J.A.F. Ramires

Different microcirculatory and interstitial matrix patterns in idiopathic dilated cardiomyopathy and Chagas' disease: a three dimensional confocal microscopy study

OBJECTIVE To analyse the morphological aspects of the extracellular matrix and microcirculation to clarify whether chronic Chagas’ cardiopathy (CCC) is an accurate model to study the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). DESIGN Thick histological myocardial sections were prepared to analyse collagen, and microcirculation was examined during confocal laser and light microscopy. SETTING The specimens were prepared at the pathology service of the Heart Institute of São Paulo, Brazil. PATIENTS Nine control hearts, eight IDCM hearts, and 10 CCC hearts were studied after necropsy. MAIN OUTCOME MEASURES The number of collagen struts per 100× field, the area of fibrosis (%), and the diameters of arterioles and capillaries were measured in each heart to establish outcome. RESULTS A smaller number (mean (SD)) of collagen struts was seen in the hearts in the IDCM group (9.1 (4.1)) than in the control (22.4 (3.2)) (p < 0.05) or CCC (15.7 (7.4)) (p > 0.05) groups. Fibrosis was greater in the CCC hearts (13.8 (10.5)%) than in the IDCM hearts (5.9 (6.6)%) (p > 0.05). Major increases in arteriole (65.4 (9.9) μm) and capillary (9.9 (1.7) μm) diameters were seen in the CCC hearts but not in the IDCM hearts (arteriole diameter 40.3 (7.9) μm; capillary diameter 7.9 (1.3) μm). CONCLUSIONS Hearts demonstrating CCC and IDCM present different extracellular and microvessel alterations. This suggests that distinct pathogenic mechanisms are responsible for each condition and that CCC is not an effective model to study IDCM.

Left Ventricular Systolic Function and Outcome After In-Hospital Cardiac Arrest

Background— The effect of prearrest left ventricular ejection fraction (LVEF) on outcome after cardiac arrest is unknown. Methods and Results— During a 26-month period, Utstein-style data were prospectively collected on 800 consecutive inpatient adult index cardiac arrests in an observational, single-center study at a tertiary cardiac care hospital. Prearrest echocardiograms were performed on 613 patients (77%) at 11±14 days before the cardiac arrest. Outcomes among patients with normal or nearly normal prearrest LVEF (≥45%) were compared with those of patients with moderate or severe dysfunction (LVEF <45%) by &khgr;2 and logistic regression analyses. Survival to discharge was 19% in patients with normal or nearly normal LVEF compared with 8% in those with moderate or severe dysfunction (adjusted odds ratio, 4.8; 95% confidence interval, 2.3 to 9.9; P<0.001) but did not differ with regard to sustained return of spontaneous circulation (59% versus 56%; P=0.468) or 24-hour survival (39% versus 36%; P=0.550). Postarrest echocardiograms were performed on 84 patients within 72 hours after the index cardiac arrest; the LVEF decreased 25% in those with normal or nearly normal prearrest LVEF (60±9% to 45±14%; P<0.001) and decreased 26% in those with moderate or severe dysfunction (31±7% to 23±6%, P<0.001). For all patients, prearrest &bgr;-blocker treatment was associated with higher survival to discharge (33% versus 8%; adjusted odds ratio, 3.9; 95% confidence interval, 1.8 to 8.2; P<0.001). Conclusions— Moderate and severe prearrest left ventricular systolic dysfunction was associated with substantially lower rates of survival to hospital discharge compared with normal or nearly normal function.

Acute and chronic effects of oestradiol on left ventricular diastolic function in hypertensive postmenopausal women with left ventricular diastolic dysfunction

Background: Left ventricular function changes in the postmenopausal state. However, there are conflicting reports about the effects of oestrogen on left ventricular diastolic function in postmenopausal women. Objective: To evaluate the acute and chronic effects of oestradiol in physiological doses on diastolic heart function in hypertensive postmenopausal women with left ventricular diastolic dysfunction. Methods: A prospective, randomised, double blind, placebo controlled study was used to evaluate the effects of oestradiol in 34 hypertensive women with left ventricular dysfunction. The acute effects of a single 1 mg oral dose of oestradiol or placebo were determined after 90 minutes. The chronic effects of 1 mg oestradiol orally/day or placebo were determined after 12 weeks. Diastolic functional indices (mitral flow and pulmonary venous flow) were assessed by Doppler echocardiography. Results: Though an appropriate serum concentration was achieved, no acute effect of oestradiol administration on left ventricular diastolic function was identified. After 12 weeks of treatment the following changes (mean (SD)) were identified in the oestradiol group: a decrease in isovolumic relaxation time from 127 (23) to 106 (16) ms (p < 0.001), and in the deceleration time of the mitral E wave from 260 (42) to 238 (20) ms (p < 0.05); and an increase in the E/A ratio from 0.8 (0.2) (basal) to 1.0 (0.2) after 12 weeks (p < 0.001). Conclusions: Hypertensive postmenopausal women who had hormone replacement therapy over a period of 12 weeks had significant improvement in left ventricular diastolic function. No changes were identified following acute administration.

Evidence for cardiac safety and antiarrhythmic potential of chloroquine in systemic lupus erythematosus.

AIMS To perform a comprehensive evaluation of heart rhythm disorders and the influence of disease/therapy factors in a large systemic lupus erythematosus (SLE) cohort. METHODS AND RESULTS Three hundred and seventeen consecutive patients of an ongoing electronic database protocol were evaluated by resting electrocardiogram and 142 were randomly selected for 24 h Holter monitoring for arrhythmia and conduction disturbances. The mean age was 40.2 ± 12.1 years and disease duration was 11.4 ± 8.1 years. Chloroquine (CQ) therapy was identified in 69.7% with a mean use of 8.5 ± 6.7 years. Electrocardiogram abnormalities were detected in 66 patients (20.8%): prolonged QTc/QTd (14.2%); bundle-branch block (2.5%); and atrioventricular block (AVB) (1.6%). Age was associated with AVB (P = 0.029) and prolonged QTc/QTd (P = 0.039) whereas anti-Ro/SS-A and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were not (P > 0.05). Chloroquine was negatively associated with AVB (P = 0.01) as was its longer use (6.1 ± 6.9 vs. 1.0 ± 2.5 years, P = 0.018). Time of CQ use was related with the absence of AVB [odds ratio (OR) = 0.103; 95% confidence interval (CI) = 0.011-0.934, P = 0.043] in multiple logistic regression. Holter monitoring revealed abnormalities in 121 patients (85.2%): supraventricular ectopies (63.4%) and tachyarrhythmia (18.3%); ventricular ectopies (45.8%). Atrial tachycardia/fibrillation (AT/AF) were associated with shorter CQ duration (7.05 ± 7.99 vs. 3.63 ± 5.02 years, P = 0.043) with a trend to less CQ use (P = 0.054), and older age (P < 0.001). Predictors of AT/AF in multiple logistic regression were age (OR = 1.115; 95% CI = 1.059-1.174, P < 0.001) and anti-Ro/SS-A (OR = 0.172; 95% CI = 0.047-0.629, P = 0.008). CONCLUSIONS Chloroquine seems to play a protective role in the unexpected high rate of cardiac arrhythmias and conduction disturbances observed in SLE. Further studies are necessary to determine if this antiarrhythmic effect is due to the disease control or a direct effect of the drug.

COMBAT--conventional versus multisite pacing for bradyarrhythmia therapy: rationale of a prospective randomized multicenter study.

COMBAT is a prospective, multicenter, randomized, blinded clinical study, with crossover design. The main objective is the comparative evaluation of atrio‐biventricular versus conventional atrioventricular stimulation (atrio and right ventricle) in patients with heart failure and bradycardia as the primary indication for pacemaker implantation. After successful atrio‐biventricular system implantation, patients will be randomized into two groups: group A—atrioventricular conventional pacing and group B—atrio‐biventricular pacing. Both groups will be programmed in DDD mode with AV delay optimized by echocardiogram. After 3 months, New York Heart Association functional class, ventricular arrhythmia density and complexity, echocardiography outcomes, 6‐min hall walk distance, quality of life and peak oxygen consumption will be assessed in all patients. Then, all patients will crossover to the other pacing regimen, with an additional AV delay adjustment by echo. Patients will be followed up for another 3 months at the end of which all evaluations will be repeated. Patients will then crossover back to their original pacing regimen for a further 3 months. At the end of this 9‐month period, patients will be reprogrammed according to their optimal pacing regime.

Effect of cholesterol lowering treatment on positive exercise tests in patients with hypercholesterolaemia and normal coronary angiograms

AIM To assess the impact of cholesterol lowering on positive exercise stress tests in hypercholesterolaemic patients with normal coronary angiograms. METHODS 43 non-diabetic patients aged 43–61 years, with total serum cholesterol concentrations of more than 7.75 mmol/l, positive exercise tests, and normal coronary angiograms, were started on the American Heart Association step 1 diet. After 12 weeks these patients were randomly assigned to treatment for another 16 weeks with the diet alone (diet group, n = 20) or with the diet plus lovastatin or simvastatin (statin group, n = 23). After this 28 week run in period, statins were withdrawn and lipid profile tests and exercise tests were done and repeated 20 weeks later. RESULTS At week 28, the statin group but not the diet group had significant reductions from baseline (week 12) in plasma total cholesterol (p < 0.0001), low density lipoprotein (p < 0.0001), and triglyceride (p < 0.0001). The number of patients with positive exercise tests decreased from 23 to three in the statin group and from 20 to 15 in the diet group (p = 0.01). After the final 20 weeks without statins, lipid profiles returned to baseline levels in all 17 patients remaining in the statin group, and exercise tests were again positive in 15 of these patients. CONCLUSIONS In hypercholesterolaemic patients with normal coronary arteries, cholesterol lowering treatment reduces myocardial ischaemia, as shown by the beneficial effects on exercise testing.

Influence of leukocytes and glycemia on the prognosis of patients with acute myocardial infarction

BACKGROUND Previous studies have demonstrated that leukocytosis and hyperglycemia verified at the admission of patients with acute myocardial infarction (AMI) are associated with intrahospital mortality. However, little is known on the long-term impact of these markers. OBJECTIVE To evaluate the short-and long-term influence of the levels of glucose and leukocytes on the prognosis of patients with AMI. METHODS A total of 809 patients with AMI were retrospectively assessed (mean age: 63.2 +/- 12.87 yrs) and prospectively and consecutively included in a specific database. RESULTS a) At the intrahospital phase, the mean values were compared between patients that died and those who survived: Leukocytosis: 12156+/-5977 vs 10337+/-3528 (p=0.004, 95%CI = 976-2663); Glucose 176+/-105 mg/dl vs 140+/-72 mg/dl (p<0.001, 95%CI = 19.4 - 52.6), respectively. b) With the adjusted mode, the same pattern was observed [p values: 0.002 (t-ratio 3.05), 0.04 (t-ratio 2.06), respectively]. c) Long-term follow-up: the univariate analysis showed P values of 0.001 (t-ratio 3.3), <0.001 (t-ratio 4.16), respectively. The multivariate analysis showed P=0.001 (t-ratio 3.35), 0.08 (t-ratio 1.75), respectively. (d) After the exclusion of the intrahospital deaths, the leukocyte (P=0.989) and glucose levels (P=0.144) did not remain significantly correlated with mortality. The same result was observed at the multivariate analysis. CONCLUSION The levels of glucose and leukocytes at the hospital admission of patients with AMI are excellent predictors of intrahospital mortality and poor predictors of long-term death.Resumen Fundamento: Estudios previos demostraron que tanto la leucocitosis como la hiperglucemia verificadas cuando de la admision de pacientes con infarto agudo de miocardio (IAM), estan correlacionadas con la mortalidad intrahospitalaria. Sin embargo, poco se sabe acerca del impacto de esos marcadores a largo plazo. Objetivo: Evaluar, a corto y largo plazos, la influencia de los niveles de glucosa y leucocitos en el pronostico de pacientes con IAM.Metodos: Se analizaron, retrospectivamente, a 809 pacientes (edad promedio 63,2 ± 12,87 anos) con IAM, incluidos de forma prospectiva y consecutiva en banco de datos especifico.Resultados: a) En la fase intrahospitalaria se compararon los valores promedio obtenidos entre pacientes que murieron o supervivieron: leucocitosis 12.156±5.977 vs 10.337±3.528 (p=0.004, 95% IC= 976-2663); glucosa 176±105 mg/dl vs 140±72 mg/dl (p<0.001, 95% IC= 19.4 – 52.6), respectivamente. b) En el modo ajustado, se verifico el mismo es - tandar [valores de p: 0.002 (t-ratio 3.05), 0.04 (t-ratio 2.06), respectivamente]. c) Seguimiento a largo plazo: el analisis univariado revelo valores de P de 0.001 (t-ratio 3.3), <0.001 (t-ratio 4.16), respectivamente. Ya el analisis multivariado: P=0.001 (t-ratio 3,35), 0.08 (t-ratio 1,75), respectivamente. d) Tras la exclusion de las muertes intrahospitalarias, los niveles leucocitarios (P=0.989) y la glucemia (P=0.144) no permanecieron correlacionadas significativamente con la

Effects of estradiol on myocardial global performance index in hypertensive postmenopausal women

The objective of this study was to assess the acute and chronic effects of estradiol on the myocardial performance index (MPI) in hypertensive postmenopausal women. There are conflicting reports on the effects of estrogen on left ventricular function in postmenopausal women, and we are unaware of any study on the myocardial performance index in the postmenopausal state. We undertook a prospective, randomized, double-blind, placebo-controlled study in 34 women, distributed into an estradiol group or a placebo group. After 90 min and at 12 weeks of administration of 1 mg of oral estradiol we evaluated, by Doppler echocardiography, its effects on the MPI. The estradiol group showed no alteration in the MPI after 90 min of the administration of estradiol. On the other hand, after 12 weeks of treatment we observed a statistically significant decrease of isovolumic relaxation time, from 127 ± 23 ms to 106 ± 16 ms (p < 0.001 and of the MPI from 0.63 ± 0.13 to 0.48 ± 0.09 (p < 0.01) and an increase in ejection time, from 297 ± 32 ms to 330 ± 31 ms (p < 0.01). In conclusion, estrogen replacement therapy over a period of 12 weeks showed a significant improvement in the MPI in hypertensive postmenopausal women, whereas the acute administration did not have any effect.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus With Stable Ischemic Heart Disease

Background— The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results— Outcome data were analyzed by intention to treat; the Kaplan–Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P=0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P=0.76). In the coronary artery bypass grafting stratum (n=763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P=0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P=0.010) and cardiac death or MI (P=0.03) were also less frequent. Reduction in MI (P=0.001) and cardiac death/MI (P=0.002) was significant only in the insulin sensitization group. Conclusions— In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Effects of estradiol alone and combined with norethisterone acetate on pulse-wave velocity in hypertensive postmenopausal women

Background. Arterial hypertension and postmenopausal reduction of estrogen levels may be involved in modifications of the stiffness of large arteries. Objectives. To evaluate the pulse-wave velocity (PWV) and indirectly the arterial stiffness in hypertensive postmenopausal women submitted to hormone therapy with estradiol alone or combined with norethisterone acetate. Subjects. Forty-five hypertensive postmenopausal women were double-blindly, randomly assigned to three arms of treatment: placebo (group I); estradiol 2 mg/day (group II); or estradiol 2 mg/day and norethisterone acetate 1 mg/day (group III). Methods. Arterial stiffness was assessed from PWV measurements of the common carotid and femoral arteries (CF-PWV) and the common carotid and radial arteries (CR-PWV) obtained using the automatic Complior® device, taken at baseline and after 12 weeks of treatment. Results. After the 12-week treatment, values of CF-PWV and CR-PWV were not significantly different (p = 0.910 and p = 0.736, respectively) among the groups. Systolic blood pressure showed a positive correlation with CF-PWV in groups II and III (p = 0.02 and p < 0.001, respectively). Conclusions.  PWV and arterial stiffness in postmenopausal hypertensive women did not reduce over a 12-week treatment with estradiol alone compared with the same period of treatment with estradiol combined with norethisterone acetate.