Conjugated equine estrogen, raloxifene and arterial stiffness in postmenopausal women.

METHODS: We analyzed the influence of conjugated equine estrogen (CEE) and raloxifene on arterial stiffness. Sixty-seven healthy, normotensive women 1-10 years into menopause were assigned to receive oral placebo, conjugated equine estrogen 0.625 mg, or raloxifene 60 mg. Arterial stiffness was evaluated by measuring the carotid-femoral and femoral-dorsalis pedis pulse wave velocity (CF PWV, FP PWV). Systolic pressure augmentation index (AI) at the carotid artery was obtained with applanation tonometry. RESULTS: Arterial stiffness was not affected by any treatment regimen: placebo (CF PWV before vs. after: 644 vs. 626 cm/s, p = 0.09; FP PWV before vs. after: 1006 vs. 1012 cm/s,p = 0.77; AI before vs. after = 30 vs. 29%, p = 0.55), CEE (CF PWV before vs. after: 642 vs. 600 cm/s, p = 0.11; FP PWV before vs. after: 952 vs. 971 cm/s, p = 0.66; AI before vs. after: 25 vs. 32%, p = 0.82), and raloxifene (CF PWV before vs. after: 636 vs. 601 cm/s, p = 0.12; FP PWV before vs. after: 964 vs. 941 cm/s, p = 0.62; AI before vs. after: 25 vs. 25%, p = 0.65). A correlation occurred between basal stiffness and the degree of reduction in indexes measured, indicating that the higher the basal stiffness, the greater the degree of reduction, particularly in the CEE group: CF PWV (r = - 0.602, p = 0.001); FP PWV (r = - 0.455, p = 0.022); AI (r = - 0.410, p = 0.042). CONCLUSIONS: Conjugated equine estrogen and raloxifene do not seem to affect arterial stiffness of healthy normotensive women less than 10 years since menopause. Reduction in arterial stiffness seems related to its basal level.

Effects of conjugated equine estrogens or raloxifene on lipid profile, coagulation and fibrinolysis factors in postmenopausal women.

OBJECTIVES: To compare the effect of conjugated equine estrogens (CEE) and raloxifene on lipid profile and hemostasis. MATERIALS AND METHODS: A double-blind, randomized and parallel study was performed with 90 healthy postmenopausal women, aged 54 +/- 5 years, divided into three groups and submitted to daily therapy with either CEE 0.625 mg, raloxifene 60 mg or placebo for 4 months. The lipid profile, coagulation and fibrinolytic factors were analyzed. RESULTS: CEE increased the levels of high density lipoprotein cholesterol (HDL-C) from 49.0 to 56.8 mg/dl (p < 0.001), very low density lipoprotein cholesterol (VLDL-C) from 17.2 to 22.3 mg/dl (p < 0.001), and triglycerides from 86.0 to 111.7 mg/dl (p < 0.001), and decreased the levels of low density lipoprotein cholesterol (LDL-C) from 121.0 to 106.5 mg/dl (p < 0.001). The only significant effect of raloxifene was an increase in the levels of HDL-C from 46.0 to 47.8 mg/dl (p = 0.019). There was no significant reduction in LDL-C, from 115.5 to 110.2 mg/dl (p = 0.06), VLDL-C, from 21.7 to 20.0 mg/dl (p = 0.201), and triglycerides, from 108 to 100 mg/dl (p = 0.201). CEE decreased the levels of fibrinogen, from 370.5 to 326.8 g/l (p = 0.039) and the levels of antithrombin III, from 99.5 to 93.2% (p < 0.001). Raloxifene decreased the levels of fibrinogen, from 354.7 to 302.0 g/l (p = 0.009) and the levels of antithrombin III, from 102.4 to 98.5% (p = 0.039). CEE increased levels of protein C from 103.7 to 115.3 mg/l (p < 0.001) and raloxifene did not change the levels of protein C (107.9 to 105.1 mg/l; p = 0.158). CEE decreased the antigen levels of tissue plasminogen activator (t-PA) from 8.8 to 6.8 U/ml (p < 0.001), and of plasminogen activator inhibitor (PAI-1) from 30.8 to 21.6 U/ml (p < 0.010), whereas raloxifene had no significant effect on either t-PA, from 9.6 to 9.2 U/ml (p = 0.235) or PAI-1 antigen levels, from 32.1 to 30.4 U/ml (p = 0.538). CONCLUSION Both CEE and raloxifene exert significant effects on the lipid and coagulation profile. CEE had a more significant effect on fibrinolysis than raloxifene. These effects may have a significant impact on the cardiovascular risk that needs to be confirmed in larger studies.

Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease.

OBJECTIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6+/-4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5+/-3.8) and diltiazem (3.2+/-4.2) when compared with placebo (7.9+/-8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2+/-31.9min; diltiazem: 19.3+/-29.6min; placebo: 46.1+/-55.3min; p<0.05). CONCLUSION: In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.

Clinical predictors of prognosis in severe aortic stenosis in unoperated patients > or = 75 years of age.

In elderly patients with severe aortic stenosis, clinical evaluation can dictate decision making. Asymptomatic patients in normal sinus rhythm, without left atrial enlargement and without bundle branch block, can be safely followed clinically, regardless of echocardiographic findings.

Hemodynamic effects of unloading the old heart.

A reduction in upright exercise capacity with aging in healthy individuals is accompanied by acute left ventricular (LV) dilatation and impaired LV ejection. To determine whether acute vasodilator administration would improve LV ejection during exercise, sodium nitroprusside (NP) was administered to 16 healthy subjects, ages 64-84 yr, who had been screened for the absence of coronary heart disease by prior exercise thallium scintigraphy. Infusion of NP (0. 3-1.0 microgram. kg(-1). min(-1)), titrated to reduce the resting mean arterial pressure 10% (and eliminate the late augmentation of carotid arterial pressure), increased LV ejection fraction (EF) compared with placebo during upright, maximal graded cycle exercise at all work rates and permitted an equivalent stroke volume and stroke work from a smaller end-diastolic volume. The maximum increase in exercise EF in older subjects during NP infusion was equal to that in healthy, younger (22-39 yr) control subjects. The maximum cycle work rate and cardiac index were unchanged compared with placebo. Thus combined preload and afterload reduction with NP in older individuals improves overall LV ejection phase function: exercise LV stroke work is reduced, EF is increased, and stroke volume is maintained in the setting of a reduced ventricular size. These findings suggest that at least some of the age-associated decline in cardiac function during maximal aerobic exercise may be secondary to adverse loading conditions.

Atrial fibrillation in endomyocardial fibrosis is a marker of worse prognosis.

We studied the incidence of AF in patients with endomyocardial fibrosis (EMF) and its influence on prognosis and associated clinical events. One hundred and sixty consecutive patients with EMF were followed for a mean period of 4 years. Their mean age was 39.7 years. There were 114 women. During follow-up there were 56 deaths. Eighty-eight patients (55%) were submitted to surgical intervention. AF was observed in 58 cases (36.2%). The presence of AF was associated with a greater prevalence of dyspnea, peripheral edema, hepatomegaly, lower left ventricular ejection fraction, lower right ventricular systolic pressure (37.8 vs 45.6 mmHg, P=0.0392), and greater incidence of tricuspid regurgitation (86.0 vs 63.2%, P=0.004). AF was more frequent among patients in whom the disease involved the right ventricle, particularly those with intense fibrosis. Overall, patients with AF had a higher mortality rate than those who did not have AF (43.1 vs 30.3%, P=0.0195), but among those submitted to surgery, AF did not have an impact on survival. In conclusion, AF is frequent among patients with EMF. It is more prevalent among patients with right ventricular involvement and its presence is associated with a greater incidence of heart failure. AF is associated with worse prognosis, but surgery potentially reverses this bad evolution.

Tratamento medicamentoso da insuficiência cardíaca em hospital terciário de Säo Paulo / Heart failure medical treatment in a tertiary hospital of Säo Paulo

OBJETIVO - Verificar como são tratados pacientes com insuficiência cardíaca (IC) em hospital terciário de Säo Paulo. MÉTODOS - Analisados 100 pacientes com IC, em tratamento ambulatorial, com idade média de 56,8 anos, sendo 76 homens. Todos realizaram estudo ecocardiográfico, que identificou diâmetros ventriculares entre 48 e 89mm (média 65,9) e fraçäo de ejeçäo (FE) entre 0,22 e 0,59 (média 0,43). A etiologia da disfunçäo ventricular (DV) foi isquêmica em 42 casos, cardiomiopatia dilatada em 28, secundária à valvopatia em 12, doença de Chagas em 10 e cardiomiopatia hipertensiva em 8. Analisou-se a terapêutica prescrita, se continha inibidores da enzima conversora de angiotensina (IECA) e qual a sua dosagem. Foi analisado, também, se a etiologia ou o grau de DV tinha influência na prescrita. RESULTADOS - Oitenta e sete pacientes receberam IECA, sendo que em 31 a dose foi inferior à preconizada nos grandes estudos. Digoxina foi prescrita em 69 casos, diuréticos em 85 e ácido acetilsalicílico em 33. Dividindo os pacientes os pacientes em dois grupos, com FE maior e menor que 0,45, observamos que, no último, foi maior a prescrição de IECA (91,5 'por cento' vs 80,4 'por cento') e maior o uso de doses adequadas (61 'por cento' vs 48,7 'por cento'). CONCLUSÄO - A maioria dos pacientes foi tratada conforme recomendaçöes atuais, apresentando boa tolerabilidade para IECA, contudo 1/3 deles não usou IECA em dose considerada adequada. Esquemas terapêuticos com betabloqueadores e inibidores da angiotensina II não fizeram parte da prática clínica rotineira.

[Cardiac amyloidosis. A disease with many faces and different prognosis]. / Amilóidose cardíaca. Uma doença de muitas faces e diferentes prognósticos.

PURPOSE: To identify the principal forms of cardiac amiloydosis presentation in a terciary hospital. METHODS: Eight cases with cardiac amyloidosis were identified. Five were women, their ages ranged from 23 to 83 years (mean 62). After a medical history and clinical examination the patients were submitted to complementary tests: electrocardiogram (EKG), echocardiogram (ECHO), scintigraphy with technecium pirophosphate and cardiac biopsy these results allowed the identification of their clinical situation. RESULTS: Seven patients referred dyspnea, 6 were in heart failure, 1 patient had syncope. The EKG identified complete atrioventricular (AV) block in 4 patients, and antero septal inactive area in the other 4. The ECHO showed normal cardiac diameter in all (mean left ventricular diastolic diameter of 46.8) and slight reduction of left ventricular ejection fraction; hypertrophy of the left ventricular septal and posterior walls in all cases, in 7 cases there was a hyper refractile granular sparkling ECHO. Two different groups were identified: one with complete AV block and the second with restrictive cardiomyopathy. The prognosis was different in these two groups. Those with complete AV block evolved better after pacemaker implantation and those with restrictive cardiomyopathy had refractory heart failure and 3 of them died. CONCLUSION: The increased free wall and septal thickness, the slight systolic dysfunction and the infiltration aspect at ECHO allow us to identify the great majority of the cases. Those patients with restrictive cardiomyopathy evolve with refractory heart failure and most of them die in a few months.

Amilóidose cardíaca. Uma doença de muitas faces e diferentes prognósticos / Cardiac amyloidosis. A disease with many faces and different prognoses

OBJETIVO - Avaliar as formas de apresentaçäo da amilóidose cardíaca em hospital terciário. MÉTODOS - Nos últimos 15 anos, foram identificados 8 pacientes com amilóidose, sendo 5 mulheres, com idades entre 23 e 83 (média 62) anos. Após anamnese e exame físico foram submetidos a eletrocardiograma (ECG), ecocardiograma (ECO), estudo com pirosfofato de tecnécio e biópsia endomiocárdica, cujos resultados permitiram caracterizar suas formas clínicas. RESULTADOS - Sete pacientes apresentavam dispnéia aos esforços, 6 quadro de insuficiência cardíaca congestiva (ICC), 1 síncopes. O ECG identificou bloqueio atrioventricular total (BAVT) em 4 casos e área eletricamente inativa ântero-septal em outros 4. O ECG mostrou diâmetros normais em todos e fraçäo de ejeçÝo discretamente reduzida em 6. Hipertrofia do septo e parede posterior em todos, sendo em 7 com aspecto sugestivo de doença de depósito (aspecto granuloso). Os dados clínicos caracterizam dois grupos. um com BAVT e outro com cardiomiopatia restritiva. A evoluçäo foi difrente com melhora clínica após o implante de marcapasso no primeiro grupo e má evoluçäo no grupo com cardiomiopatia restritiva que evoluiu de maneira refratária, 3 falecendo em menos de 6 meses após diagnóstico. CONCLUSÄO - A presença de aumento da espessura das paredes ao ECO, discreta disfunçäo sistólica e aspecto de doença de depósito identifiram a quase totalidade dos casos. Cardiomiopatia restritiva e distúrbio de conduçÝo foram as formas de apresentaçäo, sendo o prognóstico muito reservado nos pacientes com forma restritiva, evoluindo para ICC refratária

[Medical treatment of heart failure at a tertiary hospital of São Paulo]. / Tratamento medicamentoso da insuficiência cardíaca em hospital terciário de São Paulo.

PURPOSE: To study how patients with heart failure (HF) are treated in a tertiary hospital in São Paulo. METHODS: One hundred patients with HF during ambulatory care were analyzed. Seventy-six were men, and the average population age was 56.8 years old. All patients were submitted to echocardiogram, which identified ventricular diameters ranging between 48 and 89 mm (average 65.9) and ejection fraction (EF) between 0.22 and 0.59 (average 0.43). The cause of HF was ischemic in 42 cases, dilated cardiomyopathy in 28, valvular heart disease in 12, Chagas' disease in 10 and systemic hypertension in 8 patients. The prescribed treatment was analyzed, with attention to the prescription and dosage of angiotensin converting enzyme (ACE) inhibitors. We also analyzed whether the cause and/or the degree of HF influenced the treatment chosen. RESULTS: Eighty-seven patients received ACE inhibitors, 31 received doses below those recommended in the large trials. Digoxin was prescribed in 69 cases, diuretics in 85, and aspirin in 33. When dividing the patients according to EF, the group with EF below 0.45 was prescribed more often ACE inhibitors (91.5% vs 80.4%) and had more often usage of adequate doses (61% vs 48.7%). CONCLUSION: In this sample the majority of the patients were treated according to modern recommendations and tolerated well ACE inhibitors, however 1/3 did not receive ACE inhibitors in the recommended doses. Treatment based on betablockers or angiotensin II inhibitors were not routinely employed.

[Risk factors in elderly patients selected by primary care physicians for hypolipemic treatment]. / Fatores de risco em pacientes idosos selecionados por médicos da comunidade para tratamento hipolipemiante.

PURPOSE: To evaluate the influence of age on response to pravastatin treatment in patients treated by community physicians. METHODS: According to age, 873 patients were divided in three groups: group A with ages ranging from 45 to 59 years (n = 55), group B with ages from 60 to 64 years (n = 182) and group C with ages from 65 to 70 years (n = 143). After four weeks only with diet orientation, patients received 10 mg/day of pravastatin for 12 weeks. RESULTS: There was a greater prevalence of risk factors in elderly patients: hypertension (45.7%, 54.4% and 57.1% in groups A, B and C respectively p = 0.0165), diabetes mellitus (9.3%, 17.6% and 25.8% respectively in groups A, B and C p < 0.0001), and previous heart disease (23.1%, 34.3% and 34.7% in groups A, B and C respectively p < 0.001). During the period of diet orientation there was a similar total cholesterol reduction in the three groups (about 10.5%), the reduction reached 30.0% with the introduction of pravastatin for 12 weeks. Low density cholesterol level decreased during the diet period in the three groups (about 10.5%), pravastatin prescription induced further reduction (about 31.7%). The high density cholesterol level (HDL) increased significantly with pravastatin treatment (12.7%). After pravastatin treatment the increase in HDL levels was more significantly among those patients with initial low levels of HDL (< 35 mg/dL) in the three groups. CONCLUSION: In patients selected by community physicians to receive lipid lowering therapy, increased age was associated with greater prevalence of risk factors and heart disease. Regardless of age, there was a good response to pravastatin treatment, however less than half of patients had received treatment prior to the protocol.

Validation of carotid artery tonometry as a means of estimating augmentation index of ascending aortic pressure.

Our objective was to validate a carotid artery tonometry-derived augmentation index as a means to estimate augmentation index (AI) of ascending aortic pressure under various physiological conditions. A total of 66 patients (50 men, 16 women; mean age, 55 years; range, 21 to 78 years; 44 in Taiwan and 22 in the United States) undergoing diagnostic catheterization were studied. Arterial pressure contours were obtained simultaneously from the right common carotid artery by applanation tonometry with an external micromanometer-tipped probe and from the ascending aorta by a micromanometer-tipped catheter at baseline (n = 62), after handgrip (n = 36), or after sublingual nitroglycerin administration (n = 17). The AI (expressed as percentage values) was calculated as the ratio of amplitude of the pressure wave above its systolic shoulder to the total pulse pressure. The carotid AI was consistently lower than the aortic AI, but the two were highly correlated at baseline and after both handgrip and nitroglycerin. Mean +/- SD and correlation coefficients were baseline (14 +/- 16, 28(+) +/- 17, .77), handgrip (18 +/- 19, 32(+) +/- 15, .86), and nitroglycerin (7 +/- 12, 18(+) +/- 13, .52). In addition, after adjusting for age, sex, height, blood pressure, heart rate, and study site, the changes of both AIs from baseline values with handgrip or nitroglycerin were highly associated such that the aortic AI could be approximated from the carotid AI with appropriate regression equations. The high correlations and predictable changes after interventions between the central AI and those estimated from noninvasive carotid tonometry suggest that this technique may have wide applicability for many cardiovascular studies.

Mechanism of adenosine-induced elevation of pulmonary capillary wedge pressure in humans.

BACKGROUND: Continuous intravenous administration of adenosine to humans often results in a paradoxical rise in pulmonary capillary wedge pressure (PCWP), whereas arterial resistance is lowered and cardiac output and heart rate increase. This is believed to be due to diastolic stiffening of the ventricle or to a negative inotropic effect. In the present study, we tested these and other mechanisms by using pressure-volume (PV) analysis and echocardiography. METHODS AND RESULTS: Fifteen patients with normal rest left ventricular function underwent cardiac catheterization and received adenosine at a rate of 140 micrograms/kg per minute IV for 6 to 10 minutes. PV relations were measured in 9 patients (without coronary artery disease) using the conductance catheter method. In 6 additional patients with coronary artery disease, echocardiograms were used to assess wall thickness and function, and aortic and coronary sinus blood, lactate, oxygen, and adenosine levels were measured. Adenosine increased PCWP by 19% (+2.6 mm Hg) in both patient groups while lowering arterial load by 30% and increasing cardiac output by 45% (all P < .001). There was no significant effect of adenosine on mean linear chamber compliance or monoexponential elastic stiffness, as the diastolic PV relation was unchanged in most patients. Diastolic wall thickness also was unaltered. Thus, the PCWP rise did not appear to be due to diastolic stiffening. Adenosine induced a rightward shift of the end-systolic PV relation (ESPVR) (+12.7 +/- 3.7 mL) without a slope change. This shift likely reflected effects of afterload reduction, as other indexes (stroke work-end-diastolic volume relation and dP/dtmax at matched preload) were either unchanged or increased. Furthermore, this modest shift in ESPVR was more than compensated for by vasodilation and tachycardia, so reduced systolic function could not explain the increase in PCWP. There also was no net lactate production to suggest ischemia. Rather than arising from direct myocardial effects, PCWP elevation was most easily explained by a change in vascular loading, as both left ventricular end-diastolic volume and right atrial pressure increased (P < .05). This suggests that adenosine induced a redistribution of blood volume toward the central thorax. CONCLUSIONS: PCWP elevation in response to adenosine primarily results from changes in vascular loading rather than from direct effects on cardiac diastolic or systolic function.

Contribution of external forces to left ventricular diastolic pressure. Implications for the clinical use of the Starling law.

OBJECTIVE: To test whether a substantial proportion of measured resting left ventricular diastolic pressure stems from forces external to the left ventricle (such as right-heart filling) in normal and chronically diseased hearts. DESIGN: Nonrandomized study with single intervention. SETTING: University hospital. PATIENTS: 29 patients referred for cardiac catheterization who had normal left ventricles and ejection fractions (n = 12); chronic heart disease due to idiopathic dilated cardiomyopathy (n = 6); ischemic heart disease (n = 6); or left ventricular hypertrophy (n = 5). INTERVENTION: Acute reduction of external forces imposed on the left ventricle using balloon obstruction of inferior vena caval inflow to the right heart. MEASUREMENTS: Continuous catheter-derived left ventricular pressure-volume data before and after abrupt obstruction of inferior vena caval inflow. Diastolic pressures were measured at the same volume just before atrial systole before and after sudden decrease of external (right-heart and pericardial) forces. The resulting decline in pressure was a measure of the contribution of these external forces to resting left ventricular diastolic pressure. RESULTS: The decline in pressure when external forces were released averaged -19% +/- 13% with minimal change in left ventricular end-diastolic volume (-3.66% +/- 6.7%) and cardiac output (-5% +/- 8%). In all patients combined, the decline in pressure when external forces (delta Pd) were released correlated with resting left ventricular diastolic pressure (LVPd) given by: delta Pd = 0.38 x (LVPd-6) [r = 0.86, P < 0.0001]. This indicates that when resting diastolic pressure was more than 6 mm Hg, almost 38% of the pressure was due to external factors. This percentage was similar among all subgroups. Furthermore, the left ventricular diastolic pressure could be reduced by this percentage with only minimal compromise to ventricular filling and cardiac output. CONCLUSIONS: A substantial proportion of measured resting left ventricular diastolic pressure stems from forces extrinsic to the left ventricle rather than from diastolic stiffness in the left ventricle itself. This markedly influences the dependence of cardiac output on filling pressure and has important implications for clinical application of the Starling law.

[The relationship between conventional ECG and the culprit coronary artery in acute myocardial infarct]. / Relação entre o ECG convencional e a artéria coronária responsável no infarto agudo do miocárdio.

PURPOSE: To evaluate electrocardiogram (ECG) in detecting acute myocardial infarction (AMI) during the first 12 hours of symptoms and its relationship to the culprit coronary artery. METHODS: We studied 68 patients aged 55.6 (30 to 76) years, 61 males, with AMI confirmed by elevated CKMB isoenzyme and cinecoronariography (CINE). In all of them we obtained two ECG: first (i), with < 12 hours of symptoms and a second, > or = 5 days during evolution. ECG were analyzed in order to disclose up and downward ST-T segments > or = 1 mm, new Q waves > or = 0.04 s and R/S > or = 1 plus downward ST-T segment in leads V1 and V2. Then we have done correlation between these and the culprit coronary lesions at CINE. RESULTS: The culprit coronary lesions were: right coronary artery (RCA) in 16, left circumflex (LC) in 26 and left anterior descending (LAD) in 31 cases. According to the ECG, the RCA determined inferior AMI in all patients and the LC only in 62% of cases. Posterior AMI due to LC was seen in 81% of cases at ECG and, associated with lateral AMI, in 52%. Lone lateral AMI was seen in 5% and true posterior in 14% of cases, all of them due to LC. CONCLUSION: False negative ECG (i) in AMI is in fact due to LC occlusion which, frequently, causes posterior wall more then inferior wall myocardial infarction at ECG.