Ioannis Rizos

Electrophysiologic testing in assessment of therapy with sotalol for sustained ventricular tachycardia.

Eighteen patients with sustained ventricular tachycardia underwent electrophysiologic studies to establish the therapeutic efficacy of sotalol. In each patient ventricular tachycardia could be reproducibly initiated by programmed stimulation during control studies. Sotalol prevented induction of sustained ventricular tachycardia in 12 of the 18 patients (67%). Prolongation of the QTC interval and of ventricular refractoriness was regularly observed after sotalol but did not reliably predict prophylactic efficacy. Severe adverse effects, including congestive heart failure and sinus node dysfunction, were noted early during sotalol therapy in three patients. Nine patients were placed on long-term oral treatment with sotalol and four patients on another effective agent. In these 13 patients, complete (12 patients) or partial (one patient) long-term prophylaxis against ventricular tachycardia was documented over a mean follow-up period of 16 months (range 8 to 24). The study suggests that sotalol can provide effective prophylaxis against sustained ventricular tachycardia; this prophylactic efficacy is not typical for pure beta-adrenergic antagonism but may at least partly result from experimentally observed prolongation of the ventricular action potential duration.

Isolated Left Ventricular Noncompaction: An Unclassified Cardiomyopathy with Severe Prognosis in Adults

Noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy, which appears to represent an arrest in intrauterine endomyocardial morphogenesis. It is diagnosed both in children and adults. Its common presentation involves heart failure symptoms, ventricular tachyarrhythmias and thromboembolic events, but the age of onset varies widely. The diagnosis is made by the combined appearance of numerous, excessively prominent trabeculations and multiple deep intertrabecular recesses perfused from the ventricular cavity, commonly involving the apical and midventricular segments of the left ventricle. Although the peculiar echocardiographic picture may possibly lead to the correct diagnosis, this condition may be often misdiagnosed or unrecognized since it is not widely known.

Differential effects of sotalol and metoprolol on induction of paroxysmal supraventricular tachycardia

Seventeen patients with recurrent paroxysmal supraventricular tachycardia (SVT) underwent serial electrophysiologic studies to compare the effects of i.v. sotalol (1.5 mg/kg) and i.v. metoprolol (0.15 mg/kg). The plasma concentrations of sotalol (2.1 +/- 1.1 microgram/ml) and metoprolol (67 +/- 15 ng/ml) were within the therapeutic range. Before drug administration, sustained SVT could be reproducibly induced in all patients. Sotalol prevented induction of sustained SVT in 10 of 17 patients (59%) and metoprolol in 4 (28%) (p less than 0.05). In 6 of 8 patients with atrioventricular (AV) nodal reentrance, the site of action of sotalol was the anterograde or the retrograde limb, reflecting an increase in refractoriness in both pathways of the circus movement. In 4 of 9 patients with AV reentrance, the site of action of sotalol was exclusively the AV nodal pathway; conduction through the extranodal accessory tract appeared to be unchanged, but its anterograde effective refractory period was prolonged (from 285 +/- 25 to 322 +/- 28 ms, p less than 0.001; mean +/- standard deviation). In the 7 patients in whom sotalol did not prevent sustained SVT, the tachycardia cycle length increased from 347 +/- 42 to 392 +/- 45 ms (p less than 0.01). Compared with sotalol, metoprolol had qualitatively similar but quantitatively less potent effects on the AV nodal pathways; however, different from sotalol, metoprolol had no effect on extranodal accessory tracts. The study suggests that at therapeutic plasma concentrations, sotalol would be effective in preventing clinical SVT in a significant proportion of patients refractory to metoprolol; because sotalol not only has beta-blocking properties but also results in acute prolongation of the action potential duration, this combination of class II and III activity may contribute to its superior prophylactic efficacy compared with pure beta blockade.

Lipoprotein-Associated Phospholipase A2 Bound on High-Density Lipoprotein Is Associated With Lower Risk for Cardiac Death in Stable Coronary Artery Disease Patients : A 3-Year Follow-Up

OBJECTIVES The aim of this study was to examine the prognostic value of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) associated with high-density lipoprotein (HDL) (HDL-Lp-PLA(2)) in patients with stable coronary artery disease (CAD). BACKGROUND Lp-PLA(2) is a novel risk factor for cardiovascular disease. It has been postulated that the role of Lp-PLA(2) in atherosclerosis may depend on the type of lipoprotein with which it is associated. METHODS Total plasma Lp-PLA(2) and HDL-Lp-PLA(2) mass and activity, lipids, and C-reactive protein were measured in 524 consecutive patients with stable CAD who were followed for a median of 34 months. The primary endpoint was cardiac death, and the secondary endpoint was hospitalization for acute coronary syndromes, myocardial revascularization, arrhythmic event, or stroke. RESULTS Follow-up data were obtained from 477 patients. One hundred twenty-three patients (25.8%) presented with cardiovascular events (24 cardiac deaths, 47 acute coronary syndromes, 28 revascularizations, 22 arrhythmic events, and 2 strokes). Total plasma Lp-PLA(2) mass and activity were predictors of cardiac death (hazard ratio [HR]: 1.013; 95% confidence interval [CI]: 1.005 to 1.021; p = 0.002; and HR: 1.040; 95% CI: 1.005 to 1.076; p = 0.025, respectively) after adjustment for traditional risk factors for CAD. In contrast, HDL-Lp-PLA(2) mass and activity were associated with lower risk for cardiac death (HR: 0.972; 95% CI: 0.952 to 0.993; p = 0.010; and HR: 0.689; 95% CI: 0.496 to 0.957; p = 0.026, respectively) after adjustment for traditional risk factors for CAD. CONCLUSIONS Total plasma Lp-PLA(2) is a predictor of cardiac death, while HDL-Lp-PLA(2) is associated with lower risk for cardiac death in patients with stable CAD, independently of other traditional cardiovascular risk factors.

Evolutionary pattern and prognostic importance of heart rate variability during the early phase of acute myocardial infarction.

AIMS To investigate the evolution of time domain heart rate variability in the early phase of acute myocardial infarction (MI) and assess its prognostic ability. METHODS We analysed several measures of heart rate variability (SDNN, SDANN, SDNN index, RMSSD) in 138 patients at days 0, 1 and 5+/-1 after hospital admission for acute MI. Results were correlated with infarct site, clinical variation and clinical outcome (death, MI, PTCA, CABG surgery). RESULTS Measures of heart rate variability (SDNN, SDANN and SDNN index) declined during the first 24 h after acute MI (P<0.01) and increased to admission levels after about 5 days. SDNN values on day 0, 1 and 5 respectively were: 86+/-35, 75+/-28 and 87+/-27 ms. Patients with anterior infarction had lower heart rate variability than patients with inferior infarction on all test days but similar evolution patterns. After 3 years of follow-up there were 12 cardiac deaths (8.7%) and six resuscitated arrests and 33 (24%) new MIs, or revascularisation procedures. The evolutionary pattern of heart rate variability was similar in survivors to those who died although values were generally lower. Mortality was significantly higher in the group with SDNN<50 ms at day 1 (P<0.01) and 5 (P<0.05), but not at day 0. CONCLUSIONS Our findings show that autonomic imbalance, already evident on the day of the acute event, progresses further over the next 24 h and recovers over the next few days. Low heart rate variability as early as 24 h after acute MI may be a useful predictor of cardiac mortality and contribute to the early risk stratification and therapeutic management of patients.

Novel association patterns of cardiac remodeling markers in patients with essential hypertension and atrial fibrillation

BackgroundMatrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are essential for the cardiac extracellular matrix (ECM) remodeling. We investigated differences in serum levels of these markers between patients with atrial fibrillation (AF) and sinus rhythm (SR).MethodsSerum levels of MMP-2, MMP-3, MMP-9 and TIMP-1 were measured in 86 patients: 27 on SR without any AF history, 33 with paroxysmal and 26 with permanent AF. All subjects had essential hypertension, normal systolic function and no coronary artery disease.ResultsPatients with AF had higher MMP-2, MMP-3 and MMP-9 and lower TIMP-1 compared to SR subjects (all p < 0.001). Paroxysmal AF was associated with higher MMP-2 levels compared to permanent AF (p < 0.001). Matrix metalloproteinase-9 but not MMP-3 was higher in permanent compared to paroxysmal AF group (p < 0.001). Patients with AF had lower levels of TIMP-1 compared to those with SR while permanent AF subjects had lower TIMP-1 levels than those with paroxysmal AF (p < 0.001 for both comparisons). Lower TIMP-1 was the only independent factor associated with AF (OR: 0.259, 95%CI: 0.104-0.645, p = 0.004).ConclusionsIn hypertensives, paroxysmal AF and permanent AF differ with respect to serum MMPs. Increased MMP-2 is associated with paroxysmal, whereas increased MMP-9 with permanent AF. Additionally, lower levels of TIMP-1 had a strong association with AF incidence.

Coronary Artery Ectasia, Aneurysm of the Basilar Artery and Varicose Veins: Common Presentation or Generalized Defect of the Vessel Wall?: A Case Report

A young man who suffered from an acute myocardial infarction is presented. He presented coronary artery ectasia along with coronary artery disease. Further evaluation revealed the presence of both a saccular aneurysm of the basilar artery as well as varicose veins of the lower limbs. A common pathogenic mechanism is discussed since all these findings are characterized by similar histologic substrate with the most profound defect being destruction of the myoelastic elements of the media.

Amiodarone in patients with recurrent sustained ventricular tachyarrhythmias: results of programmed electrical stimulation and long-term clinical outcome in chronic treatment.

Thirty-three patients with clinically recurrent ventricular tachyarrhythmias were treated with amiodarone (200 to 600 mg/day) during a mean follow-up period of 23.7 months. Prior to amiodarone therapy, sustained ventricular tachycardia or ventricular fibrillation was initiated in all patients at control electrophysiologic study; patients failed a mean of 5.7 drugs, as assessed by programmed electrical stimulation. At electrophysiologic study after a loading phase (1000 mg/day for 10 days), 10 patients had no inducible ventricular tachycardia, nine patients had nonsustained ventricular tachycardia, 13 patients had persistent sustained ventricular tachycardia, and one patient had ventricular fibrillation. Patients were continued on amiodarone alone regardless of the findings at the electrophysiologic study, and during follow-up patients with no inducible sustained ventricular tachycardia or fibrillation on amiodarone had no recurrent arrhythmias or sudden death. Six of 14 patients (43%) with sustained ventricular tachyarrhythmias still inducible had recurrent ventricular tachycardia/fibrillation, and four of them died suddenly (29%). Programmed electrical stimulation predicts a good clinical long-term outcome during amiodarone therapy. Patients with persisting fast tachyarrhythmias (cycle length less than or equal to 300 msec) on amiodarone and a low ejection fraction (less than 35%) seem to have a higher incidence of sudden death. In these patients, therapeutic approaches such as antiarrhythmic surgery or implantation of antitachycardia devices should be considered.

Hypertension and paroxysmal atrial fibrillation: a novel predictive role of high sensitivity C-reactive protein in cardioversion and long-term recurrence

The role of inflammation in maintenance of paroxysmal atrial fibrillation (PAF) in patients with hypertension and no other heart disease has not been fully elucidated yet. We investigated the association of various inflammatory markers with cardioversion and recurrence of PAF in patients with hypertension. We studied 75 patients (44 male, mean age 67.9±9.9 years) with PAF (duration from onset of symptoms<24 h) secondary to hypertension. None had heart failure or any other ongoing inflammatory process. All patients received anticoagulation and intravenous amiodarone for cardioversion. High sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and tumour necrosis factor (TNF)-α were measured on admission and 48 h later. By 48 h from admission 61/75 patients (81.3%) regained sinus rhythm (cardioverted), whereas 14/75(18.7%) remained in AF (non-cardioverted). hsCRP, IL-6 and TNF-α serum levels on admission were similar between groups. hsCRP at 48 h was the most significant factor correlated with cardioversion outcome (OR: 0.06, 95% CI: 0.01–0.47, P=0.008). During a 1-year follow-up, AF recurred in 28/61(45.9%) patients. The strongest factor associated with AF recurrence was hsCRP at 48 h ⩾2.27 mg l−1 (hazard ratio: 6.2, 95% CI: 2.2–17.6, P=0.001). hsCRP at 48 h after admission correlates with cardioversion outcome and may predict long-term AF recurrence.

Peripheral blood lymphocytes from patients with bipolar disorder demonstrate apoptosis and differential regulation of advanced glycation end products and S100B

Abstract Background: This study addresses the expression of the glycosylated proteins known as advanced glycation end products (AGEs), the calcium binding protein S100B and the apoptotic parameters cytochome c and caspase-3 activity in peripheral lymphocyte cytosolic extracts from a sample of bipolar disorder (BD) patients and healthy (control) subjects. Methods: Cross-sectional study of 35 patients with a clinical diagnosis of bipolar disease (10 euthymic, 12 depressed, 13 manic) and 10 healthy control subjects. Lymphocytes were used as a surrogate model in BD diagnosis and treatment. AGEs and S100B in lymphocyte cell extracts were measured by commercially available enzyme-linked immunosorbent assay. Results: AGEs were lower in all BD patients compared to healthy subjects. Depressed patients had approximately two-fold higher S100B levels compared to healthy subjects. Manic and depressed BD patients had increased superoxide dismutase mRNA levels. Apoptosis as measured by BAX/Bcl2 ratio, cytochrome c release, caspase-3 activity was increased in manic and depressed patients compared to healthy subjects. In the depressed patients, S100B levels correlated with cytochrome c release. Conclusions: In conclusion, our study shows decreased AGEs and increased S100B levels and caspase down-stream apoptosis in peripheral lymphocytes of BD patients that may underlie disease etiopathogenesis.