Ivabradine: a selective If current inhibitor in the treatment of stable angina

The role of heart rate reduction in the management of myocardial ischemia and chronic stable angina is pivotal. However, broad use and appropriate dosing of commonly used rate-slowing drugs is limited by their poor tolerability. Ivabradine is a selective inhibitor of the If currents of the sinoatrial node cells. If currents activity determines the slope of the depolarization curve towards the threshold level controlling heart rate in patients with sinus rhythm. Ivabradine, a compound of the benzocyclobutane (S 16257), exhibits a unique specificity for the If current and has a more favorable profile of adverse reactions compared to other If inhibitors. Accordingly, ivabradine has been used in the treatment of stable angina, where it presented anti-anginal and anti-ischemic effects equivalent to the effects of atenolol and amlodipine. Clinical studies proved the efficacy of ivabradine in patients with stable angina, while clinical data are awaited to verify its probable value in the treatment of atrial tachyarrhythmias and tachycardia due to ventricular dysfunction. Thus, the clinical value of ivabradine, which has completed clinical development for stable angina, is expected to exceed its role in the treatment of myocardial ischemia. In this context, ivabradine, promising efficacious and safe pharmacological management of heart rate, is a huge step in cardiovascular therapeutics.     

Normal values of the growth of the pulmonary arteries in children. An angiography study

Systolic and diastolic diameters of the pulmonary artery anulus (PA-A), pulmonary artery sinus (PA-S), pulmonary artery trunc (PA-St), as well as those of the right and left pulmonary arteries (RPA, LPA) were measured from cineangiograms of 51 infants, children and adolescents without heart disease (n = 16) or with cardiovascular malformations which had no hemodynamic relevance (n = 35). The following diagnostic categories were included in the normal group: pulmonary stenosis (n = 16), bicuspid aortic valve (n = 4) or subvalvular aortic stenosis (n = 2), all with a systolic gradient lower than 15 mm Hg, aberrant innominate artery (n = 5), small PDA (n = 3) or small VSD (n = 2) and patients with Kawasaki disease without coronary aneurysms (n = 3). The patients were sedated and studied in a fasting state and in the supine position. Angiocardiographies were performed in the right ventricle or/and in the pulmonary artery. A grid or the known diameter of the catheter was used for calibration purposes. The corresponding systolic and diastolic diameter values were averaged in order to obtain a mean diameter of each vascular segment. All measurements were correlated with the body length and the body surface area (BSA). A root exponential function [square root of y = a(1 - e-bx) + c] was used, the regressions coefficients of which can be explained by physiological means. In this function c2 is the theoretical minimal diameter and (a + c)2 the theoretical maximal diameter of a cardiovascular structure; in this way the growth of the cardiovascular dimensions could be well defined mathematically and correlated strongly (r = 0.99) with body length and BSA. Different exponents were found for the pulmonary artery anulus, sinus, trunc as well as right and left pulmonary arteries. All the diameters showed a systolic increase between 8 to 10% above diastolic measurements. The anulus had an average diameter 16% smaller than the sinus and 9% than the distal region of the pulmonary artery; the right pulmonary artery was 7% larger than the left. A limitation of the study was that the diameters were measured in single projections only, necessitating the assumption of a circular cross section of the cardiovascular structures. The angiographically determined PA-A was larger than those of formaldehyd-fixed hearts. This finding indicates that the fixation method may alter the anatomic structures probably due to shrinkage process. PA-S measurements were closest to echocardiographic diameters measured by other authors.     

Effect of dobutamine combined with intra-aortic balloon counterpulsation on left ventricular function early after acute myocardial infarction: experimental study

Acute myocardial infarction (AMI) causes left ventricular (LV) remodeling, which forms the substrate for its early and late complications. The purpose of this study was to compare the acute effect of dobutamine or intra-aortic balloon pumping (IABP), alone or in combination, on LV function in the early phase of an experimental AMI. In 18 pigs, AMI was induced by ligation of the left anterior descending artery (LAD). IABP or dobutamine infusion at a rate of 5 μg/kg/min, or a combination of the two, was applied immediately after ligation of the LAD. Echocardiographic measurements of the long and short LV axes were obtained before (baseline) and post LAD ligation and at the end of each intervention for 5, 15, and 30 min. The fractional shortening (FS) of both axes, as well as the ejection fraction (EF), was calculated. The combination of dobutamine with IABP increased the EF significantly after the AMI in comparison to dobutamine or IABP alone, and improved the stroke volume, cardiac output, and long axis FS in comparison to IABP alone. Dobutamine alone produced a significantly higher increase of EF in comparison to IABP alone. These results indicate that the combination of dobutamine with IABP may be useful during AMI.     

Antimicrobial susceptibility of pediatric uropathogens in Thrace,Greece

The aim of this study was to investigate the bacterial pathogens involved in pediatric urinary tract infections (UTIs) in a tertiary general hospital located in the Thrace province of Northern Greece over a 69-month period (1/2003 to 9/2008), and their antibiotic susceptibility patterns. A total of 622 episodes of UTIs in 508 children were identified. Median age of all children was 16 months (range 1 month to 14 years). Boys were significantly younger than girls (9 months vs. 24 months). Escherichia coli was the most common uropathogen and responsible for 69.1% of UTIs. Approximately half of E. coli isolates were resistant to ampicillin and 20.5% to trimethoprim/sulfamethoxazole (TMP/SMX). E. coli resistance to second-generation and third-generation cephalosporins was <4%, to aminoglycosides <8%, and to nitrofurantoin 4.4%. Pediatric E. coli urine isolates were significantly more resistant to ampicillin and ticarcillin and more sensitive to quinolones compared to adult E. coli uropathogens identified in the same hospital. E. coli resistance to ampicillin and amoxicillin/clavulanic acid was significantly higher in boys 12–23 months-old compared to girls of the same age. In conclusion, nitrofurantoin is a very good choice for chemoprophylaxis. Amoxicillin/clavulanic acid, second-generation cephalosporins, and TMP/SMX are appropriate choices for oral empirical treatment of UTIs. Parenteral aminoglycosides and second and third-generation cephalosporins are excellent treatment choices for inpatient therapy. Finally, sex and age are additional factors that should be taken into account when choosing empirical therapy for children with UTIs.     

Long‐term outcome of hypertensive patients with heart failure with mid‐range ejection fraction: The significance of blood pressure control

Heart failure (HF) with mid‐range ejection fraction (HFmrEF) is a newly suggested entity in HF. Since it has been inadequately addressed, there is an urgent need to determine the profile of HFmrEF patients and the optimal approach to their management. The present study aimed to assess the long‐term clinical outcomes of hypertensive patients with HFmrEF and the impact of blood pressure (BP) on their mortality and cardiovascular outcome. We performed a retrospective observational study that included 121 hypertensive patients with HFmrEF and 149 hypertensives with heart failure and preserved ejection fraction (HFpEF). The median follow‐up was 84 months (22‐122). Our analysis did not reveal any statistically significant difference between the two groups in total mortality (P = 0.34) or cardiovascular mortality (P = 0.54). The total mean survival time was 102.9 months (100.5‐110.1), while the mean survival time was 105.3 months (80.4‐90.2) in HFpEF and 97.6 months (92.7‐102.6) in HFmrEF. An office systolic BP > 139 mm Hg and diastolic BP > 89 mm Hg were significantly associated with both all‐cause mortality (P = 0.02 and P = 0.013, respectively) and cardiovascular mortality (P = 0.02 for both). In HFpEF patients, no significant association was found between outcome and office BP. HFpEF and HFmrEF have similar long‐term outcomes. Suboptimal BP levels are a significant risk factor for an adverse outcome in HFmrEF. Our results emphasize the importance of good BP control in order to achieve better outcomes in hypertensives with impaired EF and HF symptomatology.     

Matrix metalloproteinase (MMP-2, -9) and tissue inhibitor (TIMP-1, -2) activity in tear samples of pediatric type 1 diabetic patients

Background

The presence of matrix metalloproteinase (MMP-2, -9) and tissue inhibitor (TIMP-1, -2) activity in tear samples of pediatric type 1 diabetes mellitus (DM) patients and potential correlations with clinical parameters (Schirmer testing, glycosylated hemoglobin-HB_A1C) were investigated.

Methods

Tear samples from the right eyes of 27 type 1 DM patients and 17 healthy control subjects were included in this study. The MMP gelatinolytic activity was determined by gelatin zymography analysis using sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE), while MMP and TIMP concentrations (in ng/ml) were quantified in tears of type 1 diabetic patients and healthy controls, with the use of enzyme-linked immunosorbent assay (ELISA).

Results

MMP-9, TIMP-1, -2 levels, MMP-9/TIMP-1, and MMP-9/TIMP-2 ratios in the patient group were significantly elevated. There was a significant correlation between TIMP-2 and HB_A1C values, as well as between MMP-2 and MMP-9.

Conclusions

Significant correlations between TIMP-2 and HB_A1C and between Schirmer test results and HB_A1C were revealed. Significant increase in tear MMP and TIMP levels in pediatric type 1 diabetic patients may be suggestive of disease progression and localized pathologic remodelling. Further studies are required in order to ascertain whether MMPs and TIMPs could be employed as indicators of early disease progression.     

Spontaneous coronary artery dissection during a dobutamine stress echocardiography

We report a case of a spontaneous dissection of the right coronary artery during a dobutamine stress echocardiography (DSE) study in a middle-aged male. Our patient experienced a severe retrosternal pain of abrupt onset during the DSE study, whereas EKG was evident of significant ST segment elevation in II, III, avF, and V5-V6 leads, followed by an accelerated idioventricular rhythm. Immediate coronary angiogram revealed a minor dissection of the distal part of the right coronary artery.