Multiple endocrine neoplasia type 2A. Study of a family.

INTRODUCTION: Pheochromocytomas (Pheo) can occur sporadically, isolated or in association with other neuroendocrine lesions. In multiple endocrine neoplasia type 2A (MEN-2A), Pheo is associated to medullary thyroid carcinoma (MTC) or its precursor, C-cell hyperplasia (CCH) and parathyroid hyperplasia. Genetic screening provides early diagnosis and preventive treatment. In order to validate DNA analysis as a reliable method of early identification of gene carriers, we compared the results of genetic screening with clinical, biochemical, imaging and pathological findings in the members of an affected family. POPULATION AND METHODS: The diagnosis of a bilateral necrotic Pheo in a female patient led to the study of a family with four generations, aged 3 to 78 years (mean = 30.3 yrs). The study included a clinical examination; basal and pentagastrin stimulated calcitonin values; urinary catecholamines and their metabolites; serum calcium and a genetic study (direct sequence of PCR products from genomic DNA isolated from leucocytes using specific primers in exon 11 of the RET protooncogene of chromosome 10). The radiologic study, gammagraphic study (131I-MIBG) and magnetic resonance study were performed in members with clinical suspicion of Pheo. RESULTS: Seven out of nine patients had a mutation on codon 634 of exon 11 of RET (TGC-CGC), leading to cysteine arginine substitution in the codified protein; all gene carriers had biochemical markers of MTC/CCH and four of Pheo. The Pheo patients underwent adrenalectomy (bilateral in three) and all the gene carriers underwent prophylactic thyroidectomy. The pathologic findings were: MTC in four (metastasized in one); CCH in three and parathyroid hyperplasia in one. CONCLUSIONS: Phenotypic penetration of RET mutation was 100% for MTC/CCH, but only 57% of the gene carriers had Pheo. Genetic screening allowed early prophylactic treatment in four out of seven patients; pathologic findings revealed several evolutionary stages of the disease. Patients not yet showing Pheo are under close clinical and laboratory surveillance.

[The variability of the heart rate in the first 24 hours after fibrinolytic therapy in acute myocardial infarct]. / Variabilidade da frequência cardíaca nas primeiras 24 horas após a terapêutica fibrinolítica no enfarte agudo do miocárdio.

AIM OF THE STUDY: The role of heart rate variability changes in the appraisal of reperfusion after fibrinolytic therapy in acute myocardial infarction is still controversial. The aim of this study was to analyze the influence of reperfusion and infarct site on heart rate variability within 24 hours after infarction. PATIENTS AND METHODS: We studied 45 patients with a mean age = 56.3 +/- 12.4 years, 25 with anterior infarction and 20 with inferior infarction. The reperfusion was defined by the simultaneous presence of three classic noninvasive criteria (fast relief of pain, fast regression of ST segment elevation and early peak of CK). We studied heart rate variability parameters in time-domain and frequency-domain on a 24-hour Holter ECG started at the same time as fibrinolytic therapy. RESULTS: Thirty-three patients showed reperfusion. We did not find significant differences in the several parameters of heart rate variability between patients with reperfusion and patients without reperfusion, but the patients with anterior wall infarction showed a significant reduction in SDNN in comparison with patients with inferior wall infarction (84 +/- 28 ms vs 102 +/- 30 ms; p = 0.05). pNN50 (5.3 +/- 7.2 ms vs 10.5 +/- 9.8 ms; p = 0.04), LF (618 +/- 591 ms2 vs 1374 +/- 1761 ms2; p = 0.05) and TP (1415 +/- 1199 ms2/Hz vs 3015 +/- 4243 ms2/Hz). CONCLUSION: These data suggest a relationship between infarct severity and sympathetic activation and/or reduction of vagal modulation, but a potential beneficial effect of reperfusion on autonomic nervous system alterations was not evident in the first day of acute myocardial infarction.

[High-resolution electrocardiography in acute myocardial infarct]. / Electrocardiografia de alta resolução no enfarte agudo do miocárdio.

The author starts by highlighting the importance of risk stratification in patients who have survived a myocardial infarction. High resolution electrocardiography, also called signal-averaged electrocardiography (SAECG), appears in this setting as a diagnostic tool that, by providing important information about the way the intraventricular conduction of the electrical impulse is made, contributes to the characterization of the arrhythmogenic substrate, which is the basis of ventricular tachycardia and fibrillation. By resorting to the averaging of the electrocardiographic signal, SAECG enables us to detect ventricular late potentials whenever the analysis of that signal is made in time-domain. Further details, which will enrich the information on ventricular activation, can be obtained if the analysis is made in the frequency-domain (spectral analysis). The importance of detecting abnormalities in the SAECG recordings lies in the fact that those abnormalities are related to the occurrence of ventricular tachycardia and fibrillation, which are responsible for arrhythmic death. After referring to the criteria of positivity of SAECG and its reproducibility, the author approaches the most important part of the paper: the clinical applications of SAECG. After focusing on the interest of the method in noncoronary conditions, its usefulness in patients with acute myocardial infarction is pointed out. The author then mentions the prevalence of abnormalities in SAECG in patients with acute myocardial infarction and emphasizes the interest of the method in risk stratification. The author then presents the results of his Group in what concerns prevalence and prognosis. Finally, the author refers to the application of SAECG in other forms of coronary artery disease besides myocardial infarction.

[Angina pectoris. Silent ischemia]. / Angina de peito. Isquemia silenciosa.

One of the most difficult problems related to coronary artery disease is the detection and eventual treatment of silent myocardial ischemia (SMI). After defining the concept of SMI and total ischemia burden, the author approaches the pathophysiology of myocardial ischemia and focuses on the ischemic cascade. Concerning the detection of SMI the importance of exercise testing and Holter ECG is stressed. Following the classification of SMI proposed by P. F. Cohn, the author analyzes SMI type III with particular interest. He refers the prevalence of SMI in patients suffering from chronic stable angina, and focuses on the prognostic importance of SMI. Afterwards, the problem of treatment and prognostic implications is approached. The paper ends with mention of the results of the most important clinical trials in this field: CASIS, CAPE, TIBBS, ASIST, ACIP, TIBET.

[Coronary disease in the postmenopausal woman. The experience of an intensive care unit over 10 years]. / Doença das coronárias na mulher pós-menopáusica. Experiência de uma unidade de cuidados intensivos durante 10 anos.

OBJECTIVES: Analysis of the characteristics of acute myocardial infarction in female patients admitted to a coronary care unit during a 10 year period. DESIGN: Retrospective analysis of computerized data collected during a 10-year period in every patient with acute myocardial infarction admitted between 1986 and 1995. SETTING: A coronary care unit of a central hospital. PATIENTS AND METHODS: Data on 2439 patients were analyzed in what concerns gender, age and hospital mortality. In the restricted group of 655 patients admitted between 1993 and 1995 the prevalence of the following risk factors was assessed: arterial hypertension, dyslipidemia, smoking and diabetes mellitus. RESULTS: During a 10-year period, 1918 male (M) and 521 female (F) patients were admitted, originating a 3.5 to 1 M:F ratio. The M:F relation decreased from decade to decade from 11:1 in patients under 50 years old to 1.8:1 in patients over 70 years old. Hospital mortality was 25.9% in female patients and 12.0% in male patients (p < 0.001). Mortality was similar in males and females until 60 years of age; significant differences were found only in the seventh decade of life (25% in females vs. 12% in males, p < 0.001) and in patients over 70 years old (36% in females vs. 24% in males, p < 0.005). Hypertension was significantly move prevalent in females (66% in females vs 46% in males, p < 0.001) as well as diabetes mellitus (31% in females vs. 20% in males). Similarly, a previous history of dyslipidemia was more frequently found in females than in males, but the difference was not significant (24% vs. 19%, respectively). On the contrary, smoking was significantly less frequent in female patients (11% in female patients vs. 44% in male patients, p < 0.001). CONCLUSIONS: The probability of the occurrence of acute myocardial infarction is very low in premenopausal women. The M:F ratio decreases with aging. The risk of death progressively increases with age, and it is significantly higher in females in relation to males after the age of 60 years. Women, besides being older, have a higher prevalence of coronary artery disease risk factors, namely hypertension, diabetes mellitus and dyslipidemia.

Wall motion abnormalities and late ventricular arrhythmia during the predischarge phase of acute myocardial infarction.

BACKGROUND: Left ventricular wall aneurysm is a complication of acute myocardial infarction which has been considered a precipitating factor of cardiac failure and ventricular arrhythmia. We have evaluated the relation between severe left ventricular wall motion abnormalities and ventricular arrhythmia. METHODS: During a two-year period 146 patients admitted to a coronary care unit with acute myocardial infarction were studied. Radionuclide angiography performed within the second and the fourth weeks was used to analyse phase and wall motility changes, and patients were divided into three groups: 1) Hypokinesia and/or akinesia localized to one segment: with no or slight changes in phase image--102 patients; 2) Aneurysm: left ventricular deformity with well-defined chromatic changes in phase image--19 patients; and 3) Dyskinesia and/or extensive akinesia of two or more segments: phase image with diffuse heterogeneous changes--25 patients. Ventricular arrhythmia was studied using Holter electrocardiography taken during the second week of acute myocardial infarction. Three rhythmic profiles were considered: no premature ventricular contractions--41 patients; with three or more than three premature ventricular contractions per hour--38 patients; repetitive premature ventricular contractions--20 patients. RESULTS: Premature ventricular contractions were absent in 31 (30%) of the patients with hypokinesia/localized akinesia vs 8 (42%) of the patients with aneurysm, and vs 2 (8%) of the patients with dyskinesia/extensive akinesia. Premature ventricular contractions were frequent (> or = 3/h) in 22 (22%) of the patients with hypokinesia/localized akinesia vs 4 (21%) of the patients with aneurysm (p = 0.35; NS), and vs 12 (48%) of the patients with dyskinesia/extensive akinesia (p=0.003). Repetitive premature ventricular contractions were present in 10 (10%) of the patients with hypokinesia/localized akinesia vs 2 (11%) of the patients with aneurysm, and vs 8 (32%) of the patients with dyskinesia/extensive akinesia (p=0.008). CONCLUSIONS: We conclude that the presence of aneurysm was not associated with a higher occurrence of ventricular arrhythmia, but patients with dyskinesia/extensive akinesia had a higher occurrence of ventricular arrhythmia, > or = 3 premature ventricular contractions per hour and repetitive premature ventricular contractions. Our results suggest that ventricular arrhythmia is related to functionally severe wall motion abnormalities, and not to anatomical discriminants. This finding leads us to suggest different electrophysiological mechanisms behind these two entities.

[A case of incessant junctional tachycardia in a female patient with aneurysm of the interauricular septum]. / Um caso de taquicardia juncional incessante numa doente com aneurisma do septo interauricular.

A permanent supraventricular tachycardia (SVT) was diagnosed in a 54-year-old hypertensive but cardiologically asymptomatic female patient, admitted to a surgery department for biliary lithiasis and hepatic echinococcosis. Heart rate was about 130 bpm and ECGs showed negative P waves in leads I, II, III, aVF, and precordial leads V2 to V6, being the RP' interval longer than P'R interval. Pharmacological intervention during Holter monitoring (20 hours) was instituted: following i.v. propranolol (4 mg), heart rate progressively decreased (to 112 bpm), mainly due to an increase in SVT RP' interval, and brief, spontaneous SVT interruptions occurred, preceded by P'R interval prolongation; SVT stopped after P' recording, and resumed after 2 sinus beats, (showing enlarged P waves and slightly prolonged PR interval), induced by cycle length shortening; later on, under i.v. amiodarone infusion (100 mg/hour) and coincident with the sleeping period, SVT cycle length progressively increased (to 600 msec), due to equivalent increases in P'R and R'P intervals. Two premature ventricular contractions (PVC) occurred during Holter monitoring at a coupling interval of 80-85% of SVT cycle length (480 msec): one PVC apparently originated in left ventricle lateral wall, captured the atria, which were activated 75 msec earlier than expected; the other PVC, apparently originated in left ventricle septoapical region, did not interfere with SVT cycle length. Before these data, a diagnosis of circus movement tachycardia, incorporating a concealed accessory pathway with slow retrograde conduction and ventricular insertion in the postoroseptal or left posterior paraseptal region, and showing minor impairment of antegrade AV nodal conduction, was made. Invasive electrophysiological study was then discarded. With combined oral antiarrhythmic therapy (amiodarone, 600 mg/d), plus propafenone, 450 mg/d), sinus rhythm was permanently restored, with evidence of intraatrial block, slightly prolonged PR interval and no preexcitation. Transesophageal echocardiography revealed a small atrial septal aneurysm associated with a small atrial septal defect; echocardiographic features were consistent with the hypothesis of incomplete regression of the atrial septal aneurysm after partial closure of the atrial septal defect. Abdominal surgery (cholecystectomy plus partial hepatic pericystectomy) was performed without any complications or SVT recurrences. During a 6-month follow-up period, maintaining amiodarone (200 mg/d) and propafenone (450 mg/d), the patient remained SVT-free, and Holter monitoring performed at 3 and 5 months showed permanent sinus rhythm and 1:1 AV conduction with slightly prolonged PR interval (less than 0.29 sec and shortening at faster heart rates). This case documents Holter monitoring capability for the evaluation of tachycardia mechanisms in patients with permanent SVT.

[Rhythmic profiles of the late phase of acute myocardial infarction as a function of age]. / Perfis rítmicos da fase tardia do enfarte agudo do miocárdio em função da idade.

OBJECTIVES: To evaluate the incidence of ventricular arrhythmias in the late phase of acute myocardial infarction (AMI) and to compare it with the following clinical parameters: age, sex, AMI localization, ventricular function (Killip classes), maximal creatinokinase (CK max) and the presence of sinus tachycardia. DESIGN: Prospective study, during a period of 31 months, of a non-selected group of patients with AMI. SETTING: Coronary Care Unit (UTIC-Arsénio Cordiero). PATIENTS: Non-selected group of 153 patients with acute myocardial infarction who survived the second week of disease. MATERIAL AND METHODS: 24-hour Holter ECG performed between the 4th and the 25th day of AMI. The patients were divided into two groups according to the hourly frequency of premature ventricular beats (PVB): less than 3 per hour (PVB less than 3/h) and 3 or more per hour (PVB greater than or equal to 3/h). RESULTS: PVB greater than or equal to 3/h occurred in 36 patients (24%). There was no differences in the occurrence of ventricular arrhythmias between sex, AMI localization, AMI size evaluated by CK max, and the presence of sinus tachycardia. Patients in Killip class III had more ventricular arrhythmias (67%) than patients in Killip class I (23%) (p less than 0.005), in Killip class II (18%) (p = 0.007), and in Killip IV (0%) (p = 0.017). In patients with serious left ventricular failure (classes III + IV) the ventricular arrhythmias were not significantly higher (40%) than in patients without serious left ventricular failure (classes I + II) (22%) (chi 2 = 2.5; p less than 0.25 NS). Patients with less than 41 years old had less PVB greater than or equal to 3/h (4%) than patients between ages 41-69 (24%) (p less than 0.05), and than patients over 70 years old (47%) (p = 0.00075). CONCLUSIONS: The majority of patients (76%) showed a low risk rithmic profile (PVB less than 3/h) in the late phase of AMI. Among all parameters the age of the patients was the one best related to the occurrence of ventricular arrhythmias. Sex, AMI localization, AMI size, and the presence of sinus tachycardia were not related to the presence of PVB. A slight tendency was found in patients with heart failure to have more PVB. On the other hand the elder group carried a statistically significant risk factor for a higher occurrence of ventricular premature beats.

[Arrhythmia and sudden death in congestive heart insufficiency]. / "Arritmias e morte súbita na insuficiência cardíaca congestiva".

The author emphasizes the current reawakening of interest of clinicians and investigators in congestive heart failure (CHF) as a consequence of the known bad prognosis of this syndrome and the new diagnostic techniques and drugs they may use in patients with this syndrome. The central topic of the paper deals with the relation between arrhythmias and sudden death (SD) in patients with CHF and is subdivided in five points: 1. Prevalence of SD in patients suffering from CHF; 2. Prevalence of ventricular arrhythmias in patients with CHF; 3. Prognostic value of ventricular arrhythmias on survival in patients with CHF; 4. Effect of antidysrhythmic drugs on survival in patients suffering from CHF; and 5. Different repercussion of drug therapy on rhythmic profile of patients with CHF. The analysis of these five points is supported by a revision of the literature on this subject and leads to some final comments, in which the author tries to do the state-of-the-art of the problem of the relation between arrhythmias and SD in patients suffering from CHF.

[Holter ECG in evaluating myocardial ischemia. Validation using the exercise test]. / O ECG de Holter na avaliação da isquemia miocárdica. Validação pela prova de esforço.

OBJECTIVES: Validation of ST-T ischemic changes in the Holter system by those recorded in the 12-lead ECG during the exercise test. DESIGN: The changes induced by the exercise test in the ST segment of the two Holter leads--aVF e V5 like--were compared with the changes simultaneously registered in the 12-lead ECG. SETTING: Exercise Test Laboratory and Holter Laboratory of the UTIC-Arsénio Cordeiro. Hospital de Santa Maria de Lisboa. PATIENTS: 31 patients, 23 male and 8 female, with a mean age of 55 +/- 7 years, 84% with ischemic heart disease. METHODS: The patients underwent a treadmill exercise test. 28 with the Bruce protocol and 3 with the Naugton protocol, during which the electrocardiogram was registered simultaneously with a 2-channel Holter recorder and by a conventional 12-lead system. The changes induced in the ST segment in the two systems were compared. RESULTS: The results of the two tests were concordant in 94% of the patients. In 4 patients (13%) there was not a good correlation between the inferior and anterior leads of the two methods, which diverged mainly between the Holter lead aVF and the inferior leads of the conventional ECG. The morphology of the ST depression was similar in both methods, and the severity of ST depression as judged by its amplitude showed an excellent positive linear correlation (r = 0.8542, p less than 0.001). CONCLUSIONS: The sensitivity and the specificity of the Holter system is similar to the conventional 12-lead ECG in detecting ischemic changes during exercise whenever they have electrocardiographic evidence.

[2 cases of acute myocardial infarct complicated by fatal pulmonary embolism]. / Dois casos de enfarte agudo do miocárdio complicados por embolismo pulmonar fatal.

Two cases of pulmonary embolism with lethal course in the setting of acute myocardial infarction are presented. Both cases are clinically characterized by a late pulmonary embolism occurrence (2nd and 3rd week, respectively), and the presence of a large infarct, heart failure during acute myocardial infarction evolution and the interruption of anticoagulant therapy due to a complication. From the anatomic point of view, both cases had large hearts and very large biventricular infarctions. On the other hand, deep venous plexus constituted the pulmonary embolism origin in one case, and right ventricular thrombosis in the other.

[Comparison of Holter electrocardiography and thallium 201 scintigraphy in the detection of myocardial ischemia]. / Comparação entre a electrocardiografia de Holter e a cintigrafia com tálio 201 na detecção de isquemia miocárdica.

OBJECTIVE OF THE STUDY: To compare ischemic changes (I) detected by Holter ECG (H ECG) to the myocardial perfusion defects found in 201 TI myocardial perfusion scintigraphy. DESIGN: 201 TI exercise test was made during the performance of a 24 hours H ECG. The validation of ST segment changes detected by H ECG during the exercise test was made on basis of reversible myocardial perfusion defects (RPD) detected on 201 TL and a relation between ST segment changes detected during the remaining 24 hours recording period and 201 TI (TI) RPD was established. SETTING: The patients (pt) included in the study have come from Cardiology and Heart Surgery Clinics of a Central teaching hospital. MATERIAL AND METHODS: 20 pt with a high coronary artery disease prevalence have been submitted to a two lead (V5 and aVF) 24 hour H ECG during which they have performed a symptom limited bicycle exercise test followed by an injection of 201 TI with acquisition 5 minutes later. Ischemic episodes detected on H ECG were quantified and their relation with heart rate and symptoms was established. As far as 201 TI studies are concerned the fixed and reversible perfusion defects as well as their location were evaluated. RESULTS: 1. H ECG: 6 pt (30%) presented ST changes on H ECG during the exercise test and a total of 9 pt (45%) had ST changes during exercise and during the remaining period of H ECG. 2. TI: 19 pt presented perfusion defects images (fixed in 7, reversible in 14, both kinds of defects in 7). 3. H ECG validation: H ECG during exercise presented I in 6 out of 14 pt with RPD on TI (sensitivity = 43%). Six of these 8 pt, with negative H and positive TI, had a chronic myocardial infarction. All the 6 pt with negative TI had negative H ECG (specificity = 100%). 4. H ECG TI comparison: 7 (50%) of the 14 pt with RPD had ST changes on 24 hrs H ECG. Seven of 11 pt with negative H ECG had RPD in TI. Two pt with negative TI had positive H ECG. These 2 pt had during H ECG a higher heart rate (HR) than the HR recorded during the exercise test. CONCLUSIONS: 1. In pt with known CAD, TI has a high sensitivity and specificity to show perfusion defects. 2. Considering TI as gold standard, H ECG showed to be a useful method to detect I in the studied population (sens. = 43%; spec. = 100%). 3. H ECG revealed to be an important diagnostic tool in detecting additional I episodes beyond the ones recorded during TI exercise test.