BACKGROUND: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. METHODS: The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC(50)), 90% inhibitory concentration (IC(90)) and dose-response curve slopes were determined for each drug. RESULTS: ENF and T-1249 were significantly less active on HIV-2 than on HIV-1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC(50) and IC(90) values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC(90) values (42.7 versus 9.7 nM; P<0.0001) and lower slope values (0.7 versus 1.3; P<0.0001) than HIV-1. HIV-2 R5 variants derived from AIDS patients were significantly less sensitive to MVC than variants from asymptomatic patients, this being inversely correlated with the absolute number of CD4(+) T-cells. CONCLUSIONS: T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK-779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage.