Hypertrophic cardiomyopathy in a Portuguese population: mutations in the myosin-binding protein C gene.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease and is often a consequence of mutations in the myosin-binding protein C gene (MYBPC3). Until now, however, no systematic review has been published on mutations of this gene in a Portuguese population. OBJECTIVES: In a Portuguese population of HCM patients: 1) to determine the prevalence of mutations in the MYBPC3 gene; 2) to characterize the mutations genetically; 3) to analyze the phenotype and compare it with the genotype-phenotype correlations for mutations in this gene described in the literature. METHODS: We studied 45 consecutive index patients with HCM (41 with familial HCM). In each patient, we performed a genetic study to detect mutations in the MYBPC3 gene. Once a mutation was identified and genetically characterized, a broad phenotypic evaluation was performed. The genetic and clinical data were then compared with those described in the literature. RESULTS: Of the 45 patients, 5 (11.1%) showed mutations in the MYBPC3 gene (2 deletions and 3 missense mutations), all in patients with familial HCM. Of these, 4 were 'new' mutations: Ala 522 Thr (exon 17); Gli 1205 Asp (exon 32); Lis 505 Del (exon 17) and Lis 813 Del (exon 25). The other mutation, Arg 502 Gln (exon 17), had been previously described in the literature. Three of the 5 mutations were located in exon 17. Four of these 5 patients were symptomatic, mainly with heart failure and supraventricular arrhythmias. No patient was at high risk for sudden cardiac death. Most of the patients had non-obstructive HCM. The ECG, echocardiogram, Holter monitoring and treadmill exercise test showed highly variable results, reflecting the heterogeneity typical of this disease. CONCLUSIONS: In a Portuguese population of 45 HCM patients, 5 (11.1%) had mutations in the MYBPC3 gene (3 missense mutations--theoretically less frequent in the MYBPC3 gene--and 2 deletions). Four of these were 'new' mutations and 3 of them were located in exon 17 (which may be a 'hot spot' for MYBPC3 gene mutations in the Portuguese population). In all the patients, the phenotypic expression was different from that usually described for these mutations; in 3 of our patients, the clinical manifestations and penetrance were of early onset and one patient had a highly symptomatic form of obstructive hypertrophic cardiomyopathy. These data reflect the large number of exceptions to the classic genotype-phenotype correlations in HCM, highlighting the role of other factors, genetic and non-genetic, in regulating penetrance, clinical expression and prognosis in each family and in each individual patient.

Acute coronary syndromes in smokers: clinical and angiographic characteristics.

UNLABELLED: Smoking is a major and reversible risk factor for coronary artery disease. The present work aims to define the risk factors, angiographic and clinical characteristics and evolution of acute coronary syndromes in smokers. METHODS: We studied 521 consecutive patients with acute coronary syndrome admitted to the intensive care unit who underwent catheterization. We assessed the population in terms of risk factors, pathology (unstable angina or acute myocardial infarction), coronary morphology, left ventricular function, the need for intervention, evolution and complications over a one-year period. The characteristics of smokers were then compared with those of non-smokers. RESULTS: Of the 521 patients with acute coronary syndrome (391 men), 182 (35 %) were smokers. The smokers were younger than the non-smokers (56.3+/-9.5 versus 66.4 +/- 7.8; p < 0.001), were more frequently male (91 versus 66%; p < 0.001), and presented more risk factors (43% with 3 or more risk factors versus 17% in non-smokers; p < 0.001), more obesity (11 versus 5%; p < 0.01), and less diabetes (19 versus 37%; p < 0.001). Smokers presented greater prevalence of acute myocardial infarction (57 versus 40%; p < 0.001) and less unstable angina. Coronary morphology was not significantly different in smokers compared to non- smokers and left ventricular function after the aculte coronary syndrome was similar in both groups. Smokers less frequently underwent surgery during hospitalization (22% versus 35%; p < 0.01) but needed angioplasty as often as non-smokers (48% versus 16%; NS). Smokers presented more frequent complications (angina, heart failure, re-infarction or CABG) than non-smokers (26% versus 17%; p < 0.01), during the first year of follow-up. One-year mortality was similar in both groups. The results were not significantly different when adjusted for gender. CONCLUSIONS: On average, acute coronary syndrome occurred 10 years earlier in smokers than in non-smokers. The former generally presented more risk factors, lower prevalence of diabetes and higher of obesity, more myocardial infarctions and less unstable angina. After the acute coronary syndrome, at one year, smokers presented more complications than non-smokers but had similar mortality.

Acute coronary syndrome in a diabetic population--risk factors and clinical and angiographic characteristics.

INTRODUCTION: Diabetes is not only a risk factor for coronary artery disease but also influences its presentation and evolution. OBJECTIVES: The objective of this work is to define the risk factors, clinical and angiographic characteristics, and evolution of acute coronary syndrome in a population of diabetic patients. METHODOLOGY: We studied 521 patients suffering from acute coronary syndrome, consecutively hospitalized in the Cardiology Intensive Care Unit who underwent cardiac catheterization during their hospitalization, in terms of risk factors for coronary disease, pathology (unstable angina versus acute myocardial infarction), coronary morphology, left ventricular function, need for intervention during hospitalization, evolution and complications during one-year follow-up. The characteristics of the diabetic patients with acute coronary syndrome were compared to those of non-diabetic patients. RESULTS: Of the 521 patients suffering from acute coronary syndrome (391 male), 159 (30.5%) were diabetic. The diabetic patients suffering from acute coronary syndrome generally presented fewer risk factors for coronary artery disease, with a lower prevalence of smoking (p < 0.001), greater prevalence of family history of coronary artery disease (p < 0.01), more unstable angina and less acute myocardial infarction (both p < 0.001), than the nondiabetic patients. After the acute coronary syndrome the diabetic patients more frequently presented disease of the left anterior descending artery, left ventricular function was worse and there was a greater need for coronary artery bypass graft surgery and less percutaneous transluminal coronary angioplasty than in the non-diabetic patients (p < 0.05 for all). In terms of evolution, they presented greater complications and more mortality over a year (p < 0.05). CONCLUSION: Diabetes constitutes a powerful risk factor for coronary artery disease and its complications, and should therefore be taken into consideration in clinical approaches to this pathology.

New classification of aortic dissection with reference to a case report.

The authors present a case report of a patient who was diagnosed with aortic dissection during a hemodynamic exam following acute myocardial infarction. With reference to this case, the European Society of Cardiology's latest classification of aortic dissection, published in 2001, is also presented. The patient had the usual risk factors described for aortic dissection, which are simultaneously those for coronary disease. The patient reported an isolated episode in the past of retrosternal pain, radiating to the back, which may have been caused by the aortic dissection. Since then he had been asymptomatic. Four years later, the patient was admitted to hospital following an anteroseptal acute myocardial infarction; fibrinolysis was contraindicated due to recent episodes of rectal bleeding and the patient underwent hemodynamic study (coronary angiography). Due to difficulties in manipulating the guide wire during this exam, aortography was performed, which showed aneurysm and Stanford type B aortic dissection of the thoracic aorta. During hospitalization, a thoracic-abdominal CT scan was performed, which confirmed chronic type B aortic dissection (with intraluminal thrombi). The authors present their reasons for considering this case to be Class 4 according to the new sub-types/classes of aortic dissection of the European Society of Cardiology (ESC): Class 1--Classical aortic dissection Class 2--Intramural hematoma/hemorrhage Class 3--Subtle/discrete aortic dissection Class 4--Plaque rupture/ulceration Class 5--Iatrogenic/traumatic aortic dissection. The authors consider this case to be of interest because of its rarity, the risk that fibrinolysis could have represented, and its categorization according to the latest classification of aortic dissection by the ESC.

Heart transplantation in Portugal: current status and future perspectives.

No other form of therapy, whether medical or surgical, has an impact comparable to heart transplantation on the quality of life and survival of selected patients with severe heart failure. In the EU and in the USA about 10 patients per million of population are transplanted each year. In Portugal, a country with a population of 10 million, 100 patients should be transplanted each year, but only 12 patients were in fact transplanted in 1999. We rank 17th, in terms of the rate of heart transplantation per million of population, among the 23 European countries with registries of this activity. This is due to structural and organizational deficiencies of three main types: the lack of professional teams dedicated to severe heart failure treatment and heart transplantation; the lack of infrastructure, particularly heart failure wards and heart failure outpatient clinics; and the inappropriate distribution of the tasks associated with heart transplantation and patient follow-up. We present an estimate of the number of potential heart transplant candidates in Portugal, based on the EPICA study and a prediction of the resources needed for a successful heart transplantation program serving a population of 2 million. This was based on what is known of the natural history, morbidity and mortality of severe heart failure, on our own experience in this field, and finally on the experience of a large international heart transplantation center. The recommendations of the British Transplantation Society and those of the Department of Cardiothoracic Surgery of Stanford University were also taken into account.

Risk factors and clinical angiographical characteristics of myocardial infarction in women.

INTRODUCTION: Myocardial infarction has a higher incidence in men. However, in women, although less frequent, it has a worse prognosis. OBJECTIVE: With the present work we aim to define the clinical and angiographical characteristics and evolution of myocardial infarction in women compared with men. METHODOLOGY: We studied 235 sequential inpatients with acute myocardial infarction in the Intensive Care Unit who underwent post-infarction catheterization. We then compared female with male patients in terms of risk factors, location and type of infarction, coronary morphology and post-infarction complications. RESULTS: About 22% of the patients hospitalized following myocardial infarction were female. The women were older than the men (65.9 +/- 11.2 vs. 60.3 +/- 11.9; p < 0.01), and had a higher prevalence of high blood pressure (71% vs. 54%, p < 0.05) and a lower prevalence of smoking (19% vs. 50%, p < 0.001). Post-infarction angina was more frequent in women (50% vs. 23%, p < 0.001). Neither Q-wave versus non-Q wave myocardial infarction nor its location were significantly different between the sexes. In terms of coronary morphology, myocardial infarction without significant lesions was more frequent in women (10% vs. 3%, p < 0.05) and there were no significant.