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Atualizacao das Diretrizes em Cardiogeriatria da Sociedade Brasileira de Cardiologia – 2019

Age is an important modifying factor of endothelial structure and function in humans. Mechanisms involved in the reduction of age-related endothelium-dependent vasodilation are caused mainly by a primary alteration in the l -arginine-NO pathway. Oxidative stress in the arterial wall plays an important role in the elderly, as it compromises NO bioavailability. The compromise of endothelium-dependent vasodilation in hypertension appears to represent an acceleration of the changes seen in aging. Endothelial dysfunction contributes to making vascular aging a strong risk factor for the development of cardiovascular diseases. On the other hand, experimental evidence suggests that dietary restriction stimulates preservation of vascular function through several mechanisms such as sirtuins, AMP kinase, insulin/insulin-like growth factor 1, and TOR kinase protein. However, controversies still remain as to how caloric restriction improves mitochondrial performance and whether this is sufficient to delay cell and age-dependent decline of the organism.

Acute coronary syndromes (ACS) are the leading causes of death in the elderly. The suspicion and diagnosis of ACS in this age group is more difficult, since typical angina is less frequent. The morbidity and mortality is greater in older age patients presenting ACS. Despite the higher prevalence and greater risk, elderly patients are underrepresented in major clinical trials from which evidence based recommendations are formulated. The authors describe, in this article, the challenges in the diagnosis and management of ST elevation myocardial infarction in the elderly, and discuss the available evidence.

The coupling between arterial elastance ( EA; net afterload) and left ventricular elastance ( ELV; pump performance), known as EA/ ELV, is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in ELV versus EA. This normal exercise-induced reduction in EA/ ELV decreases with advancing age. We hypothesized that sodium nitroprusside (SNP) can acutely ameliorate the age-associated deficits in EA/ ELV. At rest and during graded exercise to exhaustion, EA was characterized as end-systolic pressure/stroke volume and ELV as end-systolic pressure/end-systolic volume. Resting EA/ ELV did not differ between old (70 ± 8 yr, n = 15) and young (30 ± 5 yr, n = 17) subjects because of a tandem increase in EA and ELV in older subjects. During peak exercise, a blunted increase in ELV in old (7.8 ± 3.1 mmHg/ml) versus young (11.4 ± 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in EA/ ELV in old (0.25 ± 0.11) versus young (0.16 ± 0.05) subjects. SNP administration to older subjects lowered resting EA/ ELV by 31% via a reduction in EA (10%) and an increase in ELV (47%) and lowered peak exercise EA/ ELV (36%) via an increase in ELV (68%) without a change in EA. Importantly, SNP attenuated the age-associated deficits in EA/ ELV and ELV during exercise, and at peak exercise EA/ ELV in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in EA/ ELV, EA, and ELV, in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.

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.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).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.

The authors evaluated levels of inflammatory markers in 34 chronic heart failure (CHF) out-patients age 65 years and over, with (N=18) and without (N=16) major depressive disorder (MDD), and healthy-control subjects (N=13). Patients with CHF had left-ventricular ejection fractions0.40 and were in the New York Heart Association functional class II or III. The authors used the SCID DSM-IV to diagnosis MDD. High-sensitivity C-reactive protein levels were significantly higher in patients with CHF and MDD as compared with healthy-control subjects. No differences regarding tumor necrosis factor(alpha) or interleukin(6) were found among the three groups.

The effects of isolated estrogen therapy on the hemostatic system and arterial distensibility were determined in postmenopausal females with type 2 diabetes mellitus. This was a prospective nonrandomized study of 19 subjects (age, 56.2 +/- 4.7 years; body mass index, 27.8 +/- 2.4 kg/m(2) [mean +/- SD]). Inclusion was done after 2 months of glycemic and blood pressure control. The study consisted of 4 months of placebo treatment immediately followed by an equal period of oral conjugated equine estrogens (CEE) 0.625 mg/d. Measures included anthropometrics, a metabolic profile (oral glucose tolerance test and fasting glycated hemoglobin, total cholesterol and fractions, and triglyceride levels), and coagulation and fibrinolytic factors at the end of the placebo period and after 4 months of oral CEE. Conjugated equine estrogen therapy decreased plasminogen activator inhibitor 1 (placebo x CEE: 16.33 +/- 9.11 x 13.08 +/- 8.87 UI/mL, P.03) and increased factor VIII activity (134.11% +/- 46.18% x 145.33% +/- 42.04%, P.04). An increase in high-density lipoprotein cholesterol levels (placebo x CEE: 42.47 +/- 6.80 x 53.32 +/- 11.89 mg/dL, P.01), and a decrease in glycated hemoglobin (8.45% +/- 1.30% vs 7.58% +/- 1.06%, P.02) and in fasting glucose levels (121.51 +/- 21.05 x 111.21 +/- 20.74 mg/dL, P = .02) followed CEE therapy. Pulse wave velocity and augmentation index were performed by applanation tonometry and were obtained at the end of the placebo period (placebo), again after an intravenous load of 1.25 mg of CEE (short-term), and after 4 months of oral CEE (long-term). A significant decrease in central (carotid-femoral) pulse wave velocity was seen both after short- and long-term CEE (placebo vs short-term vs long-term: 9.36 +/- 2.58 vs 8.26 +/- 2.20 vs 7.98 +/- 1.90 m/s, respectively [analysis of variance, P.03]; placebo vs short-term, P.05; placebo vs long-term, P.01), whereas augmentation index decreased only after long-term CEE (placebo vs short-term vs long-term: 39.14% +/- 6.94% vs 37.48% +/- 8.67% vs 34.3.3% +/- 8.11% [analysis of variance, P.05], respectively; placebo vs long-term, P.05). Long-term administration of CEE leads to an improvement in fibrinolysis and arterial distensibility, associated with an increase of the intrinsic coagulation pathway in postmenopausal women with type 2 diabetes mellitus.

To compare the effect of conjugated equine estrogens (CEE) and raloxifene on lipid profile and hemostasis.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.CEE increased the levels of high density lipoprotein cholesterol (HDL-C) from 49.0 to 56.8 mg/dl (p0.001), very low density lipoprotein cholesterol (VLDL-C) from 17.2 to 22.3 mg/dl (p0.001), and triglycerides from 86.0 to 111.7 mg/dl (p0.001), and decreased the levels of low density lipoprotein cholesterol (LDL-C) from 121.0 to 106.5 mg/dl (p0.001). 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% (p0.001). 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 (p0.001) 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 (p0.001), and of plasminogen activator inhibitor (PAI-1) from 30.8 to 21.6 U/ml (p0.010), 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.

OBJETIVE: 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

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 μg ⋅ 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.

OBJECTIVES: Though elderly persons with chronic atrial fibrillation have more comorbidities that could limit indications for the chronic use of anticoagulants, few studies have focused on the risk of falls within this particular group. To evaluate the predictors of the risk of falls among elderly with chronic atrial fibrillation, a cross-sectional, observational study was performed. METHODS: From 295 consecutive patients aged 60 years or older with a history of atrial fibrillation who were enrolled within the last 2 years in the cardiogeriatrics outpatient clinic of the Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 107 took part in this study. Their age was 77.9±6.4 years, and 62 were female. They were divided into two groups: a) no history of falls in the previous year and b) a history of one or more falls in the previous year. Data regarding the history of falls and social, demographic, anthropometric, and clinical information were collected. Multidimensional assessment instruments and questionnaires were applied. RESULTS: At least one fall was reported in 55 patients (51.4%). Among them, 27 (49.1%) presented recurrent falls, with body lesions in 90.4% and fractures in 9.1% of the cases. Multivariate logistic regression showed that self-reported difficulty maintaining balance, use of amiodarone, and diabetes were independent variables associated with the risk of falls, with a sensitivity of 92.9% and a specificity of 44.9%. CONCLUSION: In a group of elderly patients with chronic atrial fibrillation who were relatively independent and able to attend an outpatient clinic, the occurrence of falls with recurrence and clinical consequences was high. Difficulty maintaining balance, the use of amiodarone and a diagnosis of diabetes mellitus were independent predictors of the risk for falls. Thus, simple clinical data predicted falls better than objective functional tests.

To identify features predictive of hospital coronary artery bypass graft (CABG) surgery in patients with acute coronary syndromes (ACSs).Data from 17,434 patients enrolled in an observational study were analysed. Patients in private hospitals were more likely to undergo CABG than those in public hospitals (10.3% vs. 6.9%, P0.01); CABG was more frequent in the USA than in Europe (11.9 % vs 3.5%, P0.01). Clinical features independently predictive of CABG on multivariable analysis included no previous CABG, male sex, history of angina, hypertension, hyperlipidaemia, or diabetes, no history of atrial fibrillation or congestive heart failure, ST depression in multiple territories, and absence of ST elevation. These factors were assigned a score to quantify the likelihood of CABG (c-statistic 0.69). This score was predictive regardless of ACS subgroup (c-statistic 0.65-0.71) and remained predictive across institutions regardless of the frequency with which CABG was performed. The score was of greatest clinical utility among hospitals performing CABG in10% of their ACS patients.Identifying ACS patients likely to undergo CABG using clinical features alone remains difficult. In hospitals with higher rates of surgical revascularisation, a subgroup of patients with an approximate 30% likelihood of CABG can be identified. Therapy in these patients can be tailored to minimise bleeding risk without compromising outcomes.

To study the prognostic value of exercise stress test variables in elderly patients with coronary atherosclerosis and exercise-induced ischemia.Sixty-four elderly patients (61 men, 73 +/- 5 years old) with coronary atherosclerosis, verified by cardiac catheterization, that were clinically stable, had a left ventricle ejection fraction greater than or equal to 0.40 and developed myocardial ischemia during the exercise stress test were studied. The patients were evaluated every six months for cardiac events (death, myocardial infarction, unstable angina, angioplasty and myocardial revascularization).After a mean follow-up period of 48 months, 23 (36%) patients suffered cardiac events. There was no clinical or angiographical differences among the patients that suffered cardiac events and those that did not. Using multivariate analysis, the presence of chest pain during the exercise stress test (relative risk 2.668, p = 0.031) and the heart rate at the onset of ischemia (relative risk 0.966, p = 0.009) were associated with cardiac events.In this elderly population, the presence of chest pain during the exercise stress test and the heart rate at the onset of ischemia were associated with cardiac events. These variables could be useful for risk evaluation in patients with stable coronary atherosclerosis.

OBJETIVO: Estudar o valor prognóstico das variáveis do teste ergométrico em pacientes idosos com doença aterosclerótica coronariana e isquemia induzida pelo esforço. MÉTODOS: Foram estudados 64 pacientes idosos (61 homens, idade de 73 ± 5 anos) com doença aterosclerótica coronariana, comprovada por coronariografia, clinicamente estável, fração de ejeção de ventrículo esquerdo maior ou igual a 0,40 e isquemia miocárdica durante o teste ergométrico. A cada seis meses, os pacientes foram avaliados para eventos cardíacos (morte, infarto do miocárdio, angina instável, angioplastia e revascularização do miocárdio). RESULTADOS: Após seguimento médio de 48 meses, 23 (36%) pacientes sofreram eventos cardíacos. Não houve diferença clínica e angiográfica entre os pacientes que sofreram o evento e os que não o sofreram. Pela análise multivariada, a presença de dor precordial durante o teste ergométrico (risco relativo de 2,668 e p = 0,031) e a freqüência cardíaca no início da isquemia (risco relativo de 0,966 e p = 0,009) foram associadas a eventos cardíacos. CONCLUSÃO: Nessa população idosa, a presença de dor precordial durante o teste ergométrico e a freqüência cardíaca no início da isquemia foram associadas a eventos cardíacos. Essas variáveis podem ser úteis para avaliação do risco de pacientes com doença aterosclerótica coronariana estável. OBJECTIVE: To study the prognostic value of exercise stress test variables in elderly patients with coronary atherosclerosis and exercise-induced ischemia. METHODS: Sixty-four elderly patients (61 men, 73 ± 5 years old) with coronary atherosclerosis, verified by cardiac catheterization, that were clinically stable, had a left ventricle ejection fraction greater than or equal to 0.40 and developed myocardial ischemia during the exercise stress test were studied. The patients were evaluated every six months for cardiac events (death, myocardial infarction, unstable angina, angioplasty and myocardial revascularization). RESULTS: After a mean follow-up period of 48 months, 23 (36%) patients suffered cardiac events. There was no clinical or angiographical differences among the patients that suffered cardiac events and those that did not. Using multivariate analysis, the presence of chest pain during the exercise stress test (relative risk 2.668, p = 0.031) and the heart rate at the onset of ischemia (relative risk 0.966, p = 0.009) were associated with cardiac events. CONCLUSION: In this elderly population, the presence of chest pain during the exercise stress test and the heart rate at the onset of ischemia were associated with cardiac events. These variables could be useful for risk evaluation in patients with stable coronary atherosclerosis.

Background Metabolic syndrome and abdominal obesity are risk factors for cardiovascular diseases in middle age women but, not completely understood in older people. In this study we analyzed the association between metabolic syndrome and abdominal obesity and the occurrence of cardiovascular events in these elderly women. Methods A prospective follow-up study included 516 consecutive women aged 60–84years who sought medical care at a geriatric outpatient facility. The presence of metabolic syndrome and higher quartiles of waist circumference and waist-to-hip ratio were analyzed as predictive variables, and were adjusted for age, smoking, and previous cardiovascular diseases. The outcomes were the occurrence of stroke, myocardial infarction, evidence of coronary artery disease, or cardiovascular death. Results During a mean follow-up of 6.6years, 94 (18.2%) cardiovascular events were observed (48 fatal and 46 non-fatal). Metabolic syndrome was diagnosed in 206 women (39.9%). After adjustments for confounding variables, metabolic syndrome and waist-to-hip ratio above the 75th percentile (>0.98) were predictors of the outcomes, but greater waist circumference (>96cm) was not. Adjusted hazard ratios for these variables were: metabolic syndrome, 1.66, 95% CI −1.11 to 2.47, p =0.01; waist-to-hip ratio, 1.72, 95% CI −1.05 to 2.82; p =0.03 and waist circumference, 1.37, 95% CI −0.91 to 2.07, p =0.12. Conclusion Metabolic syndrome and high waist-to-hip ratio were associated with increased risk of cardiovascular events in the studied sample.

We investigated whether Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP) are present in aortic valve stenosis (AS).Immunohistochemistry was utilized to identify CP antigens, in situ hybridization to identify MP DNA, and electron microscopy was used to evaluate the following three groups: Normal - 11 normal autopsy valves; Atherosclerosis - 10 autopsy valves from patients with systemic atherosclerosis and no AS; and AS - 14 surgical specimens of AS analyzed in 3 sub-regions: AS-Preserved - peripheral, preserved regions; AS-Fibrosis - peri-calcified fibrotic tissue; and AS-Calcification - calcified nodules.The positive area fraction of CP antigen median values were 0.09, 0.30, 0.18, 1.33, and 3.3 in groups Normal, Atherosclerosis, AS-Preserved, AS-Fibrosis, and AS-Calcification, respectively. CP density was significantly greater in Atherosclerosis and AS-Calcification than in Normal (P0.05). Within the AS group, the amount of CP was greater in the Calcification and Fibrosis regions (P0.05). MP-DNA positive area fraction (median values) were 0.12, 0.44, 0.07, 0.36, and 1.52 in groups Normal, Atherosclerosis, AS-Preserved, AS-Fibrosis, and AS-Calcification, respectively. The amount of MP-DNA was greater in AS-Calcification than in Normal (P0.05). Within the AS group, MP-DNA was in larger quantity in the Calcification and Fibrosis regions (P0.05).AS Calcified nodes present higher concentration of CP and MP suggesting that these bacteria may be associated with the development of calcification and inflammation. This adds novel similarities between AS and the atherosclerosis process, which may have infection mechanisms involved.

OBJETIVO: Investigar se chlamydia pneumoniae (CP) ou mycoplasma pneumoniae (MP) estão presentes na estenose da valva aórtica (EA). MÉTODOS: Imuno-histoquímica foi utilizada para identificar os antígenos de CP (Ag-CP), a hibridização in situ para identificar o DNA de MP, e microscopia eletrônica para avaliação dos dois agentes, nos grupos: normal - 11 valvas normais de autópsia; aterosclerose - 10 valvas de pacientes com aterosclerose sistêmica de autópsia e sem EA; e EA - 14 espécimes cirúrgicos provenientes de pacientes com EA analisados em 3 sub-regiões: EA-preservada - regiões mais preservadas na periferia da valva; EA-fibrose - tecido fibrótico peri-calcificação; e EA-calcificação - nódulos calcificados. RESULTADOS: As medianas da fração de área positiva para Ag-CP foram 0,09; 0,30; 0,18; 1,33; e 3,3 nos grupos acima descritos, respectivamente. A densidade de CP foi significativamente maior nos grupos aterosclerose e EA-calcificação em relação ao normal (p

To assess whether hormone replacement therapy with estrogens in association with progestogens in postmenopausal hypertensive women alters postprandial triglyceridemia and vascular reactivity.A double-blind, placebo-controlled, crossover study was carried out with 15 postmenopausal women (age range: 50 to 70 years, mean = 61.6 +/- 6 years) randomly assigned to 2 weeks of placebo or oral ingestion of 0.625 mg of equine conjugated estrogens and 2.5 mg of medroxyprogesterone, fed a high-fat diet (897 calories; 50.1% fat). Vascular reactivity (VR - % of vessel diameter variation in the fasting period and 2 hours after meals) was measured by using the automated ultrasound method. Lipid profile and glycemia during the fasting period and 2 hours after a high-fat meal were measured.With placebo, vascular reactivity (VR) decreased from 3.20 +/- 17% during the fasting period to -2.1 +/- 30% 2 hours after the meal (P = 0.041). With the hormone replacement therapy, vascular reactivity decreased from 6.14 +/- 27% during the fasting period to - 0.05 +/- 18% 2 hours after the meal (P = NS). Postprandial triglyceridemia increased as follows: 35 +/- 25% with placebo; and 12 +/- 10% with hormone replacement therapy (P0.05).In postmenopausal hypertensive women, 2 weeks of hormone replacement with an association of estrogens and progestogens decreased hypertriglyceridemia after a high-fat meal, an effect that may reduce the endothelial dysfunction occurring in the postprandial period.

OBJECTIVE: To assess whether hormone replacement therapy with estrogens in association with progestogens in postmenopausal hypertensive women alters postprandial triglyceridemia and vascular reactivity. METHODS: A double-blind, placebo-controlled, crossover study was carried out with 15 postmenopausal women (age range: 50 to 70 years, mean = 61.6 ± 6 years) randomly assigned to 2 weeks of placebo or oral ingestion of 0.625 mg of equine conjugated estrogens and 2.5 mg of medroxyprogesterone, fed a high-fat diet (897 calories; 50.1% fat). Vascular reactivity (VR - % of vessel diameter variation in the fasting period and 2 hours after meals) was measured by using the automated ultrasound method. Lipid profile and glycemia during the fasting period and 2 hours after a high-fat meal were measured. RESULTS: With placebo, vascular reactivity (VR) decreased from 3.20 ± 17% during the fasting period to -2.1 ± 30% 2 hours after the meal (P=0.041). With the hormone replacement therapy, vascular reactivity decreased from 6.14 ± 27% during the fasting period to - 0.05 ± 18% 2 hours after the meal (P=NS). Postprandial triglyceridemia increased as follows: 35 ± 25% with placebo; and 12 ± 10% with hormone replacement therapy (P < 0.05). CONCLUSION: In postmenopausal hypertensive women, 2 weeks of hormone replacement with an association of estrogens and progestogens decreased hypertriglyceridemia after a high-fat meal, an effect that may reduce the endothelial dysfunction occurring in the postprandial period.

Background The process of aortic degeneration associated with calcified aortic stenosis shares many similarities with coronary artery atherosclerosis. Inflammation and infection are involved in both diseases. Chlamydia pneumoniae has been identified in atherosclerotic plaques. However, the studies about the presence of C. pneumoniae in degenerative aortic stenotic valves are not conclusive. Objective We investigated whether an association exists between the density of C. pneumoniae and fibrosis or calcification in aortic stenosis. Design Autopsy and surgical specimens were divided into 3 groups: Normal, 11 normal autopsy valves Atherosclerosis, 10 autopsy valves from patients with systemic atherosclerosis and no aortic stenosis and Aortic stenosis, 14 surgical specimens of aortic valves replaced due to aortic stenosis. Setting Heart Institute (InCor), University of Sao Paulo Medical School. Patients Aortic valves from patients aged 52±16 years, 69±9 years, and 71±8 years. Invention Specimens were evaluated by immunohistochemical technique (to detect C. pneumoniae antigens), in situ hybridization, and electron microscopy (to quantify the density of C. pneumoniae in the valves). Measurements The aortic stenosis group was analyzed according to 3 subregions: aortic stenosis-preserved, peripheral preserved regions; aortic stenosis-fibrosis, peri-calcified fibrotic tissue; and aortic stenosis-calcification, calcified nodules. Results The median values of C. pneumoniae antigens were 0.09, 0.30, 0.18, 1.33, and 3.3 in groups Normal, Atherosclerosis, Aortic stenosis-preserved, Aortic stenosis-fibrosis, and Aortic stenosis-calcification, respectively. The amount of C. pneumoniae was greater in the Atherosclerosis and Aortic stenosis-calcification groups than in the Normal group ( P C. pneumoniae was greater in the Aortic stenosis group in the calcified and fibrotic regions than in preserved region ( P Conclusion An association was found between the higher density of C. pneumoniae and fibrosis/calcification in stenotic aortic valves.

To assess the strategy of titration for prescribing an efficient dosage of propranolol to reduce myocardial ischemia in the elderly.The study comprised 14 elderly men (73.6 +/- 5.3 years) with stable coronary heart disease documented on coronary cineangiography, ischemic response to exercise testing, and preserved left ventricular function. Titration was performed to identify the dosage of propranolol that would cause a 15% reduction in heart rate at the end of a 50 W load (corresponding to normal daily activities in the elderly) in weekly exercise tests. Synchronous scintigraphic study of the cardiac chambers was performed at rest and during exercise prior to and after propranolol use.The reductions in heart rate with the 50 W load and at rest were similar (21% vs 20%; P=0.5100). Propranolol improved the duration of exercise (12.2 +/- 2.0 min vs 13.1 +/- 1.8 min; P=0.0313) and abolished the changes in the ST segment induced by exercise in 8 (57%) patients. At rest, the ejection fraction was not modified by the beta-blocker. During maximum exercise, propranolol reduced the end-systolic volume index and increased ejection fraction.The strategy of using beta-blockers to reduce heart rate by 15% with a 50 W load is safe and beneficial in the elderly patient with myocardial ischemia and preserved ventricular function. The dose of beta-blocker used reduced myocardial ischemia and improved tolerance to exercise without hampering ventricular performance during maximum exercise.

OBJETIVO: Avaliar estratégia de titulação para prescrever uma dose de propranolol que seria eficiente em reduzir isquemia do miocárdio em idosos. MÉTODOS: Foram estudados 14 homens idosos (73,6 ± 5,3 anos), portadores de doença coronariana estável, documentada pela cinecoronariografia, com resposta isquêmica ao teste ergométrico e função ventricular esquerda preservada. O propranolol foi titulado a fim de atingir redução de 15% na freqüência cardíaca, ao final da carga de 50 W (correspondente às atividades diárias normais de idosos), em testes ergométricos semanais e feito estudo cintilográfico sincronizado das câmaras cardíacas, em repouso e durante exercício, antes e após seu uso. RESULTADOS: As reduções da freqüência cardíaca na carga de 50 W e em repouso foram semelhantes (21% vs 20%; p=0,5100). O propranolol melhorou a duração do exercício (12,2 ± 2,0 min vs 13,1 ± 1,8 min; p=0,0313) e aboliu as alterações do segmento ST induzidas pelo exercício em 8 (57%) pacientes. Em repouso, a fração de ejeção não foi modificada pelo betabloqueador. Durante o exercício máximo, o propranolol reduziu o índice de volume sistólico final e aumentou a fração de ejeção. CONCLUSÃO: A estratégia de empregar betabloqueadores para reduzir a freqüência cardíaca em 15% na carga de 50 W é segura e benéfica nos idosos com isquemia miocárdica e função ventricular preservada. A dose utilizada reduziu a isquemia miocárdica e melhorou a tolerância ao exercício, sem prejudicar o desempenho ventricular durante exercício máximo. OBJECTIVE: To assess the strategy of titration for prescribing an efficient dosage of propranolol to reduce myocardial ischemia in the elderly. METHODS: The study comprised 14 elderly men (73.6 ± 5.3 years) with stable coronary heart disease documented on coronary cineangiography, ischemic response to exercise testing, and preserved left ventricular function. Titration was performed to identify the dosage of propranolol that would cause a 15% reduction in heart rate at the end of a 50 W load (corresponding to normal daily activities in the elderly) in weekly exercise tests. Synchronous scintigraphic study of the cardiac chambers was performed at rest and during exercise prior to and after propranolol use. RESULTS: The reductions in heart rate with the 50 W load and at rest were similar (21% vs 20%; P=0.5100). Propranolol improved the duration of exercise (12.2 ± 2.0 min vs 13.1 ± 1.8 min; P=0.0313) and abolished the changes in the ST segment induced by exercise in 8 (57%) patients. At rest, the ejection fraction was not modified by the beta-blocker. During maximum exercise, propranolol reduced the end-systolic volume index and increased ejection fraction. CONCLUSION: The strategy of using beta-blockers to reduce heart rate by 15% with a 50 W load is safe and beneficial in the elderly patient with myocardial ischemia and preserved ventricular function. The dose of beta-blocker used reduced myocardial ischemia and improved tolerance to exercise without hampering ventricular performance during maximum exercise.

To assess the relation between the evolution of cognitive performance and the prognosis of elderly patients after compensation of advanced heart failure.Thirty-one patients older than 64 (68 +/- 7) years and admitted with New York Heart Association class IV heart failure and ejection fraction = 0.45 (0.38 +/- 0.06) were consecutively selected. They underwent cognitive tests (digit span, digit symbol, letter cancellation, trail making A and B) and the 6-minute walking test 4 days before (T1) and 6 weeks after (T2) hospital discharge, and their performances were compared using the t test. The prognostic value of the scores of the cognitive tests was analyzed with logistic regression, and the value of greatest accuracy of the tests was associated with the prognosis determined by the ROC curve.After 24.7 months, 17 (55%) patients had died. The performances in the 6-minute walking test and most cognitive tests improved between T1 and T2. The digit span score of the survivors ranged from 3.9 to 5.2 (P=0.003) and remained unaltered among those who died (4.1 to 3.9; P=0.496). An improvement0.75 points in the score was associated with mortality (relative risk of 8.1; P=0.011).In the elderly, after compensation of advanced heart failure, the lack of evolutionary improvement in cognitive performance was associated with a worse prognosis.

OBJECTIVE: To assess the relation between the evolution of cognitive performance and the prognosis of elderly patients after compensation of advanced heart failure. METHODS: Thirty-one patients older than 64 (68 ± 7) years and admitted with New York Heart Association class IV heart failure and ejection fraction = 0.45 (0.38 ± 0.06) were consecutively selected. They underwent cognitive tests (digit span, digit symbol, letter cancellation, trail making A and B) and the 6-minute walking test 4 days before (T1) and 6 weeks after (T2) hospital discharge, and their performances were compared using the t test. The prognostic value of the scores of the cognitive tests was analyzed with logistic regression, and the value of greatest accuracy of the tests was associated with the prognosis determined by the ROC curve. RESULTS: After 24.7 months, 17 (55%) patients had died. The performances in the 6-minute walking test and most cognitive tests improved between T1 and T2. The digit span score of the survivors ranged from 3.9 to 5.2 (P=0.003) and remained unaltered among those who died (4.1 to 3.9; P=0.496). An improvement < 0.75 points in the score was associated with mortality (relative risk of 8.1; P=0.011). CONCLUSION: In the elderly, after compensation of advanced heart failure, the lack of evolutionary improvement in cognitive performance was associated with a worse prognosis.

In this study the authors sought to determine the prevalence and long-term prognostic value of low triiodothyronine levels in elderly patients with heart failure and no thyroid disease. Lower levels of triiodothyronine are more prevalent in patients with advanced heart failure without thyroid disease, and this may have prognostic implications. However, this hormonal milieu has not been investigated in elderly patients. The authors prospectively followed a consecutive sample of 69 elderly patients aged 76.5+/-5.9 years with heart failure and 44 age-matched controls without heart failure between March 1997 and September 2000 at the Geriatric Cardiology Outpatient Clinic of the Heart Institute of Sao Paulo, Brazil. Events analyzed included death, hospitalization, and the combined end point of death or hospitalization. The study revealed that levels of triiodothyronine were lower in heart failure patients than in controls (89+/-23 vs. 101+/-16 ng/dL, p=0.001). During the follow-up period of 14.3+/-8.1 months there were 19 deaths and 33 hospitalizations in the heart failure group. The combined end point of death or hospitalization occurred in 38 patients. Triiodothyronine levels were lower in heart failure patients who had a cardiovascular event than in event-free patients (82.7+/-24.8 vs. 96.7+/-19.2 ng/dL, p=0.012). The odds ratio for events was 9.8 (95% confidence interval, 2.2-43, p=0.004) for patients in the lowest tertile of triiodothyronine, that is, lower than 80 ng/dL, compared with patients with levels above 80 ng/dL. The authors conclude that among elderly patients with heart failure, lower triiodothyronine concentrations are more prevalent and are associated with a worse prognosis.

OBJECTIVE: To assess the relation between P-wave and QT dispersions in elderly patients with heart failure. METHODS: Forty-seven elderly patients (75.6±6 years) with stable heart failure in NYHA functional classes II or III and with ejection fractions of 37±6% underwent body surface mapping to analyze P-wave and QT dispersions. The degree of correlation between P-wave and QT dispersions was assessed, and P-wave dispersion values in patients with QT dispersion greater than and smaller than 100 ms were compared. RESULTS: The mean values of P-wave and QT dispersions were 54±14 ms and 68±27 ms, respectively. The correlation between the 2 variables was R=0.41 (p=0.04). In patients with QT dispersion values > 100 ms, P-wave dispersion was significantly greater than in those with QT dispersion values < 100 ms (58±16 vs 53±12 ms, p=0.04 ). CONCLUSION: Our results suggest that, in elderly patients with heart failure, a correlation between the values of P-wave and QT dispersions exists. These findings may have etiopathogenic, pathophysiologic, prognostic, and therapeutic implications, which should be investigated in other studies.

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.

OBJETIVO: Verificar como são tratados pacientes com insuficiência cardíaca (IC) em hospital terciário de São 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 fração de ejeção (FE) entre 0,22 e 0,59 (média 0,43). A etiologia da disfunção 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 prescrição. 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 em dois grupos, com FE maior e menor que 0,45, observamos que, no último, foi maior a prescrição de IECA (91,5% vs 80,4%) e maior o uso de doses adequadas (61% vs 48,7%). CONCLUSÃO: A maioria dos pacientes foi tratada conforme recomendações 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. 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 89mm (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.

OBJETIVO: Avaliar as formas de apresentação 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 pirofosfato 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 ECO mostrou diâmetros normais em todos e fração de ejeção 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 evolução foi diferente com melhora clínica após o implante de marcapasso no primeiro grupo e má evolução no grupo com cardiomiopatia restritiva que evoluiu de maneira refratária, 3 falecendo em menos de 6 meses após diagnóstico. CONCLUSÃO: A presença de aumento da espessura das paredes ao ECO, discreta disfunção sistólica e aspecto de doença de depósito identificaram a quase totalidade dos casos. Cardiomiopatia restritiva e distúrbio de condução foram as formas de apresentação, sendo o prognóstico muito reservado nos pacientes com forma restritiva, evoluindo para ICC refratária. PURPOSE: To identify the principal forms of cardiac amiloydosis presentation in a terciary hospital. METHODS: Eight cases whith cardiac amyloidosis were identified. Five were woman, 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 pirophosfate and cardiac biopsy these results allowed the identification of their clinical situation. RESULTS: Seven patients refered 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 refractary 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.

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 μg/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 max 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 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.

S - Hypertension, Vascular Disease, and Prevention 269A 1201-81 N-Terminal Pro Brain Natrlureti¢ Peptide (NT-proBNP) Predicts Left Ventriculer Function and Mortality in Hemodlalysis Patients but Not Cardiac Death: A Two- Year Outcome Study Joseoh P. Lonohitano. William L. Henhch, Paul D. Light, Eric Tiblier, Heidi Sparger, Mathew M. Smilay, John Badalamenti, Juergen Trawinski, Christopher R. deFilippi, University of Maryland, Baltimore, Maryland, University of Texas Medical Branch, Galveston, Texas. NT-proBNP is a stable marker of left ventricular (LV) dysfunction in the general popula- tion, but its predictive value in patients on chronic hemodialysis (HD), a group with chronic volume overload as well as a large burden of ischemic heart disease and cardio- vascular death, is unknown. This prospective study of 224 HD patients was designed to learn the predictive value of NT-proBNP for death, LV function and the magnitude of CAD. HD pts from 5 HD centers (age 60±15 years, 54% male, 48% diabetic) in whom NT-proBNP levels (mean of two values, one month apart, normal 0.40 (9956±11420 vs. 4853±5940, p=0.0013). The Table depicts NT-proBNP by quartiies, and shows the corresponding mortality (%), depressed LVEF (%), mean LV mass, multives- sel CAD (%) and cardiac death or non-fatal MI (%). Overall mortality, LV dysfunction and LV mass increased with risifig NT-proBNP levels but NT-proBNP was not predictive of multivessel CAD or cardiac death. We conclude that NT-proBNP levels are high in most HD pts, and that levels >2800 pmol/ L are associated with a marked decrease in LVEF and risk of all cause mortality in a large percentage of pts but are not a marker of atheroscierotic burden or CV death, Quartile 1 2 3 4 pvaluefortrend NT-proBNP (pmol/L) 87-1246 1247-27662792-66986730-55164 Death (% pts) 23.2 23.2 46.4 44.6 0.006 LVEF< 0.40 (% pts) 2.6 9.8 22.6 27.3 0.008 LV mass (g/m 2) 130-~31 133+31 137±44 160±39 0.002 Multivessel CAD (% pts) 42.1 18.1 5.6 47.6 0.790 CV Death or Non-Fatal MI 16.1 17.9 16.1 22.6 0.450 (% pts)