Amit Nussbacher

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

BACKGROUNDnContinuous 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.nnnMETHODS AND RESULTSnFifteen 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.nnnCONCLUSIONSnPCWP elevation in response to adenosine primarily results from changes in vascular loading rather than from direct effects on cardiac diastolic or systolic function.

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.

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

Objectivesu2003To compare the effect of conjugated equine estrogens (CEE) and raloxifene on lipid profile and hemostasis. Materials and methodsu2003A double-blind, randomized and parallel study was performed with 90 healthy postmenopausal women, aged 54u200a±u200a5 years, divided into three groups and submitted to daily therapy with either CEE 0.625u2009mg, raloxifene 60u2009mg or placebo for 4 months. The lipid profile, coagulation and fibrinolytic factors were analyzed. Resultsu2003CEE increased the levels of high density lipoprotein cholesterol (HDL-C) from 49.0 to 56.8u2009mg/dl (pu200a<u200a0.001), very low density lipoprotein cholesterol (VLDL-C) from 17.2 to 22.3u2009mg/dl (pu200a<u200a0.001), and triglycerides from 86.0 to 111.7u2009mg/dl (pu200a<u200a0.001), and decreased the levels of low density lipoprotein cholesterol (LDL-C) from 121.0 to 106.5u2009mg/dl (pu200a<u200a0.001). The only significant effect of raloxifene was an increase in the levels of HDL-C from 46.0 to 47.8u2009mg/dl (pu200a=u200a0.019). There was no significant reduction in LDL-C, from 115.5 to 110.2u2009mg/dl (pu200a=u200a0.06), VLDL-C, from 21.7 to 20.0u2009mg/dl (pu200a=u200a0.201), and triglycerides, from 108 to 100u2009mg/dl (pu200a=u200a0.201).u2003CEE decreased the levels of fibrinogen, from 370.5 to 326.8u2009g/l (pu200a=u200a0.039) and the levels of antithrombin III, from 99.5 to 93.2% (pu200a<u200a0.001). Raloxifene decreased the levels of fibrinogen, from 354.7 to 302.0u2009g/l (pu200a=u200a0.009) and the levels of antithrombin III, from 102.4 to 98.5% (pu200a=u200a0.039). CEE increased levels of protein C from 103.7 to 115.3u2009mg/l (pu200a<u200a0.001) and raloxifene did not change the levels of protein C (107.9 to 105.1u2009mg/l; pu200a=u200a0.158).u2003CEE decreased the antigen levels of tissue plasminogen activator (t-PA) from 8.8 to 6.8u2009U/ml (pu200a<u200a0.001), and of plasminogen activator inhibitor (PAI-1) from 30.8 to 21.6u2009U/ml (pu200a<u200a0.010), whereas raloxifene had no significant effect on either t-PA, from 9.6 to 9.2u2009U/ml (pu200a=u200a0.235) or PAI-1 antigen levels, from 32.1 to 30.4u2009U/ml (pu200a=u200a0.538). Conclusionu2003Both 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.

Predictors of the risk of falls among elderly with chronic atrial fibrillation

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.

Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside

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

Clinical Predictors of Prognosis in Severe Aortic Stenosis in Unoperated Patients >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.

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

OBJECTIVEnAntihypertensive 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.nnnMETHODSnFollowing 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.nnnRESULTSnBoth 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).nnnCONCLUSIONnIn 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.

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 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.

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.

Efeitos agudos dos estrogênios associados a progestogênios sobre a trigliceridemia e reatividade vascular pós-prandial

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.