Difference In Effective Refractory Period Research Articles

Highlights From the Circulation Family of Journals.

Highlights From the Circulation Family of Journals.

Programmed His Bundle Pacing: A Novel Maneuver for the Diagnosis of His Bundle Capture.

During permanent nonselective His bundle (ns-HB) pacing, it is crucial to confirm HB capture/exclude that only right ventricle (RV) myocardial septal pacing is present. Because the effective refractory period (ERP) of the working myocardium is different than the ERP of the HB, we hypothesized that it should be possible to differentiate ns-HB capture from RV myocardial capture using programmed extrastimulus technique. In consecutive patients during HB pacemaker implantation, programmed HB pacing was delivered from the screwed-in HB pacing lead. Premature beats were introduced at 10-ms steps during intrinsic rhythm and also after a drive train of 600 ms. The longest coupling interval that resulted in an abrupt change of QRS morphology was considered equal to ERP of HB or RV myocardium. Programmed HB pacing was performed from 50 different sites in 32 patients. In 34 of 36 cases of ns-HB pacing, the RV myocardial ERP was shorter than HB ERP (271.8±38 versus 353.0±30 ms; P<0.0001). Programmed HB pacing using a drive train resulted in a typical abrupt change of paced QRS morphology: from ns-HB to RV myocardial QRS (34 of 36 cases) or to selective HB QRS (2 of 36 cases). Programmed HB pacing delivered during native conduction resulted in obtaining selective HB QRS in 20 of 34 and RV myocardial QRS in 14 of 34 of the ns-HB cases. In RV myocardial-only pacing cases (false ns-HB pacing, n=14), such responses were not observed-the QRS morphology remained stable. Therefore, the programmed HB pacing correctly diagnosed all ns-HB cases and all RV myocardial pacing cases. A novel maneuver for the diagnosis of HB capture, based on the differences in ERP between HB and myocardium, was formulated, assessed, and found as diagnostically valuable. This method is unique in enabling to visualize selective HB QRS in patients with otherwise obligatory ns-HB pacing (RV myocardial capture threshold <HB capture threshold).

Ventricular Endocardial Tissue Geometry Affects Stimulus Threshold and Effective Refractory Period

Background: Understanding the biophysical processes by which electrical stimuli applied to cardiac tissue may result in local activation is important in both the experimental and clinical electrophysiology laboratory environments, as well as for gaining a more in-depth knowledge of the mechanisms of focal-trigger-induced arrhythmias. Previous computational models have predicted that local myocardial tissue architecture alone may significantly modulate tissue excitability, affecting both the local stimulus current required to excite the tissue and the local effective refractory period (ERP). In this work, we present experimental validation of this structural modulation of local tissue excitability on the endocardial tissue surface, use computational models to provide mechanistic understanding of this phenomena in relation to localized changes in electrotonic loading, and demonstrate its implications for the capture of afterdepolarizations.Methods and Results: Experiments on rabbit ventricular wedge preparations showed that endocardial ridges (surfaces of negative mean curvature) had a stimulus capture threshold that was 0.21 ± 0.03 V less than endocardial grooves (surfaces of positive mean curvature) for pairwise comparison (24% reduction, corresponding to 56.2 ± 6.4% of the energy). When stimulated at the minimal stimulus strength for capture, ridge locations showed a shorter ERP than grooves (n = 6, mean pairwise difference 7.4 ± 4.2 ms). When each site was stimulated with identical-strength stimuli, the difference in ERP was further increased (mean pairwise difference 15.8 ± 5.3 ms). Computational bidomain models of highly idealized cylindrical endocardial structures qualitatively agreed with these findings, showing that such changes in excitability are driven by structural modulation in electrotonic loading, quantifying this relationship as a function of surface curvature. Simulations further showed that capture of delayed afterdepolarizations was more likely in trabecular ridges than grooves, driven by this difference in loading.Conclusions: We have demonstrated experimentally and explained mechanistically in computer simulations that the ability to capture tissue on the endocardial surface depends upon the local tissue architecture. These findings have important implications for deepening our understanding of excitability differences related to anatomical structure during stimulus application that may have important applications in the translation of novel experimental optogenetics pacing strategies. The uncovered preferential vulnerability to capture of afterdepolarizations of endocardial ridges, compared to grooves, provides important insight for understanding the mechanisms of focal-trigger-induced arrhythmias.

Electrophysiological properties of the South Asian heart

ObjectiveThe South Asian population has a lower burden of arrhythmia compared with Caucasians despite a higher prevalence of traditional cardiovascular risk factors. We aimed to determine whether this was due...

Renal denervation regulates the atrial arrhythmogenic substrates through reverse structural remodeling in heart failure rabbit model

BackgroundHeart failure (HF) causes atrial remodeling and increases the incidence of atrial fibrillation (AF). Renal denervation (RDN) has been shown to decrease the development of AF. This study aimed to identify the effects of RDN on the atrial arrhythmogenic substrates in HF. MethodsRabbits were classified into four groups: control (n=9), RDN (n=10), HF (n=6) and HF-RDN (n=9). Surgical and chemical RDN was approached through bilateral retroperitoneal flank incisions in RDN and HF-RDN. Rapid ventricular pacing of 400bpm for 4weeks was applied in HF and HF-RDN. After 4weeks, the rabbits were sacrificed and atrial myocardium were harvested for Western blot and Trichrome stain. ResultsThe bi-atrial effective refractory period (ERP) of HF was significantly longer compared with that of control and RDN. In right atrium, the ERP of HF was also significantly longer compared with that of HF-RDN, but there was no significant difference in left atrial ERP. In bi-atrium, ion channel protein expressions of CaV1.2, NaV1.5, Kir2.1 SERCA2 and NCX were similar among 4 groups. However, the degree of atrial fibrosis was extensive in bi-atrium of HF, when compared to that of control, RDN and HF-RDN. ConclusionThe ERP of HF-RDN is partially shortened by RDN compared with that of HF. There are no differences ionic channel protein expressions in bi-atrium among all groups. The degree of atrial fibrosis is severe in HF, but not in HF-RDN, suggesting that RDN may regulate the atrial arrhythmogenic substrates in HF mostly through reverse structural remodeling.

Electrical Remodeling in Persistent Atrial Fibrillation May Be Mediated by Changes in the IKATP Channel

The goal of this study was to measure the effective refractory period (ERP), the conduction velocity (CV) and the wavelength (WL) after cardioversion in patients with persistent atria] fibrillation (AF) and to determine the effects of the adenosine triphosphate sensitive potassium channel (KATP) opening agent, nicorandil, on those parameters in patients with persistent AF.METHODS: Patients with AF underwent elective cardioversion followed by measurement of ERP and CV before and after administration of nicorandil. Parameters were measured again one week later, and the ERP and the CV was used to calculate WL.RESULTS: ERP was significantly shorter immediately after termination of AF than at the 1‐week time point (193.4 vs. 228.7 msec p &lt; 0.01). While there was no significant difference in ERP immediately after termination of AF when comparing measurements taken before and after the administration of nicorandil, ERP at the 1‐week time point was shorter after nicorandil administration than before nicorandil administration (193.4 vs. 191.4 msec, n.s.; 228.7 vs. 217.2msec, p &lt; 0.01). Further, WL was higher at the 1‐week time point after nicorandil administration than before nicorandil administration.CONCLUSIONS: These data indicate that the electrical remodeling that occurs after cardioversion is at least partially mediated by changes in KATP channel behavior. Further, the electrophysiologic properties, that is, nicorandil prolonging the WL, may be of benefit in reducing the recurrence rate of AF.

Electrical Remodeling in Persistent Atrial Fibrillation May Be Mediated by Changes in the IKATP Channel

The goal of this study was to measure the effective refractory period (ERP), the conduction velocity (CV) and the wavelength (WL) after cardioversion in patients with persistent atria] fibrillation (AF) and to determine the effects of the adenosine triphosphate sensitive potassium channel (KATP) opening agent, nicorandil, on those parameters in patients with persistent AF. METHODS: Patients with AF underwent elective cardioversion followed by measurement of ERP and CV before and after administration of nicorandil. Parameters were measured again one week later, and the ERP and the CV was used to calculate WL. RESULTS: ERP was significantly shorter immediately after termination of AF than at the 1-week time point (193.4 vs. 228.7 msec p < 0.01). While there was no significant difference in ERP immediately after termination of AF when comparing measurements taken before and after the administration of nicorandil, ERP at the 1-week time point was shorter after nicorandil administration than before nicorandil administration (193.4 vs. 191.4 msec, n.s.; 228.7 vs. 217.2msec, p < 0.01). Further, WL was higher at the 1-week time point after nicorandil administration than before nicorandil administration. CONCLUSIONS: These data indicate that the electrical remodeling that occurs after cardioversion is at least partially mediated by changes in KATP channel behavior. Further, the electrophysiologic properties, that is, nicorandil prolonging the WL, may be of benefit in reducing the recurrence rate of AF.

Electrophysiologic and blood-flow responses in the endocardium and epicardium to disopyramide and MS-551 during myocardial ischemia in the dog.

The aim of this study was to determine whether a quantitative relation exists between changes in regional myocardial blood flow (RMBF) and those in electrophysiologic determinants recorded via left ventricular endocardial and epicardial bipolar electrograms after administration of disopyramide (DP) and a class III antiarrhythmic drug, MS-551 (MS), during myocardial ischemia in the dog. Dogs were given DP (1 mg/kg, i.v., n = 14), MS (1 mg/kg, i.v., and 0.1 mg/kg/min, d.i.v., n = 13), or saline (n = 12). The effective refractory period (ERP) was determined by an S1-S2 extrastimulus method, and RMBF by a nonradioactive microsphere technique. The duration of regional electrograms (DRE) was measured as an indicator of conduction time in the myocardium. DP blunted ischemia-induced shortening of ERPs and lengthened DREs at the endocardial and epicardial sites, with a greater effect seen epicardially (p < 0.01 each). DP reduced RMBF, especially at the endocardial surfaces of the ischemic zone (p < 0.05). MS prolonged ERPs at the endocardial and epicardial sites in the ischemic and normal zones (p < 0.05-0.01), but there were no significant differences between the two sites. MS prolonged DREs (p < 0.05), but the magnitude of the prolongation of the DREs was similar to the values in the control group. MS had no effects on RMBF. DP treatment prolonged DREs at both sites in the ischemic zone more markedly than MS or saline treatment (p < 0.01 each). DP reduced RMBF at the endocardial site of the ischemic zone more markedly than MS or saline (p < 0.05 in each). Accordingly, MS prolonged ERPs, but did not increase disparities between endocardial and epicardial sites in the ischemic myocardium, whereas DP had a greater ERP-prolonging effect at the epicardial site than at the endocardial site. DP reduced endocardial RMBF more markedly than epicardial RMBF. These observations suggest that differences in ERPs between endocardial and epicardial ischemic myocardium caused by DP treatment are not due to the difference in RMBF reduction between the two tissue layers, and that DP and MS do not affect the same population of ion channel(s) when ERPs are prolonged.

Effects of pilsicainide and propafenone on vagally induced atrial fibrillation: role of suppressant effect in conductivity

The effects of pilsicainide on vagally induced atrial fibrillation and on electrophysiological parameters were compared with those of propafenone in α-chloralose-anesthetized dogs. Conduction velocity, effective refractory period, wavelength, averaged atrial fibrillation cycle length and activation sequence in the right atrial free wall were determined before and after drug administration. Pilsicainide (2 mg/kg/5 min and 3 mg/kg/h)( n=10) or propafenone (2 mg/kg/15 min and 4 mg/kg/h)( n=10) was intravenously infused during stable atrial fibrillation sustaining >30 min. Pilsicainide terminated atrial fibrillation in nine dogs, while propafenone did so in three ( p<0.01). After the drug, conduction velocity was suppressed more in the pilsicainide than in the propafenone group( p<0.01). There was no difference in effective refractory period after drug between the two groups. Mean wavelength was prolonged from 46.0 to 70.4 mm in the pilsicainide group and from 45.0 to 110.8 mm in the propafenone ( p<0.01 vs. pilsicainide). Activation mapping during atrial fibrillation showed Type II or III atrial fibrillation as previously defined [Konings, K.T.S., Kirchhof, C.J.H.J., Smeets, J.R.L.M., Wellens, H.J.J., Penn, O.C., Allessie, M.A., 1994. High-density mapping of electrically induced atrial fibrillation in humans. Circulation. Vol. 89, pp. 511–521.] before the drug, and changed to Type I before atrial fibrillation termination. Thus, pilsicainide was more effective to terminate vagally induced atrial fibrillation than was propafenone despite a greater effect of propafenone than of pilsicainide on wavelength. In this canine atrial fibrillation model, the suppression of conduction velocity may play an important role in changing the activation pattern of atrial fibrillation and thus, terminating atrial fibrillation.

Reappraisal of effective refractory period testing

To test the hypothesis that effective refractory period (ERP) testing is an accurate and reproducible measure of the cardiac refractory period, 4 pigs and 12 dogs were studied. We define the conventional ERP as the longest S1-S2 interval associated with noncapture and the triplicate ERP as the average of three ERP values determined by the up-down algorithm. We also determined the probability curve for noncapture after testing multiple S1-S2 intervals. The results showed that the difference between the coupling intervals associated with a 0 and a 100% probability of noncapture was 13 +/- 1 (range 12-16) ms for pigs and 9 +/- 2 (range 4-12) ms for dogs. The conventional and the triplicate ERP were associated with a 71 +/- 20% (range 26-100%) and a 60 +/- 21% (range 12-100%) probability of noncapture, respectively. We conclude that the ERP is a probability function. Therefore a single ERP determination cannot be used as an accurate and reproducible measure of cardiac refractory period unless it is used to detect potential differences in ERP that exceed 16 ms in pigs or 12 ms in dogs. A probability function curve determination will be needed if smaller differences in the ERP are to be detected.

Refractoriness as a determinant of tachycardia inducibility in the right ventricle

The use of more than one right ventricular site for programmed electrical stimulation has been reported to increase the number of patients in whom ventricular tachycardia can be provoked. To determine a possible reason for these observations, programmed ventricular tachycardia studies were evaluated in 316 patients (185 men and 131 women) with a mean age of 63 ± 7 years who presented with ventricular tachycardia or cardiac arrest. The underlying cardiac disease was atherosclerosis (81%), cardiomyopathy (15%), valvular heart disease (3%), and miscellaneous conditions (1%). Programmed electrical stimulation studies employed a six-beat pacing train, at a cycle length of 500 msec with the introduction of one to three premature stimuli at twice diastolic threshold at the right ventricular apex. If ventricular tachycardia at the right ventricular apex could not be provoked in a patient, the study was repeated at the right ventricular outflow tract. A total of 36 patients were studied at the right ventricular outflow tract. Eleven (31%) were provoked into ventricular tachycardia, while 25 (69%) were not. No difference existed between the QRS, QT, and QT c intervals between those having ventricular tachycardia provoked at the outflow tract compared to those without inducible tachycardia at the right ventricular outflow tract. The effective refractory period was 280 ± 5 msec at the right ventricular outflow tract in those patients not inducible, and 226 ± 4 msec in those inducible ( p < 0.05). We defined the change in ventricular refractory period as the difference in the effective refractory period at the right ventricular outflow tract minus the effective refractory period at the right ventricular apex. The change in effective refractory period was −16 ± 2 msec for the 11 inducible patients and 8 ± 3 msec for the noninducible group ( p < 0.01). Thus, patients who are inducible for ventricular tachycardia at programmed ventricular stimulation at the right ventricular outflow tract have a shorter effective refractory period, and the difference in effective refractory period compared to the apex in the inducible group is also shorter. The earlier introduction of premature stimuli at the right ventricular outflow tract may permit a critically timed stimulus to initiate ventricular tachycardia.