Usefulness of the Calgary Syncope Symptom Score for the diagnosis of vasovagal syncope in the elderly.

AIMS: The Calgary Syncope Symptom Score (CSSS) has been validated as a simple point score of historical features with high sensitivity and specificity for the diagnosis of vasovagal syncope (VVS) in younger populations without evidence of structural heart disease. Our purpose was to evaluate the performance of the CSSS in an elderly population with suspected VVS. METHODS AND RESULTS: Hundred and eighty patients of ≥60 years of age (mean 73.4 ± 7.8) with suspected clinical diagnosis of VVS were studied. The CSSS (VVS score ≥-2) was calculated in all patients prior to undergoing head-up tilt test (HUT). A standardized HUT protocol with active nitroglycerin phase was used to reproduce syncopal symptoms as gold standard for diagnosis of VVS. Hundred and forty patients had positive HUT response. Eighty-three patients (42.3%) had CSSS ≥-2 suggesting a diagnosis of VVS. The Calgary Syncope Symptom Score sensitivity was 0.51 [95% confidence interval (CI) 0.42-0.59] and specificity 0.73 (95% CI 0.52-0.85) with positive predictive value and negative predictive value of 0.87 (95% CI 0.77-0.93) and 0.30 (95% CI 0.21-0.40), respectively. One hundred (55.6%) patients had previous history of mild cardiovascular disease documented during assessment prior to HUT. In this population sensitivity and specificity was markedly reduced: 0.13 (95% CI 0.05-0.29) and 0.70 (95% CI 0.57-0.80), respectively. CONCLUSION: The CSSS has a lower sensitivity and specificity in an elderly population presenting with syncope compared to previously validated data in young adults, particularly in elderly patients with previous history of mild cardiovascular disease. A modified CSSS may be needed to improve specificity and sensitivity in this population.

Lack of association between IL-6-174G/C gene polymorphism and Chagas disease.

The aim of this study was to investigate the role of the IL-6-174G/C gene polymorphism in susceptibility/resistance to Trypanosoma cruzi infection in two independent cohorts from Colombia and Peru. We determined the IL-6-174G/C genotypes in a sample of 399 seronegative individuals and 317 serologically positive patients from Colombia and Peru. All individuals are from regions where T. cruzi infection is endemic. No statistically significant differences in the frequency of IL-6-174G/C gene polymorphism between chagasic patients and controls or between asymptomatic and individuals with cardiomyopathy were observed. Our results do not support an evidence for a major role contribution of this IL-6 gene polymorphism in the susceptibility to or clinical manifestations of Chagas disease in these studied cohorts.

A placebo-controlled trial of intravenous and oral disopyramide for prevention of neurally mediated syncope induced by head-up tilt.

OBJECTIVES: A double-blind randomized trial was designed to determine the efficacy of intravenous and oral disopyramide phosphate in preventing neurally mediated syncope induced by a head-up tilt test. BACKGROUND: Neurally mediated syncope is a frequent cause of syncope and may be induced by head-up tilt testing. Recent uncontrolled trials have suggested that disopyramide may be an effective therapy in patients with neurally mediated syncope. METHODS: Twenty-two consecutive patients with recurrent neurally mediated syncope and two or more successive positive head-up tilt test responses were randomly allocated to receive either intravenous disopyramide or placebo. Head-up tilt testing at 60 degrees was performed for 15 min. If presyncope or syncope was not provoked, isoproterenol infusion was started at a rate of 1 microgram/min and the rate gradually increased until a 25% increase in heart rate was achieved. Eleven patients were subsequently randomized in crossover fashion to receive oral disopyramide (800 mg/day) or placebo during 1 week. The primary end point was prevention of syncope or presyncope provoked by head-up tilt testing. RESULTS: Head-up tilt test results were positive for syncope in 12 (75%) of 16 patients receiving intravenous placebo and in 12 (60%) of 20 patients receiving disopyramide (p = 0.55 Fisher exact test, 95% confidence interval [CI] -14% to 40%). In the intravenous phase, complete crossover was achieved in 15 patients. Head-up tilt test results during this phase were positive in 13 patients (87%) receiving placebo and in 12 patients (80%) receiving disopyramide (p = 0.50 Fisher exact test, 95% CI -19% to 32%) and were positive in all patients receiving their initially randomized drug or placebo. In the oral phase, head-up tilt results were positive in only two patients (18%) assigned to placebo and in three patients (27%) receiving disopyramide (p = 0.54 Fisher exact test, 95% CI -42% to 24%). A mean follow-up time of 29 +/- 8 months was obtained in 21 of the 22 patients. Syncope recurred in 3 (27%) of the 11 patients receiving disopyramide and 3 (30%) of the 10 patients not treated pharmacologically (p > 0.05). CONCLUSIONS: Intravenous disopyramide was ineffective for the prevention of neurally mediated syncope provoked by head-up tilt testing. No significant effect was observed after oral therapy with disopyramide. There was a striking decrease in the incidence of positive tilt test results over time regardless of intervention, thus discouraging the use of head-up tilt as the single method of assessing therapeutic efficacy. Recurrence of syncope after the investigative protocol was infrequent over long-term follow-up regardless of treatment group.

Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing.

OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p < 0.05). Although most patients showed a strong inverse relation between arterial pressure and muscle sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction < or = 30%) showed no relation between arterial pressure and sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular rather than dual-chamber pacing may be due in part to increased sympathetic nervous outflow.

Effect of adenosine or adenosine triphosphate on antidromic tachycardia.

OBJECTIVES: This study was designed to determine the effect of adenosine or adenosine triphosphate (ATP) on antidromic tachycardia. BACKGROUND: Adenosine and adenosine triphosphate are useful for differential diagnosis of wide QRS tachycardia. It has been believed that tachycardia termination caused by these agents is due to the preferential depressive effect on the atrioventricular (AV) node, whereas their effect on accessory pathways is minimal. METHODS: We studied the effect of adenosine or ATP on the termination pattern of antidromic tachycardia in 17 patients (10 men, 7 women; mean age [+/- SD] 32 +/- 11 years) with one or more accessory pathways. Adenosine (6 to 12 mg [n = 10]) or ATP (8 to 20 mg [n = 7]) was injected rapidly through a central venous line and followed by 10 ml of saline flush after induction of sustained antidromic tachycardia. RESULTS: Tachycardia was terminated in < 2 min in 14 patients (82%) after the injection and remained unchanged in 3 (18%). Tachycardia termination was due to conduction block in the accessory pathway (anterograde limb) in seven patients (50%) and in the AV node (retrograde limb) in another seven. Adenosine or ATP caused accessory pathway block in seven (88%) of the eight patients lacking retrograde accessory pathway conduction and in none of the nine patients having retrograde accessory pathway conduction (p < 0.01). All five patients with an atriofascicular accessory pathway and unidirectional anterograde conduction had tachycardia termination due to anterograde accessory pathway block after injection of adenosine or ATP. CONCLUSIONS: 1) Adenosine or ATP effectively terminates antidromic tachycardia; 2) the termination is related to block in either the accessory pathway or the AV node; 3) accessory pathway block occurs in patients with a unidirectional, anterogradely conducting accessory pathway, especially an atriofascicular accessory pathway.

Diagnostic utility of mechanical, pharmacological and orthostatic stimulation of the carotid sinus in patients with unexplained syncope.

OBJECTIVES: The purpose of the present study was to systematically evaluate the diagnostic utility of mechanical, pharmacological and orthostatic stimulation of the carotid sinus in a consecutive series of patients with recurrent unexplained syncope. BACKGROUND: Carotid sinus hypersensitivity (CSH) is an infrequently recognized cause of recurrent unexplained syncope usually diagnosed by carotid sinus massage (CSM) in the supine position. The diagnostic utility of systematic assessment of mechanical, pharmacological and orthostatic stimulation of the carotid sinus has not been clearly established. METHODS: Eighty consecutive patients (63 +/- 12 years) with a history of recurrent unexplained syncope (mean episodes: 6 +/- 3); 30 age-matched controls (65 +/- 14 years) and 16 patients (59 +/- 12 years) with syncope not related to CSH were studied. Pharmacological stimulation of the carotid sinus was achieved by randomly administering bolus injections of nitroprusside and phenylephrine. Mechanical stimulation of the carotid sinus was performed by CSM applied for 5 s in the supine position and after 2 min at 60 degrees. A 60 degree low-dose isoproterenol head-up tilt test (HUTT) was also performed for a total duration of 30 min. RESULTS: Carotid sinus hypersensitivity was elicited by CSM in the supine position in seven (8.7%) patients, two (6.6%) controls and one (6.3%) patient with syncope unrelated to CSH, compared with 48 (60%) patients, two (6.6%) controls and one (6.3%) syncope unrelated to CSH patient after 60 degree HUTT, increasing the diagnostic yield by 51%. Baroreceptor gain was significantly reduced in the CSH group. Head-up tilt test was positive in 12 (25%) patients with CSH, two (6.6%) controls and two (12%) with documented syncope but not positive in any of the patients in which syncope remained unexplained. Diagnostic accuracy was enhanced by 38% (31% supine vs. 69% upright) when CSM was performed at 60 degrees. CONCLUSIONS: CSH was documented in 68% of patients, 8.7% in the supine position and 60% in the upright position. Sensitivity was increased by 51%, and diagnostic accuracy was enhanced by 38% by performing CSM in the upright position. Decreased baroreceptor gain was documented and may play a role in the pathophysiology of CSH.

Elimination of slow pathway conduction: an accurate indicator of clinical success after radiofrequency atrioventricular node modification.

OBJECTIVES: The purpose of this study was to determine the optimal end point of radiofrequency atrioventricular (AV) node modification using anatomically guided slow pathway approaches in patients with AV node reentrant tachycardia. BACKGROUND: The optimal end point for AV node modification using radiofrequency energy is uncertain, although elimination of inducible AV node reentrant tachycardia has been used. METHODS: We followed up 51 consecutive patients (40 women, 11 men, mean age +/- SD 41 +/- 16 years) with symptomatic AV node reentrant tachycardia for 12 +/- 6 months (range 4 to 24) after radiofrequency AV node modification using an anatomically guided slow pathway approach. Inducible AV node reentrant tachycardia was eliminated in all patients, whereas residual slow pathway conduction persisted in 12 patients (24%) after ablation. One study was complicated by complete AV block and two patients were lost to follow-up (one with and one without residual slow pathway conduction). RESULTS: Clinical recurrence of AV node reentrant tachycardia was documented in seven patients (14%) 3 days to 3 months (median 1 month) after ablation. The recurrence rate was significantly higher in patients with than in those without residual slow pathway conduction (6 [55%] of 11 vs. 1 [3%] of 37, p < 0.01). The recurrence rate was not different between patients with only residual slow pathway conduction and those with residual slow pathway conduction and inducible single echo cycles (three [60%] of five in both groups, p = NS). The number of radiofrequency energy applications was not significantly different between those without and those with recurrence (20 +/- 17 vs. 16 +/- 9, p = NS). Junctional tachycardia during application of radiofrequency energy tended to be more frequently observed in those with a successful outcome (77% vs. 57%, p > 0.05). Of the 22 patients who underwent modification before 1992, residual slow pathway conduction was present in 9 (41%) of 22 patients. Atrioventricular node reentrant tachycardia recurred in five (56%) of these nine patients. A greater effort made in 1992 to eliminate slow pathway conduction in 29 patients resulted in residual slow pathway conduction in only 3 (11%) with recurrence in 2 (4%). CONCLUSIONS: Complete elimination of slow pathway conduction is feasible in the majority of patients. Elimination of slow pathway conduction is highly predictive of long-term success after AV node modification using an anatomically guided approach.

Effect of shock timing on efficacy and safety of internal cardioversion for ventricular tachycardia.

OBJECTIVES: We examined the effect of shock timing within the QRS complex on cardioversion efficacy in a randomized crossover test of shocks delivered at two timing intervals relative to QRS onset. BACKGROUND: The local ventricular electrogram is used in implantable cardioverter-defibrillators to synchronize cardioversion shocks to terminate ventricular tachycardia. However, the timing of the local electrogram relative to global ventricular depolarization is variable, depending on the site of ventricular tachycardia origin. METHODS: Transvenous defibrillation leads were positioned in the right ventricular apex (cathode), coronary sinus and superior vena cava (anodes) of patients with sustained monomorphic ventricular tachycardia. After repeat ventricular tachycardia induction, sequential shocks with energy settings of 0.5 to 22 J were delivered simultaneously with QRS onset (QRS + 0 shock) or 100 ms after QRS onset (QRS + 100 shock). QRS onset was determined from the surface electrocardiogram. Cardioversion threshold, defined as the lowest shock energy for successful ventricular tachycardia termination, was measured for these two timings. RESULTS: Fifteen patients (13 men, 2 women; mean [+/- SD] age 60.5 +/- 7.7 years) completed testing. Cardioversion threshold was significantly lower with QRS + 100 shocks than QRS + 0 shocks (3.1 +/- 3.5 vs. 10.5 +/- 7.4 J, p < 0.01). Thirteen patients (87%) experienced ventricular tachycardia acceleration with QRS + 0 shocks, but only three patients (20%) had ventricular tachycardia acceleration using QRS + 100 shocks (p < 0.01). Of the 32 failed QRS + 0 shocks, 25 (78%) caused ventricular tachycardia acceleration, whereas only 5 (36%) of the 14 failed QRS + 100 shocks caused ventricular tachycardia acceleration (p < 0.05). Cardioversion threshold was not correlated with ventricular tachycardia cycle length, QRS duration, left ventricular ejection fraction or left ventricular diastolic volume (p = NS). CONCLUSIONS: Internal cardioversion shocks delivered late in the QRS complex during ventricular tachycardia are more effective and have a lower risk of ventricular tachycardia acceleration than those delivered near QRS onset.

Clinical and quantitative coronary angiographic predictors of coronary restenosis: a comparative analysis from the balloon-to-stent era.

OBJECTIVES: We sought to assess whether coronary stents have modified the predictive value of demographic, clinical and quantitative coronary angiographic (QCA) predictors of coronary restenosis. BACKGROUND: A systematic analysis in a large cohort of registries and randomized trials of the percutaneous transluminal coronary angioplasty (PTCA) and stent era has never been performed. METHODS: A total of 9,120 treated lesions in 8,156 patients included in nine randomized trials and 10 registries, with baseline, post-procedural and six-month follow-up QCA analyses, were included in this study. Predictors of restenosis were identified with univariate and multivariate logistic regression analyses. Interaction terms were introduced in the regression equation to evaluate whether the predictors of restenosis were common to both eras or specific for either one of the revascularization techniques. RESULTS: The restenosis rate was 35% after PTCA and 19% after angioplasty with additional stenting. In the univariate analysis, favorable predictors were previous coronary artery bypass graft surgery (CABG), stent use, stent length and a large pre-procedural minimal lumen diameter (pre-MLD); unfavorable predictors were weight, body mass index, diabetes mellitus, multi-vessel disease, lesion length and a high residual post-procedural diameter stenosis (post-DS). Predictors specific for the PTCA population were a large post-procedural MLD (post-MLD) as favorable and a severe pre-procedural DS (pre-DS) as unfavorable. Favorable predictors specific for the stent population were a large post-MLD and a large pre-procedural reference diameter (pre-RD). In the multivariate analysis, the best model included the following favorable predictors: stent use, a large post-MLD, previous CABG and the interaction term between stent use and a large post-MLD; unfavorable predictors were lesion length and diabetes mellitus. CONCLUSIONS: There are no major differences in demographic and clinical predictors of coronary restenosis between PTCA and stent populations. In the modern (stent) era, a severe pre-DS is no longer an unfavorable predictor of restenosis. Still important, but more so in the stent population, is a large post-MLD (optimal result). Finally, a larger pre-RD became a favorable predictor with the advent of stenting.

Cerebral hemispheric lateralization in cardiac autonomic control.

OBJECTIVE: To identify cerebral hemispheric lateralization in cardiac autonomic control. PATIENTS: Eight patients undergoing an intracarotid amobarbital sodium test as a presurgical evaluation of temporal lobe epilepsy. DESIGN: Power spectral analysis of heart rate variability before and after intracarotid amobarbital injection. SETTING: University hospital and research center. MAIN OUTCOME MEASURE: The changes in the ratio of low-frequency (LF) (sympathetic) to high-frequency (HF) (parasympathetic) power (LF/HF ratio), a measure of sympathovagal balance, after hemispheric inactivation. RESULTS: The LF/HF ratio changed as follows: right preinactivation = 3.81 +/- 0.96, postinactivation = 3.40 +/- 1.23; left preinactivation = 2.74 +/- 0.49, postinactivation = 4.34 +/- 0.59 (mean +/- SEM). The test of interaction between laterality and inactivation using a 2-way repeated-measures analysis of variance was statistically significant (P = .001). The increased ratio on the left side (1.61 +/- 0.70) was statistically significant (P = .03), but the decrease on the right side (-0.40 +/- 0.46) was not (P < or = .70). CONCLUSIONS: These findings suggest that there is a cerebral lateralization in cardiac autonomic control and that the right cerebral hemisphere predominantly modulates sympathetic activity. This study may help identify subgroups of patients with intracranial disease at high risk of cardiac complications.

Time and frequency domain analyses of heart rate variability during orthostatic stress in patients with neurally mediated syncope.

The role of autonomic balance during upright tilt in patients with neurally mediated syncope is unclear. To assess the characteristics of autonomic tone during orthostatic stress, 15 patients (mean age 32 years) with recurrent episodes of syncope (> or = 2) and a positive response to a 30-minute 60 degrees upright tilt were compared with the following control groups: (1) 15 patients (mean age 33.5 years) with > or = 2 episodes of recurrent syncope and a negative tilt response, and (2) 15 age- and sex-matched healthy volunteers (mean age 34 years) with no previous history of presyncope or syncope. Time domain measurements assessed were mean RR interval, standard deviation of normal RR intervals, and percentage of normal consecutive RR intervals differing by > 50 ms. Frequency domain measurements of the low-frequency (LF) and high-frequency (HF) bands were obtained, and the LF/HF ratio was also calculated. All variables were calculated in the supine position and during the first 5 minutes of upright tilt. No significant difference was observed in the time and frequency domain variables in the supine position between control groups with a negative head-up tilt response and the group with a positive response. The percentage of normal consecutive RR intervals differing by > 50 ms during the first 5 minutes of head-up tilt was significantly higher in the group with positive tilt tests than in the controls (25 +/- 12% vs 7 +/- 4%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Can serial tilt testing be used to evaluate therapy in neurally mediated syncope?

The role of serial head-up tilt testing for the evaluation of therapeutic efficacy of neurally mediated syncope is reviewed. The evidence available suggests that guiding therapy based on serial head-up tilt response may not be appropriate, and large placebo-controlled trials should be conducted to address this issue.

A prospective randomized comparison of autodecremental pacing to burst pacing in device therapy for chronic ventricular tachycardia secondary to coronary artery disease.

A number of modes of antitachycardia pacing therapies are available in the newer generations of implantable cardioverter/defibrillators. The efficacy of synchronized burst overdrive pacing for the termination of induced and spontaneous monomorphic ventricular tachycardia (VT) was compared with synchronized autodecremental (ramp) pacing in 21 patients who received an implantable antitachycardia pacemaker/cardioverter/defibrillator for treatment of recurrent sustained monomorphic VT. Patients undergoing serial noninvasive VT induction studies after device implantation were prospectively randomized to receive trials of burst or ramp pacing therapies in a crossover study design. Antitachycardia pacing therapies were equally efficacious in treating induced VT (68% for ramp, 76% for burst pacing trials). The efficacy of ramp (93%) and burst (96%) pacing therapies was significantly higher in terminating spontaneously occurring episodes of VT than in terminating induced episodes (p = 0.001). The incidence of tachycardia acceleration was similar for both modes of pacing. The incidence of VT acceleration was lower for spontaneously occurring episodes of VT (0.01%) than for induced episodes of VT (6%, p < 0.01). Thus, antitachycardia pacing is an effective therapy for episodes of monomorphic VT, and the risk of accelerating VT to a hemodynamically unstable form is low. Antitachycardia pacing therapies are more effective against spontaneously occurring episodes than induced episodes of VT. Differences in tachycardia cycle length and duration may contribute to these effects.

Concomitant mitral valve or atrial septal defect surgery and the modified Cox-maze procedure.

Atrial fibrillation (AF) is generally associated with rheumatic valve disease and atrial septal defects (ASD) in young adults. Surgical correction of both disorders fails to convert to sinus rhythm or prevent further episodes of paroxysmal or chronic AF in most patients. The role and efficacy of combining mitral valve surgery or ASD correction with AF surgery in this setting has not been widely addressed and remains to be established. The present study prospectively assessed the recovery of sinus rhythm, functional status, and atrial function in 21 patients (mean age 42 +/- 9.2 years) who underwent a modified Cox-maze procedure concomitant with mitral valve or ASD surgery at our institution between March 1993 and February 1995. Seventeen (81%) had chronic AF, and 4 (19%) had paroxysmal AF, with a mean AF duration of 3.5 +/- 3.6 years (range 0.6 to 15.3). Concomitant surgery was performed in 9 patients (42.9%) with mitral stenosis, 5 (23.8%) with mitral regurgitation, 1 (4.8%) with mitral and aortic regurgitation, and 3 (14.3%) with ASD. Eighteen patients (86%) were in New York Heart Association class II to IV before operation. Doppler echocardiography was performed in all patients before surgery, and 1 week, and 3 and 6 months after surgery in patients maintaining sinus rhythm. One patient with severe mitral stenosis and depressed ventricular function died in the immediate postoperative period. Sinus rhythm was restored in the immediate postoperative period in 7 patients (35%), and in another 10 patients (50%) before discharge (mean 5.8 +/- 2 days). Overall, sinus rhythm was restored before discharge in 17 patients (85%); 3 (15%) patients required antiarrhythmic therapy. Doppler echocardiography performed 3 months after surgery documented atrial contractility (A and E waves) in 12 patients (71%). After a mean follow-up period of 8 months (range 3 to 23), 18 (90%) remained in sinus rhythm. Sinus rhythm was successfully restored and maintained in most patients with drug refractory AF undergoing a concomitant Cox-maze procedure with mitral valve or ASD surgery improving atrial function and New York Heart Association class.

Pathophysiologic basis for vasodepressor syncope.

The current knowledge regarding the pathophysiologic basis of the vasodepressor response was reviewed. The balance of evidence indicates that the mechanoreceptor hypothesis seems unlikely to be the sole afferent alteration that leads to the vasodepressor response. Alternative afferent mechanisms should include neurohumoral mediated sympathoinhibition triggered by opioid mechanisms as well as impaired endothelial and NO responses to orthostatic stress in susceptible individuals. It is possible that impaired cardiovagal and sympathetic outflow control of arterial baroreceptors is enhanced by the aforementioned mechanisms. The role of central sympathoinhibition and vagal excitation triggered directly from pathways within the temporal lobe or triggered by alterations in regional cerebral blood flow should be considered as potential alternative mechanisms. Efferent autonomic outflow during vasodepressor syncope include sympathetic neural outflow withdrawal in addition to activation of parasympathetic outflow to the heart and abdominal viscera. Further human research is needed to understand the underlying mechanisms that result in the described neural and vascular responses.

Reduced-dose warfarin or interrupted warfarin with heparin bridging for pacemaker or defibrillator implantation: a randomized trial.

BACKGROUND: Perioperative management with reduced-dose warfarin is of potential interest by eliminating the need for bridging while still maintaining a degree of anticoagulation. The outcomes of this regimen have not been well determined. METHODS: In a randomized controlled trial we compared two regimens for management of anticoagulation with warfarin in patients with implantation of a pacemaker or defibrillator. Half dose of warfarin for 3-6 days, depending on the baseline international normalized ratio (INR), before surgery aiming at an INR of ≤ 1.7 was compared with interrupted warfarin for 5 days with preoperative bridging with low-molecular-weight heparin (LMWH) at therapeutic dose for 2.5 days. Main safety outcome was pocket hematoma. Secondary outcomes were major bleeding, thromboembolism - all within 1 month, days of hospitalization and number of patients requiring correction of INR with vitamin K. RESULTS: The study was planned for 450 patients but it was discontinued prematurely due to a change in practice. Pocket hematoma occurred in 4 of 85 patients (5%) randomized to the bridged regimen and in 3 of 86 patients (3%) randomized to reduced-dose warfarin. One pocket hematoma in each group was severe. There were no major hemorrhages or thromboembolism within the 1-month window. Duration of hospitalization was similar in the two groups. Correction of INR the day before surgery with vitamin K had to be used for significantly more patients in the reduced-dose warfarin group (41%) than in the bridged regimen group (6%). CONCLUSION: The reduced-dose warfarin regimen appeared to have similar safety after device implantation as interrupted warfarin with preoperative LMWH bridging. Due to premature discontinuation no firm conclusion can be drawn. The reduced-dose warfarin regimen often failed to achieve the intended preoperative INR. ClinicalTrials.gov Identifier: NCT 02094157.

Sex differences in cardiac autonomic function of depressed young adults.

BACKGROUND: Cardiac autonomic dysfunction has been proposed as an important contributing factor to the increased cardiovascular risk observed in major depression (MDD). However, the evidence regarding alterations in heart rate variability (HRV) in otherwise healthy depressed subjects has been inconclusive. METHODS: A case-control study in 50 treatment-naïve young adults with a first MDD episode without comorbid psychiatric disorders and 50 healthy control subjects was conducted. Time- and frequency-domain indexes of HRV were determined at baseline supine and after 5-min of orthostatic stress at 60°. RESULTS: There were no significant differences in the time- or frequency-domain variables of HRV between depressed patients and controls. However, a random-effect ANOVA model showed that during orthostatic stress depressed men had a reduced HRV and decreased parasympathetic activity compared to control subjects, while no differences were found between depressed women and controls. CONCLUSION: These results suggest a sex-dependent relationship between major depression and cardiac autonomic dysfunction and provide one potential explanation for sex differences in the association of depressive symptoms with cardiovascular morbidity.

Neurocardiology. Neurogenic syncope.

Neurogenic syncope is one of the most frequent causes of recurrent syncope in patients with structurally normal heart. The mechanisms leading to neurogenic syncope remain poorly understood. Evidence recently obtained from several laboratories suggests that impaired arterial baroreflex adaptation to orthostatic stress, in addition to cessation of vasoconstrictive sympathetic traffic, contributes to the development of hypotension and bradycardia that determine the vasovagal response. Neurogenic syncope encompasses a wide range of reflexogenic syncope that includes the vasovagal type, micturition syncope, carotid sinus hypersensitivity and post-prandial syncope. Head-up tilt testing has become the diagnostic tool of choice for the evaluation of patients with recurrent neurogenic syncope, providing an acceptable sensitivity and high specificity that is largely dependent on the type of tilt protocol used to induce neurogenic syncope. This chapter will review the pathophysiology, diagnosis and therapeutic approach to the patient with neurogenic syncope.