Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial.

BACKGROUND: Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope. OBJECTIVE: To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481). SETTING: 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom. PATIENTS: Patients with recurrent vasovagal syncope and no serious comorbid conditions. INTERVENTION: Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months. MEASUREMENTS: The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up. RESULTS: The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups. LIMITATION: Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center. CONCLUSION: Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden. PRIMARY FUNDING SOURCE: The Canadian Institutes of Health Research.

A proof of principle study of atomoxetine for the prevention of vasovagal syncope: the Prevention of Syncope Trial VI.

AIMS: There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope. METHODS AND RESULTS: Vasovagal syncope patients were given two doses of study drug [randomized to atomoxetine 40 mg (n = 27) or matched placebo (n = 29)] 12 h apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate (HR), blood pressure (BP), and cardiac haemodynamics were recorded using non-invasive techniques and stroke volume modelling. Patients were 35 ± 14 years (73% female) with medians of 12 lifetime and 3 prior year faints. Fewer subjects fainted with atomoxetine than with placebo [10/29 vs. 19/27; P = 0.003; risk ratio 0.49 (confidence interval 0.28-0.86)], but equal numbers of patients developed presyncope or syncope (23/29 vs. 21/27). Of patients who developed only presyncope, 87% (13/15) had received atomoxetine. Patients with syncope had lower nadir mean arterial pressure than subjects with only presyncope (39 ± 18 vs. 69 ± 18 mmHg, P < 0.0001), and this was due to lower trough HRs in subjects with syncope (67 ± 30 vs. 103 ± 32 b.p.m., P = 0.006) and insignificantly lower cardiac index (2.20 ± 1.36 vs. 2.84 ± 1.05 L/min/m2, P = 0.075). There were no significant differences in stroke volume index (32 ± 6 vs. 35 ± 5 mL/m2, P = 0.29) or systemic vascular resistance index (2156 ± 602 vs. 1790 ± 793 dynes*s/cm5*m2, P = 0.72). CONCLUSION: Norepinephrine transporter inhibition significantly decreased the risk of tilt-induced syncope in VVS subjects, mainly by blunting reflex bradycardia, thereby preventing final falls in cardiac index and BP.

Intraosseous Administration of Tissue Plasminogen Activator on a Mobile Stroke Unit.

Objective: Mobile stroke units offer improved time to administration of thrombolytics for ischemic stroke patients. Acquisition of intravenous (IV) access, however, can be challenging in the prehospital environment leading to treatment delays. Intraosseous (IO) access is commonly used in the prehospital setting for a variety of conditions and may serve as a viable means for tPA (tissue plasminogen activator) administration. Methods/Results: We describe 3 cases in which tPA was administered via IO access on a mobile stroke unit as part of the Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services (BEST-MSU) trial. Conclusion: No adverse events were observed in the process of obtaining IO access or administering tPA.

Novel criterion for the differential diagnosis of wide QRS complexes and wide complex tachycardia using the initial activation of QRS on leads V1 and V2: Differential diagnosis of wide QRS based on V1-V2.

BACKGROUND: Many diagnostic criteria for the differential diagnosis of wide complex tachycardia (WCT) are complex and not completely accurate. Incorrect diagnosis is also related to error in applying criteria. OBJECTIVES: To propose a novel reliable criterion for wide QRS complexes' differential diagnosis. MATERIAL AND METHODS: One hundred Electrocardiograms (ECGs) with wide QRS complexes were analyzed using the ECG software. Five variables were measured during the first 20 ms of QRS in leads V1 and V2 and compared between premature ventricular contraction (PVC) and conducted supraventricular impulse with bundle branch block (BBB) groups. The best discriminant variable was identified. The validity of this variable was tested on a group of 20 patients who had WCT during an electrophysiology study. RESULTS: Almost all variables were statistically different between PVC and BBB groups. The sum of voltages in absolute value of vectors during the initial 20 ms of the QRS in leads V1 and V2 (ΣV1 + V2) was the most discriminant between the two groups (131 ±â€¯85 microvolt [µV] vs. 498 ±â€¯392 µV, p < 0.01). A ΣV1 + V2 < 258 µV (rounded to <0.25 millivolt [mV]) diagnosed PVCs with good sensitivity and specificity (90% and 85% respectively). The ΣV1 + V2 in WCT group had lower values in VT versus supra-ventricular tachycardia (SVT) group (0.53 ±â€¯0.35 mV vs. 1.79 ±â€¯1.04 mV, p = 0.004). CONCLUSIONS: The ΣV1 + V2 < 258 µV is a reliable criterion for PVC diagnosis. It could be measured accurately using ECG Software, which could be programmed to calculate it automatically, limiting the risk of human error. The ΣV1 + V2 also seems capable of discriminating between VT and SVT.

Physical counter-pressure manoeuvres in preventing syncopal recurrence in patients older than 40 years with recurrent neurally mediated syncope: a controlled study from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3)†.

AIMS: Physical counter-pressure manoeuvres (PCM) are effective in young patients with vasovagal syncope and recognizable prodromal symptoms. The aim of this study was to investigate their effectiveness in patients ≥40 years with severe neurally mediated syncope (NMS) enroled in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3). METHODS AND RESULTS: In the ISSUE-3 study, 63 out of 162 patients had a diagnosis of hypotensive NMS (Types 2, 3, and 4A) documented by implantable loop recorder; of these, 40 were instructed to perform isometric leg and arm PCM therapy. Their mean age was 62 ± 13 years; 47% of patients had a history of some episodes without prodrome. A group of 45 untreated patients acted as controls. The primary endpoint was the time to first syncope recurrence. During follow-up, syncope recurred in 15 PCM patients (37%) and in 24 control patients (53%) (P = 0.14). At 21 months, the modelled syncope recurrence rates were 42% [95% confidence interval (CI): 27-61] and 64% (95% CI: 48-80), respectively (P = 0.27). CONCLUSION: In conclusion, many ISSUE-3 patients affected by hypotensive NMS have syncopal recurrence despite PCM. Older age and the absence of sufficiently long recognizable prodromal symptoms in the ISSUE-3 population might have hampered the effectiveness of PC therapy.

Clinical predictors of Fidelis lead failure: report from the Canadian Heart Rhythm Society Device Committee.

BACKGROUND: Approximately 268,000 Fidelis leads were implanted worldwide until distribution was suspended because of a high rate of early failure. Careful analyses of predictors of increased lead failure hazard are required to help direct future lead design and also to inform decision making on lead replacement. We sought to perform a comprehensive analysis of all potential predictors in a multicenter study. METHODS AND RESULTS: A total of 3169 Sprint Fidelis leads were implanted in 11 centers with a total of 251 failures. Lead failure rates at 3, 4, and 5 years were 5.3%, 10.6%, and 16.8%, respectively. The rate of lead failure continues to accelerate (P<0.001). There were 4 independent predictors of failure: center, sex, access vein, and previous lead failure. Women had a higher hazard of failure (hazard ratio 1.51; 95% confidence interval, 1.14-2.04; P=0.005). Both axillary and subclavian access increased the hazard of failure (P=0.007); hazard ratio for axillary was 1.94, (95% confidence interval, 1.23-3.04) and for subclavian 1.63 (95% confidence interval, 1.08-2.46). Previous lead failure increased the hazard of a subsequent Fidelis failure with a hazard ratio of 3.12 (95% confidence interval, 1.80-5.41; P<0.001). CONCLUSIONS: The rate of Fidelis failure continues to increase over time, with failures approaching 17% at 5 years. Women, patients with leads inserted via the subclavian or axillary vein, and those with a previous lead fracture were at greatest risk of Fidelis failure. Our data suggest that Fidelis replacement should be strongly considered at the time of generator replacement.

Low body mass index is associated with a positive response during a head-up tilt test.

BACKGROUND: To describe the association between body mass index (BMI) and a positive response during a head-up tilt test (HUT) in patients referred for an investigation of syncope. METHODS: Observational study of patients referred for the diagnostic evaluation of syncope. Patients were divided into four groups according to their BMI: <18.5 kg/m(2), 18.5-24.9 kg/m(2), 25-29.9 kg/m(2), and > 30 kg/m(2). RESULTS: A total of 419 patients were evaluated. The mean age was 43 ± 22 years, and 62% were female. The prevalence of a positive tilt test was different between groups when stratified by BMI (P = 0.01), with a higher proportion of patients with positive tests among those with BMI <18.5 kg/m(2) compared with other groups (P = 0.05). Multivariate analysis also showed that underweight patients had a 3.9 times higher risk for a positive HUT response (P = 0.01); additionally, the use of contraceptive drugs was associated with a protective effect during HUT (odds ratio: 0.35, confidence interval: 0.19-0.45, P = 0.001). CONCLUSION: In our sample, changes in BMI are associated with a positive response for HUT, and oral contraceptives seemed to protect against this response. Further studies are needed with larger numbers of patients to corroborate this finding.

Psychological impact of surveillance in patients with a defibrillator lead under advisory: a prospective evaluation.

BACKGROUND: Implantable cardioverter defibrillator (ICD) leads are subject to technical failures and the impact of the resulting public advisories on patient welfare is unclear. The psychological status of patients who received an advisory for their Medtronic Fidelis ICD lead (Medtronic Inc., Minneapolis, MN, USA) and followed either by self-surveillance for alarm or home monitoring with CareLink was evaluated prospectively and compared to patients with ICDs not under advisory. METHODS: One hundred sixty consecutive consenting patients (90 alarms, 24 Carelinks, 46 controls) were recruited within 1.5 years of advisory notification. Advisory patients were seen immediately before being told that the automatic lead surveillance utilized since the advisory had been inadequate in warning of impending fracture, as well as 1 and 6 months after programming was optimized. Depression, anxiety, quality of life (QoL), and ICD-related concerns were assessed. RESULTS: Symptoms of depression and state anxiety were experienced by 31% and 48% of patients, respectively. QoL was impaired on all subscales. No significant group differences in distress and ICD-related concerns emerged at baseline or at follow-up. At baseline, alarm patients reported greater limitations because of body pain compared to controls (P < 0.05). All patients showed a significant reduction in body pain-related QoL at the final versus first two evaluations (P < 0.001). Advisory patients were significantly less satisfied with surveillance at follow-up than at baseline (P < 0.05). CONCLUSIONS: There was limited evidence for worse psychosocial functioning in those at risk for ICD lead fracture, irrespective of surveillance method. However, many control and advisory patients experienced chronic distress for which counseling may prove beneficial.

Gynecological and menstrual disorders in women with vasovagal syncope.

PURPOSE: Vasovagal syncope (VVS) is a chronic debilitating condition seen mostly in young women of reproductive age. There are anecdotal reports of increased syncope and presyncope around menstruation. This case-control study assessed the effects of the menstrual cycle on lightheadedness episodes and compared the gynecological and pregnancy history of VVS patients to healthy subjects. METHODS: A custom-designed gynecological and menstrual cycle questionnaire was previously developed for patients with orthostatic intolerance. This questionnaire was administered to female patients with VVS (n = 128) as a part of the multicenter Second Prevention of Syncope Trial, and to gender-matched healthy subjects (n = 92). RESULTS: VVS patients and healthy subjects reported significant variability in self-reported lightheadedness throughout the menstrual cycle. Both cohorts experienced greatest lightheadedness during menses (53 ± 2 vs. 56 ± 4), which decreased during the follicular phase (44 ± 2 vs. 41 ± 4). VVS patients reported less severity in premenstrual symptoms (Fisher's method P = 2.7E-06) compared to healthy controls. There is no difference in the incidence of gynecological abnormalities (Fisher's exact P = 0.193) and pregnancy complications (P = 1.0) between the two cohorts. VVS patients have similar pregnancy rates compared to healthy subjects (P = 0.674). CONCLUSION: The severity of lightheadedness varies during the menstrual cycle and is similar in both VVS patients and healthy controls. VVS patients have no greater risk of gynecological abnormalities and pregnancy complications than healthy subjects.

A randomized-controlled pilot study comparing ICD implantation with and without intraoperative defibrillation testing in patients with heart failure and severe left ventricular dysfunction: a substudy of the RAFT trial.

INTRODUCTION: The need to perform defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion is controversial. In the absence of randomized trials, some regions now perform more than half of ICD implants without DT. METHODS: During the last year of enrolment in the Resynchronization for Ambulatory Heart Failure Trial, a substudy randomized patients to ICD implantation with versus without DT. RESULTS: Among 252 patients screened, 145 were enrolled; 75 randomized to DT and 70 to no DT. Patients were similar in terms of age (65.9 ± 9.3 years vs 67.9 ± 8.9 years); LVEF (24.7 ± 4.6% vs 23.6 ± 4.6%), QRS width (154.8 ± 23.5 vs 155.8 ± 23.6 ms), and history of atrial fibrillation (5% vs 6%). All 68 patients in the DT arm tested according to the protocol achieved a successful DT (≤25 J); 96% without requiring any system modification. No patient experienced perioperative stroke, myocardial infarction, heart failure (HF), intubation or unplanned ICU stay. The length of hospital stay was not prolonged in the DT group: 20.2 ± 26.3 hours versus 21.3 ± 23.0 hours, P = 0.79. One patient in the DT arm had a failed appropriate shock and no patient suffered an arrhythmic death. The composite of HF hospitalization or all-cause mortality occurred in 10% of patients in the no-DT arm and 19% of patients in the DT arm (HR = 0.53, 95% CI: 0.21-1.31, P = 0.14). CONCLUSIONS: In this randomized trial, perioperative complications, failed appropriate shocks, and arrhythmic death were all uncommon regardless of DT. There was a nonsignificant increase in the risk of death or HF hospitalization with DT.

Empiric pacemaker compared with a monitoring strategy in patients with syncope and bifascicular conduction block--rationale and design of the Syncope: Pacing or Recording in ThE Later Years (SPRITELY) study.

AIM: This study seeks to identify the optimal management strategy for patients with syncope in the context of bifascicular block and preserved left ventricular systolic function. METHODS AND RESULTS: This multicentre, randomized, open label, parallel group pragmatic randomized trial will test the hypothesis that a strategy of empiric permanent pacemaker implantation in patients with syncope and bifascicular heart block improves future outcome more effectively than a strategy of therapy guided by prolonged monitoring with an implantable loop recorder (ILR). A total of 120 patients with bifascicular block, preserved left ventricular function, and ≥ 1 syncopal spell in the preceding year will be randomized to receive a permanent pacemaker or ILR in at least 20 centres in Canada, the USA, Asia, and Europe. The primary outcome measure will be a composite of Major Adverse Study-Related Events (MASRE) in a 2-year observation period, wherein the events are death, syncope, symptomatic bradycardia, asymptomatic diagnostic bradycardia, and acute and chronic device complications. Prespecified secondary endpoints will include syncope symptoms, quality of life, and economic burden. CONCLUSION: This trial will provide high-level and generalizable evidence for the use of either permanent pacing or implantable loop recorders as a first line intervention for patients with syncope, preserved systolic function, and bifascicular block.

Assessment of the sensitivity of detecting drug-induced QTc changes using subject-specific rate correction.

AIMS: To quantify the sensitivity of QT heart-rate correction methods for detecting drug-induced QTc changes in thorough QT studies. METHODS: Twenty-four-hour Holter ECGs were analyzed in 66 normal subjects during placebo and moxifloxacin delivery (single oral dose). QT and RR time series were extracted. Three QTc computation methods were used: (1) Fridericia's formula, (2) Fridericia's formula with hysteresis reduction, and (3) a subject-specific approach with transfer function-based hysteresis reduction and three-parameter non-linear fitting of the QT-RR relation. QTc distributions after placebo and moxifloxacin delivery were compared in sliding time windows using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) served as a measure to quantify the ability of each method to detect moxifloxacin-induced QTc prolongation. RESULTS: Moxifloxacin prolonged the QTc by 10.6 ± 6.6 ms at peak effect. The AUC was significantly larger after hysteresis reduction (0.87 ± 0.13 vs. 0.82 ± 0.12, p<0.01) at peak effect, indicating a better discriminating capability. Subject-specific correction further increased the AUC to 0.91 ± 0.11 (p<0.01 vs. Fridericia with hysteresis reduction). The performance of the subject-specific approach was the consequence of a substantially lower intra-subject QTc standard deviation (5.7 ± 1.1 ms vs. 8.8 ± 1.2 ms for Fridericia). CONCLUSION: The ROC curve provides a tool for quantitative comparison of QT heart rate correction methods in the context of detecting drug-induced QTc prolongation. Results support a broader use of subject-specific QT correction.

Complications associated with revision of Sprint Fidelis leads: report from the Canadian Heart Rhythm Society Device Advisory Committee.

BACKGROUND: It has been observed that replacement of an implantable cardioverter-defibrillator generator in response to a device advisory may be associated with a substantial rate of complications, including death. The risk of lead revision in response to a lead advisory has not been determined previously. METHODS AND RESULTS: Twenty-five implantable cardioverter-defibrillator implantation and follow-up centers from the Canadian Heart Rhythm Society Device Advisory Committee were surveyed to assess complication rates as a result of lead revisions due to the Sprint Fidelis advisory issued in October 2007. As of June 1, 2009, there had been 310 lead failures found in 6237 Sprint Fidelis leads in Canada (4.97%) over a follow-up of 40 months. There were 469 leads to be revised, 66% for confirmed fracture. Of the patients who underwent revision, 95% had a new lead inserted, whereas 4% had a pace/sense lead added. The lead was removed in 248 cases (53%), by simple traction in 61% and by laser lead extraction in 33%. Complications were encountered in 14.5% of the lead revisions; 7.25% of these were major, whereas 7.25% were minor. There were 2 deaths (0.43%). The overall risk of complications (19.8%) was greater in those who underwent lead removal at the time of revision than in those whose leads were abandoned (8.6%; P=0.0008). CONCLUSIONS: The overall rate of major complications that arose from lead revision due to the Sprint Fidelis advisory was significant. This must be taken into account when lead revision is planned in those patients who have not yet demonstrated an abnormality in lead performance.

Improved Flutter Ablation Outcomes Using a 10mm-tip Ablation Catheter.

INTRODUCTION: Radiofrequency(RF) ablation has become the first line of therapy for atrial flutter(AFL). Advances in catheter and mapping technologies have led to better understanding and different approaches for treating this arrhythmia. We describe the results of different approaches to ablate this arrhythmia. MATERIALS AND METHODS: A cohort of 198 patients with isthmus dependent AFL. The techniques used were: 10mm-tip catheter with power set to 100w, 8mm-tip catheter with power set to 60W and irrigated tip catheter. RESULTS: 212 procedures, including redos were done in 198 consecutive patients. We used irrigated tip catheters in 14 procedures, 8mm-tip in 55 procedures, and 10mm-tip in 143 procedures. Bidirectional block was achieved in 97.6% of cases with all techniques, with no difference among them. Procedure time was shorter in the 10mm-tip versus 8mm-tip(69.6±30.6min vs.105±43min) or irrigated tip(180±90min) (P<0.05). Fluoroscopy time was also shorter in the 10mm-tip versus 8mm-tip (24±18min vs. 37±23min) or irrigated tip (110±25min)(P<0.05). The cumulative incidence of failure during follow-up was 1.2%/year in the 10mm, 10.1%year in the 8mm and 6.9%year in the irrigated tip. The survival free of a new procedure was significantly higher among 10mm patients. CONCLUSIONS: In our series we found a high rate of acute success with the use of different techniques for AFL ablation. Procedure and fluoroscopic times were shorter with the use of 10mm-tip as compared with the others techniques. The long-term risk of recurrence was lower when we used the 10mm-tip catheter and the survival free of a second procedure was higher among patients treated with this catheter.

Effect of metoprolol on quality of life in the Prevention of Syncope Trial.

INTRODUCTION: Vasovagal syncope is common, often recurrent, and reduces quality of life. No therapies have proven useful to improve quality of life in adequately designed randomized clinical trials. Beta-blockers have mixed evidence for effectiveness in preventing syncope. METHODS: The Prevention of Syncope Trial was a randomized, placebo-controlled, double-blind, multinational, clinical trial that tested the hypothesis that metoprolol improves quality of life in adult patients with vasovagal syncope in a 1-year observation period. Randomization was stratified in strata of patients <42 and > or =42 years old. The quality of life questionnaires Short Form-36 (SF-36) and Euroqol EQ-5D were completed at baseline and after 6 and 12 months of treatment by 204, 132, and 121 patients, respectively. RESULTS: There were 208 patients, mean age 42 +/- 18, of whom 134 (64%) were females. All had positive tilt tests. There was no improvement in quality of life during the trial in the entire group or in either treatment arm. Patients in the metoprolol treatment arm did not have improved quality of life compared to the patients in the placebo arm using either the SF-36 or EQ5D after either 6 or 12 months. Finally, there was no improvement in quality of life associated with metoprolol use in patients either <42 or > or =42 years of age. CONCLUSION: Metoprolol does not improve quality of life in patients with recurrent vasovagal syncope and a positive tilt test.

Design and use of a quantitative scale for measuring presyncope.

INTRODUCTION: Vasovagal syncope is common and distressing. One important symptom is presyncope, but there are no clinimetric measures of this. We developed the Calgary Presyncope Form (CPF) and used it to test whether metoprolol reduces presyncope in a randomized trial. METHODS: The CPF captures the frequency, duration, and severity of presyncope. We administered it to participants in the Prevention of Syncope Trial (POST), a randomized clinical trial that tested the hypothesis that metoprolol reduces syncope and presyncope in adult patients with vasovagal syncope. RESULTS: The CPF was completed by 44 patients on metoprolol and 39 patients on placebo, of a total of 208 subjects. Completion of the CPF for each of the threedimensions was 84-87% in the 83 respondents. Results were centrally distributed in duration and severity dimensions, but not in frequency. Patients had a median of 1.2 presyncopal spells per day, with a median moderate severity, lasting a median 10 minutes. The 3 scales were statistically independent of each other. These results were independent of subject age, and results in all 3 dimensions were stable over the observation period. There was no significant difference between patients on metoprolol and placebo in any dimension. CONCLUSION: The 3-dimensional CPF is simple, easy to use, stable over time, measures 3 independent variables, and documents that metoprolol does not reduce presyncope.

Meta-Analysis Comparing Neurohumoral Antagonist Use in Patients ≥75 Years Versus <75 Years Receiving Cardiac Resynchronization Therapy.

Neurohumoral antagonists are the foundation of heart failure therapy in patients with reduced left ventricular ejection fraction. Cardiac resynchronization therapy (CRT) has also been associated with improved outcomes in these patients. We aimed to evaluate the use of neurohumoral antagonists in patients ≥75 years compared with <75 years of age receiving CRT. We searched electronic databases, up to December 20, 2016 for all studies reporting medication use in patients ≥75 years and <75 years of age who received CRT. We used random-effects meta-analysis models to summarize the studies. We retained 12 studies (1 randomized trial and 11 observational studies) enrolling 5,728 ≥75 years old and 9,549 patients of <75 years old. There were lower use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers in patients ≥75 years compared with patients <75 years (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.47 to 0.74, p < 0.0001). In addition, there were lower use of mineralocorticoid receptor antagonists in patients ≥75 years compared with patients <75 years (OR 0.48, 95% CI 0.40 to 0.57, p < 0.0001). The use of ß blockers was nonsignificantly lower in patients ≥75 years compared with patients <75 years (OR 0.70, 95% CI 0.47 to 1.03, p = 0.07). In conclusion, neurohumoral antagonists appeared to be underused in patients ≥75 years compared with patients <75 years receiving CRT. Consideration should be given to increase neurohumoral antagonism in patients ≥75 years referred for CRT.

Cervical vagosympathetic and mediastinal nerves activation effects on atrial arrhythmia formation.

In anesthetized dogs both epi-and endocardial atrial activation maps and corresponding isointegral repolarization maps were created before and during right or left mediastinal nerve (RMN and LMN) and cervical vagus nerve (CVN) stimulation. Right mediastinal nerve stimulation typically caused sinus slowing, atrial tachycardia (AT), followed by atrial fibrillation (AF). Activation maps during AT showed epicardial breakthroughs from the right atrial free wall or Bachmann's bundle. Left mediastinal nerve stimulation (LMN) rarely caused sinus slowing and ATs originated mostly from Bachmann's bundle or from the pulmonary vein ostial region. Atrial repolarization changes induced by neural stimulation were measured by integrating the area subtended by 161 epicardial unipolar electrograms. Atrial tachycardia epicardial breakthrough sites were closely associated with the border zone where repolarization changes occurred. Both AT and AF were abolished by I.V. atropine, as were sinus bradycardia and atrial repolarization effects of nerve stimulation. Shortening of latency of onset and duration of AT by I.V. timolol suggest concurrent activation of adrenergic efferent neurons. In conclusion, juxta-cardiac mediastinal nerve stimulation can induce atrial fibrillation from multiple, discrete right and left atrial sites, which correspond to localized repolarization changes. Secondly, sinus bradycardia is not a necessary index of parasympathetic neurally induced atrial fibrillation.

Simple risk stratification score for prognosis of syncope.

PURPOSE: The aim of this study is to describe a new simple score to predict the occurrence of severe adverse events in patients admitted for syncope to a tertiary cardiology referral center. METHODS: Three hundred ninety-three subjects with emergency department visits for syncope were identified and followed prospectively. The primary endpoint was death or unplanned hospital admission after the syncopal episode. The score consisted of sum of the following: previous syncope (2 points), an abnormal electrocardiogram (3 points), and history of heart disease (4 points). The accuracy of our score was compared to other scores available in the literature. RESULTS: Of the 393 subjects, 87 were diagnosed with syncope secondary to structural or electrical heart disease and 306 with noncardiac syncope. The primary endpoint occurred in 202 cases, including death occurring in 25 patients during the 12-month follow-up. The 30-day event rate for the primary endpoint was 26.5 %. The c-statistic for the new score was 0.76 (95 % CI 0.71-0.80) similar to other scores when applied to our sample. Patients with a score of 3 out of 9 had a hazard ratio of 3.46 (95 % CI 1.22-6.11) for death during the follow-up. CONCLUSIONS: In the study population, the new syncope score detected patients with an increased risk of death after discharge from a syncopal event. Our score predicted adverse events comparably to other scores reported in the literature. It has the advantage of being simple and easily obtained from the history and an inexpensive noninvasive test-the ECG.

Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial.

BACKGROUND: There is limited evidence whether being on fludrocortisone prevents vasovagal syncope. OBJECTIVES: The authors sought to determine whether treatment with fludrocortisone reduces the proportion of patients with recurrent vasovagal syncope by at least 40%, representing a pre-specified minimal clinically important relative risk reduction. METHODS: The multicenter POST 2 (Prevention of Syncope Trial 2) was a randomized, placebo-controlled, double-blind trial that assessed the effects of fludrocortisone in vasovagal syncope over a 1-year treatment period. All patients had >2 syncopal spells and a Calgary Syncope Symptom Score >-3. Patients received either fludrocortisone or matching placebo at highest tolerated doses from 0.05 mg to 0.2 mg daily. The main outcome measure was the first recurrence of syncope. RESULTS: The authors randomized 210 patients (71% female, median age 30 years) with a median 15 syncopal spells over a median of 9 years equally to fludrocortisone or placebo. Of these, 96 patients had ≥1 syncope recurrences, and only 14 patients were lost to follow-up before syncope recurrence. There was a marginally nonsignificant reduction in syncope in the fludrocortisone group (hazard ratio [HR]: 0.69: 95% confidence interval [CI]: 0.46 to 1.03; p = 0.069). In a multivariable model, fludrocortisone significantly reduced the likelihood of syncope (HR: 0.63; 95% CI: 0.42 to 0.94; p = 0.024). When the analysis was restricted to outcomes after 2 weeks of dose stabilization, there was a significant benefit due to fludrocortisone (HR: 0.51; 95% CI: 0.28 to 0.89; p = 0.019). CONCLUSIONS: The study did not meet its primary objective of demonstrating that fludrocortisone reduced the likelihood of vasovagal syncope by the specified risk reduction of 40%. The study demonstrated a significant effect after dose stabilization, and there were significant findings in post hoc multivariable and on-treatment analyses. (A randomised clinical trial of fludrocortisone for the prevention of vasovagal syncope; ISRCTN51802652; Prevention of Syncope Trial 2 [POST 2]; NCT00118482).