Theofilos M. Kolettis

Pioglitazone vs glimepiride: Differential effects on vascular endothelial function in patients with type 2 diabetes

OBJECTIVE The aim of this study was to compare the effect of glimepiride and pioglitazone on endothelial function in patients with type 2 diabetes already on metformin. METHODS Twenty-eight patients with type 2 diabetes already on metformin, without known cardiovascular disease, were randomized in 2 groups; glimepiride (4 mg od) was added in group A (n=14) and pioglitazone (30 mg od) in group B (n=14) for 6 months. Flow-mediated dilation (FMD) in the brachial artery was assessed in all patients, at baseline and at follow-up. RESULTS The 2 groups did not differ in age (mean+/-S.D., 63.6+/-7.3 years vs 62.8+/-7.2 years respectively), or any measured variable at baseline. Fasting glucose and glycated haemoglobin improved similarly in both groups. There were significant differences between the 2 groups in the absolute changes observed at follow-up in waist circumference, +1.86+/-3.11 cm vs -1.86+/-1.88 cm in groups A and B respectively; fasting insulin levels, +14.79+/-12.56 pmol/L vs -25.84+/-28.09 pmol/L; homeostasis model assessment (HOMA), +0.66+/-1.01 vs -1.83+/-1.38; HDL cholesterol levels, -0.07+/-0.22 mmol/L vs +0.14+/-0.20 mmol/L and FMD, +0.14+/-1.09% vs +2.02+/-2.05% (p<0.05 for all). The only independent predictor factor of the FMD improvement was treatment-induced changes in HOMA (R(2): 0.488, slope: -0.782, [95% CI: -1.128, -0.436], p=0.0001). CONCLUSIONS In patients with type 2 diabetes already on metformin, addition of pioglitazone as compared to glimepiride, improved endothelial function despite similar glycemic control. The improvement in endothelial function was mainly due to a reduction in insulin resistance.

Variation of inflammatory indexes after electrical cardioversion of persistent atrial fibrillation. Is there an association with early recurrence rates

Inflammation has been recently implicated in the pathophysiology of atrial fibrillation (AF). The aim of this study was to examine the variation of inflammatory indexes during the first week after successful electrical cardioversion of persistent AF. Successive measurements of white blood cell (WBC) count, C‐reactive protein (CRP) and fibrinogen levels were performed in 30 cardioverted patients. At the end of the 7‐day follow‐up period, AF had recurred in 30% of patients. A significant variance was found in serial measurements of fibrinogen levels in the two groups (non‐relapse and relapse, p = 0.005). Fibrinogen levels increased significantly in patients who relapsed into AF, but remained stable in patients who remained in sinus rhythm. In the latter patients, CRP values tended to decrease post‐cardioversion, but WBC count was significantly lower (p < 0.001) on the 7th day (6083 ± 1335), compared with baseline values (6648 ± 1395). The variation of inflammatory indices post‐cardioversion might have prognostic implications with regard to sinus rhythm maintenance.

Management of Inadvertent Left Ventricular Permanent Pacing

Inadvertent implantation of a pacemaker lead in the left ventricle is an uncommon complication. We report a case of a permanent pacemaker lead inadvertently placed through the left subclavian artery, across the aortic valve into the left ventricle. A chest X-ray one month after the procedure showed an unusual course of the lead and a 12-lead ECG and a transthoracic echocardiogram confirmed the diagnosis. The patient refused surgical removal and remained on fulll anticoagulation. No clinical events were recorded during a 3-year follow-up. In such cases we propose life-long full anticoagulation as an alternative to surgical lead extraction.

Provocation of Neurocardiogenic Syncope During Head-up Tilt Testing in Children: Comparison Between Isoproterenol and Nitroglycerin

OBJECTIVE. Although nitroglycerin- and isoproterenol-augmented tilt tests are of equal value in the diagnosis of neurocardiogenic syncope in adults, no data exist in children. We compared the sensitivity and specificity of the 2 tests in a pediatric population. PATITENS AND METHODS. We studied 85 patients (33 boys; mean age: 11.6 ± 2.9 years). Of them, 56 had a diagnostic history of neurocardiogenic syncope, whereas 29 served as controls. After a negative passive phase, they were randomly assigned to either intravenous isoproterenol or sublingual nitroglycerin, and tilt was continued for 20 minutes. RESULTS. Sensitivity was 0.78 for the isoproterenol test and 0.79 for the nitroglycerin test, but specificity was significantly higher for isoproterenol test compared with nitroglycerin test. In patients with a positive test, the duration of the recovery period was significantly longer after nitroglycerin (8.4 ± 2.7 minutes) than after isoproterenol (5.1 ± 1.6 minutes). CONCLUSIONS. Nitroglycerin- and isoproterenol-augmented tilt tests are associated with equal sensitivity in the diagnosis of neurocardiogenic syncope in children and adolescents. However, nitroglycerin results in more false-positive tests and produces more prolonged vasovagal symptoms. Our data do not support the routine use of nitroglycerin in the evaluation of syncope in this age group.

Effects of atrial, ventricular, and atrioventricular sequential pacing on coronary flow reserve.

KOLETTIS, T.M., et al.: Effects of Atrial, Ventricular, and Atrioventricular Sequential Pacing on Coronary Flow Reserve. Experimental animal data have indicated that altered left ventricular depolarization sequence as a result of right ventricular pacing may diminish coronary blood flow in the distribution of the left anterior descending coronary artery. To further investigate this, we compared the effects of atrial, ventricular, and atrioventricular (AV) sequential pacing on coronary flow reserve. Twenty‐seven patients (24 male, mean age 55 ± 7 years) with normal left anterior descending coronary arteries were studied. Coronary flow reserve was calculated as the ratio of mean flow velocity at maximal coronary vasodilatation to mean flow velocity at baseline. The study consisted of two parts. In the first part, AV sequential pacing was compared to atrial pacing at the same rate; coronary flow reserve did not differ significantly between the two pacing modes (14 patients, 4.85 ± 1.88 vs 5.47 ± 1.55, respectively, P > 0.05). In the second part, all three pacing modalities were compared; coronary flow reserve was significantly higher during ventricular compared to AV sequential pacing, but not significantly different compared to atrial pacing (3.69 ± 1.42 vs 2.90 ± 0.86 vs 3.11 ± 0.89, respectively, P < 0.05). This difference was secondary to a significant decrease in mean baseline velocity during ventricular pacing, while mean velocity during hyperemia was comparable between the three pacing modes. It is concluded that AV sequential pacing does not appear to exert a significant effect on coronary flow reserve. Ventricular pacing, however, may lower resting coronary blood velocity in some patients, without affecting maximal coronary blood velocity, resulting in a higher coronary flow reserve.

Coronary artery disease and ventricular tachyarrhythmia: pathophysiology and treatment

Ventricular tachyarrhythmias are common consequences of coronary artery disease. During the prehospital phase of acute myocardial infarction (MI), ischemia-induced electrophysiological changes and genetic factors are responsible for their occurrence, but the precise pathophysiologic mechanisms are ill-understood. Primary percutaneous coronary interventions (PCIs) have decreased the incidence of ventricular tachyarrhythmias during subsequent stages, and future treatments ameliorating reperfusion injury may provide further progress. In the chronic phase, antiarrhythmic drug therapy targeted toward arrhythmogenic substrate has relatively limited value, but alternative approaches are still uncertain. By contrast, prompt arrhythmia termination by implantable cardioverter-defibrillators (ICDs) is highly effective, although risk-stratification algorithms in candidate patients are inadequate. This review explores current views in the pathophysiology and treatment of ventricular tachyarrhythmias at different clinical stages.

Localization of accessory pathways by the electrocardiogram: which is the degree of accordance of three algorithms in use?

We evaluated the extent of agreement among three algorithms used for the localization of accessory pathways in patients with overt preexcitation. By the use of one algorithm, three independent couples of observers localized the accessory pathway in 95 consecutive patients showing overt preexcitation in the 12‐lead surface electrocardiogram. We defined the following regions: Left atrioventricular ring (LAVR), Right atrioventricular ring (RAVR), Left lateral/left anterolateral (LL/LAL), Left posterior/left posterolateral (LP/LPL), Left posteroseptal (LPS), Right midseptal (RMS), Right posteroseptal (RPS), Right posterior/right posterolateral (RP/RPL), Right lateral/right anterolateral (RL/RAL), and Right anterior/right anteroseptal (RA/RAS). The extent of agreement in each region was evaluated and compared with the expected one, as calculated from the reported. The extent of agreement was as expected: (1) high in the regions LAVR, RAVR, LL/LPS and (2) limited in the regions LPS, RPS, and (3) clearly lower than expected in the regions LP/LPL, RA/RAS, RMS, RL/RAL. In cases with total or partial disagreement, the number of electrocardiograms with duration of QRS complex smaller than 120 ms was greater than in cases with total agreement (30/46 vs 22/50, P < 0.05). The observed agreement among algorithms is clearly lower than the expected one. Minimal preexcitation, limited number of patients, and arbitrarily defined regions were possibly the reasons for some unexpected results. (PACE 2004; 27:189–193)

Coronary vasoconstriction after coronary angioplasty is attenuated by endothelin a receptor antagonism

P studies have demonstrated distal coronary vasoconstriction immediately after percutaneous transluminal coronary angioplasty (PTCA). It was presumed that this coronary vasoconstriction is the result of intimal injury or endothelial dysfunction,1 abnormal autoregulatory tone,2–4 formation of vasoactive substances,5,6 impaired release of endothelialderived relaxing factor,7 and activation of adrenergic neural reflexes.8 Endothelin-1 (ET-1) levels have been found to be elevated after PTCA.9 ET-1 produces very potent and marked vasoconstriction in vitro as well as in vivo.10 ET-1 binds to at least 2 receptors: in blood vessels, endothelin A (ETA) receptors are present only on vascular smooth muscle cells and cause contraction, whereas endothelin B receptors are on endothelium, causing vasodilatation, and on vascular smooth muscle cells, causing contraction. In healthy men, the major receptor causing vasoconstriction, at least in the systemic circulation, is the ETA receptor.11–13 Endogenously produced ET-1 contributes to the maintenance of basal coronary artery tone in humans with and without coronary artery disease.14 The aim of this study was to test the hypothesis that ETA receptor stimulation contributes to the coronary artery vasoconstriction observed after PTCA. We studied 22 consecutive patients, mean age 58 6 7 years, scheduled to undergo elective PTCA for an isolated obstructive lesion and willing to participate. The study conformed to the principles outlined in the Declaration of Helsinki, and was approved by the hospital ethics committee. All patients gave informed consent. All patients fulfilled the following entry criteria: (1) history of chronic stable angina pectoris

Growth hormone decreases phase II ventricular tachyarrhythmias during acute myocardial infarction in rats.

3 months, and (2) angiographic appearance of lesions displaying an internal diameter reduction .50%. Exclusion criteria were unstable angina, a history of previous myocardial infarction, left main stem disease, angiographic evidence of coronary collaterals, total and subtotal occlusive lesions, lesions adjacent to a bifurcation, diabetes mellitus, depressed left ventricular function (,55%), valvular heart disease, systolic blood pressure ,100 mm Hg, or any concurrent illness. Patients were randomly allocated to receive an intracoronary infusion of BQ-123 (n 5 11) or normal saline 0.9% (n 5 11). The 2 groups had similar clinical characteristics (Table 1). All procedures were performed in patients in the fasting state, without the use of premedication. Antianginal medications were discontinued for

Increased Vascular Inflammation in Early Menopausal Women Is Associated with Hot Flush Severity

12 hours before the procedure. No other medication apart from heparin and BQ-123 was given until the end of the protocol. PTCA was performed using a standard technique.9 Heparin was administered as a bolus at the beginning (5,000 IU intra-arterially) and during the procedure to maintain an activated clotting time of .300 seconds. Two balloon inflations were performed for each patient with a 5-minute resting interval. If the clinical and angiographic result was satisfactory after the second balloon inflation, the patient was randomized to 1 of the 2 groups. Patients who developed dissections at the dilated site, needed stent implantation for any reason, or had an unsatisfactory angiographic result after the second balloon inflation were excluded from the study. Hemodynamic measurements (heart rate and blood pressure) and coronary arteriograms recorded by hand injection were recorded at baseline (before angioplasty initiation) and 5 and 25 minutes after the second balloon inflation, with the guidewire in place. The study was completed when the arteriogram was obtained 25 minutes after the second balloon inflation. Five minutes after the second balloon inflation, BQ-123 (Clinalfa, Switzerland) or saline was infused through the guiding catheter at a constant rate of 1 ml/min (300 nmol/min) for 20 minutes. This dose of BQ-123 (total dose of 6 mmol) has been shown not to From Onassis Cardiac Surgery Center, Athens, Greece; and Department of Medical Sciences, University of Edinburgh, Western General Hospital, Edinburgh, Scotland. Dr. Kyriakides address is: Onassis Cardiac Surgery Center, 356 Sygrou Avenue, Athens 17674, Greece. E-mail: zskyr@otenet.gr. Manuscript received September 7, 2000; revised manuscript received and accepted November 6, 2000. TABLE 1 Clinical and Angiographic Characteristics of the Patients Studied