Ferhan Özmen

P Wave Dispersion on 12-Lead Electrocardiography in Patients with Paroxysmal Atrial Fibrillation

The prolongation of intraatrial and interatrial conduction time and the inhomogeneous propagation of sinus impulses have been shown in patients with atrial fibrillation. Recently P wave dispersion (PWD), which is believed to reflect inhomogeneous atrial conduction, has been proposed as being useful for the prediction of paroxysmal atrial fibrillation (PAF). Ninety consecutive patients (46 men, 44 women; aged 55 ± 13 years) with a history of idiopathic PAF and 70 healthy subjects (42 men, 28 women; mean age, 53 ± 14 years) were studied. The P wave duration was calculated in all 12 leads of the surface ECC. The difference between the maximum and minimum P wave duration was calculated and this difference was defined as P wave dispersion (PWD = Pmax ‐ Pmin). All patients and controls were also evaluated by echocardiography to measure the left atrial diameter and left ventricular ejection fraction (LVEF). There was no difference between patients and controls in gender (P = 0.26), age (P = 0.12), LVEF (66 ± 4% vs 67 ± 5%, P = 0.8) and left atrial diameter (36 ± 4 mm vs 34 ± 6 mm, P = 0.13). P maximum duration was found to be significantly higher in patients with a history of PAF (116 ± 17 ms) than controls (101 ±11 ms. P < 0.001). P wave dispersion was also significantly higher in patients than in controls (44 ± 15 ms vs 27 ± 10 ms, P < 0.001). There was a weak correlation between age and P wave dispersion (r = 0.27, P < 0.001). A P maximum value of 106 ms separated patients with PAF from control subjects with a sensitivity of 83%, a specificity of 72%, and a positive predictive accuracy of 79%. A P wave dispersion value of 36 ms separated patients from control subjects with a sensitivity of 77%, a specificity of 82%, and a positive predictive accuracy of 85%. In conclusion, P maximum duration and P wave dispersion calculated on a standard surface ECG are simple ECG markers that could be used to identify the patients with idiopathic paroxysmal atrial fibrillation.

P Wave Dispersion in Hypertensive Patients with Paroxysmal Atrial Fibrillation

It is important to assess the risk of developing paroxysmal atrial fibrillation (PAF) in hypertensive patients since hypertension is a common disorder predisposing to PAF. We sought to determine if patients with hypertension at risk of PAF can be identified while in sinus rhythm by measurements of P wave dispersion. Twelve‐lead surface electrocardiograms were recorded in 44 hypertensive patients with history of PAF (group I, mean age = 60) and in 50 hypertensive patients without history of AF (group II, mean age = 57). The maximum P wave duration, the minimum P wave duration, and P wave dispersion (Pd = Pmax ‐Pmin) were calculated from 12‐lead surface ECGs. Left atrial dimension (LAD) and left ventricular ejection fraction (LVEF) were measured by echocardiography. P wave dispersion was significantly greater in group I than group II (50 ± 12 vs 38 ± 8 ms, P = 0.001). P minimum (75 ± 13 vs 87 ± 11 ms, P = 0.001) and LVEF (0.63 ± 0.05 vs 0.67 ± 0.04, P = 0.03) were significantly lower in group I than group II. However P maximum and LAD were not significantly different in group I than group II (P > 0.05). In univariate analysis, P minimum, P wave dispersion, and LVEF were significant predictors of PAF, whereas only P wave dispersion remained a significant independent predictor of PAF in a multivariate analysis. Measurement of P wave dispersion in sinus rhythm may be a useful noninvasive clinical tool to identify patients with hypertension at risk of developing atrial electrical instability and atrial fibrillation.

Increased plasma levels of soluble selectins in patients with unstable angina

BACKGROUND Inflammation plays an important role in the pathogenesis of unstable angina. Adhesion molecules, such as selectins, mediate the interactions between leukocytes, platelets and endothelial cells during inflammation and thrombogenesis. HYPOTHESIS The purpose of this study was to determine whether soluble E-selectin, P-selectin and L-selectin levels are increased in patients with unstable angina (UA). METHODS Soluble E-, P- and L-selectin levels were measured by enzyme-linked immunoassay in the peripheral blood of 23 patients with UA, 26 patients with stable angina (SA) and 15 control patients with angiographically normal coronary arteries. RESULTS Soluble E-selectin levels were significantly higher in patients with UA (45+/-11 ng/ml) than in controls (30+/-8 ng/ml, P<0.001), or patients with SA (34+/-8 ng/ml, P=0.001). Similarly, plasma levels of P- and L-selectin were significantly higher in patients with UA (427+/-144 and 772+/-160 ng/ml, respectively) than in patients with SA (278+/-79 and 643+/-94 ng/ml, respectively, P<0.005 vs. UA for both), or control patients (189+/-43 and 601+/-126 ng/ml, respectively, P=0.001 vs. UA for both). CONCLUSIONS Plasma levels of soluble selectins were increased in patients with UA compared with patients with SA or patients without angiographically visible coronary artery disease. Measurements of these adhesion molecules may be helpful as non-invasive markers of coronary plaque destabilization in UA.

Acute Anterior Myocardial Infarction Following a Mild Nonpenetrating Chest Trauma A Case Report

Myocardial infarction in patients under age 45 years is a relatively unusual phenomenon; blunt chest trauma is one of the nonatherosclerotic mechanisms leading to acute myocardial infarc tion in young adults. The authors report a rare case of anterior myocardial infarction in a 22-year- old man following a mild nonpenetrating chest trauma whose left chest was elbowed during a soccer game.

Left Ventricular Long-Axis Function Is Reduced in Patients with Rheumatic Mitral Stenosis

Left ventricular long‐axis function evaluated by M‐mode or tissue Doppler echocardiography has been shown to be useful indexes of left ventricular systolic function; however it has not been evaluated in patients with mitral stenosis. We examined the left ventricular long‐axis function of the patients with pure mitral stenosis and normal global systolic function as assessed by fractional shortening of the left ventricle (LV). Fifty‐two patients with pure mitral stenosis and twenty‐two healthy controls were evaluated by echocardiography. Although there was no statistically significant difference in global systolic function, M‐mode derived systolic motion of the septal side and (12 ± 3 vs 14.4 ± 1.5 mm, P = 0.016) the lateral side of mitral annulus (13.2 ± 3 vs 16.8 ± 2 mm, P = 0.001) were both significantly lower in the patients with mitral stenosis than control subjects. Similarly tissue Doppler systolic velocity of the septal annulus (7.6 ± 1.1 vs 10.4 ± 3.2 cm/s, P = 0.03) and lateral mitral annulus (7.6 ± 1.1 vs 10.4 ± 3.2 cm/s, P = 0.003) were also significantly lower in patients with mitral stenosis than in controls. There was a statistically significant correlation between septal annular motion and annular velocity (r = 0.643, P = 0.002). Septal annular motion and annular velocity were also correlated with left atrial ejection fraction (r = 0.338, P = 0.005 and r = 0.676, P = 0.001, respectively). Thus, patients with mitral stenosis had significantly impaired long‐axis function evaluated by M‐mode or tissue Doppler echocardiography despite normal global systolic function. (ECHOCARDIOGRAPHY, Volume 21, February 2004)

Assessment of Heart Rate Turbulence in the Acute Phase of Myocardial Infarction for Long-Term Prognosis

SADE, E., et al.: Assessment of Heart Rate Turbulence in the Acute Phase of Myocardial Infarction for Long‐Term Prognosis. This study is designed to assess the value of heart rate turbulence (HRT) in the acute phase of MI for prediction of long‐term mortality risk. The study included 128 consecutive acute MI patients with 24‐hour Holter recordings to evaluate HRT (turbulence onset and slope), SDNN, mean RR interval, and ventricular premature beat frequency. LVEF was evaluated by two‐dimensional echocardiography. Data from 117 patients (mean age 58 ± 11 years) were available for further analysis. Twelve patients died during follow‐up (mean 312 ± 78 days). Although SDNN < 70 ms was the most powerful predictor of mortality among all presumed risk factors (hazard ratio 20 [95% CI 2.6–158]; P = 0.004) in univariate Cox regression analysis, in multivariate analysis LVEF ≤ 0.40 and turbulence slope ≤2.5 ms/RR interval were the only independent predictors of mortality (hazard ratio 6.9 [95% CI 1.8–26]; P = 0.006, hazard ratio 7.3 [95% CI 1.4–37]; P = 0.016, respectively). Addition of HRT parameters for LVEF increased remarkably the positive predictive value (60%) without any decrease in the negative predictive value (92%). Blunted HRT reaction within the first 24 hours of acute MI is an independent predictor of long‐term mortality. Furthermore, its predictive power is comparable and also additive to that of LVEF. (PACE 2003; 26[Pt. I]:544–550)

Assessment of Autonomic Nervous System Functions in Patients with Vitamin B12 Deficiency by Power Spectral Analysis of Heart Rate Variability

The purpose of this study was to test the autonomic nervous system function of patients with vitamin B12 deficiency (megaloblastic anemia) by measuring heart rate variability (HRV). The study population consisted of 17 vitamin B12 deficient patients and 15 age‐ and sex‐matched normal volunteers. HRV was measured by power spectral analysis from which power of the low frequency (LF) peak (0.04–0.15 Hz), normalized units of the LF peak (LFNU), power of the high frequency (HF) peak (0.15–0.4 Hz), normalized units of the HF (HFNU), and ratio of power of LF to power of HF (LF:HF) were calculated. Vitamin B12 deficient patients had lower LF, LFNU, HF, HFNU, and LF:HF ratio than normal volunteers (P < 0.05). Decreases in sympathetic indices (LF and LFNU) were greater than those measured in parasympathetic indices (HF and HFNU). All HRV parameters correlated positively with the level of vitamin B12 (P < 0.001) and negatively with the duration of disease (P < 0.001). After vitamin B12 replacement the HEV parameters of patients and controls became comparable (P > 0.05). Our data suggest that autonomic sympathetic and parasympathetic nervous activities are decreased in patients with vitamin B12 deficiency, an abnormality that can be corrected by vitamin B12 replacement therapy.

Effects of short-term atorvastatin treatment on global fibrinolytic capacity, and sL-selectin and sFas levels in hyperlipidemic patients with coronary artery disease

BACKGROUND The beneficial effects of HMG-CoA reductase inhibitors (statins) in patients with coronary artery disease (CAD) appear to be attributable not only to their lipid-lowering properties, but also to their therapeutic effects on the coagulation system, and anti-inflammatory effect. Furthermore, statins mitigate the apoptosis of vascular smooth muscle cells (VSMC) and macrophages in atherosclerotic plaques. HYPOTHESIS The purpose of this study was to evaluate the effects of short-term atorvastatin treatment on the fibrinolytic system and systemic inflammatory status, and on apoptosis in hyperlipidemic patients with CAD. METHODS The study population consisted of 36 hyperlipidemic patients (14 women and 22 men, mean age 53+/-9 years) with stable CAD, untreated with lipid-lowering medications. Serum lipoproteins, fibrinogen levels, sFas and sL-selectin, and global fibrinolytic capacity (GFC) were measured at baseline and after 12 weeks of treatment with atorvastatin, 10 mg/day. RESULTS Atorvastatin treatment decreased serum low-density lipoprotein (-39%, P=0.0001), total cholesterol (-32%, P=0.0001), and triglycerides (-22%, P=0.0001), and increased high-density lipoprotein (+13%, P=0.0001) at 12 weeks compared to baseline. These effects were associated with a decrease in plasma fibrinogen from 331+/-73 to 298+/-58 mg/dl (P=0.0001), and sL-selectin levels from 666+/-201 to 584+/-162 ng/ml (P=0.0001). sFas levels and GFC increased from 3754+/-1264 to 4873+/-1835 pg/ml and from 3.5+/-2.4 to 5.6+/-2.9 microg/ml, respectively (both P=0.0001). CONCLUSIONS These results suggest that lipid lowering with atorvastatin therapy significantly increases GFC, decreases fibrinogen levels, and causes leukocyte deactivation. Our findings also suggest that atorvastatin treatment mitigates apoptosis of VSMC in the atherosclerotic plaque. These effects of atorvastatin may, in part, explain the early decrease in cardiovascular events observed in clinical trials of statins.

Patients with paroxysmal atrial fibrillation but not paroxysmal supraventricular tachycardia display evidence of platelet activation during arrhythmia.

It is well known that chronic atrial fibrillation (CAF) and paroxysmal atrial fibrillation (PAF) are associated with a hypercoagulable state. However, pathological hemostatic changes during the paroxysmal supraventricular tachycardia (PSVT) have not yet been elucidated. To determine platelet activity in patients with PSVT, PAF and CAF, we examined the levels of β-thromboglobulin (BTG) and platelet factor 4 (PF4) during tachyarrhythmia attacks. We measured the levels of BTG and PF4, as an index of platelet activation in 15 patients with PAF (9 men, mean age 45 ± 11), and 14 patients with PSVT (8 men, mean age 40 ± 10). Levels were compared to 22 age and sex-matched healthy controls in sinus rhythm and with 25 patients with CAF (16 men, mean age 51 ± 12). Blood samples were taken during arrhythmia and 24 hours after conversion to sinus rhythm. Patients taking medications or have clinical conditions that may affect the BTG and PF4 levels were excluded. In patients with PAF, BTG and PF4 levels were significantly higher than in controls ( p<0.009, and p = 0.002, respectively), and in patients with PSVT ( p<0.04, and p = 0.009, respectively), however, BTG and PF4 levels were significantly lower than CAF patients ( p = 0.002, and p = 0.02, respectively). Moreover, BTG and PF4 levels were significantly decreased 24 hours after conversion to sinus rhythm ( p<0.0001, and p = 0.004, respectively). Although BTG and PF4 levels in patients with PSVT were significantly lower than in patients with PAF ( p = 0.04, and p = 0.009, respectively) and CAF ( p = 0.0001, and p = 0.0001, respectively), BTG and PF4 levels were similar to controls and did not change significantly after recovery to sinus rhythm ( p = NS for all). These results indicate that there was no platelet activation in patients with PSVT during tachyarrhythmia but significantly increased platelet activity in PAF and CAF patients. There was a significant decrement of the platelet activity to a level of control subjects twenty-four hours after cardioversion of PAF.

Thrombopoietin inside the pulmonary vessels in patients with and without pulmonary hypertension.

There is substantial evidence that platelet production and release take place in the lungs. Thrombopoietin (Tpo) stimulation can cause platelet release in the pulmonary vasculature. On the other hand, myelofibrosis can occur in Tpo-overexpressing transgenic mice models, and there is unexplained pulmonary hypertension in chronic myeloproliferative disorders including primary myelofibrosis. In this study, we aimed to assess local Tpo concentrations inside the pulmonary artery and associated vessels in humans. We measured Tpo concentrations in plasma samples taken concurrently from the right ventricle, the pulmonary artery, and the left ventricle during cardiac catheterization in patients with and without pulmonary hypertension. The study group comprised 10 patients with normal pulmonary arterial pressure (Group A, male/female 4/6, mean age 48 +/- 19) and 14 patients with pulmonary hypertension (Group B, male/female 9/5, mean age 57 +/- 16). The Tpo levels inside the right ventricle, the pulmonary artery and the left ventricle were 33.3 +/- 15.6, 47.2 +/- 33.9, and 34.4 +/- 18.6 pg/ml, respectively, in Group A; and 85.0 +/- 39.8, 128.4 +/- 50.4, and 81.5 +/- 35.5 pg/ml, respectively, in Group B. Levels of the Tpo were significantly higher in all three localizations in Group B compared to Group A. Moreover, the Tpo concentration inside the pulmonary artery is significantly higher than the Tpo concentrations in the right and left ventricles in Group B patients. There were positive correlations between the Tpo levels and pulmonary artery systolic pressure over the whole patient group. In conclusion, there could be an association between pulmonary hypertension and Tpo level. Moreover, lung vasculature holding the major regulatory thrombopoietic hormone, Tpo, may be an important place for megakaryocytopoiesis.Platelets of patients with uremia develop a defective platelet function and have a decreased production of thromboxane B2 (TxB2). Activated platelets generate thromboxane from free arachidonate that is previously released from the membrane phospholipids (PLs) by phospholipases. Phospholipase A2 (PLA2) release up to 70% of the arachidonate in normal platelets, and to date, the activity of this enzyme in uremia is unknown. This work studied the PLA2 activity in the platelets of nine uremic patients and nine healthy volunteers. Washed platelets were labelled with [ 14 C]arachidonic acid and activated with calcium ionophore A-23187 (4 w gr/ml). Lipids were resolved by TLC and identified by autoradiography. The distribution of [ 14 C]arachidonic acid in the five major platelet phospholipids was found to be normal. Uremic platelets released more radioactivity than normal platelets (19.0 - 5.2% versus 11.3 - 1.6%, P = 0.001). The production of both, radioactive thromboxane B2 and hydroxyheptadecatrienoic acid was normal (2.6 - 1.2% and 3.5 - 1.6% of total radioactivity respectively), but the formation of the lipoxygenase metabolite hydroxyeicosatetraenoic acid was increased with respect to the controls (12.9 - 4.6% vs 7.0 - 1.3% of total radioactivity, P = 0002). In conclusion, platelets of patients with uremia have an increased activity of phospholipase A2 and produce increased amounts of hydroxyeicosatetraenoic acid, an inhibitor of the platelet function.