Theophylline in the prevention of vasovagal syncope recurrences.

OBJECTIVES: The present work aimed to study the efficacy and patient compliance of oral theophylline treatment in the prevention of vasovagal syncope recurrences. BACKGROUND: High blood adenosine may trigger vasovagal syncope. Theophylline is an adenosine receptor antagonist. METHODS: In 44 patients with vasovagal syncope (8 men and 34 women, age 46.4±3.2 years) with an average 4.8±0.74 syncopal episodes (range 1-20, median 4,5 episodes) oral theophylline therapy was started with dose 2x100/200 mg, which was further increased if necessary. All patients were treated by non-pharmacological measures which were not effective. Patients were followed in regular intervals on an outpatient basis in 6-month intervals. RESULTS: After the start of treatment patients were followed for the mean of 17.1±2.1 months (2-51 months, median 12 months). The total number of syncopal episodes decreased from 4.8±0.74 to 1.73±0.45 (p=0.0006). The occurrence of syncopal episodes per year decreased from 4.07±0.80/year to 1.50±0.54 /year during the treatment period (p=0.001). After a gradual increase in theophylline dosage, in 34 patients no syncopal recurrences were observed. In 10 persons syncopal recurrences persisted despite treatment. Side effects leading to discontinuation of treatment were present in 14 patients - gastrointestinal intolerance (7 patients), palpitations (6 patients) and headache (3 patients). CONCLUSION: The addition of oral theophylline preparation to non-pharmacological treatment led to a marked reduction of syncopal recurrence in patients with vasovagal syncope. About one-third of study subjects discontinued therapy because of side effects (Tab. 2, Fig. 4, Ref. 22). Text in PDF www.elis.sk Keywords: heophylline, adenosine, vasovagal syncope, treatment.

Adenosine, adenosine- deaminase and implantable recorder outcome in syncopal patients.

BACKGROUND: Adenosine test was proposed as a tool for identification of syncopal patients who benefit from pacemaker implantation. Aim of the study was to assess the relationship between adenosine levels, the outcome of adenosine test and results of implantable loop recorder (ILR) monitoring in patients with syncope. METHODS: In 29 patients (mean age 59 ± 11 years, 15 men, 14 women) with unexplained syncope ILR was implanted. In addition, adenosine test (intravenous injection of 20 mg adenosine bolus) and assays of plasmatic adenosine and adenosine-deaminase were performed. RESULTS: Adenosine test was positive in 15 patients and negative in 14 patients. Patients with positive adenosine test had lower adenosine levels compared to patients with negative test (8.86 ± 2.07 ng/ml vs. 15.18 ± 2.14 ng/ml, p = .04). No difference was observed in adenosine deaminase levels (16.35 ± 2.20 IU/l vs. 13.20 ± 2.48 IU/l, p = .40). There was a negative correlation between adenosine level and AVB duration during adenosine test (p = .04; R2  = 0.22). Patients with positive adenosine test had more frequent asystole during ILR monitoring than patients with negative test (9 pts vs. 1 pt, p = .005). Adenosine levels were lower in patients with asystolic syncope on ILR compared to vasodepressor syncope 8.20 ± 2.86 ng/ml versus 13.27 ± 7.26 ng/ml, p = .05). CONCLUSIONS: Patients with positive adenosine test have decreased production of endogenous adenosine compared to patients with negative adenosine test. Positivity of adenosine test and low adenosine level in the peripheral blood were associated with more frequent asystolic episodes during ILR monitoring.

Etiology of syncope in patients with preexisting atrioventricular conduction disorders.

BACKGROUND: The discussion about the feasibility of empiric pacemaker implantation in patients with preexisting atrioventricular (AV) conduction disorders continues. The aim of the study was to determine the etiology of syncope and the need for pacemaker insertion in patients with AV conduction impairment using implantable loop recorder (ILR). METHODS: ILR was implanted after negative diagnostic workup in 37 patients with syncope (24 men, 13 women, age 72 ± 10 years) and preexisting impairment of AV conduction. First-degree AV block (AVB I) was present in 26 patients, and bundle branch block (BBB) in 17 patients. RESULTS: ILR-based diagnosis was made in 28 patients (75%)-sinus arrest in 13 patients, complete AVB in 10 patients, and vasodepressor syncope in five patients. In patients with preexisting BBB, sinus arrest occurred during ILR monitoring significantly more frequently than in patients without BBB (53% vs 20%, P = .03). Complete AVB was significantly less common in patients with preexisting BBB than in patients without BBB (12% vs 40%, P = .04). On multivariate regression analysis, the only independent predictor of AVB occurrence during ILR monitoring was preexisting AVB I (P = .03). The only independent predictor of sinus arrest during ILR monitoring was preexisting BBB (P = .03). CONCLUSIONS: In patients with preexisting AV conduction disorders, prevailing syncopal mechanism during ILR monitoring was asystole. However, sinus arrest occurred more often than complete AVB and was predicted by preexisting BBB. Preexisting AVB was a predictor of complete AVB during ILR monitoring.

Improvement in low upright baroreflex sensitivity is associated with positive clinical effect of orthostatic training.

AIM: To assess the clinical efficacy of orthostatic training (OT) and its effect on the autonomic activity. METHODS: OT was performed in 38 patients (13 males, age 36.4 ± 15.2 years). Baroreflex sensitivity (BRS), heart rate variability, and quality of life (SF 36) were assessed before and after 6 months of OT. Patients with no recurrence of syncope and reduction of the presyncope number to one-third or less were classified as responders. RESULTS: Compliance to OT was low. Only 55% (38 from 69 patients) completed the training programme; 28 patients were responders (74%) and 10 patients were nonresponders. Before OT, BRS in upright position was lower in responders than in nonresponders (sitting: 8.05 ± 3.94 ms/mm Hg vs 12.51 ± 5.3 ms/mm Hg, P = 0.04, standing: 5.08 ± 2.34 ms/mm Hg vs 7.54 ± 2.16 ms/mm Hg, P = 0.02). After OT, BRS increased in responders (sitting: 8.05 ± 3.94 ms/mm Hg to 9.31 ± 4.49 ms/mm Hg, P = 0.05; standing: 5.08 ± 2.34 ms/mm Hg to 5.96 ± 2.38 ms/mm Hg, P = 0.03). No differences in supine BRS were observed. In responders, low frequency (LF) and high frequency (HF) power in sitting and standing positions significantly increased after OT (P < 0.05). In nonresponders, there was no significant rise in BRS, LF, and HF after OT. A significant increase in quality of life was noted in responders, but not in nonresponders. CONCLUSIONS: OT reduced symptoms in 74% patients who trained regularly. However, the compliance to training was low. Possible mechanism of OT is reconditioning effect on baroreceptor reactivity in upright position.

[Adenosine - a mediator with multisystemic effects (or a hormone?)]. / Adenozín - mediátor s multisystémovými úcinkami (alebo hormón?).

Adenosine is a nucleoside regulating many physiological and pathological processes in human organism. It is produced by almost all cells and is metabolised by adenosinedeaminase enzyme. Effect of adenosine is mediated by three types of adenosine receptors. Adenosinergic system significantly influences function of cardiovascular system, furthemore it plays a key role in sleep homeostasis, in regulation of bone metabolism and activation of immune system. Adenosine mediates effect of various hormones, but also adenosine itself has its own autocrine, paracrine and systemic effects. Changes in endogenous adenosine levels, or changes of adenosine receptor sensitivity, may play a role in ethiopathogenesis of many diseases. Thus adenosinergic system can become a target for new therapeutical possibilities in many fields of medicine.Key words: adenosine - adenosinedeaminase - cardiovascular system - diabetes mellitus - hormone.

Gene Polymorphism of the Adenosine A2a Receptor in Patients with Vasovagal Syncope.

BACKGROUND: Adenosine may play a role in the pathogenesis of vasovagal syncope (VVS). The aim of the study was to evaluate the adenosine A(2A) receptor gene 1083 T > C polymorphism in patients with syncope and its possible association with results of head-up tilt test (HUT). METHODS: Three hundred and forty-seven consecutive patients (mean age 47.3 ± 18.5 years, 132 men, 215 women) with one or more syncopal episodes underwent HUT as part of standardized diagnostic evaluation. HUT was positive in 207 patients (75 males, mean age 44.7 ± 18.6 years) and negative in 140 patients (58 males, mean age 48.17 ± 18.8 years). One thousand and eighty-three T > C single nucleotide polymorphism in the adenosine A(2A) receptor gene (rs5751876) was evaluated in 347 patients with syncope and in 85 subjects without history of syncope (54 men, mean age 41.7 ± 16.3). RESULTS: Adenosine A(2A) receptor 1083 T > C polymorphism was not associated with the positivity of HUT. Blood pressure and heart rate response to tilting was similar in all genotypes. Low frequency (LF) power was significantly lower in CC genotype compared to CT genotype in early phase of tilt (log LF 2.69 ± 0.61 vs 3.20 ± 0.60; P = 0.01) and at the time of syncope (log LF 2.60 ± 0.63 vs 2.77 ± 0.48; P = 0.04). CONCLUSIONS: Adenosine A(2A) receptor 1083 T > C polymorphism is not associated with the positivity of HUT and its proposed role in predisposition to VVS was not confirmed. CC genotype may be associated with lower sympathetic activity during HUT.

Global myocardial contractile reserve assessed by high-dose dobutamine stress echocardiography predicts response to the cardiac resynchronization therapy.

BACKGROUND: Myocardial contractile reserve (CR) is a strong prognostic factor in patients with heart failure. The presence of significant myocardial fibrosis can lead to a reduced response to cardiac resynchronization therapy (CRT). We assumed that myocardial CR assessed by high-dose dobutamine stress echocardiography (DSE) would predict response to CRT. METHODS: Fifty-two consecutive symptomatic patients with heart failure (New York Heart Association [NYHA] class III), with depressed ejection fraction (EF) of the left ventricle (26.3 ± 6.9%) and dyssynchronous contractions (QRS duration 149.8 ± 23.8 msec) underwent DSE before CRT implantation. The difference in EF at rest and at peak (40 µg/kg per minute) DSE indicated global CR. Responders to CRT were defined by a decrease in left ventricular end-systolic volume of ≥15% and/or an increase in EF of ≥5% after 6 months of CRT. RESULTS: During high-dose dobutamine infusion, responders (28 patients, 54%) showed a greater increase in EF compared with nonresponders (Δ 11 ± 7% vs. Δ 2 ± 9%, P = 0.007). CR correlated moderately with an improvement in EF after 6 months of CRT (r = 0.50, P = 0.0009). Furthermore, responders showed significant improvement in clinical status, evaluated by a reduction in NYHA functional class (-0.8 ± 0.6 vs. 0.1 ± 0.4, P = 0.02), compared with nonresponders. A 7% exercise-induced increase in EF yielded sensitivity of 79% and specificity of 87% in predicting the response to CRT after 6 months. CONCLUSIONS: Myocardial CR assessed by high-dose DSE can play a potentially important role in identifying responders to CRT.

[Importance of EKG in patients wuth resynchronization therapy]. / Význam EKG u pacientov s resynchronizacnou liecbou.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms and survival in patients with chronic heart failure. The presence of electrocardiographic (ECG) signs of electrical dyssynchrony during ventricular contractions are an essential criterion for the implantation of CRT. Nevertheless, 1/3 proportion of patients who undergo CRT do not seem to respond favorably. Aim of study was to investigate the relevant ECG parameters prior to CRT (as well as their postimplantation changes) and to determine their relation to predicting favorable response to CRT. METHODS: 52 symptomatic patients (age 62.2 ± 10.5 years, 39 men) with severe left ventricular (LV) systolic dysfunction (ejection fraction 26.3% ± 6.9%) with QRS 120 ms underwent CRT implantation. In early pre- and postimplantation CRT period the following ECG parameters were recorded: QRS complex width and morphology (complete and atypical left bundle branch block, nonspecific intraventricular conduction delay), the size of R and S wave. After 6 months of CRT, responders were definied by improvement of LV ejection fraction > 5 % and/or reduction of end-systolic LV volume > 15 %. RESULTS: The incidence of left bundle branch block (complete or atypical) prior to CRT implantation was higher in responders compared to non-responders group (64% vs 35%, p = 0.036). After implantation of CRT, responders showed significant narrowing of the QRS complex, while non-responder`s QRS complex width remained unchanged (QRS -18 ± 22 ms vs 1 ± 27 ms, p = 0.018). Furthermore QRS complex reduction led to increase in LV ejection fraction (r = 0.47, p = 0.001) and to reduction of LV end-systolic volume (r = 0.42, p = 0.004). R and S changes between responders and non-responders did not differ (p = 0.598 respectively, P = 0.685). CONCLUSION: The presence of complete left bundle branch block before CRT implantation is associated with a better response to CRT compared to other myocardial intraventricular conduction disturbances. Post-implantation narrowing of QRS complex appears to be an early predictor of favorable response to CRT.

Increased adrenocortical activity in patients with vasovagal syncope.

OBJECTIVE: Syncope is a transient loss of consciousness resulting from cerebral hypoperfusion. Vasovagal syncope (VVS) is a form of orthostatic intolerance (OI). Its clinical signs such as dizziness and hypotension may mimic symptoms of adrenal insufficiency. The objective of this study was to evaluate the adrenal gland function in patients with vasovagal syncope after stimulation with synthetic adrenocorticotropic hormone (ACTH). DESIGN: Case-control study on patients with VVS and healthy controls. METHODS: The study involved 42 participants, including 27 patients diagnosed with VVS using the head-up tilt test and 15 healthy individuals with no history of syncope or any orthostatic symptoms. Serum cortisol and aldosterone concentrations were measured under basal conditions and at 30 and 60 min after intramuscular ACTH stimulation. RESULTS: Patients with VVS had significantly higher cortisol levels at baseline (441 ± 143 vs. 331 ± 84.7 nmol/L, p = 0.01), at 30 min (802 ± 143 vs. 686 ± 105 nmol/L, p = 0.01) and at 60 min (931 ± 141 nmol/L vs. 793 ± 147 nmol/L, p = 0.001) after ACTH administration (Synacthen 250 µg). Plasma aldosterone increased after ACTH stimulation, but did not show significant differences among groups. Furthermore, there was also no significant correlation between cortisol levels and blood pressure or heart rate. CONCLUSION: Patients diagnosed with VVS have higher cortisol levels both at baseline and after ACTH stimulation. This finding indicates that individuals with VVS have higher adrenocortical activity potentially as a response to the orthostatic stress induced by syncope, which acts as a stressful stimulus on the autonomic nervous system.

Application of Liquid Chromatography Coupled to Mass Spectrometry for Direct Estimation of the Total Levels of Adenosine and Its Catabolites in Human Blood.

Adenosine is a multifunctional nucleoside with several roles across various levels in organisms. Beyond its intracellular involvement in cellular metabolism, extracellular adenosine potently influences both physiological and pathological processes. In relation to its blood level, adenosine impacts the cardiovascular system, such as heart beat rate and vasodilation. To exploit the adenosine levels in the blood, we employed the liquid chromatography method coupled with mass spectrometry (LC-MS). Immediately after collection, a blood sample mixed with acetonitrile solution that is either enriched with 13C-labeled adenosine or a newly generated mixture is transferred into the tubes containing the defined amount of 13C-labeled adenosine. The 13C-enriched isotopic adenosine is used as an internal standard, allowing for more accurate quantification of adenosine. This novel protocol for LC-MS-based estimation of adenosine delivers a rapid, highly sensitive, and reproducible means for quantitative estimation of total adenosine in blood. The method also allows for quantification of a few catabolites of adenosine, i.e., inosine, hypoxanthine, and xanthine. Our current setup did not allow for the detection or quantifying of uric acid, which is the final product of adenosine catabolism. This advancement provides an analytical tool that has the potential to enhance our understanding of adenosine's systemic impact and pave the way for further investigations into its intricate regulatory mechanisms.

The Role of Adenosine and Its Degradation Enzymes - Adenosinedeaminase and Adenosinekinase in Pathogenesis of Vasovagal Syncope.

INTRODUCTION: Adenosine is mediator regulating physiological and pathological processes in organism. It probably plays a role in pathogenesis of vasovagal syncopes (VVS), too. Adenosine, its receptors and degradation enzymes- adenosinedeaminase (ADA) and adenosinekinase (ADK), are called the adenosinergic system. AIM: We aimed to evaluate serum levels of adenosine, ADA and ADK in patients with tilt-induced VVS and compare them to tlit-negative controls. Secondary aim was to compare the levels between the types of VVS and correlate them with hemodynamic parameters. SUBJECTS AND METHODS: Altogether 132 individuals were involved in this study (age 39,88±15,64 years, 51 males). All patients underwent head up tilt test (HUTT) in differential diagnosis of syncope. Blood sampling was performed before and after HUTT. Baseline and stimulated serum levels of adenosine, ADA and ADK were evaluated by ELISA method. RESULTS: HUTT was positive in 91 patients (HUTT+), 41 individuals were negative (HUTT-). HUTT+ patients had higher baseline and stimulated adenosine levels, when compared to HUTT- population. The rise in adenosine was higher in HUTT+ group. On the other hand, the increase of ADA was significantly higher in HUTT- subjects. Among HUTT+ group, the highest adenosine was found during vasodepressoric VVS. CONCLUSION: Adenosinergic system may play role in pathogenesis of VVS. Patients with VVS have higher adenosine levels, that may be caused by attenuated degradation. Adenosine seems to be involved predominantly in vasodepressoric type of VVS. Further research evaluating complex function of adenosinergic system in these patients is needed.

A prospective study of the standardized diagnostic evaluation of syncope.

AIMS: To evaluate the aetiology and the diagnostic yield of the standardized diagnostic work-up based on European Society of Cardiology guidelines in the syncope unit. METHODS AND RESULTS: A total of 501 patients (191 men and 310 women), mean age 65 years (44-75 years), were prospectively evaluated. They underwent initial evaluation (history, physical evaluation, and a 12-lead electrocardiogram) and subsequently targeted tests that differed according to suspected aetiology. Initial evaluation resulted in diagnosis in 155 patients--reflex syncope (93), arrhythmogenic syncope (62), and pacemaker malfunction (7). In 22 patients with solitary syncope, a diagnostic algorithm was stopped after initial evaluation. In 139 patients with organic heart disease, cardiac syncope was found in 83 patients and reflex syncope in 30 patients. In 185 patients without organic heart disease, reflex syncope was diagnosed in 127 patients, cardiac syncope in 30 patients, and vascular syncope in 2 patients. Vasovagal syncope was the most common type of syncope (43%), followed by bradyarrhythmias (25%), tachyarrhythmias (9%), and orthostatic hypotension (5%). Aetiology of syncope remained unknown in 11% of patients. Diagnostic yield of specific examinations was as follows: head-up tilt 52%, implantable loop recorder 51%, electrophysiologic study 33%, initial evaluation 31%, EKG Holter 12%, orthostatic test 10%, transoesophageal stimulation 9%, carotid sinus massage 4%, and echocardiography 2%. CONCLUSION: Standardized diagnostic evaluation determined the aetiology of syncope in 89% of patients. Diagnostic yield of specific diagnostic procedures was different. Initial evaluation resulted in diagnosis in one-third of patients.

Use of an implantable loop recorder to increase the diagnostic yield in unexplained syncope: results from the PICTURE registry.

AIMS: To collect information on the use of the Reveal implantable loop recorder (ILR) in the patient care pathway and to investigate its effectiveness in the diagnosis of unexplained recurrent syncope in everyday clinical practice. METHODS AND RESULTS: Prospective, multicentre, observational study conducted in 2006-2009 in 10 European countries and Israel. Eligible patients had recurrent unexplained syncope or pre-syncope. Subjects received a Reveal Plus, DX or XT. Follow up was until the first recurrence of a syncopal event leading to a diagnosis or for ≥1 year. In the course of the study, patients were evaluated by an average of three different specialists for management of their syncope and underwent a median of 13 tests (range 9-20). Significant physical trauma had been experienced in association with a syncopal episode by 36% of patients. Average follow-up time after ILR implant was 10±6 months. Follow-up visit data were available for 570 subjects. The percentages of patients with recurrence of syncope were 19, 26, and 36% after 3, 6, and 12 months, respectively. Of 218 events within the study, ILR-guided diagnosis was obtained in 170 cases (78%), of which 128 (75%) were cardiac. CONCLUSION: A large number of diagnostic tests were undertaken in patients with unexplained syncope without providing conclusive data. In contrast, the ILR revealed or contributed to establishing the mechanism of syncope in the vast majority of patients. The findings support the recommendation in current guidelines that an ILR should be implanted early rather than late in the evaluation of unexplained syncope.

Clinical history in the diagnosis of the cardiac syncope­the predictive scoring system.

BACKGROUND: Cardiac syncope represents clinical situation with serious prognosis. The aim of the present study was to develop the diagnostic scoring system based on the clinical history allowing to distinguish between cardiac and noncardiac syncope. METHODS: Clinical history was obtained in the form of the structured questionnaire in 60 patients with cardiac syncope (mean age 70 ± 10 years, 33 men) an in 140 patients with noncardiac syncope (mean age 45 ± 20 years, 44 men). Multivariate regression analysis identified seven variables that were included in the final regression model. RESULTS: The age above 55 years, presence of structural heart disease, syncope in supine position, absence of prodromal symptoms, and chest pain before syncope were predictive of cardiac syncope. Predictors of noncardiac syncope were recovery duration of more than 1 minute and syncope occurring immediately after standing up. A diagnostic point score was derived from the regression coefficients. The sum of the points identified patients with cardiac syncope if the diagnostic point score was ≤2. Diagnostic performance of the score was assessed on the validation group of 67 patients with syncope (21 patients with cardiac syncope and 46 patients with noncardiac syncope). Sensitivity was 81%, specificity 84.8%, positive predictive value 70.8%, and negative predictive value 90.7%. CONCLUSION: Predictive model based on parameters form clinical history of the patients may help to distinguish between cardiac and other causes of syncope.

Left atrial appendage strain rate is associated with documented thromboembolism in nonvalvular atrial fibrillation.

BACKGROUND: The left atrial appendage (LAA) strain and strain rate have not yet been studied in the prediction of cardiac thromboembolism. Therefore, this study aimed to evaluate the significance of LAA strain and strain rate as assessed by speckle-tracking imaging in relation to documented thromboembolic events. METHODS: A group of 80 patients with a mean age of 65 years who were referred for electrical cardioversion of nonvalvular atrial fibrillation was retrospectively analyzed. Each patient underwent 2D transesophageal echocardiography (TEE). Velocity vector imaging (VVI)-derived LAA strain and strain rate in parallel with other conventional TEE predictors were analyzed in terms of their association with previous embolic stroke and peripheral embolization. RESULTS: By comparing the two groups of patients with (22/80) and without embolic events (58/80), patients with embolic events were older, had higher CHA2DS2-VASc scores, higher incidence of coronary artery disease and LAA thrombi, and worse LAA strain and strain rate. Moreover, patients without embolization more often used anticoagulants than patients with embolic events. After adjusting for the abovementioned embolic risk factors, only the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years [double weight], diabetes mellitus, stroke [double weight], vascular disease, age from 65 to 74 years, sex category) score and the LAA strain rate remained as significant predictors of embolic events. CONCLUSION: The results of the study show that the VVI-derived LAA strain rate is a significant predictor of documented ischemic stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. Its predictive power is similar to the predictive power of the CHA2DS2-VASc score.

Hemodynamic parameters and heart rate variability during a tilt test in relation to gene polymorphism of renin-angiotensin and serotonin system.

PURPOSE: The aim of the study was to evaluate the renin-angiotensin system and serotonin transporter gene polymorphisms in relation to hemodynamic parameters and heart rate variability during a head-up tilt test (HUT) in patients with vasovagal syncope. METHODS: DNA was collected from 191 patients (mean age 44+/-18 years, 61 men, 130 women). The following gene polymorphisms were determined in genomic DNA: angiotensin-converting enzyme insertion/deletion polymorphism (I/D ACE), angiotensinogen gene polymorphism (M 235), angiotensin II receptor type 1 (ATR1) polymorphism (A 11666C), and polymorphism of serotonin transporter gene (5HTTLPR).Heart rate variability during HUT was assessed in 5-minute intervals by low frequency, high frequency, standard deviation of the normal-to-normal (SDNN), and root mean square successive difference parameters. RESULTS: AA genotype of A 1166C polymorphism was associated with lower minimal systolic blood pressure (SBP) and diastolic blood pressure (DBP) during HUT compared with other genotypes (minimal SBP: AA 59.6+/-21,8, AC 79.9+/-22.7, CC 65.4+/-22.7 mmHg, P=0.007), (minimal DBP: AA 36.4+/-22.7, AC 52.3+/-22.9, CC 45.4+/-19.5 mmHg, P=0.007).AA genotype was also associated with higher SDNN compared to other genotypes in the early phase of HUT (SDNN in 5 minutes of tilt: AA 59.7+/-24.6, AC 50.6+/-20.6, CC 46.0+/-13.2, P=0.01) and at syncope occurrence (SDNN: AA 71.0+/-20.9, AC 58.2+/-17.9, CC 58+/-10, P=0.04) CONCLUSION: AA genotype of A 1166C polymorphism in the ATR1 gene may be associated with hypotension and decline in sympathetic tone during HUT. Its role in genetic predisposition to vasovagal syncope cannot be excluded.

Clinical characteristics associated with bradycardia and asystole in patients with syncope undergoing long-term electrocardiographic monitoring with implantable loop recorder.

BACKGROUND: The aim of this retrospective single center cohort study was to assess the occurrence of bradycardia during implantable loop recorder (ILR) monitoring in patients with unexplained syncope and negative conventional testing and to identify clinical predictors of bradycardia and pacemaker implantation. METHODS: An ILR was implanted in 112 patients (31 men, 81 women, mean age 64 ±13 years) with syncope which was not explained after conventional diagnostic work-up. Clinical variables were compared between patients with and without pacemaker implantation. RESULTS: A diagnosis was made in 67 patients (60%), including non-arrhythmic (vasodepressor) syncope (27 patients), sinus bradycardia or asystole (23 patients), atrioventricular (AV) block (14 patients) and bradycardic atrial fibrillation (3 patients). The mean time to diagnosis was 233 ± 282 days. A pacemaker was implanted in 40 patients (36%). Male gender, age above 65 years, hypertension, presence of structural heart disease, absence of prodromal symptoms, trauma secondary to syncope, asymptomatic sinus bradycardia and first-degree AV block were clinical predictors of pacemaker implantation in univariate analysis. Of the independent predictive factors three remained significant in multivariate analysis: absence of prodromal symptoms before the loss of consciousness (odds ratio OR 3.38, p = 0.01, 95% confidence interval CI 1.24-9.20), male gender (OR 3.22, p = 0.01, 95% CI 1.26-8.20) and age >65 years (OR 2.94, p = 0.02, 95% CI 1.14-8.33). CONCLUSIONS: In patients undergoing ILR implantation bradycardia is a frequent finding despite the negative conventional diagnostic testing. Absence of prodromal symptoms, male gender and age >65 years are risk factors for bradycardia and pacemaker implantation.

Incremental value of global longitudinal strain in prediction of all-cause mortality in predialysis and dialysis chronic kidney disease patients.

BACKGROUND: The aim of this prospective study was to investigate the prediction of all-cause mortality from global longitudinal strain (GLS) in two groups of chronic kidney disease patients (CKD): predialysis and dialysis. METHODS: In 89 patients undergoing echocardiography, 37.2 % predialysis (16/43) and 58.6 % dialysis patients (27/46) died during the mean follow-up 70.2 ± 35 months. In addition to conventional echocardiographic measurements, GLS was assessed by velocity vector imaging from three standard apical views. RESULTS: Cox proportional hazards regression enter model showed the following variables to predict survival: the only significant predictor of survival in predialysis patients, among the set of conventional echocardiographic parameters was GLS (HR, 0.58; 95 % CI, 0.39-0.87; p = 0.01). In the group of dialysis patients GLS with E/Em ratio remained as significant predictors of survival (HR, 0.72; 95 % CI, 0.56-0.92; p = 0.01, and HR, 1.02; 95 % CI, 1.004-1.04; p = 0.01, respectively). GLS ≥ - 13.2 % had 58.3 % sensitivity and 91.7 % specificity for prediction of mortality in predialysis patients, and GLS ≥ - 12.02 % had 73.3 % sensitivity and 78.9 % specificity for prediction of mortality in dialysis patients. In dialysis group E/Em ratio ˃ 17.02 had 71.4 % sensitivity and 84.2 % specificity for prediction of mortality. CONCLUSIONS: Our study demonstrates the incremental value of GLS in prediction of all-cause mortality during a long follow-up period in CKD patients. GLS together with E/Em ratio may be used for the assessment of left ventricular systolic and diastolic function and risk stratification of CKD patients in different stages of renal failure.

Enhanced plasma catecholamine and cAMP response during the head-up tilt test in patients with vasovagal syncope.

AIMS: Vasovagal syncope appears related to transient changes in sympathetic neural outflow. Several studies have documented sympathetic inhibition at the time of syncope. However, data on the activity of the sympathetic nervous system a short time before the onset of syncope are controversial. The aim of the study was to examine sympathoadrenal activity by measuring levels of plasma catecholamines and plasma cAMP in patients with vasovagal syncope induced in the head-up tilt test (HUT). METHODS AND RESULTS: Sixty-one syncopal patients (age 35 +/- 15 years) underwent the passive HUT (60 degrees, 45 minutes). Blood samples for measurement of noradrenaline (NA), adrenaline (A) and dopamine (D) were obtained prior to tilt (0 minutes), at 5 minutes of tilt and at syncope or at the end of the HUT (45 minutes). Two samples were obtained for measurement of cAMP: at 0 minutes and at the end of the test. Plasma levels of NA, A and D were measured using high-performance liquid chromatography; plasma cAMP was measured using a radioimmunoassay technique. Thirty-three patients (15 men, age 35 +/- 16 years) developed vasovagal syncope during the test (HUT-positive); twenty-eight patients (15 men, age 34 +/- 14 years) completed the test without syncope (HUT-negative). No significant differences in NA, A and D were observed between the two groups at baseline or at 5 minutes of tilt. At the time of syncope, catecholamine levels in HUT-positive patients were higher than baseline levels (NA 428 vs. 209 pg/ml, A 90 vs. 55 pg/ml, D 297 vs. 142 pg/ml) and higher than in HUT-negative patients (NA 428 vs. 263 pg/ml, A 98 vs. 67 pg/ml, D 297 vs. 195 pg/ml). cAMP levels increased at syncope and were higher than in non-syncopal patients at the end of the HUT (607 +/- 460 vs. 328 +/- 297 nmol/ml). CONCLUSION: Vasovagal syncope induced by tilt testing is associated with increased levels of noradrenaline, adrenaline, dopamine and cAMP. These results suggest that sympathoadrenal activation antecedes development of vasovagal syncope and may play a role in its pathophysiology.