Cassiano Abreu-Lima

Increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities – cross-sectional study of the general population

BackgroundWe aimed to assess whether we could identify a graded association between increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities independently of predicted risk of coronary heart disease by the Framingham risk score.MethodsWe conducted a cross-sectional study on a random sample of the urban population of Porto aged 45 years or over. Six hundred and eighty-four participants were included. Data were collected by a structured clinical interview with a physician, ECG and a transthoracic M-mode and 2D echocardiogram. The metabolic syndrome was defined according to ATPIII-NCEP. The association between the number of features of the metabolic syndrome and the cardiac structural and functional abnormalities was assessed by 3 multivariate regression models: adjusting for age and gender, adjusting for the 10-year predicted risk of coronary heart disease by Framingham risk score and adjusting for age, gender and systolic blood pressure.ResultsThere was a positive association between the number of features of metabolic syndrome and parameters of cardiac structure and function, with a consistent and statistically significant trend for all cardiac variables considered when adjusting for age and gender. Parameters of left ventricular geometry patterns, left atrial diameter and diastolic dysfunction maintained this trend when taking into account the 10-year predicted risk of coronary heart disease by the Framingham score as an independent variable, while left ventricular systolic dysfunction did not. The prevalence of left ventricular diastolic dysfunction, and the mean left ventricular mass, left ventricular diameter and left atrial diameter increased significantly with the number of features of the metabolic syndrome when additionally adjusting for systolic blood pressure as a continuous variable.ConclusionIncreasing severity of metabolic syndrome was associated with increasingly compromised structure and function of the heart. This association was independent of Framingham risk score for indirect indices of diastolic dysfunction but not systolic dysfunction, and was not explained by blood pressure level.

Clinical syndrome suggestive of heart failure is frequently attributable to non-cardiac disorders : population-based study

To assess how often the clinical syndrome (CS) of heart failure is attributable to alternative, including non‐cardiac, explanations.

Population based study on the prevalence of the stages of heart failure

Heart failure (HF) is a major health issue. The heterogeneous nature of the syndrome impairs agreement on a standard definition. The high prevalence of HF with preserved left ventricular (LV) systolic function and asymptomatic LV systolic dysfunction, and the need for objective evidence of cardiac structural or functional abnormalities for HF diagnosis increase the difficulty in achieving a consensual definition. We aimed at estimating the age and sex specific prevalence of the American College of Cardiology (ACC)/American Heart Association (AHA)1 stages of HF in a representative sample of non-institutionalised adults from Porto, Portugal. Within a population health survey (participation 70%),2 we measured the prevalence of HF among participants aged ⩾ 45 years.2 The local ethics committee approved the study. Participants provided written informed consent. Hypertension was defined as blood pressure ⩾ 140/90 mm Hg or treatment with medication, and diabetes mellitus was defined as self reported or fasting blood glucose ⩾ 7 mmol/l. The metabolic syndrome was defined according to the National Cholesterol Education Program-Adult Treatment Panel III, obesity as body mass index ⩾ 30 kg/m2, and excessive alcohol intake as > 100 or > 80 g/day in men and women, respectively. Coronary artery disease was defined as self reported diagnosis of angina or myocardial infarction or pathological Q waves on ECG. Chronic lung disease was defined as previous chronic bronchitis or moderate to severe obstruction …

A new ECG classification system for myocardial infarction based on receiver operating characteristic curve analysis and information theory.

An optimized three-lead ECG hierarchial decision-tree type of classification system for myocpardial infarction is presented. For selection of the best threshold values for each criterion and the best association of features, we developed a procedure based on ‘receiver operating characteristic’ (ROC) curve data analysis and information theory. Optimization was obtained through maximization of information content of the criteria. The classifier is based on nine measurements that can be easily obtained by hand (Q X duration, Q/R Y amplitude, R Y amplitude, Q/R Y duration, Q Z amplitude, QRS and Taxes in the horizonital plane, Q Z duration and R Z amplitude) and achieved a satisfactory performance in an independent group of patients (true-positive ratio 0.853, false-positive ratio 0.105, average information content 0.308 bits).

Utilidad del diagnóstico molecular en una familia con síndrome de Marfan y un fenotipo vascular atípico

Marfan syndrome is mainly caused by mutations in the FBN1 gene. Diagnosis is usually based on clinical criteria, but the phenotypic presentation varies widely among affected individuals. Aortic dissection or rupture is the cause of death in over 90% of untreated patients. Early identification of individuals at risk is important given the availability of medical and surgical treatment that can significantly improve life-expectancy. Molecular testing could provide an etiologic diagnosis in patients who present with milder or atypical clinical forms of the disease. Moreover, it could contribute to preventive treatment in carriers, inform genetic counseling and offer reassurance to unaffected individuals. By describing a family with Marfan syndrome in whom the disease presented in an atypical aggressive form, this article highlights the value of tests for detecting FBN1 mutations in selected cases.

Diagnostic challenges of Marfan syndrome in an XYY young man.

Tall stature is a common feature of both Marfan syndrome and XYY syndrome. Differential diagnosis between these entities has important prognostic implications. We report the case of a 21-year-old young man with a previously known diagnosis of XYY syndrome, in whom the identification of a fibrilin-1 mutation was determinant to establish an appropriate diagnosis, medical follow-up, and genetic counselling.

Frontal-plane QRS axis revisited: Accuracy of current approximations and reappraisal of their merit in the diagnosis of right ventricular hypertrophy

The frontal-plane mean QRS vector orientation (AQRSxy)--the so-called electrical axis--is an ECG feature commonly used for the diagnosis of right ventricular hypertrophy and is correctly measured by calculating the areas subtended by QRS deflections in two different leads. To overcome the drawbacks of doing this by hand, two alleged approximations of AQRSxy have become popular and are in current use: one is based on the measurement of QRS component wave peak amplitudes and the other on the estimation of the half-area vector of the frontal plane loop. The values obtained with the correct and the two more practical methods are compared and their diagnostic efficiency is assessed by means of a procedure for ECG criteria optimization based on the receiver operating characteristics (ROC) curve analyzed in terms of information theory. The authors conclude that the two more popular methods for AQRSxy determination provide similar values that, although correlated with the true measure of the parameter are statistically different from it. On the other hand, the diagnostic efficiency of AQRSxy alone, regardless of the method by which it is computed, is only as good as, if not bettered by, other much more easily measurable frontal-plane parameters (ie, left to rightward forces amplitude ratio in adults and rightward forces amplitude in pediatric patients).

Right bundle branch block combined with left axis deviation: A vectorcardiographic study of 48 cases

Summary The vectorcardiograms (VCGs) of 48 patients with complete right bundle branch block combined with marked left axis deviation were studied and compared with electrocardiographic and clinical data. In these patients the VCG enables two patterns to be separated, i.e., type A (28 cases) and B (11 cases), with a different position and rotation of the horizontal loop. Type A configuration is similar to uncomplicated RBBB. Type B shows an anteriorly displaced loop with clockwise rotation. The ECG fails to distinguish type A from B. Contrary to the hypothesis of others, data are presented indicating that an associated posterior infarction cannot be, at least in some cases, the explanation for type B pattern. Type B reveals a more serious prognosis than type A mainly as regards the tendency to develop complete A-V block (18% as against 75%). This fact can suggest a new potential clinical usefulness for the VCG.

Caracterização genotípica de uma população de doentes portugueses com síndrome de Marfan

Resumo Introducao O diagnostico da Sindrome de Marfan (SM) depende fundamentalmente de uma avaliacao clinica multidisciplinar. O seu diagnostico molecular, atraves da identificacao de mutacoes no gene FBN1, pode permitir estabelecer um diagnostico definitivo mesmo perante fenotipos atipicos ou «incompletos» e reconhecer precocemente portadores assintomaticos. Objectivos O presente trabalho teve como objectivo principal avaliar a frequencia e o tipo de mutacoes no gene FBN1, numa populacao de doentes com SM, referenciados a um centro hospitalar de cuidados terciarios, com cirurgia toracica. Metodos A nossa amostra incluiu 30 individuos com SM (provenientes de 14 familias), que foram avaliados em consulta de Cardiologia, Reumatologia e Oftalmologia. Em todos os casos foi efectuada a pesquisa de mutacoes no gene FBN1 a partir de ADN obtido de amostras de sangue periferico, utilizando a tecnica de amplificacao por Polymerase Chain Reaction e posterior sequenciacao genica. Resultados Identificamos 12 mutacoes distintas nas 14 familias estudadas. Destas, apenas duas estavam previamente descritas na literatura, sendo as restantes 10, novas mutacoes. Encontramos mutacoes missense em 36% dos casos e mutacoes conduzindo a formacao de codoes de terminacao prematura em 50% dos casos. Conclusoes Este trabalho constitui a primeira descricao de resultados de analise genotipica em doentes portugueses com SM, de que temos conhecimento. Com este trabalho, realcamos a importância de uma avaliacao clinica multidisciplinar e da utilidade da pesquisa de mutacoes no gene FBN1 em casos seleccionados. Ao descrever 10 novas mutacoes, contribuimos ainda para a ampliacao do espectro de variantes do gene da FBN1 associadas a SM.INTRODUCTION The diagnosis of Marfan syndrome (MFS) depends on a multidisciplinary clinical evaluation. Molecular study to identify mutations in the FBN1 gene can establish a definitive diagnosis even with atypical or «incomplete» phenotypes and enable earlier diagnosis in asymptomatic patients. OBJECTIVES The aim of the present work was to evaluate the frequency and type of FBN1 gene mutations in a population of Marfan syndrome patients referred to a tertiary care center with cardiothoracic surgery. METHODS Our sample included 30 individuals with MFS (from 14 families), evaluated in cardiology, rheumatology and ophthalmology consultations. In all patients, DNA was extracted from a peripheral blood sample and mutation screening of the entire coding sequence of the FBN1 gene was then performed, using the polymerase chain reaction. RESULTS We identified 12 different mutations in the 14 families studied. Of these, only two had been previously described in the literature, while the other 10 were found to be new mutations; 36% of patients carried a missense mutation and 50% carried a mutation leading to a premature termination codon. CONCLUSIONS To the best of our knowledge this is the first genotypic description of Portuguese patients with MFS. In this study, we highlight the need for comprehensive clinical evaluation of these patients and the value of FBN1 mutation analysis in selected cases. By describing 10 new mutations, we have also helped broaden the spectrum of known FBN1 mutations associated with MFS.

Genotypic characterization of a Portuguese population of Marfan syndrome patients

Abstract Introduction The diagnosis of Marfan syndrome (MFS) depends on a multidisciplinary clinical evaluation. Molecular study to identify mutations in the FBN1 gene can establish a definitive diagnosis even with atypical or “incomplete” phenotypes and enable earlier diagnosis in asymptomatic patients. Objectives The aim of the present work was to evaluate the frequency and type of FBN1 gene mutations in a population of Marfan syndrome patients referred to a tertiary care center with cardiothoracic surgery. Methods Our sample included 30 individuals with MFS (from 14 families), evaluated in cardiology, rheumatology and ophthalmology consultations. In all patients, DNA was extracted from a peripheral blood sample and mutation screening of the entire coding sequence of the FBN1 gene was then performed, using the polymerase chain reaction. Results We identified 12 different mutations in the 14 families studied. Of these, only two had been previously described in the literature, while the other 10 were found to be new mutations; 36% of patients carried a Missense mutation and 50% carried a mutation leading to a premature termination codon. Conclusions To the best of our knowledge this is the first genotypic description of Portuguese patients with MFS. In this study, we highlight the need for comprehensive clinical evaluation of these patients and the value of FBN1 mutation analysis in selected cases. By describing 10 new mutations, we have also helped broaden the spectrum of known FBN1 mutations associated with MFS.