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.

The effects of cigarette smoking on the heterogeneity of ventricular repolarization.

BACKGROUND: Although the circulatory effects of cigarette smoking have been studied extensively, its impact on ventricular repolarization has not been adequately evaluated. METHODS: The goal of our study was to determine whether cigarette smoking influences the spatial and temporal heterogeneity of ventricular repolarization in a population of young, healthy, male subjects. A digital 12-lead surface electrocardiogram was obtained from 1394 men recruited from the Hellenic Air Force and classified as smokers and nonsmokers. The maximum, minimum, and median QT intervals, QT dispersion (QT maximum - QT minimum), the rate-corrected maximum and median QT intervals, the slopes of the QT maximum/RR and QT median/RR regression equations, and the vectorcardiographic markers spatial T amplitude and spatial QRS-T angle were evaluated in the 2 groups. RESULTS: Heart rate was significantly higher (P <.001) in smokers (n =691) compared with nonsmokers (n = 703). QT maximum, QT minimum, and QT median were significantly lower (P <.001), whereas the rate-corrected QT maximum (P =.04) and QT median (P =.06) were marginally higher in smokers than in nonsmokers. The spatial T amplitude was lower (P =.002), whereas the spatial QRS-T angle was higher (P =.01) in smokers compared with nonsmokers. Neither QT dispersion nor the slopes of the QT/RR and the spatial descriptors/RR regression equations differed between smokers and nonsmokers. CONCLUSIONS: Ventricular repolarization is altered in young male cigarette smokers. The differences in the heterogeneity of ventricular repolarization between smokers and nonsmokers are mainly due to heart rate differences between the 2 study groups.

Radiofrequency catheter ablation of posteroseptal accessory pathways--results of a step-by-step ablation approach.

INTRODUCTION: Transcatheter radiofrequency ablation of posteroseptal accessory pathways (AP) is challenging. A number of different interventional approaches have been suggested by different groups. The selection of the initial approach is crucial in order to reduce radiation exposure and the number of unsuccessful lesions applied. We present our ablation technique as guided by a simplified electrocardiographic analysis of the delta wave polarity and the electrophysiologic mapping results. METHODS AND RESULTS: Out of 35 manifest APs encountered in the right (n=17) or the left posteroseptum (n=18) in 35 patients, 34 were successfully ablated. Despite their left sided location, 7 of the 18 "left" sided APs were ablated after switching from an initial arterial to a venous approach looking for an appropriate target site in the right posteroseptal space or within the coronary sinus network. The other 11 left sided APs were ablated in the mitral ring, on 2 occasions, on their atrial aspect through a retrograde transmitral approach. On the contrary, 16 of the 17 "right" sided APs were successfully ablated exclusively through a venous approach. Fourteen of these were ablated in the right posteroseptum, in 2 cases, only after reaching their ventricular aspect. Two right sided APs were interrupted in the coronary sinus os and the middle cardiac vein respectively. CONCLUSION: It appears that even though the electrocardiographic and electrophysiologic location of the AP in the posteroseptal space helps select the appropriate initial approach, it does not always guarantee a successful ablation procedure in the expected site of the corresponding atrioventricular ring. Not uncommonly, it will be necessary to look after intermediate target sites within the coronary sinus to improve the overall ablation success rate.

In-hospital mortality of habitual cigarette smokers after acute myocardial infarction; the "smoker's paradox" in a countrywide study.

AIMS: Habitual cigarette smokers, paradoxically, present improved short-term prognosis after acute myocardial infarction, a phenomenon often termed "smoker's paradox". We sought to examine cigarette smokers' post-infarction survival advantage in a countrywide survey of unselected, consecutive patients presenting with acute myocardial infarction. METHODS AND RESULTS: The study population was derived from the registry of the Hellenic study of acute myocardial infarction, which recruited 7433 consecutive patients with acute myocardial infarction from 76, out of a total of 86, hospitals countrywide. Cigarette smokers presented with lower unadjusted mortality rates (7.4% vs 14.5%, P<0.001), were younger, predominantly of male gender and were less likely to suffer from diabetes mellitus and arterial hypertension. When all univariate predictors of poor outcome were included as covariates in multivariate analysis, smoking status was not significantly associated with inhospital mortality (relative risk=1.12, 95% CI=0.86-1.44, P=0.399). The beneficial effect of thrombolytic therapy was independent of the smoking status in both univariate and multivariate analysis. CONCLUSION: Unadjusted mortality rates are significantly lower in smokers, but age accounted for much of their seemingly improved outcome. When a number of additional clinical variables were taken into consideration, no significant influence of habitual smoking on early outcome following acute myocardial infarction was observed.

P-wave dispersion: a novel predictor of paroxysmal atrial fibrillation.

BACKGROUND: The prolongation of intraatrial and interatrial conduction time and the inhomogeneous propagation of sinus impulses are well known electrophysiologic characteristics in patients with paroxysmal atrial fibrillation (AF). Previous studies have demonstrated that individuals with a clinical history of paroxysmal AF show a significantly increased P-wave duration in 12-lead surface electrocardiograms (ECG) and signal-averaged ECG recordings. METHODS: The inhomogeneous and discontinuous atrial conduction in patients with paroxysmal AF has recently been studied with a new ECG index, P-wave dispersion. P-wave dispersion is defined as the difference between the longest and the shortest P-wave duration recorded from multiple different surface ECG leads. Up to now the most extensive clinical evaluation of P-wave dispersion has been performed in the assessment of the risk for AF in patients without apparent heart disease, in hypertensives, in patients with coronary artery disease and in patients undergoing coronary artery bypass surgery. P-wave dispersion has proven to be a sensitive and specific ECG predictor of AF in the various clinical settings. However, no electrophysiologic study has proven up to now the suspected relationship between the dispersion in the atrial conduction times and P-wave dispersion. The methodology used for the calculation of P-wave dispersion is not standardized and more efforts to improve the reliability and reproducibility of P-wave dispersion measurements are needed. CONCLUSIONS: P-wave dispersion constitutes a recent contribution to the field of noninvasive electrocardiology and seems to be quite promising in the field of AF prediction.

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 (> 6 months) MI, and 50 healthy controls were evaluated. The maximum and minimum QT and JT intervals and QT and JT dispersion were manually measured from a digitally recorded 12-lead ECG. X, Y, and Z leads were reconstructed from the 12-lead ECG. 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 not 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.

The spatial QRS-T angle as a marker of ventricular repolarisation in hypertension.

Ventricular repolarisation abnormalities are important in arrhythmia provocation. The dispersion of repolarisation duration is not the only aspect of repolarisation heterogeneity. Spatial vectorcardiographic descriptors constitute a novel approach to quantify ventricular repolarisation. To test the ability of vectorcardiographic descriptors to discriminate between hypertensives with high or low blood pressure (BP), 110 treated hypertensives (mean age 63.6 +/- 12.1 years) were classified in the high (systolic BP > or = 160 mm Hg or diastolic BP > or = 95 mm Hg) (n = 67), or the low (systolic BP < 160 mm Hg and diastolic BP <95 mm Hg) (n = 43) BP group. The maximum QT, JT, and T peak-T end intervals and the QT, JT, and T peak--T end dispersion were calculated from a digitally recorded 12-lead electrocardiogram (ECG). X, Y, and Z leads were reconstructed from the 12-lead ECG. 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 calculated. The spatial QRS-T angle was higher in patients with high compared to those with low BP (P = 0.025). All conventional ECG markers of the dispersion of ventricular repolarisation duration failed to demonstrate significant differences between hypertensives with high or low BP. In conclusion, the spatial QRS-T angle was significantly increased in those treated hypertensive patients who showed repeatedly high BP values. Hence, we may suggest that the angle between the directions of ventricular depolarisation and repolarisation is a sensitive marker of the repolarisation alterations in systemic hypertension. Journal of Human Hypertension (2001) 15, 63-70

Changes of the T-wave amplitude and angle: an early marker of altered ventricular repolarization in hypertension.

BACKGROUND: The heterogeneity of ventricular repolarization is an important proarrhythmic factor. QT dispersion has been proposed to reflect the inhomogeneity of ventricular repolarization, but a poor reproducibility limits its clinical applicability. Reliable noninvasive methods to quantify abnormalities in ventricular repolarization are still lacking. The T-loop morphology analysis is a novel method aimed at quantifying ventricular repolarization. HYPOTHESIS: To test the ability of the T-loop morphology analysis to discriminate between hypertensive patients and healthy subjects, 105 hypertensive patients (mean age 63.6 +/- 12.3 years) and 110 healthy controls (mean age 49.7 +/- 14.3 years) were evaluated. METHODS: The maximum QT interval (QT maximum), the minimum QT interval (QT minimum), and their difference (QT dispersion) were calculated from a digitally recorded 12-lead electrocardiogram (ECG) in both study groups. X, Y, and Z leads were reconstructed from the 12-lead ECG, and the amplitude of the maximum T vector (T amplitude) and the angle between the maximum T vector and X axis (T angle) were calculated from the projection of the T loop in the frontal plane. RESULTS: T amplitude (p < 0.001), T angle (p = 0.05), and QT dispersion (p = 0.04) were significantly different between hypertensive patients and controls, while QT maximum (p = 0.14) and QT minimum (p = 0.35) did not differ between the groups. T amplitude was the only marker which differed between hypertensive patients without ECG criteria for left ventricular hypertrophy and controls (p = 0.002). CONCLUSIONS: T-loop features and particularly T amplitude are significantly different between hypertensive patients and healthy controls and may serve as early markers of repolarization abnormalities in a hypertensive population.

Increased variance of P wave duration on the electrocardiogram distinguishes patients with idiopathic paroxysmal atrial fibrillation.

We hypothesized that the variance of P wave duration (P variance) in the 12-lead ECG could reflect the spatial dispersion of P wave duration due to inhomogeneous and delayed propagation of sinus impulses in the atria, and moreover could present better reproducibility than maximum P wave duration and P wave dispersion that have already been used for the prediction of idiopathic paroxysmal AF. We also tested a semiautomated PC-based method to improve the accuracy and reproducibility of P wave measurements. A 12-lead ECG was obtained from 60 patients with idiopathic paroxysmal AF and from 50 healthy controls. All ECGs were analyzed manually using magnifying lens and calipers, while 20 randomly selected ones were scanned and analyzed on screen using common commercial software. P maximum, P dispersion, and P variance were all significantly higher in patients with paroxysmal AF than in controls. A P maximum value of 110 ms, a P dispersion value of 40 ms, and a P variance value of 120 ms2 separated patients from controls with a sensitivity of 88%, 83%, and 80%, respectively and a specificity of 75%, 85%, and 74%, respectively. The reproducibility of P variance was higher compared to P dispersion and P maximum. Finally, the PC-based method significantly increased accuracy and reproducibility of P wave measurements. Thus, the variance of P wave duration could be a useful ECG marker for the prediction of paroxysmal idiopathic AF and the use of PC-based methods may enhance the accurate measuring of P wave duration on the ECG.

Implantable defibrillator therapy in Naxos disease.

Naxos disease is a unique form of right ventricular cardiomyopathy with a high prevalence of malignant ventricular arrhythmias, including sudden cardiac death. As a hereditary systemic disease confined to a small island, it has been closely studied over the last 15 years. The implantation of an automatic defibrillator provides an alternative form of antiarrhythmic management to improve life expectancy in these high risk cardiac patients. We present the first two Naxos disease patients with malignant ventricular arrhythmias who had defibrillator implantation.

Mild left ventricular hypertrophy in essential hypertension: is it really arrhythmogenic?

Left ventricular hypertrophy (LVH) has been associated with an increased incidence of ventricular arrhythmias and sudden cardiac death in hypertensive patients. However, it is not known whether this relationship exists in early asymptomatic hypertensives with mild LVH. We prospectively examined 100 consecutive patients with essential hypertension, 35 without and 65 with mild LVH on echocardiography. All underwent a detailed noninvasive arrhythmia work-up and were subsequently followed-up for 3 +/- 1 years in an ambulatory hypertension clinic. None of the 12-lead electrocardiographic parameters examined differed between the two hypertensive groups. A similarly low incidence of simple forms of ventricular ectopy was present in both groups, whereas complex forms of ventricular ectopy were extremely rare in either group. The signal-averaged electrocardiographic parameters examined were also not significantly affected by the presence of mild LVH. Arrhythmia-related symptoms or malignant ventricular arrhythmia events were not observed in either group of patients during follow-up with antihypertensive treatment. The latter resulted in LVH regression in the 65 patients with mild LVH at baseline. It appears that mild LVH among ambulatory hypertensive patients does not carry an additive arrhythmogenic risk and can be successfully reversed with the appropriate antihypertensive therapy, with no need of additional antiarrhythmic management.

The role of carotid atherosclerosis in the distinction between ischaemic and non-ischaemic cardiomyopathy.

AIM: Sometimes ischaemic cardiomyopathy is a result of severe coronary artery disease of an occult course, without typical symptoms or evidence of myocardial infarction. This form of presentation is usually indistinguishable from non-ischaemic dilated cardiomyopathy. Carotid bifurcation atherosclerosis and coronary artery disease have been shown to be strongly associated. We prospectively examined the value of extracranial carotid atherosclerosis in the distinction between ischaemic and non-ischaemic aetiology in patients with clinically unexplained cardiomyopathy. METHODS AND RESULTS: Seventy-eight patients with undetermined dilatation and diffuse impairment of the left ventricular contraction were studied within 28 months. They underwent carotid scan and coronary arteriography. Carotid atherosclerosis was found to be very common in ischaemic and rare in non-ischaemic cardiomyopathy. The presence of at least one abnormal carotid finding (intima-media thickness >1 mm, plaques, severe carotid stenosis) was 96% sensitive and 89% specific for ischaemic cardiomyopathy. CONCLUSION: Carotid scanning may be a useful screening and decision making tool in patients with cardiomyopathy of indecisive cause. Patients with carotid atherosclerosis are likely to suffer from severe coronary artery disease. Coronary angiography and subsequent myocardial viability studies, when indicated, could be considered early during their evaluation. In contrast, a negative carotid scan predicts non-ischaemic cardiomyopathy.

Clinical and electrocardiographic predictors of recurrent atrial fibrillation.

Patients with frequent episodes of paroxysmal atrial fibrillation (AF) are prone to develop permanent AF and have an increased thromboembolic risk. We have previously shown that P wave dispersion (P dispersion), defined as the difference between the maximum and the minimum P wave duration, and maximum P wave duration (P maximum) can distinguish patients with paroxysmal lone AF. The ability of those ECG markers and of other clinical and ECG variables to detect patients at risk for recurrent AF was tested in 88 patients, aged 64 +/- 12 years. All patients had a history of symptomatic episodes of AF during the last 2 years and had not previously received any antiarrhythmic prophylaxis. P maximum and P dispersion were calculated from a 12-lead surface ECG recorded in all patients during sinus rhythm. A computerized ECG system was used and P maximum and P dispersion were calculated on screen from the averaged complexes of all 12 leads. Age (P = 0.01), history of organic heart disease (P = 0.03), P maximum (P < 0.001), minimum P wave duration (P = 0.05), and P dispersion (P < 0.001) were found to be significant univariate predictors of recurrent AF, whereas only P maximum (P < 0.001) and age (P = 0.037) remained significant independent predictors of frequent AF paroxysms in the multivariate analysis. It is concluded that advanced age and prolonged P wave duration may be used as predictors of frequently relapsing AF. Therefore, simple AF predictors exist that could possibly distinguish the patients in whom prophylaxis with antiarrhythmic medicines should be instituted.

Comparison of different methods for manual P wave duration measurement in 12-lead electrocardiograms.

To determine whether different methods for the manual measurement of P wave duration are mutually consistent, we evaluated the intraobserver and interobserver errors of P wave measurements obtained in three different ways: (1) by cursor on a high resolution computer screen (on screen), (2) by calipers and a magnifying glass (on paper), and (3) by a high resolution digitizing board (on board). The agreement between the methods was assessed in 30 normal subjects and 30 patients with a history of atrial fibrillation. The maximum P wave duration (P maximum), the minimum P wave duration (P minimum), mean P wave duration (P mean), P wave dispersion (P dispersion = P maximum - P minimum), and the standard deviation of the P wave duration in all measured leads (P SD) were calculated from a 12-lead electrocardiogram in each subject. Only P maximum, P mean, and P dispersion were significantly higher in patients than in controls with all three methods. Intraobserver and interobserver relative errors were significantly different among the three methods; the lowest errors were associated with the on-screen measurement. The agreement between the three different methods was acceptable for P maximum, P mean, and P SD and rather poor for P minimum and P dispersion in both groups. The differences of the measurement by different methods did not consistently differ between the two groups. Hence, the on-screen measurements are consistent with other manual methods and provide more stable results. Manual measurement of ECG patterns should be preferably performed with digital ECG recordings displayed on a high resolution computer screen.

Effects of ischemia on P wave dispersion and maximum P wave duration during spontaneous anginal episodes.

P wave dispersion (P dispersion), defined as the difference between the maximum and the minimum P wave duration, and maximum P wave duration (P maximum) are electrocardiographic (ECG) markers that have been used to evaluate the discontinuous propagation of sinus impulses and the prolongation of atrial conduction time, respectively. To study the effects of myocardial ischemia on P dispersion and P maximum, 95 patients with coronary artery disease (CAD) and typical angina pectoris and 15 controls with angina like symptoms underwent 12-lead surface ECG during and after the relief of pain. During pain and during the asymptomatic period, P maximum and P dispersion were calculated from the averaged complexes of all 12 leads. P dispersion increased significantly during spontaneous angina (45+/-17 ms) compared to the asymptomatic period (40+/-15 ms), P < 0.001 only in the patient group. Both P maximum and P dispersion showed higher values during angina in those patients who developed diffuse ischemia, as estimated with ST segment changes in multiple ECG leads. P dispersion showed higher values during the anginal episode in patients with left ventricular dysfunction, independently of the presence of a previous myocardial infarction. Atrial conduction abnormalities, as estimated with P maximum and particularly P dispersion, are significantly influenced by myocardial ischemia in patients with CAD and spontaneous angina.