Pharmacotherapy of neurally mediated syncope.

A wide variety of pharmacological agents are currently used for prevention of recurrent neurally mediated syncope, especially the vasovagal faint. None, however, have unequivocally proven long-term effectiveness based on adequate randomized clinical trials. At the present time, beta-adrenergic receptor blockade, along with agents that increase central volume (eg, fludrocortisone, electrolyte-containing beverages), appear to be favored treatment options. The antiarrhythmic agent disopyramide and various serotonin reuptake blockers have also been reported to be beneficial. Finally, vasoconstrictor agents such as midodrine offer promise and remain the subject of clinical study. Ultimately, though, detailed study of the pathophysiology of these syncopal disorders and more aggressive pursuit of carefully designed placebo-controlled treatment studies are essential if pharmacological prevention of recurrent neurally mediated syncope is to be placed on a firm foundation.

Atrioventricular dissociation exacerbating posturally-induced syncope.

We report a case of an 85-year-old patient with posturally-induced syncope in whom symptoms were reproduced during tilt table testing in conjunction with development of an accelerated junctional rhythm with isorhythmic atrio-ventricular (AV) dissociation. That loss of AV synchrony was crucial to development of hypotension and syncope was demonstrated during electrophysiologic testing in which both an accelerated junctional rhythm and an inducible atypical AV nodal re-entrant tachycardia (AVNRT) were induced. The accelerated junctional rhythm was accompanied by moderate hypotension with the patient in the supine posture, whereas blood pressure was well maintained during atypical AVNRT despite a much faster ventricular rate. Thus, symptomatic hypotension due to AV dissociation, presumably the result of transient autonomic disturbance, may be another manifestation of neurally-mediated syncope.

Atrial fibrillation: defining potential curative ablation targets.

The concept that atrial fibrillation (or at least certain forms of the arrhythmia) may be amenable to reversal or amelioration by transcatheter ablation techniques has become increasingly accepted in recent years. As yet, however, the techniques being studied for ablation of atrial fibrillation address neither known critical anatomic elements nor well defined electrophysiologic markers. The approaches, although essentially empirical, are conceptually based on the 'multiple wavelet' or 'focal origin' hypotheses. To date, addressing 'focal origin' atrial fibrillation by transcatheter ablation has been the more encouraging. However, as technology evolves, both in terms of catheter design and possibly endocardial mapping techniques, approaches to wavelet or rotor mechanisms may become similarly effective. This communication examines concepts regarding the manner in which atrial fibrillation is initiated and maintained. The goals are to better understand the encouraging success of empirical ablation methods, and possibly derive insights which may help refine ablation targeting in the future.

Cerebral infarction associated with oral verapamil overdose.

Verapamil is a widely used calcium channel blocker. Side effects with oral use are usually mild, however, major hemodynamic complications and death can occur if the drug is given in overdose. We describe a case of cerebral infarction associated with attempted suicide with verapamil overdose, the first reported to our knowledge.

Assessment of ischemic changes by ambulatory ECG-monitoring: comparison with 12-lead ECG during exercise testing.

The accuracy of commercially available ambulatory electrocardiographic monitoring (AEM) systems for reproducing ischemic changes has been questioned. Since these systems are widely used for evaluation of ST-segment changes, both for prognostic purposes and for assessment of the efficacy of antiischemic drugs, such doubts must be clarified. For this purpose, we recorded electrocardiograms (ECGs) during exercise testing, using split leads, simultaneously with a 12-lead electrocardiograph and with the Marquette AEM recorder. We studied 29 patients with proven coronary artery disease and positive exercise tests and 19 individuals with low likelihood of coronary artery disease and negative stress tests. All 29 patients who had ST-segment depression during exercise as recorded on the 12-lead ECG had ST-segment depression in at least one of the three AEM leads (resembling the V5, V3, and aVF leads of the 12-lead system). The maximal degree of ST-segment depression with AEM was similar to 12-lead ECG (2.3 mm and 2.1 mm, respectively). The best lead for ischemia detection with AEM was the V5 type, which detected ischemic changes in 26 of the 29 patients, while the 12-lead V5 detected ischemia in 24 patients. The inferior AEM lead detected ischemia in only 4 patients, while the aVF lead of the 12-lead ECG detected ischemia in 23 patients. Of the 19 patients with negative exercise tests only 1 patient had a 1-mm ST-segment depression on AEM. Thus, of the 48 patients studied, similar responses were observed in 47. The results of indicate that the Marquette AEM system is as accurate as the 12-lead ECG in detecting ischemic changes and in assessing their severity.

Catecholamine response during haemodynamically stable upright posture in individuals with and without tilt-table induced vasovagal syncope.

AIM: Changes in circulating catecholamine concentrations during vasovagal faints have been the subject of considerable study. However, whether catecholamines are part of the triggering mechanism, or principally reflect attempted compensation for an evolving circulatory crisis is unknown. To address this issue, we determined whether the circulating catecholamine response to upright posture differs among patients with and without inducible vasovagal faints at a time when there is no detectable haemodynamic compromise. METHODS AND RESULTS: Blood samples for measurement of adrenaline and noradrenaline (Norepi) concentrations were obtained in the baseline state, and at both 2-3 min and 4-6 min of upright posture in 22 patients undergoing head-up tilt-table testing for evaluation of syncope of unknown cause. In 11 individuals tilt-testing induced syncope at >5 min head-up posture (Group 1). In 11 other individuals tilt testing did not result in syncope (Group 2). Supine arterial catecholamine levels were comparable in the two groups. However, adrenaline concentrations during upright posture tended to be greater at 2-3 min and were significantly greater at 4-6 min in Group 1 than in Group 2 (P< 0.01). These differences occurred in the absence of significant intergroup differences in mean arterial pressure or cardiac cycle lengths. Norepi concentrations also increased in both groups, but without significant differences. CONCLUSION: Circulating adrenaline concentrations in posturally induced vasovagal faints rise more rapidly in vasovagal fainters than in comparably posturally stressed non-fainters, and were significantly greater in fainters prior to either detectable haemodynamic compromise or diminution of circulating Norepi levels. These findings suggest that a premonitory rise in adrenaline concentrations occurs in vasovagal fainters unassociated with an evolving circulatory crisis.

Syncope in pharmacologically unmasked Brugada syndrome: indication for an implantable defibrillator or an unresolved dilemma?

A 30-year-old Caucasian male was referred for evaluation of a 2-year history of recurrent post-exertion lightheadedness and near syncopal spells in the setting of a family history of unexplained sudden cardiac death. Cardiac evaluation demonstrated normal heart structure, but the 12-lead surface ECG was suggestive of but not diagnostic of Brugada syndrome. An exercise stress test reproduced the patient's usual symptoms during the recovery period, and was consistent with a typical vasovagal faint. The same symptoms were observed during a head-up tilt table test. However, given the family history and ECG, pharmacological testing with procainamide, isoprenaline and metoprolol, as well as programmed ventricular stimulation, were undertaken. Pharmacological provocation further supported a diagnosis of Brugada syndrome, whereas programmed ventricular stimulation was considered non-diagnostic regarding ventricular tachyarrhythmia susceptibility. Consequently, despite ECG and pharmacological findings suggestive of Brugada syndrome, there appeared to be sufficient evidence to believe that this patient's symptoms were the result of neurally mediated syncope and not due to ventricular tachyarrhythmias. The patient was treated with midodrine, and has remained symptom-free for 16 months. Thus, given the frequency with which vasovagal syncope occurs in young patients, its occurrence is not unexpected in individuals with concomitant diagnoses such as Brugada syndrome. In as much as current recommendations favour implantable defibrillators in symptomatic Brugada syndrome, the identification of other causes of syncope in such patients poses an uncomfortable, and currently unsettled dilemma.

Improving standard cardiopulmonary resuscitation with an inspiratory impedance threshold valve in a porcine model of cardiac arrest.

To improve the efficiency of standard cardiopulmonary resuscitation (CPR), we evaluated the potential value of impeding respiratory gas exchange selectively during the decompression phase of standard CPR in a porcine model of ventricular fibrillation. After 6 min of untreated cardiac arrest, anesthetized farm pigs weighing 30 kg were randomized to be treated with either standard CPR with a sham valve (n = 11) or standard CPR plus a functional inspiratory impedance threshold valve (ITV(TM)) (n = 11). Coronary perfusion pressure (CPP) (diastolic aortic minus right atrial pressure) was the primary endpoint. Vital organ blood flow was assessed with radiolabeled microspheres after 6 min of CPR, and defibrillation was attempted 11 min after starting CPR. After 2 min of CPR, mean +/- SEM CPP was 14 +/- 2 mm Hg with the sham valve versus 20 +/- 2 mm Hg in the ITV group (P < 0.006). Significantly higher CPPs were maintained throughout the study when the ITV was used. After 6 min of CPR, mean +/- SEM left ventricular and global cerebral blood flows were 0.10 +/- 0.03 and 0.19 +/- 0.03 mL. min(-1). g(-1) in the Control group versus 0.19 +/- 0.03 and 0.26 +/- 0.03 mL. min(-1). g(-1) in the ITV group, respectively (P < 0.05). Fifteen minutes after successful defibrillation, 2 of 11 animals were alive in the Control group versus 6 of 11 in the ITV group (not significant). In conclusion, use of an inspiratory impedance valve during standard CPR resulted in a marked increase in CPP and vital organ blood flow after 6 min of cardiac arrest.