Repeating noninvasive risk stratification improves prediction of outcome in ICD patients.

BACKGROUND: Noninvasive risk stratification aims to detect abnormalities in the pathophysiological mechanisms underlying ventricular arrhythmias. We studied the predictive value of repeating risk stratification in patients with an implantable cardioverter-defibrillator (ICD). METHODS: The EUTrigTreat clinical study was a prospective multicenter trial including ischemic and nonischemic cardiomyopathies and arrhythmogenic heart disease. Left ventricular ejection fraction ≤40% (LVEF), premature ventricular complexes >400/24 hr (PVC), non-negative microvolt T-wave alternans (MTWA), and abnormal heart rate turbulence (HRT) were considered high risk. Tests were repeated within 12 months after inclusion. Adjusted Cox regression analysis was performed for mortality and appropriate ICD shocks. RESULTS: In total, 635 patients had analyzable baseline data with a median follow-up of 4.4 years. Worsening of LVEF was associated with increased mortality (HR 3.59, 95% CI 1.17-11.04), as was consistent abnormal HRT (HR 8.34, 95%CI 1.06-65.54). HRT improvement was associated with improved survival when compared to consistent abnormal HRT (HR 0.10, 95%CI 0.01-0.82). For appropriate ICD shocks, a non-negative MTWA test or high PVC count at any moment was associated with increased arrhythmic risk independent of the evolution of test results (worsening: HR 3.76 (95%CI 1.43-9.88) and HR 2.50 (95%CI 1.15-5.46); improvement: HR 2.80 (95%CI 1.03-7.61) and HR 2.45 (95%CI 1.07-5.62); consistent: HR 2.47 (95%CI 0.95-6.45) and HR 2.40 (95%CI 1.33-4.33), respectively). LVEF improvement was associated with a lower arrhythmic risk (HR 0.34, 95%CI 0.12-0.94). CONCLUSIONS: Repeating LVEF and HRT improved the prediction of mortality, whereas stratification of ventricular arrhythmias may be improved by repeating LVEF measurements, MTWA and ECG Holter monitoring.

Review on sudden death risk reduction after septal reduction therapies in hypertrophic obstructive cardiomyopathy.

Treatment of left ventricular outflow tract (LVOT) obstruction in hypertrophic obstructive cardiomyopathy (HOCM) with septal reduction, either with myectomy or alcohol septal ablation, is aiming to reduce the LVOT gradient and improve symptoms in patients who are refractory to or do not tolerate medical treatment. Apart from contributing to the evolution to heart failure, LVOT obstruction is considered a risk factor for sudden cardiac death (SCD). Both septal reduction treatments have been proven effective in reducing symptoms and seem to improve survival, which has been shown equal to the expected in the normal population. SCD is probably reduced after septal reduction, implying that LVOT obstruction is a major factor predisposing to ventricular tachyarrhythmias. Although available algorithms for SCD stratification have not been tested in patients after septal reduction treatments, effective treatment improves SCD risk profile substantially. Furthermore, high-risk patients with already implanted implantable cardioverter defibrillators (ICDs) before septal reduction show very low appropriate ICD shock rate after effective treatment. It should be noted, however, that the best outcomes for septal myectomy or ablation have been reported in HOCM patients treated in high-volume centres, which substantiates the need to refer patients to centres with high procedural expertise.

Fluoxetine vs. placebo for the treatment of recurrent vasovagal syncope with anxiety sensitivity.

AIMS: The optimal medical therapy of patients with vasovagal syncope (VVS) remains controversial. Fluoxetine is effective against anxiety and panic disorders, while its use has shown promising results for VVS. Anxiety sensitivity is a personality trait observed in a considerable proportion of patients with VVS, associated with predisposition to anxiety and panic disorders. Our aim was to examine whether fluoxetine exerts beneficial effects regarding VVS prevention in the subset of patients with anxiety sensitivity. METHODS AND RESULTS: We assessed 106 patients with typical history of recurrent VVS, without other comorbidities, and a diagnostic, positive head-up tilt test. A psychiatric examination ruled out clinical psychiatric disease. Their psychological, stress-related profile was assessed by the Anxiety Sensitivity Index (ASI) questionnaire, a 16-item questionnaire, assessing fear of anxiety-related sensations, previously studied in VVS. Patients scoring positive for ASI (n = 60, 57% of the population) were randomized in a 2:1 fashion to receive either 10-40 mg fluoxetine daily (n = 40) or placebo (n = 20), and were followed-up for 1 year. A significant difference was observed between patients receiving fluoxetine and those with placebo, regarding the distribution of syncope-free time during the study (P < 0.05). A significant difference was also observed between the two groups regarding presyncopal events and the total number of patients who experienced syncope or presyncope during follow-up. CONCLUSION: Sensitivity to anxiety is a common personality trait in recurrent VVS. Fluoxetine is superior to placebo against syncope in these patients. This drug may be a first-line pharmacological treatment for this difficult-to-treat group.

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.

Factors Associated With Insomnia in Patients Undergoing Hemodialysis.

INTRODUCTION: Insomnia is the most common sleep disorder among patients on hemodialysis and has a strong relation with fatigue, depression, low immune system, increased risk of cardiovascular problems, and low quality of life. The aim of this study was to explore the factors associated with insomnia in patients undergoing hemodialysis.  Methods: In this cross-sectional study, 100 patients on hemodialysis (75 males and 25 females) from a hemodialysis center in Greece were included. Insomnia was assessed via the "Athens Insomnia Scale (AIS)" and a questionnaire about demographic and clinical characteristics. The Kruskal-Wallis, Mann-Whitney tests, and Spearman's rho criterion were used to evaluate the association between insomnia score and patients' characteristics. Multiple linear regression was performed to assess the effect of characteristics on patients' insomnia. RESULTS: Statistically significantly high levels of insomnia were found in patients over the age of 60 years (p = 0.002), in divorced/widowed patients (p = 0.007), in patients who had comorbid diseases (p = 0.001), in patients who felt tired after hemodialysis (p = 0.001), in those who had continuous fatigue (p = 0.001) and change in body image (p = 0.003), in those who often had itching (p = 0.007) and stiffness in joints (p = 0.001) and in patients who had limitations in the clothes they could wear (p = 0.001). CONCLUSIONS: The findings of this study showed that insomnia had a strong association with increased age of patients, comorbidities, fatigue, change in body appearance, pruritus, and limitation in clothes they could wear. Therefore, there is a necessity for early assessment of sleep quality and effective treatment of sleep disorders in hemodialysis patients in order to reduce morbidity and mortality and improve the quality of their life.

Factors Associated With Fatigue in Patients Undergoing Hemodialysis.

Background and objective Fatigue is frequently experienced by patients undergoing hemodialysis and it has a negative effect on their quality of life. The aim of this study was to investigate the factors associated with fatigue in patients undergoing hemodialysis. Methods In this quantitative cross-sectional study, 100 patients on hemodialysis participated. Fatigue was evaluated via the Modified Fatigue Impact Scale (MFIS). Participants also completed a questionnaire about demographics and clinical characteristics. The Kruskal-Wallis test, the Mann-Whitney U test, and Spearman's rho criterion were used to assess the association between fatigue score and patient characteristics. Multiple linear regression was performed to assess the effect of the characteristics on patients' fatigue. Results Statistically significant high levels of physical or mental fatigue were found in older patients (p=0.001 and p=0.001), divorced/widowed patients (p=0.001 and p=0.014), those who had children (p=0.019), those who had primary education (p=0.015), those who were not informed about their health problems (p=0.003 and p=0.006), those who had comorbid diseases (p=0.001 and p=0.001), those who believed that regular information did not help to reduce stress (p=0.005 and p=0.004), patients who had insomnia (p=0.001 and p=0.001), patients who felt tired after hemodialysis (p=0.001 and p=0.001), those who thought they had a change in body image (p=0.001 and p=0.001), those who often felt stiffness (p=0.001 and p=0.001), those who sometimes felt nausea (p=0.015 and p=0.038), and those who had limitations in the clothes they could wear (p=0.001 and p=0.001). Conclusions The findings of this study showed that physical or mental fatigue had a strong association with advanced age, comorbidities, marital status, level of education, inadequate information about the disease, insomnia, and change in body appearance. Hence, renal professionals need to properly educate dialysis patients on the complicated nature of fatigue in order to manage it effectively and improve their physical, cognitive, and social wellbeing.

The role of the selective serotonin re-uptake inhibitor sertraline in nondepressive patients with chronic ischemic heart failure: a preliminary study.

BACKGROUND: Selective serotonin re-uptake inhibitors (SSRIs) have been associated with better psychiatric status, functional capacity, and fewer arrhythmias in depressive patients with heart failure (HF). In this study, we tested the impact of sertraline (an SSRI) on patients with HF, but not clinical depression. METHODS: We studied 62 clinically stable, nondepressive patients with ischemic HF (New York Heart Association class: I-II), and implantable cardioverter-defibrillator (ICD). Following psychiatric evaluation and quality of life (QoL) assessment, 24-hour electrocardiogram recordings including heart rate variability (HRV) and ICD interrogation were performed every 4 months for 1 year. Ventricular effective refractory period (ERP) at 600-, 500-, and 400-ms cycle length and the inducibility of ventricular tachycardia (VT) were assessed via the ICD. After that, sertraline 50 mg/day was administered for 12 months and the whole evaluation was repeated. RESULTS: Sertraline was associated with fewer ventricular extrasystoles per 24 hours and a significant change in HRV (increase in mean R-R, 5-minute standard deviation of RR intervals, and root mean-square difference of successive RR intervals, and reduction in ultra and very low frequency). It was also followed by an improvement in patients' QoL. A trend toward a decrease was observed in the number of recalled nonsustained VTs. The episodes of sustained VT were not significantly reduced. Ventricular ERPs and VT inducibility remained unaltered. CONCLUSION: In clinically stable, nondepressive patients with ischemic HF and ICD, sertraline is associated with reduced ventricular extrasystoles, better QoL, and a possible improvement in some HRV indexes. This suggests that SSRIs may have a favorable clinical impact on these patients, independent of the improvement in depressive symptoms.

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.

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 Begg's funnel plot and with Egger's 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.

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. METHODS: In thirty-six patients with atrioventricular (AV) block, a dual-chamber pacemaker was implanted. The ventricular electrode was placed either at the apex or at the lower septum, in a randomized sequence. Twenty-four to 48 hours following implantation, we measured LV volumes, EF, and LV dyssynchrony (by tissue Doppler imaging), both with and without pacing. Patients were reassessed echocardiographically after 12 months. RESULTS: Lower septal pacing induced a more synchronized pattern of LV contraction changes (P < 0.05). Following 12 months, differences were observed between groups regarding LV volumes and EF. EF increased within the septal group (from 52 +/- 3.3% to 59 +/- 3.0%, P < 0.05). A significant inverse relation was documented between changes in LV dyssynchrony and changes in EF (r =-0.64, P < 0.05). CONCLUSIONS: In patients with AV block, RV nonoutflow septal pacing represents an attractive alternative, since it preserves better and may even improve LV volumes and EF. Late changes in EF are associated with the changes in LV dyssynchrony imposed by pacing.

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.

Sphenopalatine ganglion block: an external gate to modulate cardiac autonomic tone and suppress premature ventricular beats?

BACKGROUND: Autonomic modulation is used for treating various cardiovascular diseases, such as cardiac arrhythmias. Sphenopalatine ganglion (SPG) block is an easy, non-invasive therapy for migraine with a potential cardiovascular impact that remains unclear. In this study, we sought to assess the effect of SPG block on cardiac autonomic tone, as expressed by heart rate variability (HRV), and on ventricular arrhythmogenesis. METHODS: Forty patients (14 male and 26 female) suffering from migraine were randomized by 1:1 to SPG block or placebo (controls) and HRV parameters were evaluated 1 hour before and hourly after the intervention. Twenty-four additional patients (11 men and 13 women) with premature ventricular contractions (PVCs) from the right ventricular outflow tract underwent the same randomization and the number of PVCs was assessed during 1 hour before and every hour after treatment. Values were summarized as median (1st-3rd quartile). RESULTS: During the first four hours after SPG block, an increase in mean RR [883 (IQR, 869-948) vs. 839 (IQR, 806-887) ms at baseline, P<0.01], SDNN [64 (IQR, 59-69) vs. 51 (IQR, 47-55) ms, P<0.01], SDANN [39 (IQR, 36-43) vs. 27 (IQR, 22-29) ms, P<0.01], ASDNN [51 (IQR, 47-53) vs. 40 (IQR, 37-44) ms, P<0.01], rMSSD [30 (IQR, 27-32) vs. 25 (IQR, 23-27) ms, P<0.01], VLF [26 (IQR, 24-29) vs. 23 (IQR, 22-25) ms2, P<0.01] and HF [14 (IQR, 11-16) vs. 11 (IQR, 9-12) ms2, P<0.01], along with a decrease in LF/HF ratio [1.7 (IQR, 1.4-1.9) vs. 2.0 (IQR, 1.7-2.5), P<0.01] was observed in patients with migraine. In patients with PVCs, the number of ectopic ventricular beats per hour was decreased for the first five hours following SPG block [360 (IQR, 264-850) from 956 (IQR, 545-1,412), P<0.001]. No such differences were observed in controls. CONCLUSIONS: SPG block is associated with a transient increase in those HRV parameters that mainly express parasympathetic activity. It is also followed by a significant decrease in ventricular arrhythmic burden. These findings imply an effect on cardiac autonomic tone with a potential favorable clinical impact on arrhythmogenesis.

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.

Effect of levosimendan on ventricular arrhythmias and prognostic autonomic indexes in patients with decompensated advanced heart failure secondary to ischemic or dilated cardiomyopathy.

Positive inotropes used for the treatment of heart failure have been arrhythmogenic. Levosimendan is a novel calcium sensitizer with vasodilating properties and a complex mechanism of action. Its effect on ventricular arrhythmias and 24-hour Holter electrocardiographically derived prognostic autonomic nervous system-related markers, because it occurs in parallel with changes in cardiac function and neurohormonal response, has not been systematically assessed. Forty-five patients (mean age 65 +/- 1.3 years) with heart failure refractory to conventional therapy and a mean ejection fraction of 23 +/- 1.2%, randomized to levosimendan or placebo, were studied. After Holter electrocardiographic recording, 1 drug was infused for 24 hours (levosimendan at a dose of 0.1 mug/kg/min). During this period, another Holter recording was performed to assess changes in ventricular arrhythmogenesis, 24-hour heart rate variability indexes, QTc, QT variability, and QT/RR slope. Clinical evaluation, echocardiography, and B-type natriuretic peptide measurements were performed at baseline and after treatment. After levosimendan, clinical and echocardiographic improvement was observed, associated with beneficial neurohormonal modulation (mean B-type natriuretic peptide level after levosimendan 668 +/- 108 vs 1,009 +/- 122 pg/ml at baseline, p <0.05). Episodes of nonsustained ventricular tachycardia increased with levosimendan (21.9 +/- 9.6 vs 3.0 +/- 1.2, p <0.05). Levosimendan and placebo exerted a neutral effect on all autonomic markers assessed. In conclusion, levosimendan at low doses increases nonsustained ventricular arrhythmias, without affecting Holter-derived, prognostically significant autonomic markers. At the same time, it is associated with improvements in cardiac function and neurohormonal response. These findings may have important clinical and prognostic implications.

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.

Acute haemodynamic effects of oestrogen administration in male patients with chronic heart failure.

BACKGROUND: Although there are many studies concerning the effects of long-term oestrogen administration on systemic haemodynamics in postmenopausal women, the effects of oestrogen in patients with chronic heart failure are not defined. AIM: The goal of this study was to evaluate the acute haemodynamic effects of oestrogen in male patients with chronic heart failure. METHODS AND RESULTS: We studied 15 men with advanced heart failure (NYHA II-IV, EF < 35%). A Swan-Ganz thermodilution catheter was advanced in their pulmonary artery and central haemodynamics were assessed at baseline, after placebo administration, and following 0.625 and 1.25 mg of oestrogen infusion. Simultaneously, all patients underwent limb plethysmography. Analysis of variance with repeated measures was used to compare the sequential measurements. Following oestrogen administration, right atrial, pulmonary artery and pulmonary capillary wedge pressures, as well as systemic, pulmonary and forearm vascular resistance were decreased; cardiac output, cardiac index, stroke volume, stroke volume index, stroke work index and forearm blood flow were increased. CONCLUSIONS: In male patients with chronic heart failure, acute oestrogen administration improves the indices of cardiac systolic performance and decreases pulmonary and systemic vascular resistance. These findings imply a beneficial effect of oestrogen in selected patients with chronic heart failure.

Effect of biventricular pacing on heart rate variability in patients with chronic heart failure.

BACKGROUND: Biventricular pacing is emerging as a long-term therapy for symptomatic heart failure. Analysis of heart rate variability (HRV) has become an important predictive tool in this syndrome. AIM OF THE STUDY: To assess whether chronic resynchronization therapy can affect HRV in patients with heart failure. METHODS AND RESULTS: Thirteen patients with heart failure were studied (mean age+/-1 S.E. 65+/-2.2 years, QRS 195+/-5.3 ms, NYHA class 3.2+/-0.1, LVEF 21+/-1.7%). The protocol included a preliminary no pacing period for 1 month following device implantation. Twenty-four hour Holter ECG recordings were performed at the end of this period (baseline) and after 3 months of biventricular stimulation (VDD mode). Prior to and following pacing patients underwent NYHA class evaluation, 6-min walk test, Quality of Life Assessment and a cardiopulmonary exercise test. Biventricular pacing improved functional class (P<0.0001) and Quality of life (P<0.0001), increased 6-min walk distance, (P=0.008) and exercise duration (P<0.0001) but had no significant effect on peak exercise VO(2). Resynchronization therapy increased mean 24-h RR (922+/-58 vs. 809+/-41 ms at baseline, P=0.006), SDNN (111+/-11 vs. 83+/-8 ms, P=0.003), SDNN-I (56+/-10 vs. 40+/-5 ms, P=0.02), rMSSD (66+/-14 vs. 41+/-8 ms, P=0.003), Total Power (5724+/-1875 vs. 2074+/-553 ms(2), P=0.03), Ultra Low Frequency Power (1969+/-789 vs. 653+/-405 ms(2), P=0.03) and Very Low Frequency Power (2407+/-561 vs. 902+/-155 ms(2), P=0.004). CONCLUSION: Biventricular pacing in heart failure improves autonomic function by increasing HRV. This may have important prognostic implications.

Electrophysiologic effects of endothelin receptor-A blockade in patients with coronary artery disease.

Selective endothelin receptor-A antagonists are a promising new treatment in patients with heart failure and/or pulmonary hypertension. Animal studies have suggested that these agents may have additional cardiac electrophysiologic actions, however, no data exist in man. We examined the effects of acute endothelin receptor-A blockade on the sinus node, the atrioventricular node and on the ventricular myocardium, in patients with single-vessel coronary artery disease and preserved left ventricular function. The selective endothelin receptor-A antagonist BQ-123 was administered by the intracoronary route, in order to achieve maximum local cardiac effects. After endothelin receptor-A blockade, QT interval increased from 373 +/- 30 msec (mean +/- SD) to 395 +/- 20 msec (p < 0.01) and QTc interval increased from 394 +/- 36 msec to 421 +/- 28 msec (p < 0.01). QT-dispersion, calculated from 12-lead ECG, decreased from 40 +/- 18 msec to 24 +/- 8 msec (p < 0.01) and QTc-dispersion decreased from 44 +/- 20 msec to 26 +/- 9 msec (p < 0.05). These changes were evident only after infusion in the left, but not in the right coronary artery. No effect was found on the sinus node, the atrioventricular node, or the ventricular effective refractory periods. We conclude that selective endothelin receptor A blockade lengthens ventricular repolarization and decreases its inhomogeneity. Further studies are needed to evaluate possible antiarrhythmic actions of this class of agent.