Circulating Tissue Inhibitor of Matrix Metalloproteinase-4 (TIMP-4) in Systemic Sclerosis Patients with Elevated Pulmonary Arterial Pressure

Decreased levels of matrix metalloproteinases (MMPs) or excess levels of their tissue inhibitors (TIMPs) may contribute to dysregulation of extracellular matrix turnover in systemic sclerosis (SSc). In a cross-sectional study of 106 SSc patients, we measured serum levels of TIMP-4 which is preferentially expressed in cardiovascular structures and searched for correlations with simultaneously performed echocardiography measurements of pulmonary artery systolic pressure (PASP), myocardial performance, and pulmonary function tests. TIMP-4, but not MMP-9, levels were significantly raised in patients with SSc than controls. However, in the subgroup of patients with PASP measurements lower to 40 mmHg (n = 69), TIMP-4 levels were comparable to controls irrespective of the presence of diffuse or limited skin involvement, or lung fibrosis. Individual PASP measurements suggestive of pulmonary hypertension were associated with increased TIMP-4 serum levels (P = .03), independently of age, extent of skin sclerosis, or lung fibrosis, suggesting a cardiopulmonary vasculature-specific role of TIMP-4 activation in SSc

Association of the 894G>T polymorphism in the endothelial nitric oxide synthase gene with risk of acute myocardial infarction

Background: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI. Methods: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population. Results: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77–1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63–2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29–4.04, P = 0.908). Conclusion: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AM

Age-related changes in P wave morphology in healthy subjects

<p>Abstract</p> <p>Background</p> <p>We have previously documented significant differences in orthogonal P wave morphology between patients with and without paroxysmal atrial fibrillation (PAF). However, there exists little data concerning normal P wave morphology. This study was aimed at exploring orthogonal P wave morphology and its variations in healthy subjects.</p> <p>Methods</p> <p>120 healthy volunteers were included, evenly distributed in decades from 20–80 years of age; 60 men (age 50+/-17) and 60 women (50+/-16). Six-minute long 12-lead ECG registrations were acquired and transformed into orthogonal leads. Using a previously described P wave triggered P wave signal averaging method we were able to compare similarities and differences in P wave morphologies.</p> <p>Results</p> <p>Orthogonal P wave morphology in healthy individuals was predominately positive in Leads X and Y. In Lead Z, one third had negative morphology and two-thirds a biphasic one with a transition from negative to positive. The latter P wave morphology type was significantly more common after the age of 50 (P < 0.01). P wave duration (PWD) increased with age being slightly longer in subjects older than 50 (121+/-13 ms vs. 128+/-12 ms, P < 0.005). Minimal intraindividual variation of P wave morphology was observed.</p> <p>Conclusion</p> <p>Changes of signal averaged orthogonal P wave morphology (biphasic signal in Lead Z), earlier reported in PAF patients, are common in healthy subjects and appear predominantly after the age of 50. Subtle age-related prolongation of PWD is unlikely to be sufficient as a sole explanation of this finding that is thought to represent interatrial conduction disturbances. To serve as future reference, P wave morphology parameters of the healthy subjects are provided.</p

Determinants of electrocardiographic and spatial vectorcardiographic descriptors of ventricular repolarization in normal subjects

he link between the dispersion of ventricular recovery times and arrhythmias has previously been demonstrated.(1) QT dispersion has been used to quantify the dispersion of ventricular refractoriness from the standard 12-lead electrocardiogram.(2) However, not only the accuracy and reproducibility of the "dispersion " indexes,(3) but also the presence of a direct link between the heterogeneity of ventricular repolarization and QT dispersion(4) has been challenged recently. Several studies have now focused on the spatial T-loop morphology features as a more accurate measure of the repolarization heterogeneity.(4-7) Although the correlation between QT dispersion and the T-loop morphology features has previously been evaluated,(8) there are no adequate data on the determinants of the spatial vectorcardiographic (VCG) descriptors of ventricular repolarization in normal subjects. The objective of the present study was to assess the clinical determinants of the electrocardiographic (ECG) and spatial VCG descriptors of ventricular repolarization in a population of young, healthy men

Role of autonomic nervous system in chronic complete heart block

Autonomic blockade was produced in 9 patients with chronic complete heart block by the intravenous administration of atropine and propranolol. Atrial and ventricular rates after injection were compared with those before. In general, the atrial rate slowed and there was no significant change in ventricular rate. However, 2 patients with an initial ventricular rate of over 40 a minute showed significant slowing. It is suggested that in chronic complete heart block the sinoatrial node is under dominant sympathetic control. High resting idioventricular rates may be partly dependent on sympathetic drivd, but this does not appreciably influence resting idioventricular rate in the majority of cases

Spatial aspects of ventricular repolarization in postinfarction patients

QT dispersion has been proposed to reflect the heterogeneity of ventricular repolarization, but a poor reproducibility limits its clinical usefulness. Spatial vectorcardiographic descriptors constitute a novel approach to quantify ventricular repolarization. To test the ability of vectorcardiographic descriptors to discriminate among different subsets of postinfarction patients, 50 consecutively recruited patients with acute MI, 50 patients with history of an old (&gt; 6 months) MI and 50 healthy controls were evaluated. The maxim um and minim um QT and JT intervals and QT and JT dispersion were manually measured from a digitally recorded 12-lead EGG. X, Y, and Z leads were reconstructed from the 12-lead EGG. The amplitude of the maximum spatial T vector (spatial T amplitude), the angle between the maximum spatial QRS and T vectors (spatial QRS-T angle), and the frontal plane QRS-T angle were automatically calculated The spatial T amplitude and the spatial QRS-T angle did nor differ between patients with a recent and those with an old MI (P = 1). QT dispersion was significantly lower in patients with an old MI than in patients with a recent one (P = 0.002). The spatial repolarization descriptors showed better short-term reproducibility than the dispersion indices. In conclusion, the spatial T amplitude and the spatial QRS-T angle are accurate measures of ventricular repolarization that do not differ between patients with recent and those with old MI. The different QT dispersion values observed in this study between the two post-MI groups should be considered cautiously because of the low accuracy of the manual measurements

Assessment of ventricular repolarization alterations in subjects with early repolarization

Background: Although the electrocardiographic (ECG) features of early repolarization (ER) have been studied extensively, no systematic quantification of ventricular repolarization in subjects with ER has been conducted so far. Methods: The objective of the present study was to evaluate ECG and spatial vectorcardiographic (VCG) descriptors of ventricular repolarization in ER subjects and to associate them with the respective indices of ventricular depolarization. A digital 12-lead surface ECG was obtained from 108 young, healthy men with ER and 108 age-matched healthy controls. The maximum Q-onset-T-end interval (QT maximum), the maximum Q-onset-T-peak interval (QTp maximum), the respective QT dispersion values (QT maximum-QT minimum), the rate-corrected QTC maximum and QTpC maximum, the QRS duration, and the VCG markers spatial T amplitude, spatial QRS amplitude and spatial QRS- Tangle, were evaluated in ER subjects and controls. Results: QT maximum (P=0.05) and QTp maximum (P=0.003) were higher in ER subjects than in controls, while QTC maximum (P&lt;0.0001)and QTpC maximum (P=0.002) were lower in ER subjects than in controls. The QRS duration (P=0.013), as well as the spatial T amplitude, the spatial QRS amplitude, and the spatial QRS-T angle were higher in ER subjects than in controls (P&lt;0.0001). The spatial T amplitude was not associated with the indices of ventricular depolarization neither in ER subjects, nor in controls. Conclusions: Ventricular repolarization, as well as depolarization, is altered in young, healthy males with ER compared to age-matched healthy controls. Ventricular depolarization and repolarization indices in ER subjects are not associated to each other. (C) 2003 Elsevier Ireland Ltd. All rights reserved