Head-up tilt test with clomipramine challenge in vasovagal syndrome--a new tilt testing protocol.

PURPOSE: The aim of the study was to randomly compare clomipramine, used as a challenge-agent during head-up tilt test, with isoproterenol, used in the conventional test, in patients with vasovagal syndrome. SUBJECTS AND METHODS: The serotonergic re-uptake inhibitor clomipramine was infused (5mg in 5min) at the start of head-up tilt test (Clom-HUT) in 126 patients (mean age 41+/-16 years) with positive history of recurrent neurocardiogenic syncope, and in 54 healthy control subjects (mean age 46+/-15 years). All subjects had also been tested with a conventional 60 degrees head-up tilt test (Con-HUT) for 30 min and, if negative, isoproterenol infusion was performed at the end of the test. The two tests were performed in a random order with a 24-h interval between them. RESULTS: Fifty-two of the 126 patients (41%) and two of the 54 controls had a positive response to Con-HUT. In the Clom-HUT the proportion of patients who experienced a positive response increased to 83% (105 subjects), while this happened only to four control subjects. The predictive accuracy of Clom-HUT increased compared to Con-HUT from 58 to 86%, respectively. CONCLUSION: The results indicate an increased responsiveness of central serotonergic neural system in subjects with vasovagal syndrome, the activation of which leads to sympathetic withdrawal. The use of clomipramine infusion during tilt test seems to improve considerably its diagnostic value.

Provocation of neurocardiogenic syncope by clomipramine administration during the head-up tilt test in vasovagal syndrome.

OBJECTIVES: We sought to test the hypothesis that activation of the serotonergic system in patients with vasovagal syndrome during the head-up tilt test provokes syncope. BACKGROUND: Central serotonergic activation participates in the pathogenesis of neurocardiogenic syncope. Drugs increasing serotonin (5-HT) in the central nervous system have not been tested as drug challenges during the head-up tilt test with clomipramine (Clom-HUT). METHODS: The serotonergic re-uptake inhibitor clomipramine was infused (5 mg in 5 min) at the start of Clom-HUT in 55 patients (mean age 40 +/- 17 years) with a positive history of recurrent neurocardiogenic syncope and in 22 healthy control subjects (mean age 46 +/- 15 years). Blood samples were taken at 0, 5, 10 and 20 min for estimation of plasma prolactin and cortisol as neuroendocrine indicators of central serotonergic responsivity. All subjects had been previously tested with a basic 60 degrees head-up tilt test (B-HUT) for 30 min, and if negative, isoproterenol infusion was given at the end of the test. RESULTS: Twenty-nine (53%) of the 55 patients and none of the 22 control subjects had a positive result in the B-HUT. With Clom-HUT, the proportion of patients who experienced a positive response increased to 80% (n = 44), although this happened to only one control subject. Prolactin and cortisol plasma levels increased significantly in the positive Clom-HUT patient group only. CONCLUSIONS: The results indicate an increased responsivity of the central serotonergic neural system in subjects with vasovagal syndrome, the activation of which leads to sympathetic withdrawal. The use of clomipramine infusion with the tilt test seems to considerably improve its diagnostic value.

Pulmonary vein flow analysis by transoesophageal echocardiogr phy in patients with chronic atrial fibrillation; 1 year follow-up after cardioversion.

AIMS: Left and right upper pulmonary vein flow can be adequately recorded by transoesophageal Doppler echocardiography. The aim of this study was to investigate whether analysis of the pulmonary venous flow velocity pattern can predict the long-term maintenance of sinus rhythm after successful cardioversion of chronic atrial fibrillation. METHODS AND RESULTS: Thirty-six consecutive patients, aged 53+/-9 years, with chronic atrial fibrillation of 5.33+/-2 months duration, were subjected to transoesophageal Doppler echocardiography to record left and right upper pulmonary venous flow, 24 h and 3 months following successful cardioversion. One year following cardioversion, 12 patients (33.3%) were in sinus rhythm (sinus rhythm group) while the remaining 24 patients were in atrial fibrillation (atrial fibrillation group). At 24 h following cardioversion, biphasic systolic forward flow in the left and/or right upper pulmonary venous flow velocity was detected in 10 patients of the sinus rhythm group and in four patients of the atrial fibrillation group (P<0001). The systolic fraction was significantly higher in the sinus rhythm group, 0.48+/-0.04 and 0.39+/-0.06, P<0.001 for the left upper pulmonary venous flow, and 0.52+/-0.05 and 0.41+/-0.04, P<0.001 for the right upper pulmonary venous flow, respectively. In patients who displayed a biphasic systolic forward flow and in whom the right upper pulmonary venous flow systolic fraction was higher than 0.50 at 24 h post-cardioversion, the probability of maintenance of sinus rhythm at 1 year exceeded 95%. CONCLUSION: The detection of a biphasic systolic forward flow in the pulmonary venous flow velocity, and of a right upper pulmonary vein systolic fraction higher than 0.50 as early as 24 h following cardioversion of chronic atrial fibrillation, identifies patients who will remain in sinus rhythm 1 year after cardioversion.

Central serotonergic responsiveness in neurocardiogenic syncope: a clomipramine test challenge.

BACKGROUND: Central serotonergic mechanisms appear to participate in the pathogenesis of recurrent neurally mediated syncope. The aim of the study was to investigate the responsiveness of the central serotonergic system by measuring the prolactin and cortisol responses to intravenous administration of the serotonin reuptake inhibitor clomipramine. METHODS AND RESULTS: Twenty subjects free of any medical treatment were tested. Twelve had a history of recurrent syncopal attacks and positive tilt test (patient group, mean age 47+/-18 years, 8 men); 8 subjects without syncope and a negative tilt test result served as control subjects (mean age 49+/-10 years, 5 men). Twenty-five milligrams of clomipramine was administered intravenously within 15 minutes, and blood samples were taken at 0, 15, 30, 45, and 60 minutes. Two days later, a tilt test was performed at 60 degrees for 30 minutes and blood samples were taken at 0, 10, 20, and 30 minutes. During the clomipramine challenge, plasma prolactin levels increased in both groups. The levels at 30 minutes were higher in the patient group compared with the control group (17.3+/-7.2 vs 9.3+/-7.6 ng/mL, P=0.05). Similar results were observed for cortisol at 30 minutes (172+/-15 vs 118+/-21 ng/mL P=0. 04) and at 45 minutes (189+/-20 vs 116+/-23 ng/mL, P=0.03). The tilt test was positive in 8 (67%) out of 12 of the patient group and negative in all control subjects. In the samples taken during the tilt test, significant increases in prolactin and cortisol were observed only in the subjects with positive tilt test results. CONCLUSIONS: Patients with a history of neurocardiogenic syncope show a higher responsiveness of the central serotonergic system to clomipramine challenge. The results support the view that central serotonergic mechanisms are involved in the pathophysiology of the syndrome.

Cardiac denervation after radiofrequency ablation of supraventricular tachycardias.

Inappropriate sinus tachycardia and atrial arrhythmias have been reported after radiofrequency ablation. Previous studies have suggested that cardiac denervation is a possible explanation for these rhythm disturbances. The aim of this study was to investigate possible alterations in autonomic innervation of the heart after ablation using the techniques of heart rate variability (HRV) analysis and metaiodobenzylguanidine (I-123 MIBG) scintigraphy. The subjects of this study were 30 consecutive patients aged 25 to 40 years, without structural heart disease, who underwent radiofrequency ablation of atrioventricular nodal slow pathways, and posteroseptal and left lateral accessory pathways because of symptomatic recurrent reentrant tachycardias. Time and frequency domain analysis of HRV after ablation revealed a significant reduction in the indexes of the mean of all 5-minute standard deviation of RR intervals (p = 0.042), low frequency (p = 0.0005), and total frequency (p = 0.008) compared with preablation values in the group of patients who underwent atrioventricular nodal slow pathway ablation. Patients who underwent ablation of a posteroseptal accessory pathway also had significant attenuation of the indexes of standard deviation about the mean RR interval (p = 0.03), standard deviation of 5-minute mean RR intervals (p = 0.006), and low-frequency (p <0.0001), and high-frequency (p <0.0001) components. Significant I-123 MIBG map defects, indicating efferent cardiac sympathetic denervation, were also found in the same groups of patients: atrioventricular nodal group (p = 0.0024), posteroseptal accessory pathway group (p = 0.0007). None of the above changes in HRV and 123-I MIBG scintigraphy were seen in patients who underwent ablation of left lateral accessory pathways. We conclude that radiofrequency ablation in the anterior, mid-, and posterior regions of the low intraatrial septum may disrupt sympathetic fibers located in these regions, causing cardiac sympathetic denervation. The density of these fibers appear to be less along the left atrioventricular groove.

CGMP levels following ANP challenge are markers of subsequent successful reversion of lone atrial fibrillation to sinus rhythm.

The aim of the present study was to assess whether cGMP release to ANP stimulation can be a biochemical marker of subsequent successful electrical cardioversion of lone atrial fibrillation to sinus rhythm. For this purpose, we studied 13 patients with chronic, lone atrial fibrillation of less than one year's duration who presented to our laboratory for electrical therapy of their arrhythmia. Prior to electrical cardioversion, peripheral venous cGMP levels were assessed at baseline and following an intravenous challenge of 50 Ug human ANP. Venous blood samples for cGMP assessment were taken a) at baseline, b) 5 and 10 mins after the end of ANP infusion. ANOVA of repeated measures was used for statistical analysis. Eight of the study patients were successfully cardioverted to sinus rhythm, while the remaining 5 were not. Although no difference was noted between the two groups regarding the mean time of arrhythmia duration as well as left atrial and ventricular dimensions, ANP stimulation provoked significantly greater cGMP release in patients whose arrhythmia reverted to sinus rhythm, when compared with that of patients whose arrhythmia persisted (p < 0.001). Therefore, cGMP levels following ANP challenge might discriminate between patients with chronic AF who are going to be successfully cardioverted and those who are not. These findings imply that the underlying atrial disease might be different in extent/nature between patients with lone AF responsive to cardioversion and those with resistant arrhythmia.

Hormonal responses during tilt-table test in neurally mediated syncope.

The hormonal profile during tilt testing was examined in syncopal patients. An increase in the growth hormones cortisol and prolactin was found during syncope, suggesting an implication of central serotonergic activation.

Decreased post-myocardial infarction heart rate variability and cardiac denervation assessed by metaiodobenzylguanidine scintigraphy.

Decreased heart rate variability, assessed 2 weeks after uncomplicated acute myocardial infarction, is related to the extent of 1-123-metaiodobenzylguanidine-derived efferent sympathetic cardiac denervation. This postinfarction cardiac denervation could be the substrate of reduced postinfarction heart rate variability.

Left atrial function and atrial natriuretic factor/cyclic guanosine monophosphate changes in DDD and VVI pacing modes.

Left atrial systolic function and the plasma of atrial natriuretic factor (ANF) and cyclic guanosine monophosphate (cGMP) were investigated as possible markers for the development of pacemaker syndrome during VVI pacing. Patients who developed pacemaker syndrome during VVI pacing had a significant decrease in left atrial emptying fraction and a substantial increase in ANF and cGMP plasma levels.

Clinical, adrenergic and heart endocrine measures in chronic atrial fibrillation as predictors of conversion and maintenance of sinus rhythm after direct current cardioversion.

The aim of this study was to evaluate clinical, adrenergic and endocrine factors that could predict sinus rhythm maintenance after direct current cardioversion in chronic atrial fibrillation. Nineteen patients with chronic non-rheumatic atrial fibrillation (mean duration 6 +/- 5 months) were studied. They were exercised 24 h before cardioversion at maximum effort with the Naughton protocol. Heart rate and blood pressure at rest and exercise were recorded and blood samples were taken for the assessment of adrenergic activity, by measuring cyclic adenosine monophosphate, heart endocrine function, atrial natriuretic peptide and its second messenger, cyclic guanosine monophosphate. Fifteen of the 19 patients were initially converted to sinus rhythm (eight patients with external and seven patients with internal DC shocks). After 3 months eight patients remained in sinus rhythm and 11 had relapsed, most of them within the first month. On exercise the chronotropic response was lower in the group who remained in sinus rhythm than in the group in atrial fibrillation (peak heart rate 147 +/- 11 beats.min-1 vs 165 +/- 24 beats.min-1 P = 0.02). During exercise, the systolic blood pressure in the sinus group reached higher values than in the group who relapsed (192 +/- 17 mmHg vs 176 +/- 18 mmHg, P = 0.03). Cyclic adenosine monophosphate increased significantly from rest to peak exercise in the sinus rhythm group (from 23 +/- 9 pmol.ml-1 to 31 +/- 15 mol.ml-1, P = 0.02) while it remained unchanged in the atrial fibrillation group (25 +/- 10 pmol.ml-1 to 24 +/- 8 pmol.ml-1, P = 0.02). For all 19 patients the difference in cyclic adenosine monophosphate between rest and exercise was negatively correlated with maximum heart rate (r = 0.58, P = 0.009). Atrial natriuretic peptide increased from rest to peak exercise in the sinus rhythm group (from 129 +/- 58 fmol.ml-1 to 140 +/- 66 fmol.ml-1) while it remained unchanged in the group in which atrial fibrillation persisted or recurred (from 112 +/- 58 fmol.ml-1 to 111 +/- 53 fmol.ml-1, P = 0.002). A significant correlation between atrial natriuretic peptide and cyclic guanosine monophosphate levels at exercise before cardioversion was found for the sinus rhythm group only (r = 0.76, P = 0.02). In patients with non-rheumatic chronic atrial fibrillation evaluation of clinical parameters such as heart rate and blood pressure changes during maximal exercise can be useful in the choice of suitable therapy. An inadequate increase in plasma cyclic-adenosine monophosphate and atrial natriuretic peptide on exercise could predict patients with more severe underlying disease, where cardioversion should not be recommended.

The effectiveness of beta-blockade and its influence on heart rate variability in vasovagal patients.

The aim of this study was to assess the effectiveness of chronic medical treatment with oral propranolol and its influence on heart rate variability in patients with vasovagal syndrome. A spectral frequency domain analysis was used for the estimation of heart rate variability characteristics. Thirty-six patients, mean age 49 +/- 17 years, with a history of recurrent syncope and positive tilt testing were involved in the study. All patients received oral propranolol (five patients also had a dual chamber inhibited DDI pacemaker implanted) for a mean time 12 +/- 6 months. One patient complained of syncope during this follow-up. The tilt test repeated in 29 patients during follow-up was negative in 28. In 20 patients treatment was discontinued for 4 days and a new tilt test was then performed. Eleven of these 20 patients (55%) had a positive test (P < 0.001 compared with the group in which treatment was continued). In the group of 11 patients in whom the tilt test became positive again after medical treatment had been withdrawn (mean age 43 +/- 20 years) and in 11 asymptomatic controls (mean age 52 +/- 19 years), with no history of syncope and negative tilt testing, the heart rate variability was assessed. The increase in the low frequency component from rest to the maximum value of heart rate variability during tilt testing was higher in the vasovagal group than in the controls (2.6 +/- 1.2 vs 1.5 +/- 0.7 P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)