The electrophysiological effects of intramuscular guinidine on the atrioventricular conducting system in man

The electrophysiological effects of intramuscular quinidine were evaluated using His bundle electrograms and the extrastimulus method. The mean mid-study plasma quinidine level was 4.6 mg. per liter. Our results show that quinidine tends to shorten A-V nodal conduction time while it routinely prolongs His-Purkinje and intraventricular conduction time. The refractory periods of the atrium and His-Purkinje system were prolonged by quinidine while the effective refractory period of the A-V node was consistently shortened. Those patients with evidence of infra-His conduction disturbances manifested no difference in their response to quinidine from the group as a whole. These studies suggest quinidine has antivagal properties which are of clinical significance. In addition, the effects of quinidine on His-Purkinje conduction and refractoriness may lead to the ventricular tachyarrhythmias implicated in “quinidine syncope” by a re-entrant mechanism.     

Unexplained syncope evaluated by electrophysiologic studies and head-up tilt testing

OBJECTIVE: To determine the clinical characteristics of subgroups of patients with unexplained syncope having electrophysiologic studies and head-up tilt testing and to assess the efficacy of various therapies. DESIGN: Retrospective study. SETTING: Inpatient services of a tertiary referral center. PATIENTS: Eighty-six consecutively referred patients with unexplained syncope. MEASUREMENTS: All patients had electrophysiologic examinations. Patients with negative results subsequently had head-up tilt testing. MAIN RESULTS: Twenty-nine (34%) patients (group 1) had abnormal electrophysiologic results, with sustained monomorphic ventricular tachycardia induced in 72%. Thirty-four (40%) patients (group 2) had syncope provoked by head-up tilt testing. The cause of syncope remained unexplained in 23 (26%) patients (group 3). Structural heart disease was present in 76%, 6%, and 30% of groups 1, 2, and 3, respectively. In group 1, pharmacologic or nonpharmacologic therapy was recommended based on electrophysiologic evaluation. All group 2 patients had negative results on head-up tilt testing while receiving oral beta blockers (27 patients) or disopyramide (7 patients). Group 3 patients did not receive any specific therapy. During a median follow-up period of 18.5 months, syncope recurred in 9 (10%) patients. CONCLUSIONS: The combination of electrophysiologic evaluation and head-up tilt testing can identify the underlying cause of syncope in as many as 74% of patients presenting with unexplained syncope. Therapeutic strategies formulated according to the results of these diagnostic tests appear to prevent syncope effectively in most patients.     

Induction of ventricular fibrillation versus monomorphic ventricular tachycardia during programmed stimulation. Role of premature beat conduction delay.

BACKGROUND. Premature stimuli can cause ventricular fibrillation (VF) during electrophysiological testing. The electrophysiological correlations associated with the onset of VF were evaluated in 40 patients who had this rhythm induced during programmed ventricular stimulation. These parameters were compared with those observed in 51 patients who had inducible sustained monomorphic ventricular tachycardia (VT) and 45 patients who had no inducible sustained ventricular tachyarrhythmias. METHODS AND RESULTS. Shortest premature coupling intervals for S2, S3, and S4 at induction of tachycardia or before achieving refractoriness, corresponding conduction latencies (defined as the time from the premature stimulus to the upstroke of the depolarization wave front recorded 35 mm away from the stimulation site), and ventricular activation times (defined as the time from the premature stimulus to the end of the depolarization wave) were compared. The mean coupling intervals were longest in the inducible VT patients: 300 +/- 30, 254 +/- 57, and 228 +/- 32 msec for S2, S3, and S4, respectively. In the inducible VF group, the coupling intervals were 260 +/- 37, 208 +/- 20, and 213 +/- 30 msec. In the group with no inducible VT or VF, these coupling intervals were 251 +/- 24 (p less than 0.01 versus inducible VT group), 209 +/- 27 (p less than 0.001 versus inducible VT group), and 194 +/- 21 msec (p less than 0.05 versus inducible VT and VF groups). The coupling interval of the last premature extrastimulus was above 200 msec in 70% of the patients in whom VF was induced. The largest increases in latency and activation times were recorded in patients in whom VF was induced. The cumulative increase in latency, defined as increased conduction time from baseline, summed for all the premature stimuli was also the greatest at initiation of VF. In contrast, the smallest increases in these parameters were noted in the patients with no inducible VT or VF. Measurements of total activation time yielded similar results as those recorded for latencies. The most important parameters distinguishing the VT patient population from the other two groups were the low ejection fractions and the longer coupling intervals at which VT was induced, whereas in the VF group, the most important discriminating factor was cumulative activation time. Sixty-three percent of the inducible VF patients presented with abnormal hearts (myocardial infarction or cardiomyopathy), whereas 88% of the inducible VT patients had abnormal hearts. In contrast, only 25% of the patients in whom no arrhythmia was induced presented with abnormal hearts. Mean ejection fraction was 32 +/- 15% for the inducible VT group, 45 +/- 13%* for the inducible VF group, and 51 +/- 17%* for patients with no inducible VT/VF (*p less than 0.001 versus VT). CONCLUSIONS. The results suggest that 1) initiation of ventricular tachycardia during programmed ventricular stimulation occurs with minimal conduction latency; 2) because of the large overlap in coupling intervals where VF or VT were induced, a single coupling interval cannot be recommended to adequately separate these groups; and 3) induction of VF was preceded by increased latency and prolongation of the local activation time. These parameters should not be allowed to prolong if VF is to be avoided during programmed stimulation. In addition, 4) the initiation of VF during electrophysiological studies is often associated with the presence of structural heart disease; such structural disease may promote conduction latency and the development of VF.     

The Novel Desmin Variant p.Leu115Ile Is Associated With a Unique Form of Biventricular Arrhythmogenic Cardiomyopathy

BackgroundArrhythmogenic cardiomyopathy (AC) is a heritable myocardial disorder and a major cause of sudden cardiac death. It is typically caused by mutations in desmosomal genes. Desmin gene (DES) variants have been previously reported in AC but with insufficient evidence to support their pathogenicity.MethodsWe aimed to assess a large AC patient cohort for DES mutations and describe a unique phenotype associated with a recurring variant in three families. A cohort of 138 probands with a diagnosis of AC and no identifiable desmosomal gene mutations were prospectively screened by whole-exome sequencing.ResultsA single DES variant (p.Leu115Ile, c.343C>A) was identified in 3 index patients (2%). We assessed the clinical phenotypes within their families and confirmed cosegregation. One carrier required heart transplantation, 2 died suddenly, and 1 died of noncardiac causes. All cases had right- and left-ventricular (LV) involvement. LV late gadolinium enhancement was present in all, and circumferential subepicardial distribution was confirmed on histology. A significant burden of ventricular arrhythmias was noted. Desmin aggregates were not observed macroscopically, but analysis of the desmin filament formation in transfected cardiomyocytes derived from induced pluripotent stem cells, and SW13 cells revealed cytoplasmic aggregation of mutant desmin. Atomic force microscopy revealed that the mutant form accumulates into short protofilaments and small fibrous aggregates.ConclusionsDES p.Leu115Ile leads to disruption of the desmin filament network and causes a malignant biventricular form of AC, characterized by LV dysfunction and a circumferential subepicardial distribution of myocardial fibrosis.     

Nutrient Composition of Six Small Indigenous Fish from NEH Region and Their Contribution Potential to Human Nutrition

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Six small indigenous fish species namely Macrognathus aral, Setipinna phasa, Clupisoma garua, Aspidoporia...     

Ventricular Fibrillation Sensing and Detection by Implantable Defibrillators: Is One Better than the Others? A Prospective,Comparative Study

INTRODUCTION: We prospectively compared the performance of the sensing and detection systems of three leading defibrillator manufacturers: Medtronic, Guidant, and Ventritex. METHODS AND RESULTS: Ventricular fibrillation signal was digitally recorded during defibrillator implantation and subsequently played back sequentially to a Medtronic Micro Jewel II 7223Cx, a Guidant MINI II 1762, and a Ventritex Cadet V-115C. The devices were programmed for single-zone detection, at nominal settings. Rate cutoff was set at 320 msec (185/min for the MINI). We analyzed 253 episodes from 47 patients. Median undersensing was 0%, 2.1%, and 5.3% for the Jewel, MINI, and Cadet, respectively (P < 0.001 for each paired comparison). Detection time was 4.1 +/- 1.6 seconds, 3.4 +/- 1.6 seconds, and 4.3 +/- 2.2 seconds for the Jewel, MINI, and Cadet, respectively (P < 0.001 between MINI-Jewel and MINI-Cadet; P < 0.01 between Jewel-Cadet). Delayed detection (detection time longer than the mean of all observations + 2 SD) occurred in 3 (1.2%), 7 (2.8%), and 18 (7.1%) episodes for the Jewel, MINI, and Cadet, respectively. Performance for all devices was worse when the short-separation integrated bipolar lead was used and when the episode followed a failed high-energy shock. CONCLUSION: Statistically significant differences were seen in sensing and detection performance among the devices and device/lead combinations during ventricular fibrillation. These differences are related to specific features of the respective devices and should be taken into account during clinical practice, as well as in future device development.