CYP2C9 genotypes and the quality of anticoagulation control with warfarin therapy among Brazilian patients.

OBJECTIVE: To evaluate the impact of the two most common CYP2C9 variant alleles (*2 and *3) on the maintenance dose of warfarin and on the quality of anticoagulation control in Brazilians. METHODS: Patients (n = 103) initiated warfarin therapy with 5 mg/day (or 2.5 mg/day when over 80 years old). The international normalized ratio (INR) was targeted between 2 and 3, monitored every week until four consecutive adequate measures had been obtained, and then monthly. Serious hemorrhagic events were defined by the need for inpatient hospitalization. CYP2C9 genotyping was obtained by PCR-RFLP. RESULTS: The frequencies of CYP2C9*2 and CYP2C9*3 were 0.097 and 0.073, respectively, with genotypic distribution fitting Hardy-Weinberg equilibrium. CYP2C9 genotype was the only clinical feature associated with the risk of severe bleeding (one-sided P = 0.019, Fisher exact method), with an odds ratio of 4.8 (95% confidence interval of 1.4-16.6) for any variant genotype as compared to CYP2C9*1*1. Patients with either CYP2C9*2 or CYP2C9*3 were equally difficult to maintain in the INR target range, showing significantly (one-sided P = 0.038, Mann-Whitney U-test) reduced ratio of adequate INR measures (0.54 +/- 0.2), when compared to CYP2C9*1*1 patients (0.63 +/- 0.2). Patients with CYP2C9*3, but not CYP2C9*2, required significantly (one-sided P = 0.001, Mann-Whitney U-test) lower warfarin maintenance doses (3.1 +/- 1.8 mg) than CYP2C9*1*1 patients (5.3 +/- 2.1 mg). CONCLUSION: Patients with either CYP2C9*2 or CYP2C9*3 show higher risk of over-anticoagulation compared to CYP2C9*1*1 subjects and could benefit from a reduction in the initial warfarin standard dose (e.g., to 2.5 mg/day).

Use of propranolol in heart failure patients: safety, tolerability, and effects on left ventricular function.

INTRODUCTION AND OBJECTIVES: Beta-blockers have been shown to improve prognosis in patients with heart failure (HF). Propranolol, which is a low-cost drug, has not been fully studied in this setting. We sought to determine the safety, tolerability and effects on left ventricular function observed with the use of propranolol in HF patients, in functional class II-IV of the New York Heart Association. POPULATION AND METHODS: Prospective study in which 20 outpatients (10 male, mean age 56 +/- 12 years, ranging from 20 to 70) were included. Mean left ventricular ejection fraction (EF) was 28%. Safety, tolerability and effects on electrocardiographic and echocardiographic variables were analyzed. Patients were evaluated in three steps: a) Step I--optimization on conventional drugs and assessment of baseline parameters; b) Step II--start of propranolol (10-20 mg/day), increasing the dose weekly to achieve a heart rate of 60 bpm, or a maximum daily dose of 120 mg; c) Step III--reappraisal of the parameters analyzed in step I, after 3 months of propranolol treatment. RESULTS: On average, after treatment with propranolol, EF increased by 52% (p = 0.0003), E wave deceleration time was prolonged by 62% (p = 0.001) and effective ventricular filling time increased by 38.5% (p = 0.0005). Two patients developed mild congestion which was controlled by increasing diuretic doses, with no need to interrupt the protocol. Four patients had bradycardia-related symptoms, controlled by reducing digoxin doses. Nine subjects developed hyperkalemia, reversed by interrupting or reducing spironolactone. CONCLUSION: Propranolol was safe and well tolerated, and had beneficial effects on ventricular function in HF patients. Its impact on mortality requires further study.

Cholinergic stimulation with pyridostigmine, hemodynamic and echocardiographic analysis in healthy subjects.

OBJECTIVE: Growing evidence suggests that sudden death after an acute myocardial infarction (AMI) correlates with autonomic nervous system imbalance. Parasympathomimetic drugs have been tested to reverse these changes. However, their effects on ventricular function need specific evaluation. Our objective was to analyze pyridostigmine's (PYR) effect on hemodynamic and echocardiographic variables of ventricular function. METHODS: Twenty healthy volunteers underwent Doppler echocardiographic evaluations, blood pressure (BP), and heart rate (HR) assessment at rest, before and 120 min after ingestion of 30 mg PYR or placebo, according to a double-blind, placebo-controlled, crossed and randomized protocol, on different days. RESULTS: PYR was well tolerated and did not cause alterations in BP or in ventricular systolic function. A reduction in HR of 10.9 +/- 1.3% occurred (p < 0.00001). There was an A wave reduction in the mitral flow (p < 0.01) and an E/A ratio increase (p < 0.001) without changes in the other diastolic function parameters (p > 0.05). CONCLUSION: PYR reduces HR and increases E/A ratio, without hemodynamic impairment or ventricular function change.

Doppler echocardiographic study in adolescents and young adults with sickle cell anemia.

OBJECTIVE: Anatomical and functional assessment of the heart through Doppler and echocardiography in patients with cell anemia (SCA). METHODS: Twenty-five patients with SCA and ages ranging from 14 to 45 years were prospectively studied in a comparison with 25 healthy volunteers. All of them underwent clinical and laboratory evaluation and Doppler echocardiography as well. The measurements were converted into body surface indices. RESULTS: There were increases in all chamber diameters and left ventricle (LV) mass of the SCA patients. It was characterised an eccentric hypertrophy of the left ventricle. The preload was increased (left ventricle end-diastolic volume) and the afterload was decreased (diastolic blood pressure, peripheral vascular resistance and end-systolic parietal stress ESPS). The cardiac index was increased due to the stroke volume. The ejection fraction and the percentage of the systolic shortening, as well as the systolic time intervals of the LV were equivalent. The isovolumetric contraction period of the LV was increased. The mitral E-septum distance and the end-systolic volume index (ESVi) were increased. The ESPS/ESVi ratio,a loading independent parameter, was decreased in SCA, suggesting systolic dysfunction. No significant differences in the diastolic function or in the pulmonary pressure occurred. CONCLUSION: Chamber dilations, eccentric hypertrophy and systolic dysfunction confirm the evidence of the literature in characterizing a sickle cell anemia cardiomyopathy.

Fatal pulmonary embolism in hospitalized patients. Clinical diagnosis versus pathological confirmation.

OBJECTIVE: To assess the incidence of fatal pulmonary embolism (FPE), the accuracy of clinical diagnosis, and the profile of patients who suffered an FPE in a tertiary University Hospital. METHODS: Analysis of the records of 3,890 autopsies performed at the Department of General Pathology from January 1980 to December 1990. RESULTS: Among the 3,980 autopsies, 109 were cases of clinically suspected FPE; of these, 28 cases of FPE were confirmed. FPE accounted for 114 deaths, with clinical suspicion in 28 cases. The incidence of FPE was 2.86%. No difference in sex distribution was noted. Patients in the 6th decade of life were most affected. The following conditions-were more commonly related to FPE: neoplasias (20%) and heart failure (18.5%). The conditions most commonly misdiagnosed as FPE were pulmonary edema (16%), pneumonia (15%) and myocardial infarction (10%). The clinical diagnosis of FPE showed a sensitivity of 25.6%, a specificity of 97.9%, and an accuracy of 95.6%. CONCLUSION: The diagnosis of pulmonary embolism made on clinical grounds still has considerable limitations.

Effects of propranolol on the QT dispersion in congestive heart failure.

OBJECTIVE: Studies have shown that therapy with beta-blockers reduces mortality in patients with heart failure. However, there are no studies describing the effects of propranolol on the QT dispersion in this population. The objective of this study was to assess the electrophysiological profile, mainly QT dispersion, of patients with heart failure regularly using propranolol. METHODS: Fifteen patients with heart failure and using propranolol were assessed over a period of 12 months. Twelve-lead electrocardiograms (ECG) were recorded prior to the onset of beta-blocker therapy and after 3 months of drug use. RESULTS: A significant reduction in heart rate, in QT dispersion and in QTc dispersion was observed, as was also an increase in the PR interval and in the QT interval, after the use of propranolol in an average dosage of 100 mg/day. CONCLUSION: Reduction in QT dispersion in patients with heart failure using propranolol may explain the reduction in the risk of sudden cardiac death with beta-blocker therapy, in this specific group of patients.

Doppler echocardiographic evaluation of HIV-positive patients in different stages of the disease.

OBJECTIVE: To evaluate by Doppler echocardiography (DE) early abnormalities of ventricular function in HIV-positive patients, as well as other cardiac abnormalities that can be detected by this method, with special emphasis on mitral valve flow. METHODS: 84 HIV-positive patients, 59 with CD4 cell count > 500/mm3 (Group A) and 25 with CD4 cell count < 500/mm3 (Group B), were analyzed. CD4 cells were counted and matched with structural data and systolic and diastolic function of the left ventricle (LV), as analyzed by DE. The results were compared with those obtained in 47 healthy individuals (Group C). RESULTS: 8% of patients in Group B had mild pericardial effusion; 31.5% showed decreased systolic function of the LV, and 12% had moderate mitral regurgitation. A wave velocity from the mitral inflow was different among the 3 groups, being higher in Group B, where the deceleration time of the E wave of the mitral inflow and the E/A ratio were significantly lower with a normal value of the isovolumic relaxation time (IVRT). CONCLUSION: HIV-positive patients with a CD4 cell count > 500/mm3 had no abnormalities by DE. Patients with a more advanced infection (those with a CD4 cell count < 500/mm3), had a significantly abnormal LV systolic function and a higher incidence of pericardial effusion and mitral regurgitation. Mitral valve inflow by Doppler did not indicate diastolic dysfunction.

[Hospital outcome and short-term follow-up of elderly patients presenting to the emergency unit with congestive heart failure]. / Evolução intra-hospitalar e seguimento pós-alta de pacientes idosos atendidos com insuficiência cardíaca congestiva na unidade de emergência.

PURPOSE: To evaluate the in-hospital (IH) outcome and the short-term follow-up of predominantly elderly patients presenting to an emergency room (ER) with congestive heart failure (CHF). METHODS: In an 11 month period, 57 patients presenting to the ER with CHF were included. Mean age was 69 +/- 15 years (27 to 94) and 39 (68.4%) were male. CHF diagnosis was based on the Boston criteria. We evaluated IH outcome and prognosis in a mean follow-up of 5.7 +/- 2.7 months (1 to 12). In addition, some mortality predictors and mechanisms of death according on the ACME system were identified. RESULTS: Eight patients (14%) died in the IH period. Modes of death were circulatory failure (CF) in 7, and peri-operative (PO) in one (aortic valve replacement). During follow-up 9 deaths occurred. Five were due to CF, 2 were sudden and 2 were PO (mitral valve replacement and ventriculectomy). Six-months and 1-year survival rates of the patients who were discharged were 82% and 66%, respectively. Sodium lower than 135 mEq/l (p = 0.004) and female gender (p = 0.038) were independent predictors of mortality. CONCLUSION: Elderly patients with CHF admitted to the ER have high in-hospital and short-term follow up mortalities. The majority die from CF due to worsening heart failure.

Evoluçäo intra-hospitalar e seguimento pós-alta de pacientes idosos atendidos com insuficiência cardíaca congestiva na unidade de emergência / Hospital outcome and short-term follow-up of predominatly elderly patients presenting to the emergency department with congestive heart failure

OBJETIVO - Conhecer a evoluçäo intra-hospitalar (IH) e pós-alta (PA) de uma populaçäo predominantemente idosa, com insuficiência cardíaca congestiva (ICC) na unidade de emergência (UE). MÉTODOS - Durante 11 meses, foram selecionados 57 pacientes consecutivos com ICC, atendidos em UE, com idade média de 69ñ15 (27 a 94) anos, sendo 39 (68,4 por cento) homens. O diagnóstico de ICC baseou-se nos critérios de Boston. Avaliou-se a evoluçäo IH e PA num período médio de 5,7ñ2,7 (1 A 12) meses, procurando-se identificar variáveis que se correlacionassem com a mortalidade e o mecanismo de morte, avaliado pelo sistema ACME. RESULTADOS - Oito (14 por cento) pacientes faleceram na fase IH, sendo 7 por falência circulatória (FC), e 1 em pós-operatório (PO). Durante o seguimento ocorreram 9 (18,4 por cento) óbitos, sendo 5 por FC, 2 mortes súbitas e 2 em (troca valvar mitral e ventriculectomia). A sobrevida dos pacientes...

[Rheumatic heart disease and infective endocarditis in a patient with acquired immunodeficiency syndrome]. / Cardiopatia reumática e endocardite infecciosa em paciente com síndrome de imunodeficiência adquirida.

A 36-old-woman was admitted with an infectious syndrome, respiratory insufficiency and vasculitis. There was a history of chronic intravenous drug abuse, sexual promiscuity and rheumatic heart disease. She had HIV positive tests. The vasculitis and heart failure worsened and the patient died of stroke. At autopsy it was found histologic evidence of AIDS, rheumatic heart disease with Aschoff nodes, infective endocarditis with cerebral abscesses and thalamic infarction.

Maximal functional capacity in patients with endomyocardial fibrosis.

We evaluated objectively the cardiocirculatory dysfunction of patients with EMF, and related the functional class (FC-NYHA) to the data obtained by analysis of maximal functional capacity. We studied 55 subjects, divided into three groups: group 1 (G1) 21 (38.1%) normal persons, group 2 (G2) seven (12.7%) patients with EMF who were in FC I or II, and group 3 (G3) 27 (49%) patients in FC III or IV. Maximal oxygen consumption (VO2max) and O2 pulse index (PO2max) were obtained using a Beckman computerized gas analyser. The mean values were significantly different among the three groups. We conclude that the greater the clinical impairment, the greater the alterations that occur in the indices of cardiac function.

[Polymorphic ventricular tachycardia. Analysis of the onset of the episodes]. / Taquicardia ventricular polimórfica. Análise do início dos surtos.

PURPOSE: To analyze the spontaneous onset of events for polymorphous ventricular tachycardia, to determine the importance of this parameter in the clinical and electrophysiologic context. METHODS: We evaluated 124 modes of onset of polymorphous ventricular tachycardias recorded by 24 hr of continuous ECG monitoring in 6 patients. Four patients were using quinidine and diuretics, and two patients only diuretics. We determined the two preceding cycle in milliseconds from the initiating events and also the induced cycle (cycles A, B and C). Careful analyses of T and U waves alternans and QT ou QTU intervals inside and outside the episodes of tachycardia. RESULTS: In 105 episodes (84%) the events were pause-dependent; in 12 episodes (10%) they occurred without pauses but after a ventricular fusion and in 7 episodes (6%) also without pauses but with sudden cycle (C) shortening (R on T phenomena). The pause-dependent episodes were only seen in patients using quinidine with the association of diuretics and non-pause related episodes were registered in patients using diuretics. All patients had prolonged QTU intervals outside the episodes. There were a linear correlation (r = 0.865) between the amplitude of the U waves of the cycles C and duration of cycles A and B, in pause-dependent episodes. CONCLUSION: The contribution of this study is that: the analyses of the spontaneous onset of polymorphous ventricular tachycardia can allow the differentiation of typic forms of torsades des de pointes (pause-dependent) and other atipic forms. The former type occurred probably as a result of EADs provoking triggered rhythms. The latter could be better explained as polymorphous ventricular tachycardia due to reentry mechanisms or enhanced automatic focus. Only the tipic forms should be acutely benefited with regularization of cardiac cycles with cardiac pacing.