Kirsten D. Schreiner

Multisite pacing for prevention of atrial tachyarrhythmias: potential mechanisms ☆

OBJECTIVES To determine the effects of single-, dual-, triple- and quadruple-site atrial pacing on atrial activation and refractoriness in normal canine hearts. BACKGROUND Multisite pacing has been suggested to be superior to single-site pacing for prevention of atrial tachyarrhythmias. However, the underlying electrophysiological mechanisms are undetermined at the moment, as is the rationale for the selection of pacing locations and the number of pacing sites. METHODS In 13 normal beagle dogs, an epicardial multielectrode (128 bipoles) and a multiplexer mapping system were used to reconstruct epicardial atrial activation patterns obtained during simultaneous stimulation from up to four electrodes located in the high and low right and left atrium, respectively. For all pacing modes (single-, dual-, triple- and quadruple-site pacing), total activation times and local effective refractory periods at eight randomly selected sites as well as local recovery intervals were determined. In a subgroup of five dogs, total epicardial activation times were also obtained during single-site septal stimulation (septal group). RESULTS Activation times and local recovery intervals were minimized by triple-site stimulation, whereas a fourth site did not produce further shortening. Septal stimulation produced epicardial activation times comparable to quadruple-site stimulation. Local refractory periods and their dispersion always remained unaffected. Functional conduction blocks apparent during single-site were found to resolve during multisite stimulation. CONCLUSIONS Multisite pacing can prevent functional conduction blocks by multidirectional excitation and a reduction in total activation time. Triple-site and, possibly, septal pacing modes are expected to be most efficient because both minimize total activation times and maximize the multidirectionality of excitation. In spite of unaffected local refractory periods, the shortening of local recovery intervals might homogenize atrial repolarization and, thus, contribute to the preventive effects of multisite pacing.

Effects of the IKr-Blocking Agent Dofetilide and of the IKs-Blocking Agent Chromanol 293b on Regional Disparity of Left Ventricular Repolarization in the Intact Canine Heart

Recent in vitro studies have described regional differences of ion current expression and function, possibly accounting for reduced homogeneity of repolarization in the heart. In 11 intact canine hearts regional disparity of repolarization was determined at baseline and after administration of the IKr blocking agent dofetilide (30 &mgr;g/kg) and the IKs-blocking agent chromanol 293b (10 mg/kg). Effective refractory periods (ERPs) were determined through up to 10 needle electrodes inserted into basal, midwall and apical regions of the left ventricular wall using the extrastimulus technique (cycle length [CL] 300 and 850 ms). At baseline (CL of 850 ms), ERPs were significantly longer in epicardial muscle layers of the apex compared to the base. In deeper muscle layers regional differences of ERPs were not detectable. Administration of dofetilide increased apico-basal disparity of repolarization, due to a more marked increase of ERPs in the apex than in the base. In contrast, homogeneous ERPs were evident along the apico-basal axis after administration of chromanol 293b. Transmural dispersion of refractoriness could not be observed in any region at baseline, or after drug-administration. In the intact canine heart, apico-basal disparity of repolarization varies between individual muscle layers. Dependent on their current specificity, antiarrhythmic agents may enhance or diminish regional disparity of repolarization.

Suppression of atrial fibrillation by multisite and septal pacing in a novel experimental model

OBJECTIVES To evaluate the preventive efficacy of multisite and septal atrial pacing in an experimental model. METHODS Sterile right atrial pericarditis was induced in 12 foxhounds to provide an anatomical substrate for atrial fibrillation (AF). As a trigger mechanism, atrial extrasystoles were simulated by constant asynchronous pacing at a cycle length of 1000 ms from randomly selected right or left atrial electrodes, using a biatrial epicardial multielectrode with 128 bipoles. Additionally, a transvenous pacing lead was screwed into the interatrial septum. Four electrodes located in the high and low right (HRA/LRA) and left atrium (HLA/LLA) were selected for preventive multisite stimulation. Constant pacing at a cycle length 30 ms below sinus rate was applied from the following site(s): HRA, septal, HRA+LRA, HRA+LLA, HRA+LRA+LLA and HRA+LRA+HLA+LLA (order randomized). Number and duration of AF episodes were studied during 10 min intervals, separated by 5 min pauses, respectively. To validate the model, the protocol was repeated 10 min after i.v. bolus administration of D,L-sotalol (1 mg/kg body weight). RESULTS The number of AF episodes decreased with increasing number of pacing sites, reaching statistical significance compared to HRA stimulation for quadruple-site and single-site septal pacing only (P<0.05). Single-site septal was as efficient as quadruple-site pacing in suppressing AF. The duration of AF episodes was not significantly affected by the pacing configuration. D,L-sotalol almost completely suppressed AF irrespective of the pacing configuration used. CONCLUSIONS In this novel experimental model, quadruple-site and septal pacing effectively suppress paroxysmal AF.

Intercaval block in normal canine hearts : role of the terminal crest.

Background—The intriguing monotony in the occurrence of intercaval conduction block during typical atrial flutter suggests an anatomic or electrophysiological predisposition for conduction abnormalities. Methods and Results—To determine the location of and potential electrophysiological basis for conduction block in the terminal crest region, a high-density patch electrode (10×10 bipoles) was placed on the terminal crest and on the adjacent pectinate muscle region in 10 healthy foxhounds. With a multiplexer mapping system, local activation patterns were reconstructed during constant pacing (S1S1=200 ms) and introduction of up to 2 extrastimuli (S2, S3). Furthermore, effective refractory periods were determined across the patch. If evident through online analysis, the epicardial location of conduction block was marked for postmortem verification of its endocardial projection. Marked directional differences in activation were found in the terminal crest region, with fast conduction parallel to and slow conduction perpendicular to the intercaval axis (1.1±0.4 versus 0.5±0.2 m/s, P <0.01). In the pectinate muscle region, however, conduction velocities were similar in both directions (0.5±0.3 versus 0.6±0.2 m/s, P =NS). Refractory patterns were relatively homogeneous in both regions, with local refractory gradients not >30 ms. During S3 stimulation, conduction block parallel to the terminal crest was inducible in 40% of the dogs compared with 0% in the pectinate muscle region. Conclusions—Even in normal hearts, inducible intercaval block is a relatively common finding. Anisotropic conduction properties would not explain conduction block parallel to the intercaval axis in the terminal crest region, and obviously, refractory gradients do not seem to play a role either. Thus, the change in fiber direction associated with the terminal crest/pectinate muscle junction might form the anatomic/electrophysiological basis for intercaval conduction block.

Tridimensional activation patterns of acquired torsade-de-pointes-tachycardias in dogs with chronic AV-block

Abstract.Background:Dogs with chronic AV block exposed to type-III antiarrhythmic agents develop polymorphic ventricular tachycardias (PVT). Controversy exists regarding PVT mechanism and underlying pathophysiology.Methods and Results:In dogs with acute (n = 10, AAVB) or chronic AV block (n = 14, CAVB, 62 ± 5 days after AV-node ablation) 60 pins (12 mm long, 4 bipolar electrodes) were inserted into both ventricles. QT intervals and effective refractory periods (ERP) at 56 ± 22 randomly selected sites (extrastimulus technique, 800 ms basic cycle length) were determined before and after Almokalant (0.34 μmol/kg). A multiplexer mapping system was used to reconstruct 3D activation patterns. The heart-to-body-weight index (HBWI) was obtained after the experiments. CAVB led to a significant increase in HBWI (11.3 ± 1.5 vs. 9 ± 1.2 g/kg BW, p < 0.001), and a significant increase in ERP (280 ± 28 ms vs. 260 ± 37 ms, p < 0.05) and QT interval (339 ± 16 vs. 288 ±12 ms, p < 0.05). Dispersion (DISP) of ERP was similar for AAVB and CAVB dogs. No AAVB dog, but 9 of 14 CAVB dogs developed PVTs in response to Almokalant. All PVTs originated from an endocardial focus. Consecutive beats continued to reveal centrifugal activation patterns in 8 of 10 episodes. In only 2 episodes was reentrant activation evident.Conclusion:Myocardial hypertrophy associated with CAVB predisposes the canine heart to druginduced PVTs. This seems to be primarily linked to prolonged repolarization. PVTs in this model are not only initiated, but also perpetuated by a centrifugal spread of activation.

Variability of Holter Electrocardiographic Findings in Patients Fulfilling the Noninvasive MADIT Criteria

SENGES, J.C., et al.: Variability of Holter Electrocardiographic Findings in Patients Fulfilling the Noninvasive MADIT Criteria. In the MADIT study, a selected group of postinfarction patients with asymptomatic nonsustained ventricular tachycardia (NSVT) has been shown to benefit from prophylactic ICD treatment. The present study analyzed the variability of NSVT in a patient population fulfilling the noninvasive MADIT criteria. Three consecutive Holter ECGs were performed in weekly intervals in 68 postinfarction patients with an LVEF ≤ 0.35. Patients with NSVT underwent programmed ventricular stimulation (PVS); patients were implanted with an ICD if sustained VT or VF was inducible. If NSVT was found in at least two recordings, the arrhythmia was defined as reproducible. In 28 (41%) of the 68 patients, NSVT was found in at least one recording. Seventeen patients revealed NSVT in the first, the remaining 11 in the second registration; no patient had NSVT only in the third Holter. Of the patients with NSVT, 50% had only one, 39% had two, and 11% had three positive recordings. Thus, reproducible NSVT was found in only 50% of the patients with NSVT. Predictors for reproducibility were LVEF > 0.27, NYHA Class I, absence of digitalis therapy, and > 2 NSVT per 24‐hour period. Reproducible NSVT was not associated with risk factors such as elevated mean heart rate, reduced heart rate variability, late potentials, or inducibility of sustained VT during PVS. During 17 ± 9 months of follow‐up, seven (10%) patients experienced arrhythmic events: two without and five with previously documented NSVT. In the latter patients, first occurrence of NSVT was consistently in the first Holter; only two of them had reproducible NSVT. In postinfarction patients, the risk factor NSVT exhibits marked spontaneous variability, especially in those with a low number of NSVT per 24‐hour period, LVEF < 0.27 or NYHA III, which limits its clinical value as a selection criterion for PVS. Reproducibility of NSVT itself does not seem to be an independent risk factor.

Refractory patterns and susceptibility to drug-induced polymorphic ventricular tachycardias in dogs with chronic atrioventricular block: relation to the type of anesthesia.

Controversy exists as to the homogeneity of repolarization throughout the canine ventricular wall in vivo. The type of anesthesia has been shown to affect regional differences in monophasic action potential duration and the inducibility of polymorphic ventricular tachycardias (PVTs) in normal canine hearts. This study was conducted to determine refractory patterns and arrhythmia susceptibility in relation to halothane or pentobarbital anesthesia in dogs with chronic atrioventricular block and biventricular hypertrophy. In 12 dogs with chronic atrioventricular block, 60 needle electrodes (12 mm long, four bipolar electrodes, interelectrode distance of 2 mm) were inserted into the left and right ventricle. Six dogs were anesthetized with pentobarbital and six with halothane. Effective refractory periods (ERPs) were determined along 14 randomly selected needles at baseline and after application of almokalant (0.34 mmol/kg) (basic cycle length 1,000 ms, extrastimulus technique). At baseline and on almokalant, ERPs were uniform, independent of the type of anesthesia. With halothane anesthesia, ERPs were significantly longer under both conditions. Almokalant induced not only a prolongation of ERP in both groups but also a significant increase in transmural dispersion of ERP and in maximum dispersion of ERP. However, local refractory gradients were not specific to any muscle layer and did not seem to be related to the occurrence of PVTs. Almokalant did not induce arrhythmias in any dog in the pentobarbital group, but in four of six animals in the halothane group, apparently due to the more marked prolongation in ERP. Independent of the type of anesthesia, hypertrophied hearts of dogs with chronic atrioventricular block exhibit uniform refractory patterns. Longer ERPs with a comparable degree of dispersion on halothane are associated with a high incidence of drug-induced PVTs, whereas shorter ERPs on pentobarbital seem to prevent arrhythmia induction.

Effects of propafenone on anisotropic conduction properties within the three-dimensional structure of the canine ventricular wall

AbstractBackground Structural complexities of the intact ventricular wall cause a very complex spread of activation. The effects of regional tissue damage and of antiarrhythmic drugs on directional differences in activation should help to further elucidate intramural conduction patterns. Methods and results In 10 healthy dogs and in 5 dogs with subacute anterior wall infarction, 6 parallel rows of 6 needle electrodes with 4 bipolar electrode pairs per needle were inserted into the left anterior ventricular wall. Using a computerized multiplexer-mapping system, the spread of activation in epi-, endo- and midmyocardial muscle layers and in the surviving epicardium, respectively, was reconstructed. Marked differences in conduction velocities relative to fiber orientation were evident in the surviving epicardium of infarcted hearts. Directional differences in conduction velocities, although less pronounced, were still preserved throughout the intact ventricular wall. Epicardial transverse conduction in intact hearts was significantly faster than transverse conduction in infarcted hearts (0.87 ± 0.11 m/s vs 0.68 ± 0.1 m/s). In normal hearts, propafenone (2 mg/kg) decreased conduction velocities primarily in longitudinal directions (−27 ± 10%), but also moderately in transverse directions (−13 ± 7%) of all muscle layers, with no significant effect on straight (−4 ± 8%), but on oblique transmural conduction (−33 ± 18%). In infarcted hearts propafenone decreased conduction particularly in longitudinal direction (−23 ± 14%) without affecting conduction transverse to the fiber orientation (+3 ± 6%). Conclusions Longitudinal intramural shortcircuits reduce directional differences in activation. Transmural infarction results in a loss of alternative intramural pathways, unmasking marked anisotrophy in the surviving epicardium. Conduction delay in intramural pathways explains the effects of propafenone on transverse and oblique transmural conduction. Primarily longitudinal conduction delay results in reduced tissue anisotropy.

Synkopenabklärung bei geriatrischen Patienten: Normalwerte, Komplikationen und Ergebnisse der invasiven elektrophysiologischen Untersuchung

Invasive electrophysiologic study (EPS) is an important tool in the assessment of patients with unexplained syncope. Especially in the elderly, the need for a complete diagnostic work-up is counterbalanced by the fear of complications associated with invasive procedures. Thus, the present study specifically addressed the question whether the risk/benefit ratio of EPS in geriatric patients with unexplained syncope justifies this invasive procedure. An invasive EPS was performed in 96 patients between 70 and 80 years and 21 patients older than 80 years. The control group consisted of 65 patients younger than 40 years. With increasing age, the diagnostic yield of EPS also increased (positive EPS finding in 20% of the control group and in 54% of the oldest patients). The majority of complications were of minor clinical significance and no significant differences were found between the three groups. Finally, no age-related difference in measured standard electrophysiological parameters was evident. Due to the high diagnostic value and the low complication rate, EPS can be recommended in elderly patients with unexplained syncope. An age-specific standardization of electrophysiologic parameters, measured during EPS, does not seem to be required. Die invasive elektrophysiologische Untersuchung hat bei der Abklärung von Synkopen unklarer Genese einen hohen Stellenwert. Im höheren Lebensalter steht dem Wunsch nach einer richtungsweisenden Diagnostik eine gewisse Zurückhaltung gegenüber invasiven, potentiell komplikationsreichen Untersuchungen entgegen. Durch einen altersspezifischen Vergleich von diagnostischem Zugewinn, Komplikationsraten und elektrophysiologischen Parametern sollte in der vorliegenden Arbeit geklärt werden, ob die invasive elektrophysiologische Untersuchung auch bei älteren Patienten empfohlen werden kann und ob altersabhängige Schwankungen von Leitungs- und Refraktärmessungen berücksichtigt werden müssen. Invasive elektrophysiologische Untersuchungen wurden bei 96 Patienten im Alter zwischen 70 und 80 Jahren sowie bei 21 über Achtzigjährigen durchgeführt. Als Vergleichsgruppe dienten 65 Patienten mit einem Lebensalter unter 40 Jahren. Mit zunehmendem Lebensalter stieg die Wahrscheinlichkeit eines richtungsweisenden Befundes in der elektrophysiologischen Untersuchung von etwa 20% bei jüngeren auf 54% bei den ältesten untersuchten Patienten. Komplikationen waren mehrheitlich von untergeordneter klinischer Bedeutung, die Komplikationsraten unterschieden sich nicht signifikant zwischen den Altersgruppen. Auch zeigten die erhobenen Refraktär- und Leitungsparameter keine eindeutige Altersabhängigkeit. Gerade beim älteren Menschen erweist sich das Verhältnis zwischen diagnostischem Zugewinn und Komplikationsrate der invasiven elektrophysiologischen Untersuchung zur Synkopenabklärung als besonders günstig. Geltende Normalwerte für Refraktär- und Leitungsparameter scheinen altersunabhängig Gültigkeit zu besitzen.

Prädiktiver Wert der Frequenz, der Dauer und der Häufigkeit ventrikulärer Salven im Langzeit-EKG für die Induzierbarkeit anhaltender Kammertachykardien

Identification of high risk patients with coronary artery disease (CAD) prone to sudden cardiac death still remains a difficult issue.    In 211 patients with CAD diagnosed by coronary angiography and documented non-sustained ventricular tachycardia (NSVT), programmed ventricular stimulation (PVS) was performed. NSVTs documented during Holter monitoring were analysed concerning frequency, duration and rate. To relate those parameters to the inducibility of sustained monomorphic ventricular tachycardias (MVT) during PVS, the total population was divided in different groups; patients with 1, 2–5 or >5 salvos within 24 h; patients having salvos with a rate of ≥150/min or <150/min; patients with 3–5, 6–10 or >10 consecutive extra beats. It could be demonstrated that in patients with CAD and NSVTs, induction of MVTs during PVS is more likely if the rate of the spontaneously occurring NSVT is ≥150/min (22.1 vs 8.9%; p=0.042). In contrast, there is apparently no correlation between the duration and incidence of NSVTs and the prevalence of MVTs during PVS. Multivariate analysis revealed the rate of documented NSVTs (odds ratio 2.98, p=0.0314) and a decrease of left ventricular ejection fraction (odds ratio 1.69; p=0.0013) as independent risk factors for the inducibility of MVTs. Conclusions CAD patients with fast salvos (≥150 beats/min) and reduced left ventricular ejection fraction are more likely to reveal inducible MVT during PVS and should, therefore, preferably be subjected to invasive risk stratification. The number of salvos per day and the number of consecutive beats, on the other hand, do not seem to be of relevant predictive value. Die Risikostratifizierung von Patienten mit koronarer Herzerkrankung (KHK) und nicht anhaltenden ventrikulären Tachykardien (NSVTs) stellt weiterhin ein klinisches Problem dar.    Die Induzierbarkeit monomorpher ventrikulärer Tachykardien (MVT) während programmierter ventrikulärer Stimulation (PVS) wurde bei 211 Patienten mit angiographisch gesicherter KHK und NSVTs untersucht, wobei eine Unterteilung in verschiedene Gruppen erfolgte: Patienten mit einer, 2–5 oder >5 Salven innerhalb von 24 h; Patienten mit einer Frequenz der Salven ≥150/min oder <150/min, Patienten mit 3–5, 6–10 oder >10 konsekutiven Extrasystolen.    Es fand sich eine signifikant höhere Induktionsrate von MVTs bei Patienten mit schnellen (≥150/min) NSVTs als bei Patienten mit langsamen NSVTs (<150/min) (22,1 vs 8,9%; p=0,042). Im Gegensatz dazu ergab sich keine Korrelation zwischen der Häufigkeit der NSVTs bzw. der Anzahl konsekutiver Schläge und der Induzierbarkeit von MVTs. In der multivariaten Analyse konnten die Frequenz der Salven (odds ratio 2,98, p=0,0314) und eine eingeschränkte linksventrikuläre Pumpfunktion (odds ratio 1,69; p=0,0013) als unabhängige Prädiktoren für die Induzierbarkeit von MVTs identifiziert werden. Zusammenfassung Aufgrund der deutlich höheren Rate an induzierbaren MVTs bei Patienten mit schnellen Salven scheint für dieses Kollektiv die Durchführung einer PVS gerechtfertigt. Im Gegensatz dazu ist die Häufigkeit und die Dauer einer NSVT ohne relevanten prädiktiven Wert für das Ergebnis der PVS.