Neurohormonal modulation: The new paradigm of pharmacological treatment of heart failure.

The current paradigm of medical therapy for heart failure with reduced ejection fraction (HFrEF) is triple neurohormonal blockade with an angiotensin-converting enzyme inhibitor (ACEI), a beta-blocker (BB) and a mineralocorticoid receptor antagonist (MRA). However, three-year mortality remains over 30%. Stimulation of counter-regulatory systems in addition to neurohormonal blockade constitutes a new paradigm, termed neurohormonal modulation. Sacubitril/valsartan is the first element of this new strategy. PARADIGM-HF was the largest randomized clinical trial conducted in HFrEF. It included 8442 patients and compared the efficacy and safety of sacubitril/valsartan versus enalapril. The primary endpoint was the composite of cardiovascular mortality and hospitalization due to HF, which occurred in 914 (21.8%) patients receiving sacubitril/valsartan and in 1117 (26.5%) patients receiving enalapril (HR 0.8, 95% CI 0.73-0.87, p=0.0000002; NNT 21). Sacubitril/valsartan reduced both primary endpoint components, as well as sudden cardiac death, death due to worsening HF, and death from all causes. Patients on sacubitril/valsartan reported less frequent deterioration of HF and of quality of life, and discontinued study medication less frequently because of an adverse event. PARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril, with a 20% greater impact on cardiovascular mortality compared to ACEIs. Accordingly, in 2016, the European (ESC) and American (ACC/AHA/HFSA) cardiology societies simultaneously issued a class I recommendation for the replacement of ACEIs by sacubitril/valsartan in patients resembling PARADIGM-HF trial participants.

Prevalence of chronic rhinosinusitis in Sao Paulo.

INTRODUCTION: Studies designed to investigate chronic rhinosinusitis (CRS) epidemiology play an important role to assess population`s distribution and risk factors to result in the development and promotion of public health policies. METHOD: This study design is a survey carried out with a complex two-stage cluster sampling plan. Personal interviews were carried out with 2,003 individuals. The questionnaire included the epidemiological criteria for CRS. Demographic data, history of physician-diagnosed respiratory diseases (asthma, sinusitis, rhinitis), smoking, family income, educational attainment, and household characteristics were also evaluated. RESULTS: The overall response rate was 93.9% of the households. Mean age was 39.8 +- 21 years; 45.33% were male. The overall prevalence of CRS in the city of Sao Paulo was 5.51%. We found a significant association between diagnosis of CRS and diagnosis of asthma and CRS and diagnosis of rhinitis and a significant association between presence of CRS and belonging to the low-income subgroup. CONCLUSION: The municipality of Sao Paulo has an urban population of 11 million. According to the present study, the prevalence of CRS is 5.51%, which represents more than 500,000 individuals affected by this condition in the city.

Cross-cultural adaptation and validation of a quality of life questionnaire: the Nasal Obstruction Symptom Evaluation questionnaire.

BACKGROUND: The Nasal Obstruction Symptom Evaluation (NOSE) instrument is a disease-specific questionnaire for assessing the outcome of an intervention in nasal obstruction in trials. This instrument is only available in the English language and cross-culturally valid questionnaires are very important for all research, including nasal obstruction. The aim of the current study was to reproduce the cross-cultural adaptation process for the NOSE questionnaire in the Portuguese language (NOSE-p). METHODOLOGY/PRINCIPAL: Cross-cultural adaptation and validation of the instrument were divided into two stages. Stage 1 involved four bilingual professionals, an expert committee and the author of the original instrument. In Stage 2, the NOSE-p was tested on 33 patients undergoing septoplasty for internal consistency, test-retest reliability, construct validity, discriminant validity, criterion validity, and response sensitivity. RESULTS: The cross-cultural adaptation process was completed and the NOSE-p was demonstrated to be a valid instrument with satisfactory construct validity. It showed an adequate internal consistency reliability and adequate test-retest reliability. It could discriminate between patients with and without nasal obstruction and it has a high response sensitivity to change. CONCLUSIONS: The cross-cultural adaptation and validation process demonstrated to be valid and the NOSE-p proved to be applicable in Brazil.

Campath-1H (alemtuzumab) as an induction agent for the prevention of graft rejection and preservation of renal function in kidney transplant patients: Philippine 3-year follow-up.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of induction with Campath-1H with low-dose cyclosporine (CsA) monotherapy using outcome measures of acute rejection episodes (ARE), chronic allograft nephropathy (CAN), graft and patient survivals, as well as malignancies and infections. MATERIALS AND METHODS: Fourteen kidney transplant recipients were randomized to receive either Campath 1H induction with CsA monotherapy (9 patients) or immunosuppression with CsA, azathioprine, and steroids (5 patients). Campath (20 mg IV) was administered within 6 hours after the anastomosis and repeated 24 hours later. Cyclosporine was started 72 hours after the first Campath dose (10 mg/kg on the first day, then 4 mg/kg/d), seeking to achieve target trough CsA levels of 90 to 110 ng/mL. This is a 3-year follow-up of the 9 patients who received Campath-1H induction. RESULTS: Six of 9 (67%) patients developed ARE (borderline ARE to Banff IB) in the Campath group compared with 1 of 5 (20%) in the other group (ARE Banff IIA). They all received methylprednisolone for 3 days with good responses. One of the 6 patients in the Campath group with ARE also displayed CAN and was converted to sirolimus; 2 others had mycophenolate mofetil and steroids added to their immunosuppression after the ARE. Creatinine levels ranged from 1 to 1.7 mg/dL at 24 to 36 months posttransplantation in both groups. Among the Campath group, 1 patient died 6 months posttransplantation with sepsis secondary to infectious diarrhea. Upper respiratory tract infections comprised the majority of infections at 24 to 36 months. No malignancies were observed. CONCLUSIONS: Three years posttransplantation, patients given Campath induction with CsA monotherapy showed a greater incidence of ARE, although renal function remained comparable to CsA-azathioprine-prednisone therapy. AREs were easily reversed with steriods. Infections were minor.

Síndrome de Wells: relato de caso / Wells syndrome: A case report

Os autores descrevem um caso de Síndrome de Wells e caracterizam os seus principais aspectos clínicos e histológicos (AU)

[Acute effects of tobacco and vascular risk modulated by genetic factors]. / Acções agudas do tabaco e risco vascular modulado por factores genéticos.

Most studies regarding the acute effects of cigarette smoking refer to the higher sympathetic and adrenomedullary activity as a result of sympathetic ganglia and adrenal medulla nicotinic receptor activation. Although it is reasonable to suppose that the renin-angiotensin system might be activated, this possible effect of nicotine has not been studied. We have studied the effects of cigarette smoking on blood pressure, cardiac output, pulse pressure, renin-angiotensin system, kinins-NO, oxidative stress and insulin. Also, we have investigated if the variability of the biochemical parameters was dependent on genetic polymorphisms of the angiotensin converting enzyme and the acute phase protein haptoglobin. 39 normotensive individuals, 18 males and 21 females, of mean age 35.4 +/- 8.9 years were included in this study. Oxidative stress was dependent on the ACE I/D and Hp1/2 polymorphisms, with the ACE DD genotype and the Hp2-2 phenotype not showing variation in the anti-oxidant defense systems, and the ACE II-ID genotypes and Hp1-1 + 2-2 phenotypes showing a higher anti-oxidant response, hence a lower cardiovascular risk being predictable in the latter individuals.

[The successes and failures in the primary prevention of coronary disease]. / Sucessos e insucessos da prevenção primária da doença coronária.

The modification of major behavioural and environmental risk factors has helped reduce coronary heart disease. It seems, however, that prevention results were not so good as expected. It is assumed that the major cause of this apparent unsuccessful data is basically due to world population ageing, as it is known that coronary heart disease is much more frequent in older people. Therefore the current life expectancy shows that the preventive measures have indeed been successful. From the analysis and discussion of the preventive epidemiological recommendations and the identification of new risk factors, the Authors suggest new strategies for health promotion and particularly for coronary heart disease reduction.

Plasma homovanillic acid and prolactin in systemic lupus erythematosus.

Prolactin (PRL) is an important immunoregulator and might have a role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of pituitary prolactin secretion is complex and involves a negative feedback process in the hypothalamus, in which dopamine plays the principal role. However, the main source of serum prolactin in lupus patients is still not clearly established. Since homovanillic acid (HVA), the principal metabolite of dopamine (DA), is removed from the brain into the blood, it would indirectly reflect DA metabolism. It is assumed that the turnover of a neurotransmitter can be determined through an analysis of its metabolites. The objective of this study was to analyse plasma samples from SLE patients to see if there were any alterations in neurally functioning DA through its principal metabolite, HVA. We also measured the levels of PRL and compared HVA and PRL with the clinical activity of the disease. Twenty-four SLE patients and fifteen healthy controls were studied. The investigation was done over a period of 3 months. The results of this study show significantly low levels of HVA in lupus patients compared to controls (P < 0.0001). This corresponds to a decrease in dopamine turnover. Hyperprolactinemia was observed in nine patients, and the average level of prolactin in lupus patients was higher than in healthy controls (P < 0.001). For the duration of the study, a significant percentage of variation was observed in the levels of HVA in the clinically active patients (P < 0.05) compared to inactive patients. When PRL was compared in these groups, throughout the study, no significant percentage of variation was observed. The relationship between HVA and PRL in healthy controls was r = 0.47, P = 0.08, and in patients was r = 0.04, P = 0.84. It is suggested that there is a probable association between plasma levels of HVA and PRL in the healthy controls and not in the SLE patients.

Characteristic generated alterations of autoantibody patterns in idiopathic thrombocytopenic purpura.

Using a Western blot technique that allows quantitative detection of antibody reactivities to a large number of antigens, serum IgG and IgM antibody repertoires were compared in a group of 19 patients with a diagnosis of idiopathic thrombocytopenic purpura (ITP) and respective healthy controls. The results show that, irrespective of the duration of thrombocytopenia, age of the patients, and type of therapy, all ITP donors share characteristic alterations of serum antibody reactivity patterns on homologous erythrocyte and liver antigens. Multiparametric analyses of the immunoreactivity data readily segregated the groups of ITP and healthy donors. Similar analyses also distinguished ITP sera from those of a group of patients with systemic lupus erythematosus (SLE). We conclude that ITP is an autoimmune disease associated with generalized alterations of antibody repertoires, that may be characteristic enough to allow for diagnosis.

Comparison between dobutamine echocardiography and thallium-201 scintigraphy in detecting residual stenosis, ischemia, and necrosis in patients with prior myocardial infarction.

BACKGROUND: Following the first attempts to detect myocardial ischemia with two-dimensional echocardiography stress testing, pharmacologic stress using dobutamine infusion has become an alternative to echocardiography exercise testing for evaluation of coronary artery disease. It has been shown that stress echocardiography has a diagnostic accuracy similar to that of an exercise thallium test. Other studies, however, indicated that radionuclide myocardial perfusion imaging was more sensitive than exercise or pharmacologic stress echocardiography for detection of ischemia or jeopardized myocardium. HYPOTHESIS: The aim of the present study was to determine the ability of dobutamine stress echocardiography in comparison with thallium-201 scintigraphy to identify multivessel disease and the presence of myocardial scar and ischemia in 60 consecutive patients who suffered a first myocardial infarction (MI). METHODS: Patients were evaluated by coronary angiography and ventriculography, thallium-201 (201TI) tomographic scintigraphy, and dobutamine echocardiography within 3 months of a first MI. Forty-seven had Q-wave MI and 13 had non-Q-wave MI. Eleven patients were excluded from final analysis-7 because of failure to achieve target heart rate in spite of the use of atropine, and 4 because of high blood pressure following the infusion of dobutamine. RESULTS: Dobutamine echocardiography showed an overall sensitivity of 43% for detection of coronary artery lesions of 50-74% diameter stenosis and 201TI scintigraphy showed a sensitivity of 71%. For detection of lesions of > or = 75% diameter stenosis, dobutamine echocardiography showed a sensitivity of 52% and 201TI a sensitivity of 70%. Overall agreement between wall motion and myocardial perfusion for detection of necrosis and/or ischemia in the infarct area was 40.4% with a kappa coefficient of 0.09 (p = 0.13). For detection of ischemic myocardium outside the infarct zone, overall agreement was 78.6% with a kappa coefficient of 0.49 (p < 0.0001). CONCLUSION: Dobutamine echocardiography results showed a lower sensitivity than myocardial perfusion images in predicting multivessel coronary artery disease, and there was poor agreement between both methods in identifying necrosis or ischemia.

[Coronary artery disease, myocardial perfusion and ventricular function in Q-wave and non-Q-wave myocardial infarcts]. / Doença arterial coronária, perfusão miocárdica e função ventricular em enfartes do miocárdio com onda Q e sem onda Q.

Controversy remains in considering non-Q wave myocardial infarction (NQMI) a distinct pathophysiological entity of Q wave myocardial infarction (QMI). In order to analyze the severity of coronary artery disease, extension of myocardial scar or myocardial ischemia and ventricular function, 78 consecutive patients with QMI and 32 with NQMI, mean age 55.4 +/- 8.5, not submitted to thrombolytic therapy, were studied. Coronary angiography, exercise thallium scintigraphy and radionuclide ventriculography were performed in all at least within 3 months of a prior myocardial infarction. In the present study the occurrence of QMI was significantly more frequent in older patients than NQMI. There was no prevalence of occlusion either in the right, left circumflex or left anterior descending coronary arteries in both groups. Ejection fraction, degree of occlusion and presence of collateral circulation showed an equal prevalence in QMI and NQMI patients. A higher incidence of multivessel disease was found in NQMI that had less necrosis than QMI patients. The prevalence of exercise induced thallium-201 redistribution defects within the infarct zone was substantially higher and involved more scar segments in NQMI patients. Physiological and clinical consequences of coronary thrombosis depends on the size and the number of diseased arteries, the approach the pathophysiologic consequences of coronary disease in terms of fractal structure has been suggested. A pronounced heterogeneity in regional myocardial blood flow in a fractal branching arterial network may be responsible for the pathophysiologic differences of coronary thrombosis between Q-wave and non Q-wave infarction.

Instability of natural antibody repertoires in systemic lupus erythematosus patients, revealed by multiparametric analysis of serum antibody reactivities.

Recent views on autoimmune diseases invoke generalized but specific perturbations in antibody repertoires, rather than the clonally restricted or non-specific polyclonal alterations proposed thus far. The present experiments analyse serum antibody reactivities in 24 systemic lupus erythematosus (SLE) patients and 17 healthy controls, using a method that quantitatively scores a large number of antibody reactivities and allows for multiparametric statistical analyses. The results show global but relatively specific perturbations in SLE antibody repertoires, and identify novel disease-associated reactivity patterns. Furthermore, a time series analysis of serum antibodies over 3 months demonstrates instability of natural antibody repertoires in individual SLE patients, contrasting with their remarkable conservation in healthy donors. Moreover, the method used clusters controls and patients independently, and might prove of diagnostic value, once large data bases are established.

[The digital image archive--its clinical applications and importance in cardiology consulting by telemedicine]. / Arquivo digital de imagens--aplicações clínicas e sua importância na consultoria cardiológica por telemedicina.

The revolution in digital technology is rapidly changing the world of telecommunications. Its applications to Medicine, and in particular to Cardiology, offer enormous benefits since communication is an essential part of medical practice. The need to improve the management of medical information is critical because of the explosion of medical knowledge, and the need to provide comprehensive documentation on patient care. The availability of a network offers many possibilities for clinical, research and teaching activities. Relevant, up-to-date scientific information is instantly available for analysis and interaction. The authors review the issue of digital communications as well as its potential application to Telemedicine, and present their preliminary experience with digital analysis and storage of echocardiographic images.

[Risk stratification and prognosis in critical surgical patients using the Acute Physiology, Age and Chronic Health III System (APACHE III)]. / Estratificação de risco e prognóstico em doentes cirúrgicos críticos utilizando o Sistema Acute Physiology, Age and Chronic Health III (APACHE III).

INTRODUCTION: Outcome prediction in critical surgical patients admitted to intensive care units (ICU) has been established using several scoring systems. To evaluate the predictive performance of the Acute Physiology, Age and Chronic Health Evaluation (APACHE III) scoring system in these patients, we studied a population admitted to a surgical ICU in our University Hospital. METHODS: We collected prospective data on 220 consecutive patients admitted over a period of 12 months. APACHE III (A3) scores were obtained over the first 24 hours of ICU admission (APACHE II scores were also calculated); data also included age, sex, acute and chronic diseases, ICU and hospital length of stay (LOS), patient location prior to ICU admission and outcome. The relationship of hospital mortality with A3 scores was analyzed using logistic regression, with the discriminatory power of these systems being assessed by the area under the ROC curve and percentage of correct classification. RESULTS: Patient's mean age was 57 +/- 17 years and 44% were male; 53.6% were elective and 46.4% were emergency postoperative patients; 5% of patients had co-morbidities; ICU mortality rate was 10% and in-hospital mortality rate (HMR) was 15%; mean ICU LOS was 3.9 +/- 5.6 days and mean hospital LOS was 9.4 +/- 8.2 days; mean scores were: APACHE III = 33 +/- 2 and APACHE II = 9 +/- 6 points. There was a significant relationship between ascending A3 scores and HMR. APACHE III had a correct classification rate of 87.3% and an area under the ROC curve of 0.830. CONCLUSIONS: In a population of critical surgical patients admitted to our ICU the APACHE III scoring system demonstrated an excellent prognostic performance as measured by contingency tables and areas under the ROC curve; this system can be a useful tool for outcome prediction in critical surgical patients.

[Rational distribution of resources in intensive medicine. Analysis of admission and discharge criteria at intensive care units]. / Distribuição racional de recursos em medicina intensiva. Análise de critérios de admissão e alta de unidades de cuidados intensivos.

Cost-containment in health care has become a major issue in today's practice of medicine. With its needs in advanced technologies and skilled personnel, intensive care is among the most expensive of all hospital activities. This fact makes the analysis of indications for intensive care unit admission, as well as early discharge, of paramount importance: patients who are not likely to benefit from intensive care are at the extremes of disease severity, since low-risk patients are not ill enough to need ICU admission and high-risk patients have a very high mortality, irrespective of intensive care treatment. In this paper we discuss, based on published evidence, the formulation of recommendations for admission and early discharge from ICUs, and also present the Society of Critical Care Medicine guidelines, on this subject.

Dynamic three-dimensional echocardiography: a new era in ultrasound technology.

The use of noninvasive methods to visualise the heart has had an extraordinary development over the last decade, with echocardiography demonstrating a particularly fast growth. Despite its unquestionable role in the diagnosis of heart disease and in the management of cardiac patients, it does have some limitations, both in the morphological visualisation, as well as in the functional assessment of the heart, such as blood flow, quantification of intracardiac volumes, etc. The recent development of dynamic three-dimensional (3D) echocardiography from two dimensional images has opened new perspectives in the study of cardiac pathophysiology. There are basically two methods of displaying three dimensional data sets: (1) a two-dimensional display from individual selected cut planes (any-plane echocardiography) or from parallel short axis cuts; (2) a volume rendered technique: from any defined cut plane, different algorithms are applied to represent the information in space. There are several potential clinical applications of 3D such as the measurement and serial follow-up of left ventricular volumes; in valvular heart disease (the abnormalities can be delineated more precisely and in greater detail than conventional imaging, including a detailed definition of mitral apparatus in mitral stenosis), in mitral valve prolapse both leaflets can be seen from the left atrial view and in endocarditis it can aid in deciding when and how to intervene; in complex congenital heart disease, such as reconstruction of double outlet right ventricle, left-sided obstructive and regurgitant lesions and subaortic obstructive cases, in atrial and ventricular septal defects, displaying size, geometry and relationships to other structures; another expression of cardiac disorders are blood flow disturbances (visualisation of flows in 3D could allow a better qualitative and quantitative assessment of their size and severity; the pictures so far generated allow a good perception of the size and shape of mitral, aortic and tricuspid regurgitation jets, by examining them from a new perspective, it also has the potential to display the flow convergence zone and quantify the regurgitant volume). Recent studies have clearly demonstrated the feasibility of performing three-dimensional imaging in a variety of cardiac diseases, but continued development of ultrasound technology must be made to improve better image resolution. The prolonged acquisition time is the most important limiting factor that currently restricts the routine use of 3D echocardiography. The development of faster computers will shorten the time needed for image acquisition, postprocessing, and data analysis, contributing to the goal of easy access and wide use. With improvements in computer technology and production of interactive software, 3D echocardiography will provide a dynamic view of the surgical anatomy of the heart. Thus, the three-dimensional reconstruction concept has the potential to and diagnostic assessment of cardiac pathology in every facet.

[Thrombolytic therapy in acute myocardial infarct--is it being used to the fullest?]. / Terapêutica trombolítica no enfarte agudo do miocárdio--estará a ser utilizada em pleno?

OBJECTIVE: To evaluate the experience with thrombolytic therapy (TT) in the treatment of patients with the discharge diagnosis of acute myocardial infarction (AMI). DESIGN: Retrospective analysis of the clinical records of patients with the discharge diagnosis of AMI, between May 1988 and December 1995. SETTING: Intensive Cardiac Care Unit (UCIM-Medicina IV) of Santa Maria University Hospital, Lisbon, Portugal. PATIENTS: 1319 patients, 958 men (73%) and 361 women, mean age 64 +/- 12 years. MAIN RESULTS: Thrombolytic therapy was administered in 391 patients (30%). Female patients received less thrombolytic therapy compared with male (17% vs. 34%; p < 0.001). Anterior wall infarction was more frequent (38%). Patients in Killip class I-II (77%) received more thrombolytic therapy than class III-IV (33% vs. 17%). The utilization rate of thrombolytic therapy increased from 25% in 1988 to 34% in 1995. Two major categories of patients were not treated with thrombolysis: 1) patients presented more than 12 hours after pain onset (38%); 2) patients without ST segment elevation or LBBB on the ECG presented (37%). Overall hospital mortality was 15.6%. The mortality in patients receiving thrombolytic therapy was significantly lower than in those excluded (9.4% vs. 18.2%; p < 0.001). CONCLUSION: Only 30% of patients with AMI receive TT. Of those excluded from this important therapeutic intervention, 75% had no ECG criteria or were outside the standard therapeutic "window". This significant group of patients need new diagnostic and intervention strategies.