Panayota Flevari

The predictive value of inflammatory and oxidative markers following the successful cardioversion of persistent lone atrial fibrillation

BACKGROUND Although there is evidence that inflammation and oxidative stress might contribute to the pathogenesis of atrial fibrillation (AF), the predictive value of inflammatory and oxidative stress markers in patients with AF has not been fully assessed. The aim of this study is to evaluate these markers as predictors of sinus rhythm (SR) maintenance, in patients with persistent lone AF. METHODS Among 268 patients with symptomatic AF, we studied 46 patients with a first episode of recently established persistent lone AF. We measured the circulating levels of hs-CRP, TNF-alpha, IL-6, IL-10, sICAM-1, sVCAM-1, malondialdehyde (MDA) and nitrotyrosine (NT) before, 1 h, 24 h, 1, 2, 4 and 6 weeks after cardioversion. During a 12-month follow-up period, AF recurrence was evaluated by Holter ECG recordings every month and when symptoms were reported. RESULTS Baseline levels of CRP, TNF-alpha, sICAM-1, MDA, and NT were elevated in patients with AF compared to controls, and higher in patients with than in those without persistent AF recurrence, while IL-6 levels were equally elevated in the two subgroups. SR maintenance was associated with lower baseline MDA values and faster decrease in IL-6, sICAM-1 and NT levels within the first 2 weeks following SR restoration. CONCLUSIONS Increased markers of inflammation and oxidative stress are found in patients with lone AF, implying that inflammation and oxidative stress may be associated with the presence of the arrhythmia. IL-6, sICAM-1, MDA and NT, assessed prior to and after the first cardioverted episode of persistent arrhythmia, appear to be reliable, early predictors of SR maintenance during the following year.

Long-term nonoutflow septal versus apical right ventricular pacing: relation to left ventricular dyssynchrony.

Background: Right ventricular (RV) apical pacing deteriorates left ventricular (LV) function. RV nonoutflow (low) septal pacing may better preserve ventricular performance, but this has not been systematically tested. Our aim was to assess (1) whether long‐term RV lower septal pacing is superior to RV apical pacing regarding LV volumes and ejection fraction (EF), and (2) if the changes in LV dyssynchrony imposed by pacing are related to the long‐term changes in LV volumes and EF.

Mortality after catheter ablation for atrial fibrillation compared with antiarrhythmic drug therapy. A meta-analysis of randomized trials

INTRODUCTION Nonrandomized studies suggest a survival benefit for patients with atrial fibrillation (AF) undergoing catheter ablation compared with antiarrhythmic drug (AAD) therapy. Data from randomized trials are lacking. We performed a meta-analysis on mortality in randomized controlled trials comparing AF ablation with AADs. METHODS Pubmed, the Cochrane Central Register of Controlled Trials, and abstracts of major conferences were searched for randomized trials comparing AF catheter ablation with AADs. Eight trials with a total of 930 patients were analyzed. Trial quality was assessed by a modified Jadad scale. Follow-up was 1 year in most trials. We assessed fixed effect risk differences (RDs) with the Mantel-Haenzel method, heterogeneity with I(2) statistic, and publication bias with Beggs funnel plot and with Eggers test. RESULTS A total of 7 deaths were reported: 3 in the ablation and 4 in the AAD arm. There was no difference in mortality between AF ablation and AAD therapy. The RD of mortality in all trials between patients randomized to ablation and those randomized to AADs was -0.003 (95% CI -0.018 to 0.013, P = .74) without evidence for heterogeneity (I(2) = 0%, P = .907). No potential publication bias was found. There was also no difference in rates of stroke or transient ischemic attack between ablation and antiarrhythmic therapy for AF (RD = 0.004, 95% CI -0.010 to 0.018, P = .54). CONCLUSION This meta-analysis of randomized controlled trials showed similar survival of patients undergoing catheter ablation for AF compared with patients treated with AADs after 12 months of follow-up. There was also no difference in the rates of stroke or transient ischemic attack. These findings can be probably explained by the low-risk young populations who were included in the trials and the relatively short 12-month follow-up.

Serum markers of deranged myocardial collagen turnover: their relation to malignant ventricular arrhythmias in cardioverter-defibrillator recipients with heart failure.

BACKGROUND Pathologic collagen remodeling has been involved in the occurrence of ventricular arrhythmias and sudden cardiac death in heart failure. The aim of the study was to investigate the relationship between malignant ventricular arrhythmias and cardiac collagen turnover indexes, expressing specific types of derangement in collagen physiology, in stable patients with an implantable cardioverter-defibrillator (ICD). METHODS Seventy-four patients with an ICD and heart failure were studied. They had coronary artery disease (n = 42) or dilated cardiomyopathy, New York Heart Association classes I and II, and left ventricular ejection fraction 29% ± 1%. An ICD had been implanted for secondary (n = 36) or primary prevention of sudden cardiac death. We assessed (1) markers of collagen types I and III synthesis and their ratio: procollagen type I carboxyterminal peptide (PICP), procollagen type III aminoterminal peptide (PIIINP), and PICP/PIIINP; (2) markers of collagen degradation, degradation inhibition, and their ratio: matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase (TIMP) 1 (TIMP-1), and MMP-9/TIMP-1. Patients were prospectively followed up for 1 year. The number of episodes necessitating appropriate interventions for ventricular tachyarrhythmias (>170 beat/min) was related to the assessed parameters. RESULTS Multivariate analysis revealed a significant relation between the number of tachyarrhythmic episodes and MMP-9/TIMP-1 (P = .007), PICP/PIIINP (P = .007), and ejection fraction (P = .04). No other significant relation was observed between arrhythmias and the remaining parameters. CONCLUSION In heart failure, biochemical markers indicative of a deranged equilirium in myocardial collagen deposition/degradation and collagen I/III synthesis are related to ventricular arrhythmogenesis. Further studies are needed to investigate their predictive ability.

Recurrent vasovagal syncope: comparison between clomipramine and nitroglycerin as drug challenges during head-up tilt testing

AIMS To compare the responses between clomipramine, a centrally acting substance, and nitroglycerin, with mainly peripheral action, when each drug is used during tilt test for the induction of vasovagal syncope (VVS). METHODS AND RESULTS Hundred patients with recurrent episodes of classical VVS underwent two tilt tests in a randomized sequence. One test included 20 min of tilt at 60 degrees with intravenous administration of 5 mg clomipramine (clomipramine tilt), whereas the other test included an initial 30 min period of passive 60 degrees tilt, followed by sublingual spray administration of 400 microg nitroglycerin (nitroglycerin tilt). Fifty asymptomatic subjects served as controls. Following clomipramine tilt, a positive response occurred in 73 patients (73%), a negative response in 23 (23%), and drug intolerance in 4 (4%). With nitroglycerin tilt, these percentages were 52, 48, and 0%, respectively. Significant differences were observed regarding positive responses (clomipramine vs. nitroglycerin: 73/100 vs. 52/100, P < 0.05), as well as negative responses (23/100 vs. 48/100, respectively, P < 0.05). A high concordance rate was observed in positive responses. CONCLUSION In the evaluation of patients with recurrent classical VVS, clomipramine tilt is associated with an increased positive yield relative to nitroglycerin tilt. This suggests that central mechanisms may be more important than peripheral ones in VVS pathogenesis.

Spironolactone improves endothelial and cardiac autonomic function in non heart failure hemodialysis patients.

Objectives: Hemodialysis patients have a cardiovascular mortality rate of 20–40 times that of the general population. Aldosterone inhibition by spironolactone has exerted beneficial, prognostically significant cardiovascular effects in patients with heart failure maintained on hemodialysis or peritoneal dialysis. Our aim was to investigate spironolactones effect in non heart failure hemodialysis patients. Methods: Fourteen stable chronic hemodialysis patients (nine men), 59.5 ± 3.1 years of age were evaluated in a sequential, fixed-dose, placebo-controlled study. Heart failure was diagnosed on the basis of signs and symptoms of heart failure or left ventricular ejection fraction less than 50%. Following an initial 4-month period of placebo administration after each dialysis, patients received spironolactone (25 mg thrice weekly after dialysis) for the next 4 months. Data were recorded at baseline, at the end of placebo administration, and at the end of spironolactone treatment and included endothelial function by forearm reactive hyperemia during venous occlusion plethysmography, cardiac autonomic status by heart rate variability in the time and frequency domain, blood pressure response, and echocardiographic and laboratory data. Results: Placebo induced no changes in the aforementioned parameters. Following spironolactone, salutary effects were observed in the extent and duration of reactive hyperemia (P < 0.05 for both), as well as in heart rate variability (P < 0.05) and blood pressure control (P < 0.05). No changes occurred in echocardiographically derived left ventricular dimensions or mass. Conclusion: Low-dose spironolactone therapy in clinically stable non heart failure hemodialysis patients is associated with favorable effects on cardiovascular parameters known to adversely affect survival, such as endothelial dysfunction and heart rate variability. Spironolactone treatment might benefit long-term cardiovascular outcome of such patients.

Minor psychiatric disorders and syncope: the role of psychopathology in the expression of vasovagal reflex.

Background: A high prevalence of minor psychiatric disorders (MPDs) has been reported in patients with vasovagal syncope (VVS). However, the relationship between the psychiatric substrate and syncope remains unclear. Methods: In order to test the hypothesis that MPDs may predispose to VVS, we assessed the prevalence of syncope, the response to head-up tilt test (HUTT) and the efficacy of psychiatric drug treatment in reducing syncopal episodes, in patients with recently diagnosed MPDs. The response to HUTT was compared with that in an equal number of matched (a) patients with VVS and (b) healthy controls. Results: A high rate of patients with MPDs (58%) had a positive HUTT. Additionally, 45% had a history of syncope; among them, the rate of positive HUTT was identical to that in the VVS group (83%). Following psychiatric drug treatment, the number of patients with syncope decreased in the MPD group (6/67 from 30/67, p < 0.01). Psychiatric symptoms and quality of life were also improved. The number of syncopal spells decreased equally in the MPD and VVS groups (0.6 ± 0.5 from 2.5 ± 1.4, p < 0.01, and 0.7 ± 0.5 from 2.7 ± 1.3, p < 0.01, respectively). Conclusion: A high proportion of patients with MPDs experience syncope, associated with a high rate of positive HUTT, comparable to that observed in VVS. Psychiatric treatment results in the improvement of syncopal and psychiatric symptoms. These findings suggest involvement of co-occurring MPDs in the pathogenesis of VVS. Therefore, the diagnosis and treatment of MPDs, when present, may be crucial for the effective therapy of vasovagal syndrome.

Acute effects of unilateral temporary stellate ganglion block on human atrial electrophysiological properties and atrial fibrillation inducibility

BACKGROUND In experimental models, stellate ganglion block (SGB) reduces the induction of atrial fibrillation (AF), while data in humans are limited. OBJECTIVE The aim of this study was to assess the effect of unilateral SGB on atrial electrophysiological properties and AF induction in patients with paroxysmal AF. METHODS Thirty-six patients with paroxysmal AF were randomized in a 2:1 order to temporary, transcutaneous, pharmaceutical SGB with lidocaine or placebo before pulmonary vein isolation. Lidocaine was 1:1 randomly infused to the right or left ganglion. Before and after randomization, atrial effective refractory period (ERP) of each atrium, difference between right and left atrial ERP, intra- and interatrial conduction time, AF inducibility, and AF duration were assessed. RESULTS After SGB, right atrial ERP was prolonged from a median (1st-3rd quartile) of 240 (220-268) ms to 260 (240-300) ms (P < .01) and left atrial ERP from 235 (220-260) ms to 245 (240-280) ms (P < .01). AF was induced by atrial pacing in all 24 patients before SGB, but only in 13 patients (54%) after the intervention (P < .01). AF duration was shorter after SGB: 1.5 (0.0-5.8) minutes from 5.5 (3.0-12.0) minutes (P < .01). Intra- and interatrial conduction time was not significantly prolonged. No significant differences were observed between right and left SGB. No changes were observed in the placebo group. CONCLUSION Unilateral temporary SGB prolonged atrial ERP, reduced AF inducibility, and decreased AF duration. An equivalent effect of right and left SGB on both atria was observed. These findings may have a clinical implication in the prevention of drug refractory and postsurgery AF and deserve further clinical investigation.

Vasodilation in Vasovagal Syncope and the Effect of Water Ingestion

Abnormal (increased, but also decreased) vasodilative responses have been observed in patients with vasovagal syncope (VVS). The objective was to assess reactive vasodilation in supine patients with VVS and its relation to severity of the syndrome. Reactive vasodilation was also assessed after a simple therapeutic intervention (water drinking). Thirty-four patients were studied, all with recurrent VVS and a recent positive head-up tilt test result. Seventeen matched healthy subjects served as controls. Venous occlusion plethysmography was used to assess forearm blood flow (FBF) and forearm vascular resistance resistance (1) at rest and (2) during reactive hyperemia. Clinical severity of the syndrome was related to the intensity and duration of the vasodilative reflex. The same plethysmographic measurements were repeated 60 minutes after drinking 500 ml of water. Before water drinking, no difference was observed between groups in baseline measurements. However, duration of hyperemia was longer in patients (p <0.05) and was related to the duration of the previous positive tilt test (r = -0.69, p <0.05) and total number of each patients symptomatic vasovagal episodes (r = 0.49, p <0.05). After water ingestion, baseline FBF decreased in patients (p <0.05) and remained stable in controls. In patients, duration of hyperemia decreased to normal values. Hyperemic FBF remained similar between groups. In conclusion, increased reactive vasodilative reflexes were observed in patients with VVS. They seemed to be of significant pathophysiologic significance. Water drinking can normalize them for >or=60 minutes.

Copeptin levels in patients with vasovagal syncope

BACKGROUND AND PURPOSE Vasovagal syncope (VVS) is linked to more than one pathophysiologic mechanisms. Copeptin, an emerging cardiovascular marker, is a surrogate for arginine-vasopressin, which increases following VVS. We aimed to assess the dynamic pattern of copeptin levels in typical VVS, categorized by the degree of vasoconstriction during orthostasis, and healthy controls. METHODS The following groups were studied: Group A (n=21), with adequate limb vasoconstriction during the first min. of tilt, assessed by limb plethysmography (at least 30% flow reduction); Group B (n=15), showing impaired vasoconstriction during orthostasis (<10% reduction); Group C (n=18), history of VVS and negative tilt test result; Group D (n=18), healthy controls. Copeptin plasma levels were assessed before and 5min following tilt test positivity or termination. RESULTS Baseline copeptin values were similar in all groups (8.3±6.4 in Group A, 5.7±2.3pmol/l in B, 6.0±1.9 in C, and 6.9±2.6 in D, p: 0.41). Significant increases in copeptin during tilt were observed in all Groups of VVS patients (A, B, C), including those with negative tilt (Group C: from 6.0±1.9 to 27.7±12.6pmol/l, p: 0.001), but not in controls. Following tilt termination, a greater increase was observed in copeptin values in Group B vs all other Groups A, C, and D (111.6±63.5 vs 29.5±51.3, 27.7±12.6, and 8.3±2.9, respectively). CONCLUSIONS Copeptin increases following tilt not only in VVS with a positive response, but also in typical history patients with a negative test. Increased copeptin levels following orthostasis may be useful for diagnosing VVS.