Search

Aims: An estimated 10,000-15,000 pacemaker and implantable cardioverter-defibrillator (ICD) leads are extracted annually worldwide using specialized tools that disrupt encapsulating fibrous tissue. Additional information is needed regarding the safety of the devices that have been approved for lead extraction. The aim of this study was to determine whether complications due to device-assisted lead extraction might be more hazardous than published data suggest, and whether procedural safety precautions are effective.Methods and Results: We searched the US Food and Drug Administration's (FDA) Manufacturers and User Defined Experience (MAUDE) database from 1995 to 2008 using the search terms 'lead extraction and death' and 'lead extraction and injury'. Additional product specific searches were performed for the terms 'death' and 'injury'. Between 1995 and 2008, 57 deaths and 48 serious cardiovascular injuries associated with device-assisted lead extraction were reported to the FDA. Owing to underreporting, the FDA database does not contain all adverse events that occurred during this period. Of the 105 events, 27 deaths and 13 injuries occurred in 2007-2008. During these 2 years, 23 deaths were linked with excimer laser or mechanical dilator sheath extractions. The majority of deaths and injuries involved ICD leads, and most were caused by lacerations of the right atrium, superior vena cava, or innominate vein. Overall, 62 patients underwent emergency surgical repair of myocardial perforations and venous lacerations and 35 (56%) survived.Conclusion: These findings suggest that device-assisted lead extraction is a high-risk procedure and that serious complications including death may not be mitigated by emergency surgery. However, skilled standby cardiothoracic surgery is essential when performing pacemaker and ICD lead extractions. Although the incidence of these complications is unknown, the results of our study imply that device-assisted lead extractions should be performed by highly qualified physicians and their teams in specialized centres. [ABSTRACT FROM AUTHOR]

Background: The Medtronic Sprint Fidelis implantable cardioverter-defibrillator high-voltage lead is prone to fracture. The October 2007 safety advisory recommended lead impedance monitoring to aid in identifying lead fractures.Objective: The aim of this single-center study was to examine the effectiveness of impedance monitoring for detecting Sprint Fidelis lead failures before they caused adverse clinical events such as inappropriate shocks.Methods: Impedance and sensing information were acquired during routine clinic and CareLink follow-up and at the time of lead failure using the Patient Alert, sensing integrity counter, nonsustained episode, and electrogram features in Medtronic pulse generators.Results: Between September 2004 and February 2008, 17 of 514 Sprint Fidelis leads (3.3%) followed up at our center failed between 11 and 35 months after implantation (mean 23.0 +/- 8.0 months). Fifteen of these failures (88%) were caused by pace-sense conductor fractures, and 2 (12%) were caused by high-voltage conductor defects. Twelve of 15 patients (80%) with pace-sense conductor fractures received inappropriate shocks; of these, 4 had no significant increase in lead impedance before they were shocked, 2 were shocked <3 hours after their lead impedances exceeded the 1,000 Omega audible alert threshold, and 2 patients did not hear the alarm. All pace-sense conductor failures whose sensing function could be evaluated (13 of 15) had oversensing based on stored data, and oversensing usually (11 of 13) preceded impedances changes.Conclusion: Impedance monitoring did not prevent inappropriate shocks in two-thirds of our patients. Thus, pace-sense conductor impedance monitoring as currently implemented does not reliably forewarn patients of a lead malfunction. Consequently, patients who have Sprint Fidelis leads remain at risk for adverse clinical events associated with pace-sense conductor fracture. [ABSTRACT FROM AUTHOR]

Background: Persistent atrial fibrillation (AF) is a complex arrhythmia, and attaining freedom from AF with ablation has been challenging., Objectives: This study evaluated a novel CARTO software algorithm based on the CARTO Ripple map for AF termination and 18-month freedom from AF., Methods: Consecutive patients who underwent first-time ablation for persistent AF were included. A high-density Ripple map was created using a Pentaray catheter. Following PVI, ablation was performed at locations with rapid Ripple activations, a protocol previously described by us. Patients were followed for 18 months to assess rhythm outcomes. A retrospective analysis was performed using the CARTO Ripple frequency software algorithm. The Ripple frequency algorithm quantifies amplitude changes in the bipolar electrogram., Results: A total of 115 AF maps were analyzed from 84 patients (mean age 65.9 years, 63.1% men). The top quartile of Ripple frequency corresponded to a visual reference with 96.7% sensitivity and 91.1% specificity. AF terminated during ablation in 88.1% of patients: pulmonary vein antrum alone (14.9%) or pulmonary vein plus nonantral sites (85.1%). The top quartile of Ripple frequency was present in nonantral areas associated with AF termination with 90.2% sensitivity and 86.5% specificity. After 14.0 ± 6.5 months and 1.2 ± 0.4 ablations, 78 (92.9%) of 84 patients were free of AF, and 79.8% were free of any atrial arrhythmia., Conclusion: A novel algorithm for automated analysis of CARTO Ripple frequency demonstrated good sensitivity and specificity for detecting atrial regions in persistent AF in which ablation is associated with frequent AF termination and freedom from AF during follow-up., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Cardiac perforation during leadless pacemaker implantation is more likely to require intervention than perforation by a transvenous lead. This study reports the consequences of Micra pacemaker perforations and related device and operator use problems based on information the manufacturer has submitted to the Food and Drug Administration (FDA)., Methods: FDA's Manufacturer and User Facility Device Experience (MAUDE) database was searched for Micra perforations. Data extracted included deaths, major adverse clinical events (MACEs), and device and/or operator use problems., Results: Between 2016 and July 2021, 563 perforations were reported within 30 days of implant and resulted in 150 deaths (27%), 499 cardiac tamponades (89%), 64 pericardial effusions (11%), and 146 patients (26%) required emergency surgery. Half of perforations were associated with 139 (25%) device problems, 78 (14%) operator use problems, and 62 (11%) combined device and operator use problems. Inadequate electrical measurements or difficult positioning were the most frequent device problems (n = 129); non-septal implants and perforation of other structures were the most frequent operator use problems (n = 69); a combined operator use and device problem resulted in 62 delivery system perforations. No device or operator use problem was identified for 282 perforations (50%), but they were associated with 78 deaths, 245 tamponades, and 57 emergency surgeries., Conclusion: The Micra perforations reported in MAUDE are often associated with death and major complications requiring emergency intervention. Device and use problems account for at least half of perforations. Studies are needed to identify who is at risk for a perforation and how MACE can be avoided or mitigated., (© 2021 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Purpose: We hypothesized that data in manufacturers' product performance reports (PPRs) can provide clinically valuable ICD and cardiac resynchronization defibrillator (CRT-D) reliability and longevity information., Methods: Data were obtained from 2019 PPRs. Kaplan-Meier (K-M) probabilities of freedom from malfunction, normal battery depletion (NBD), and NBD + malfunction were calculated for ICD and CRT-D pulse generators (PGs) with LiMnO2 or LiSVO/CFx batteries marketed in the USA from 2010 to 2019 and compared using the log-rank test. Malfunctions (MAL) included PGs that were found outside specifications., Results: Study population included 1,149,803 ICD and CRT-D PGs: Abbott (ABT; 35.1%), Biotronik (BIO; 4.6%), Boston Scientific (BSC; 23.5%), and Medtronic (MDT; 36.9%). Significant differences in reliability (p < 0.001), defined by freedom from MAL, were found between manufacturers; the majority of 6808 MAL occurred in ABT devices (n = 4045; 59.4%), followed by BSC (n = 2384; 35.0%), MDT (n = 338;5.0%), and BIO (n = 41; 0.6%). Battery failure (n = 890; 57.9%) was the most common cause of MAL compromising therapy; analysis of unique ABT battery MAL-indicated problem appeared a year prior to advisory. Significant differences (p < 0.001) in battery longevity, as defined by freedom from NBD, were found between manufacturers. Overall performance (freedom from NBD + MAL) favored BSC for CRT-D PGs and MDT and BIO for ICDs. BSC subcutaneous ICD reliability was inferior to its transvenous ICD (p < 0.001)., Conclusion: PPRs contain valuable data that can be aggregated and analyzed to inform physicians. Differences in product reliability exist between manufacturers. Battery longevity has improved, but MAL have significantly impacted performance. PPR data may be useful for assessing product problems and new technology., (© 2021. The Author(s).)

Background: Leadless intracardiac pacemakers were developed to avoid the complications of transvenous pacing systems. The Medtronic Micra™ transcatheter pacemaker is one such system. We found an unexpected number of major adverse clinical events (MACE) in the Food and Drug Administration's Manufacturers and User Facility Device Experience (MAUDE) database associated with Micra implantation., Objective: The purpose of this study was to describe these MACE and compare them to implant procedure MACE in MAUDE for Medtronic CapSureFix™ active-fixation transvenous pacing leads., Methods: During January 2021, we queried the MAUDE database for reports of MACE for Micra pacemakers and CapSureFix leads using the simple search terms "death," "tamponade," and "perforation." Reports from 2016-2020 were included., Results: The search identified 363 MACE for Micra and 960 MACE for CapSureFix leads, including 96 Micra deaths (26.4%) vs 23 CapSureFix deaths (2.4%) (P <.001); 287 Micra tamponades (79.1%) vs 225 tamponades for CapSureFix (23.4%) (P <.001); and 99 rescue thoracotomies for Micra (27.3%) vs 50 rescue thoracotomies for CapSureFix (5.2%) (P <.001). More Micra patients required cardiopulmonary resuscitation (21.8% vs 1.1%) and suffered hypotension or shock (22.0% vs 5.8%) than CapSureFix recipients (P <.001). Micra patients were more likely to survive a myocardial perforation or tear if they had surgical repair (P = .014)., Conclusion: Micra leadless pacemaker implantation may be complicated by myocardial and vascular perforations and tears that result in cardiac tamponade and death. We estimate the incidence is low (<1%). Rescue surgery to repair perforations may be lifesaving. MACE are significantly less for implantation of CapSureFix transvenous ventricular pacing leads., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

New-onset left bundle branch block (N-LBBB) after transcatheter aortic valve replacement (TAVR) is a challenging clinical dilemma. In our single-center study, 60 out of 172 patients who underwent permanent pacemaker implantation (PPM) after TAVR had N-LBBB (34.9%). At a median follow-up duration of 357 days (IQR, 178; 560 days), two patients (3.5%) were completely pacemaker-dependent, and four others (7%) were partially dependent. Twelve patients (24%) recovered conduction in their left bundle at a median follow-up duration of 5 weeks (IQR, 4; 14 weeks). Due to the lack of clinical predictors of pacemaker dependency, active surveillance is warranted and may be an alternative to permanent pacemaker implantation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) and atrial flutter (AFL) are associated with increased risk of stroke and mortality after transcatheter aortic valve replacement (TAVR). Many episodes of new-onset AF/AFL (NOAF) occur after hospital discharge and may not be clinically apparent. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented AF., Methods: From 2012 to 2017, patients who underwent pacemaker implantation after TAVR were reviewed, and pacemaker data from device checks were analyzed for detection of NOAF. Patients with prior AF/AFL were excluded. Secondary outcomes were mortality and ischemic stroke., Results: A total of 172 patients underwent TAVR and pacemaker implantation, and 95 were without pre-existent AF/AFL. Over a median follow-up of 15 months, a total of 24 patients had NOAF (25%), of which 10 patients (10.5%) had manifest NOAF detected on electrocardiography, and 14 patients (14.7%) had subclinical NOAF first identified on device interrogation. The cumulative incidence of mortality was 16.7% for NOAF and 15.5% for normal sinus rhythm (P=.83). The cumulative incidence of stroke was 12.5% for NOAF and 1.4% for normal sinus rhythm (P=.04). Subclinical NOAF patients were less likely to be started on anticoagulation compared with manifest NOAF patients (70% vs 15.3%, respectively; P=.02)., Conclusion: Subclinical NOAF is common after TAVR, usually occurs months after hospital discharge, and is associated with lack of anticoagulation therapy and increased risk of stroke. Prolonged surveillance of subclinical NOAF may be warranted after TAVR.

Objectives: This study sought to report periprocedural outcomes and intermediate-term follow-up of hemodialysis patients undergoing Micra implantation., Background: Leadless pacemakers may be preferred in patients with limited vascular access and high-infection risk, such as patients on hemodialysis., Methods: Patients on hemodialysis at the time of Micra implantation attempt (n = 201 of 2,819; 7%) from the Micra Transcatheter Pacing Study investigational device exemption trial, Micra Transcatheter Pacing System Continued Access Study Protocol, and Micra Transcatheter Pacing System Post-Approval Registry were included in the analysis. Baseline characteristics, periprocedural outcomes, and intermediate-term follow-up were summarized., Results: Patients on hemodialysis at the time of Micra implantation attempt were on average 70.5 ± 13.5 years of age and 59.2% were male. The dialysis patients commonly had hypertension (80%), diabetes (61%), coronary artery disease (39%), and congestive heart failure (27%), and 72% had a condition that the implanting physician felt precluded the use of a transvenous pacemaker. Micra was successfully implanted in 197 patients (98.0%). Reasons for unsuccessful implantation included inadequate thresholds (n = 2) and pericardial effusion (n = 2). The median implantation time was 27 min (interquartile range: 20 to 39 min). There were 3 procedure-related deaths: 1 due to metabolic acidosis following a prolonged procedure duration in a patient undergoing concomitant atrioventricular nodal ablation and 2 deaths occurred in patients who needed surgical repair after perforation. Average follow-up was 6.2 months (range 0 to 26.7 months). No patients had a device-related infection or required device removal because of bacteremia., Conclusions: Leadless pacemakers represent an effective pacing option in this challenging patient population on chronic hemodialysis. The risk of infection appears low with an acceptable safety profile. (Micra Transcatheter Pacing Study; NCT02004873; Micra Transcatheter Pacing System Continued Access Study Protocol; NCT02488681; Micra Transcatheter Pacing System Post-Approval Registry; NCT02536118)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Atrioventricular junctional (AVJ) ablation and pacemaker implantation are indicated when pharmacotherapy fails to achieve adequate rate control in atrial fibrillation (AF). The purpose of our study is to assess the feasibility and safety of concurrent Micra leadless transcatheter pacemaker implantation and AVJ ablation., Methods: We retrospectively assessed patients who underwent Micra implantation and concurrent AVJ ablation at three institutions between August 2014 and March 2016. All patients and devices were followed at baseline and at 1, 3, 6, and 12 months postimplantion., Results: Twenty-one patients with permanent AF (median age 77 [range: 62-88], female 15 [71.4%]) underwent successful Micra implantation followed by concurrent AVJ ablation. There was no device dislodgement or malfunction during the 12-month follow-up. Complete 12-month electrical performance data were available in 14 patients (67%). Among patients with the complete data set, median pacing thresholds at implant and at 1, 3, 6, and 12 months were 0.5 V (range: 0.25-0.88), 0.44 V (range: 0.25-2.0), 0.5 V (range: 0.25-1.63), 0.5 V (range: 0.25-1.13), and 0.5 V (range: 0.25-1.13) at a pulse width of 0.24 msec, respectively. Two patients died due to noncardiac causes during follow-up. There were no patients with major device-related complications., Conclusions: Concurrent Micra implantation and AVJ ablation is feasible and appears safe. There was no device dislodgement, malfunction, or significant pacing threshold rise requiring device reimplantation during the 12-month follow-up. This combined approach can be considered for patients with AF with suboptimal rate control who have failed AF catheter ablation and/or pharmacotherapy., (© 2018 Wiley Periodicals, Inc.)

Background: A leadless intracardiac transcatheter pacing system has been designed to avoid the need for a pacemaker pocket and transvenous lead., Methods: In a prospective multicenter study without controls, a transcatheter pacemaker was implanted in patients who had guideline-based indications for ventricular pacing. The analysis of the primary end points began when 300 patients reached 6 months of follow-up. The primary safety end point was freedom from system-related or procedure-related major complications. The primary efficacy end point was the percentage of patients with low and stable pacing capture thresholds at 6 months (≤2.0 V at a pulse width of 0.24 msec and an increase of ≤1.5 V from the time of implantation). The safety and efficacy end points were evaluated against performance goals (based on historical data) of 83% and 80%, respectively. We also performed a post hoc analysis in which the rates of major complications were compared with those in a control cohort of 2667 patients with transvenous pacemakers from six previously published studies., Results: The device was successfully implanted in 719 of 725 patients (99.2%). The Kaplan-Meier estimate of the rate of the primary safety end point was 96.0% (95% confidence interval [CI], 93.9 to 97.3; P<0.001 for the comparison with the safety performance goal of 83%); there were 28 major complications in 25 of 725 patients, and no dislodgements. The rate of the primary efficacy end point was 98.3% (95% CI, 96.1 to 99.5; P<0.001 for the comparison with the efficacy performance goal of 80%) among 292 of 297 patients with paired 6-month data. Although there were 28 major complications in 25 patients, patients with transcatheter pacemakers had significantly fewer major complications than did the control patients (hazard ratio, 0.49; 95% CI, 0.33 to 0.75; P=0.001)., Conclusions: In this historical comparison study, the transcatheter pacemaker met the prespecified safety and efficacy goals; it had a safety profile similar to that of a transvenous system while providing low and stable pacing thresholds. (Funded by Medtronic; Micra Transcatheter Pacing Study ClinicalTrials.gov number, NCT02004873.).

Introduction: Successful reperfusion with primary percutaneous coronary intervention (PCI) can paradoxically elicit temporary vulnerability to ventricular arrhythmia. We examined whether T-wave alternans (TWA) level is correlated with nonsustained ventricular tachycardia (NSVT) incidence in association with PCI in patients with acute ST-segment elevation myocardial infarction (STEMI)., Methods and Results: We analyzed continuous 24-hour ambulatory electrocardiograms in 48 STEMI patients during and after successful primary PCI, achieving Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. TWA was measured using modified moving average method. Maximum TWA was elevated in patients with (N = 22) compared to without (N = 26) NSVT (75.1 ± 6.3 vs 49.9 ± 3.6 μV, P < 0.005) during the 22-hour monitoring period. TWA ≥ 60μV predicted NSVT with sensitivity of 77%; specificity, 73%; positive predictive value, 71%; and negative predictive value, 79%. Area under receiver operator characteristic curve (AUC) was 0.87 for maximum TWA in predicting NSVT. By comparison, ST-segment levels did not differ in patients with versus without NSVT and were not predictive (AUC = 0.52). TWA was elevated prior to PCI and remained elevated at 30 minutes after balloon inflation despite restoration of TIMI grade 3 flow in all patients, declining by 22 hours (P < 0.05). Maximum ST-segment levels decreased from before PCI to 30 minutes after balloon inflation. TWA is regionally specific, with higher values prior to PCI in precordial lead V5 than in V1 for left coronary lesions., Conclusions: TWA may be useful in identifying individuals at heightened risk for arrhythmia in association with primary PCI and can potentially signal time-dependent changes in arrhythmia vulnerability., (© 2013 Wiley Periodicals, Inc.)

Background: The Medtronic Sprint Fidelis high-voltage implantable cardioverter-defibrillator (ICD) lead is prone to fracture. The majority of fractures involve the pace-sense (P/S) conductors and may result in multiple inappropriate shocks. The Medtronic lead integrity alert (LIA) algorithm was designed to improve early detection of transient P/S conductor fractures and to decrease the incidence and number of inappropriate shocks., Objective: The purpose of this prospective single-center study was to assess the effectiveness of the LIA algorithm for warning patients of an impending Sprint Fidelis P/S conductor fracture and for decreasing the incidence and number of inappropriate shocks., Methods: The study population included all patients who had Sprint Fidelis leads and Medtronic ICD pulse generators that were implanted and followed at the Minneapolis Heart Institute. Patients were evaluated in the clinic every 3 to 4 months or by remote monitoring using the Medtronic CareLink system. When the LIA algorithm was released in August 2008, the RAMware was downloaded to the pulse generator of all patients with the Sprint Fidelis lead. Patients and family members received educational materials and were given a demonstration of the audible alerts., Results: Between October 2004 and January 2010, 52 (11.3%) of 461 Sprint Fidelis leads failed in the study population. Inappropriate shocks were the first sign of lead failure in 18 (69%) of the 26 patients who did not have the LIA compared to 4 (17%) of 23 patients who had the LIA (P = .0004). Patients who experienced inappropriate shocks without the LIA received an average of 13.2 +/- 13.6 inappropriate shocks (range 2-54) versus 3.0 +/- 2.0 inappropriate shocks (range 2-6) in patients who had the LIA (P = .017). The audible alert was effective in 70% (16/23) and 35% (6/17) of patients with and without the LIA, respectively, whose alerts were programmed ON (P = .053). Overall, 8 (32%) of 25 patients whose audible alerts were triggered did not immediately hear or recognize the tone., Conclusion: The LIA appears to be an effective method for detecting most Sprint Fidelis lead fractures and for decreasing the incidence and number of inappropriate shocks. However, a better method for alerting patients and caregivers is needed., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Radiofrequency ablation for atrial fibrillation (AF) involves complex catheter manipulation resulting in prolonged procedure time and fluoroscopy exposure. Remote magnetic navigation (RMN) represents a novel approach toward improving the ability to perform complex ablation. Forty patients underwent ablation for AF, 20 using RMN (NIOBE II, Stereotaxis, Inc) with a 4-mm-tip magnetic catheter (Celsius, Biosense Webster) and 20 using a conventional 8-mm-tip bidirectional ablation catheter (Blazer, Boston Scientific). All patients underwent a combined wide area circumferential ablation and segmental pulmonary vein (PV) isolation using a circular mapping catheter and cavotricuspid isthmus ablation for right atrial flutter. The procedural end point was PV entrance block. There was no difference in atrial size, left ventricular systolic function, or type of AF between groups. PV entrance block was achieved in all patients. Mean procedure time was 279 +/- 60 minutes in the conventional group versus 209 +/- 56 minutes in the RMN group (p <0.001). Mean fluoroscopy time in the conventional group was 58.6 +/- 21 minutes versus 19.5 +/- 9.8 in the RMN group (p <0.001). At 1 year there were 15 patients in the conventional group and 16 in the RMN group free from clinical AF and off antiarrhythmic drugs (p = NS). There were 2 additional ablations performed for atypical atrial flutter in the conventional group and 3 in the RMN group (p = ns). Ablation catheter char formation was not observed. There were no procedural complications. In conclusion, radiofrequency ablation of AF performed with RMN is safe and feasible. Compared with conventional hand-navigated ablation, RMN ablation results in similar clinical outcomes with decreased fluoroscopy and procedure times.

Background: We have observed a higher than expected rate of Sprint Fidelis model 6949 lead failures in our practice., Objective: The aim of this study was to assess the performance of small-diameter Sprint Fidelis high-voltage ICD leads., Methods: The actuarial survival of Sprint Fidelis model 6949 leads implanted at our center was compared with that of the Sprint Quattro Secure model 6947. The United States Food and Drug Administration Manufacturers and User Facility Device Experience (MAUDE) database was searched for Sprint Fidelis models., Results: The survival of 583 Sprint Fidelis 6949 leads implanted at our center between September 2004 and February 2007 was significantly less than 285 Sprint Quattro Secure model 6947 leads implanted by us between November 2001 and February 2007 (P = .005). Six patients presented with Sprint Fidelis lead failure 4-23 months after implant. Five of the six patients experienced multiple inappropriate shocks associated with pace-sense conductor and coil fractures; the sixth patient had a fixation mechanism failure. The MAUDE search rendered reports for 679 Sprint Fidelis leads. The most frequent complaints or observations were inappropriate shocks (33%), high impedance (33%), and fracture (35%). Of 125 leads analyzed by the manufacturer, 62 involved fracture of the pace-sense conductor or coil and the high-voltage (defibrillation) conductor., Conclusions: The Sprint Fidelis high-voltage lead appears to be prone to early failure. Its use should be limited until the failure mechanism is identified and corrected. Patients should be evaluated quarterly, and automatic lead test features should be enabled. While more data are needed, routine prophylactic replacement of intact, normally functioning Sprint Fidelis leads does not appear justified.

Determining ventricular capture when using transcutaneous pacing (TCP) can be difficult. Our objective was to evaluate the use of ultrasound (US) to determine capture in patients undergoing TCP. We studied 15 patients in a convenience sample. Videotaped US views were obtained during TCP with concurrent electrocardiographic monitoring on the US screen. The treating physician made capture determinations first by using clinical indicators, followed by US images. Two reviewing physicians blinded to the treating physician's findings and to each other determined capture on videotape. Kappa levels of agreement were calculated. A value of kappa = 0.84 was found for agreement of the treating physician's findings through clinical measures and US. Agreement between the first reviewer and the treating physician had kappa =.47 and between the second reviewer and the treating physician was had kappa =.67. All P values were <.05. US and clinical impression of ventricular capture have good to excellent agreement. US may be useful for determining ventricular capture in patients undergoing TCP.

Background: A generic formulation of amiodarone was recently approved by the Food and Drug Administration based on single-dose equivalence data. Because amiodarone has complex pharmacokinetic properties, a narrow therapeutic range, and a significant adverse effect profile, concern about equivalency persists., Objective: To compare steady-state plasma concentrations of the brand-name reference product Cordarone with the AB-rated generic formulation, Pacerone, in patients exposed to both products., Methods: A retrospective analysis was performed at the Minneapolis Veterans Affairs Medical Center on 138 patients who were taking a stable dose of amiodarone before and after an amiodarone generic product substitution., Results: Seventy-seven patients had steady-state plasma concentrations documented for each product at the same dose. The mean steady-state plasma concentrations of amiodarone were not significantly different for Cordarone compared with Pacerone (1.07 +/- 0.48 vs. 1.19 +/- 0.66 micro g/mL, respectively); similarly, the concentrations of the active metabolite (desethylamiodarone) did not differ (0.95 +/- 0.30 vs. 0.96 +/- 0.49 micro g/mL, respectively). However, the variability in plasma drug concentrations between products was increased as compared to variability within each product., Conclusions: This study indicates that comparable steady-state concentrations can be achieved with a change in formulation from Cordarone to Pacerone. However, individual responses vary, suggesting that monitoring of plasma concentrations is prudent 1-3 months after any change from one product to another.

Unexpected loss of bipolar pacing function can occur in Guidant VIGOR dual chamber pacemakers with QC2 (Quick Connect) headers. In a retrospective review of 305 implanted patients, 23 exhibited unexpected loss of bipolar pacing lead function from < 1 to 51 months postimplant. Atrial lead problems were seen in 17 patients and ventricular lead problems in 6 (P < 0.05 atrial vs ventricular). Significant symptoms developed in six patients including two with syncope as a result of noncapture. No significant change in bipolar sensing function was seen. Reprogramming devices to the unipolar mode restored appropriate pacing thresholds and lead impedance. The changes in bipolar lead function are likely caused by failure of the QC2 header lead connection system over time.

Determining electrical capture when using an external cardiac pacemaker is often difficult and confusing, especially when the resulting clinical signs of an effective blood pressure and pulse are inadequate or nondetectable. The objective of this study was to determine the efficacy of using 2-dimensional ultrasound (US) in determining the presence of ventricular capture of an external cardiac pacemaker in a swine model. Five anesthetized swine underwent external cardiac pacing (ECP) at variable levels of energy output while concurrent US images and electrocardiograph monitoring were recorded on videotape. Determinations of capture/no capture were made in the laboratory. Segments of videotape were selected to be reviewed by 2 physicians blinded to these laboratory determinations of capture and to each other. Kappa levels of agreement were determined among the 3 pairs of comparisons. Seventeen segments were reviewed. Kappa levels of agreement were 0.76 for Reviewer A versus Laboratory determination, 0.88 for Reviewer B versus Laboratory determination, and 0.88 for Reviewer A versus Reviewer B. All P values were <.001. These excellent levels of agreement show that 2D US in this animal model is highly effective in determining the presence of ventricular capture in ECP.

Because congestive heart failure (CHF) promotes ventricular fibrillation (VF), we compared VF in seven dogs with CHF induced by combined myocardial infarction and rapid ventricular pacing to VF in six normal dogs. A noncontact, multielectrode array balloon catheter provided full-surface real-time left ventricular (LV) endocardial electrograms and a dynamic color-coded display of endocardial activation projected onto a three-dimensional model of the LV. Fast Fourier transform (FFT) analysis of virtual electrograms showed no difference in peak or centroid frequency in CHF dogs compared with normals. The average number of simultaneous noncontiguous wavefronts present during VF was higher in normals (2.4 +/- 1.0 at 10 s of VF) than in CHF dogs (1.3 +/- 1.0, P < 0.005) and decreased in both over time. The wavefront "turnover" rate, estimated using FFT of the noncontiguous wavefront data, did not differ between normals and CHF and did not change over 5 min of VF. Thus the fundamental frequency characteristics of VF are unaltered by CHF, but dilated abnormal ventricles sustain fewer active wavefronts than do normal ventricles.

Background: Patients with congestive heart failure (CHF) frequently die from arrhythmias, but models to study arrhythmogenic mechanisms during progressive CHF are lacking. Consequently we examined the feasibility of using dogs with an ischemic insult followed by rapid pacing to study ventricular arrhythmias in CHF. Methods: Eighteen chronically instrumented dogs had ischemic damage induced by inflating a balloon tipped catheter in a coronary artery for 90 min. After 2 weeks recovery, electrophysiologic studies were performed on no drugs, during esmolol infusion, and during isoproterenol infusion. The pacer was turned on at 250 bpm in 12 dogs, but not in six controls, and studies repeated bi-weekly for up to 6 weeks. Results: Serial echocardiograms documented progressive CHF, and serial signal averaged electrocardiograms demonstrated prolongation of total QRS, increased duration of terminal QRS<40 mv, and decreased RMS voltage of the terminal 20 ms of QRS in paced dogs. Arrhythmia severity increased as CHF progressed, but responses were quite variable, unaffected by esmolol, and minimally altered by isoproterenol. Conclusions: Ischemic left ventricular damage followed by rapid ventricular pacing in dogs produces a model that closely mimics patients with CHF and ventricular arrhythmias, including a heterogeneous pathophysiologic response to intervention.

Previous TIA or stroke, diabetes, advanced age, impaired left ventricular function, and a history of hypertension are strong risk factors in patients with nonvalvular AF. When none of these factors is present, aspirin in a dose of 325 mg offers effective protection against future stroke. When any of these factors are present, warfarin adjusted to an INR of 2.0 to 3.0 offers greater protection against future stroke than aspirin alone or aspirin and fixed-dose warfarin (INR 1.2-1.5). More data are needed before newer anticoagulants can be recommended for treatment.

The time constant (T) obtained by fitting post-exercise heart rate (HR) recovery to a first order exponential decay curve has been promoted as an index of parasympathetic activity. However, acceptance has been limited because reported data are inadequate to assess goodness of fit for the model, determine the best exercise protocol, or optimize the duration of post exercise monitoring. Consequently, we evaluated T for nine healthy volunteers (age 24-46) following treadmill exercise at maximal (max) and two stages sub-max exercise (Bruce protocol). T stabilized only after 3 min of post-exercise monitoring. With max exercise, T varied unacceptably with small changes in onset of monitoring, e.g. -16.7+/-16.6 (-13.2%) in the first 5 s, and residuals of the fitted curve were non-random. In contrast, sub-max exercise produced consistent T values, e.g. -1.9+/-3.2 (-4.2%) in the first 5 s, and residuals were more nearly random. In conclusion, first order decay is an inadequate model for HR recovery following max exercise, but may be reasonable for sub-max levels.

Background: Improvements in cardiac mapping are required to advance our understanding and treatment of arrhythmias. This study validated a new noncontact multielectrode array catheter and accompanying analysis system to provide electroanatomic mapping of the entire left ventricular (LV) endocardium during a single beat., Methods and Results: A 9F 64-electrode balloon array catheter with an inflated size of 1.8x4.6 cm was used to simultaneously record electrical potentials generated by the heart and locate a standard electrophysiology (EP) catheter within the same chamber. By use of the recorded location of the EP-catheter tip, LV geometry was determined. Array potentials served as inputs to a high-order boundary-element method to produce 3360 potential points on the endocardial surface translatable into electrograms or color-coded activation maps. Three methods of validation were used: (1) driven electrodes in an in vitro tank were located; (2) waveforms generated from the array catheter were compared with catheter contact waveforms in canine LV; and (3) sites of local LV endocardial activation were located and marked with radiofrequency lesions. Tank testing located a driven electrode to within 2.33+/-0.44 mm. Correlation of timing and morphology of computed versus contact electrograms was 0.966. Radiofrequency lesions marked 17 endocardial pacing sites to within 4.0+/-3.2 mm., Conclusions: This new system provides anatomically accurate endocardial isopotential mapping during a single cardiac cycle. The locator component enabled placement of a separate EP catheter to any site within the mapped chamber.

This study evaluated the electrophysiologic effects of a pulsed iontophoretic drug-delivery system when used in the coronary arteries. Prevention of acute thrombosis and restenosis after intravascular procedures may be enhanced by high concentrations of therapeutic agents within the vessel wall. A new intravascular drug-delivery system uses iontophoresis to maximize local tissue concentrations of drug. However, the electrophysiologic effects of such a system in coronary arteries are unknown. An iontophoretic membrane balloon-tipped catheter was placed fluoroscopically in the mid left anterior descending coronary artery of 10 anesthetized dogs. Strength-duration curves and effective refractory period (ERP) were initially determined. Threshold for capture was assessed at pulse widths of 0.5, 1.0, 2.0, 4.0, and 8.0 ms. Capture occurred at 4.9 +/- 0.9, 3.4 +/- 0.5, 2.6 +/- 0.5, 1.6 +/- 0.2, and 1.2 +/- 0.2 mA, respectively. The ERP was 169 +/- 6 ms (4.0-ms pulses at twice threshold). Then square-wave pulses for iontophoresis were R-wave synchronized and delivered at 50 and 75% of the ERP with the balloon inflated to 1 atm. Output was increased until significant arrhythmias occurred [premature beats > 10/min, supraventricular tachycardia (SVT), ventricular tachycardia (VT), ventricular fibrillation (VF)], by using sequential steps of 1, 5, 10, 15, and 20 mA. Highest average outputs achieved without an arrhythmia were 14.1 +/- 2.5 and 4.9 +/- 2.0 mA at 50 and 75% of ERP, respectively (p < 0.05). High-grade arrhythmias (pulseless VT or VF) occurred in three of four animals studied before use of a frequency limiter, which allowed current delivery only at intervals > 400 ms (thus inhibiting current activation during premature beats). No further VT or VF occurred in the remaining six animals, except for one episode of nonsustained VT (11 beats). An R-wave synchronized iontophoretic field with a response-frequency limiter can be safely used within the canine coronary arterial system at 50% of ERP with moderate outputs (5-10 mA). Increasing the stimulus duration to 75% of ERP increases arrhythmogenesis but is tolerated at lower output levels (< 5 mA).

The effectiveness of cardiopulmonary support (CPS) as a rescue method following failed angioplasty is unknown. The proximal left anterior descending (LAD) was occluded for 20 min in 21 dogs. Group 1 animals (n=15) were given CPS and group 2 animals (n=6) served as controls. During coronary occlusion, animals receiving CPS had increased mean arterial pressure (71+/- 12 vs 58+/-7 mm Hg), decreased left atrial pressure (3+/-3 vs 12+/-3 mm Hg), increased ischemic area blood flow (0.20+/-0.16 vs 0.02+/-0.04 mL/min/g) and myocardial oxygen consumption (0.014+/- 0.008 vs 0.003+/-0.006 mL O2/min/g), decreased remote area myocardial oxygen consumption (0.026+/-0.010 vs 0.091+/-0.047 mL O2/min/g), and an improved myocardial oxygen consumption index (0.60+/-0.33 vs 0.02+/-0.03) when compared with controls (p<0.05). During reperfusion (no CPS), group 1 animals had increased cardiac index (210+/-95 vs 117+/-46 mL/min/kg), renal blood flow (110+/-38% vs 53+/-45%), ischemic area blood flow (1.13+/-0.40 vs 0.58+/-0.27), and myocardial oxygen consumption (0.066+/-0.015 vs 0.032+/-0.018) when compared with controls (p<0.05). CPS improves oxidative metabolism in selective myocardial segments during coronary occlusion, promotes recovery of the postischemic myocardium, and results in improved peripheral circulation.

Transesophageal echocardiography was used to assess cardiac abnormalities associated with embolization in patients who had completed the Department of Veterans Affairs Cooperative Study of Stroke Prevention in Nonrheumatic Atrial Fibrillation at the Minneapolis and West Haven Department of Veterans Affairs Medical Centers without an embolic event. Patients were men, 71 +/- 7 years old, with atrial fibrillation of 6.2 +/- 4.3 years' duration who had received warfarin (n = 32) or placebo (n = 23) for 2 years. Thrombi were found in 5 of 55 patients (warfarin 4 and placebo 1; p = 0.39); spontaneous echo contrast was seen in 4 of 5 patients. Other abnormalities identified included spontaneous echo contrast (47%), patent foramen ovale (54%), atrial septal aneurysm (7.3%), and left ventricular thrombus (3.6%). During 34 months of posttreatment follow-up, 5 patients had a stroke (1 fatal), and 10 died. Potential sources of emboli did not predict subsequent outcome. Thus warfarin therapy did not preclude the presence of thrombi. Stroke reduction likely involves the prevention of emboli from sources in addition to the atrial appendage.

Symptomatic pulmonary emboli complicating electrophysiologic procedures are uncommon. Asymptomatic or mildly symptomatic embolic are likely much more common. This case report highlights the problem of extensive, but mildly symptomatic, pulmonary emboli occurring as a complication of electrophysiologic procedures, including catheter ablation. The role of anticoagulation during and following electrophysiologic procedures in preventing pulmonary emboli (which can have long-term sequelae) is unknown. Currently, there appears to be no consensus regarding the use of anticoagulants either during or following electrophysiologic procedures, including those involving catheter ablation. Based on the presumed frequency and potential long-term complications of pulmonary emboli, anticoagulation during electrophysiologic procedures should be recommended.

Background: Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk., Methods: We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death., Results: Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history., Conclusions: Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.

This study examined the impact of transcatheter fulguration on creatine kinase-MB release in 21 patients (age range 17-71 years). Arrhythmia diagnoses were ventricular tachycardia 9, atrial fibrillation with a rapid ventricular response 7, atrioventricular nodal reentry 2, and reciprocating tachycardia utilizing a posteroseptal accessory pathway 3. Seven patients had apparently normal hearts while 8 had ischemic heart disease and 6 cardiomyopathy. Timing of initial elevated creatine kinase-MB activity (mean 1.34 +/- 0.69 SD hours) and peak creatine kinase-MB activity (mean 3.73 +/- 0.89 SD hours) was relatively uniform in all patients. Time to peak creatine kinase-MB activity was unrelated to either underlying cardiac disease (normal: 3.9 +/- 1.0 hours; ischemic heart disease: 3.5 +/- 0.9 hours; cardiomyopathy: 3.8 +/- 0.9 hours), or fulguration site (His bundle (n = 9): 4.2 +/- 0.9 hours, proximal coronary sinus (n = 3): 3.3 +/- 0.3 hours, ventricle (n = 9): 3.4 +/- 0.8 hours). The magnitude of peak serum creatine kinase-MB activity was independent of myocardial diagnosis or fulguration site, but was linearly related to total energy delivered (r = 0.5, P less than 0.022). The latter correlation was particularly strong within cardiac diagnosis subgroups (normal: r = 0.92, P less than 0.002; ischemic heart disease: 0.73, P less than 0.04; non-ischemic cardiomyopathy: r = 0.57, P = NS). Thus, serum creatine kinase-MB activity following transcatheter fulguration is linearly related to the magnitude of delivered energy, and is similar to that observed after transient coronary artery occlusion and reperfusion.

Transmural multipolar electrodes, sonomicrometers implanted within the left ventricular wall, and cardiac electrical stimulation techniques were used to examine the effect of transient mechanically applied traction to the left ventricular free wall on local electrophysiological properties. Twenty-five open-chest dogs were atrially paced (cycle length 400 ms) followed by insertion of timed premature extrastimuli at left ventricular epicardial pacing sites either in the vicinity of (traction zone) or remote from (nontraction-control zone) the site of left ventricular free wall traction. Electrophysiological recordings were made before and during intermittent left ventricular free wall traction applied in late diastole (rate 25 cm/s; duration 170 ms). In 22 of 25 dogs, application of traction resulted in early local ventricular activation (mean activation advancement 64 +/- 15 ms), altered QRS morphology of the last conducted atrial drive train beat, and a relative prolongation of ventricular refractoriness in the traction zone. Conversely, in the nontraction-control zone, early activation did not occur and refractoriness was unchanged. Alterations in regional myocardial blood flow (assessed by microsphere technique) did not appear responsible for the observed changes. Furthermore, phenol interruption of local sympathetic or combined sympathetic and parasympathetic innervation or verapamil pretreatment had no impact on the mechanically induced electrophysiological changes. Thus, in normal myocardium in situ, regional abnormalities in wall motion may be associated with alterations of local ventricular activation and refractoriness, factors that in the diseased heart could lead to increased susceptibility to arrhythmias.

This study used transmural multipolar electrodes, ventricular pressure monitoring, and cardiac electrical stimulation techniques to examine the effects of transient aortic occlusion on ventricular refractoriness in a canine model of recent myocardial infarction. Six previously instrumented resting awake dogs were atrially paced, followed by timed premature extrastimuli inserted at epicardial pacing sites adjacent to an apical left ventricular (LV) myocardial infarction or in an LV control zone remote from the myocardial infarction. Electrophysiologic and pressure recordings were obtained before and during periods of transient aortic occlusion. Aortic occlusion was applied before the last beat of an eight-beat atrial pacing sequence and resulted in increased peak LV pressure (92.8 +/- 27.7 mm Hg, p = 0.003). Aortic occlusion shortened LV effective refractory period (ERP) recorded from the myocardial infarction border zone in both the subepicardial (-17.0 +/- 11.8 msec, p = 0.019) and subendocardial (-17.7 +/- 10.9 msec, p = 0.011) regions, whereas LVERP of the control zone was unchanged. Conduction latency of premature beats at equivalent coupling intervals and maximum latency observed were unchanged by aortic occlusion. atrioventricular conduction interval shortened in association with aortic occlusion. Thus transient aortic occlusion reduced ventricular refractoriness in the border zone adjacent to the myocardial infarction while control zone refractoriness was minimally or not changed. Heterogeneity of ventricular myocardial refractoriness may result from mechanical dysfunction, potentially increasing susceptibility to arrhythmias.

This study assessed the cardiac electrophysiologic effects of DPI 201-106 (DPI), a novel orally absorbable positive inotropic agent, the administration of which has been associated with electrocardiographic (ECG) QT and T-wave changes. In the intact conscious dog, oral administration of both 8 and 16 mg/kg DPI produced marked sinus cycle length prolongation (8 mg/kg, + 11%; 16 mg/kg, + 9%) within 60 min of DPI administration (p less than 0.05 vs. baseline). DPI also tended to prolong right atrial refractory periods, and increase sinus node recovery time. In addition, DPI exhibited a negative dromotropic effect on the atrioventricular (AV) node, prolonging both AV node effective and functional refractory periods and tending to increase the minimum atrial paced cycle length at which AV conduction of 1:1 was maintained. DPI also significantly increased right ventricular effective refractory period (ERP) at both doses studied and increased ventricular functional refractory period (FRP) at the 16-mg/kg dose. Finally, although DPI administration was associated with QT interval prolongation, this effect was slight when corrected for sinus cycle length (SCL) (QTc, +3%). When administered concomitantly with propranolol and atropine or after surgical cardiac denervation, DPI-induced electrophysiologic changes were largely attenuated or abolished. Thus, findings in this study indicate that the apparent cardiac electrophysiologic effects of DPI are predominantly of neurally mediated origin in this animal model.

This study utilized sonomicrometers transmural multipolar electrodes and cardiac electrical stimulation techniques to examine the effect on myocardial electrophysiological characteristics of altering ventricular systolic mechanical properties by transient aortic occlusion. Nine anesthetized open-chest dogs were atrially paced, and timed extrastimuli were inserted during alternate drive-train sequences at right or left ventricular (RV, LV) epicardial sites to measure ventricular effective refractory period (ERP). Sonomicrometer measurements of LV systolic mechanical parameters and both RV and LV electrophysiological findings were determined prior to and during periods of transient aortic occlusion. Aortic occlusion was applied just prior to the last beat of each eight-beat atrial drive train and released immediately following the programmed ventricular extrastimulus. Aortic occlusion increased LV systolic pressure (+42 +/- 26.6 mmHg, P less than 0.01) and diminished segmental stroke shortening (0.100 +/- 0.059 mm, P less than 0.02), shortening fraction (0.086 +/- 0.048, P less than 0.001), mean velocity of stroke shortening (0.444 +/- 0.186 mm/s, P less than 0.001), and stroke work (P less than 0.001). LV epicardial and endocardial ERP were prolonged as a result of aortic occlusion (5 +/- 7.2 and 6 +/- 6.5 ms, respectively, P less than 0.05), whereas RV ERP was unchanged. Latency of premature beats at equivalent coupling intervals was unaltered. ERP prolongation correlated most strongly with reductions of segmental stroke shortening (r = 0.928, P less than 0.001), shortening fraction (r = 0.901, P less than 0.001), and mean shortening velocity (r = 0.819, P less than 0.01). Thus transient aortic occlusion prolonged LV refractoriness, and electrophysiological changes closely paralleled the severity of systolic mechanical disturbance.

Cardiac electrophysiologic effects of verapamil in vivo are the result of both direct and indirect actions on the heart (the latter due to augmentation of sympathetic neural tone, diminution of parasympathetic neural tone, and increased circulating catecholamines). In this study we assessed the interaction of verapamil's direct and indirect actions on electrophysiologic properties of the heart in awake, previously instrumented, unsedated dogs. After administration of intravenous verapamil (0.2 mg/kg), electrophysiologic effects were assessed serially over a 1 hr period in 10 awake dogs before (group 1 studies) and during pharmacologic autonomic blockade (group 2 studies), and in a subset of these dogs (n = 5) after orthotopic cardiac transplantation (group 3 studies). In group 1 dogs, sinus cycle length (SCL) initially shortened after verapamil (postverapamil 379 +/- 50 msec vs baseline of 494 +/- 72 msec, p less than .001) and subsequently gradually prolonged. In groups 2 and 3, transient SCL shortening was absent. SCL prolonged promptly after verapamil, and sinus arrest developed in two of 10 group 2 and two of five group 3 animals. Verapamil exerted a negative dromotropic effect on atrioventricular node conduction in all three experimental groups, as assessed by drug-induced changes in minimum cycle length with sustained 1:1 atrioventricular conduction and measurements of atrioventricular node effective and functional refractory period. However, compared with findings in group 1, this negative dromotropic effect occurred more rapidly and was markedly potentiated in groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Impregnation of implantable cardiac pacemaker electrodes with dexamethasone sodium phosphate dexamethasone) has been associated with reduced energy requirements for both atrial and ventricular stimulation. To determine whether cardiac cellular electrophysiologic effects of dexamethasone could in part account for lower stimulation thresholds, conventional microelectrode recording and stimulation techniques were used to assess both the immediate (acute) effects of dexamethasone (10(-6) and 10(-4) M) in superfused isolated rabbit right atrial and right ventricular preparations, and chronic effects in rabbit right ventricular tissue following 2 weeks of either daily parenteral dexamethasone (5 mg/kg, plasma concentration approximately 1 to 5 x 10(-5) M) or saline placebo injections. In acute superfusion studies, dexamethasone resulted in a concentration dependent prolongation of spontaneous right atrial cycle length, but did not significantly affect right atrial transmembrane action potential characteristics or refractoriness. However, acute dexamethasone superfusion tended to increase right ventricular resting membrane potential and diminish stimulation threshold. On the other hand, compared to findings in saline-injected control rabbits, chronic dexamethasone injection had little effect on right ventricular stimulation threshold transmembrane action potential characteristics, or right ventricular refractoriness. Thus, the acute direct electrophysiologic effects of high-dose dexamethasone are compatible with the early reduction of cardiac stimulation thresholds associated with dexamethasone impregnated pacing electrodes. On the other hand, electrophysiologic findings in the presence of chronic dexamethasone exposure do not fully account for long-term reduction of stimulation energy requirements.

Traditional classifications of atrial tachycardias include not only rhythm disturbances arising primarily within the atria, but also dysrhythmias in which it is now recognized that participation of both atrial and non-atrial tissue is required. We prefer to consider those arrhythmias in which the atria are the principal site of electrophysiologic disturbance as "primary" atrial tachyarrhythmias. The mechanisms, diagnosis, and treatment of these "primary" atrial tachycardias are the subject of this article.

This study examined factors determining efficacy of intracavitary cardioversion of atrial tachyarrhythmias in closed chest, anesthetized dogs with talc pericarditis. Electrode catheters were positioned transvenously with the cathode in the right atrial appendage. In Group 1 dogs (n = 6), three anode sites (superior and inferior venae cavae ostia and mid-right atrium) were tested with graded energy shocks to determine the lowest effective cardioversion energy at each anode position. In Group 2 dogs (n = 9), multiple cardioversion attempts with energy levels of 0.01 to 5.0 J were used to evaluate reproducibility of energy thresholds. In Group 3 dogs (n = 6) without talc-induced pericarditis, atrial pathologic study was done after five intracavitary shocks (0.5 or 5.0 J). In Group 1, cardioversion was achieved with 0.75 J or less with no significant difference in minimal effective cardioversion energies among the three anode positions tested. In Group 2, 98 (26%) of 372 cardioversion attempts were successful. Intra-animal minimal effective cardioversion energies varied widely, and timing of shocks relative to atrial electrograms did not influence efficacy. Complications were infrequent and included delayed sinus rhythm recovery, transient atrioventricular block and ventricular fibrillation. Ventricular fibrillation occurred in 9 (2.4%) of 372 shocks, and was associated with higher delivered energies (6 of 9 with greater than or equal to 1.0 J) and with shocks delivered 116 to 180 ms after onset of the QRS complex. In Group 3, two dogs had no histologic damage, three dogs had multiple small foci of subendocardial necrosis and in one dog these foci coalesced to involve half the atrial wall thickness. Thus, low energy cardioversion of atrial tachyarrhythmias is feasible using intracavitary electrodes. Synchronization of energy delivery to the QRS complex is important to minimize risk of ventricular fibrillation.

Neurally mediated hypotension and bradycardia are believed to be common causes of syncope. We used the "upright-tilt test" (duration, less than or equal to 10 minutes) with or without an infusion of exogenous catecholamine (isoproterenol [1 to 5 micrograms per minute], given intravenously) to elicit bradycardia, hypotension, or both in 24 patients with recurrent syncope and in 18 control subjects. A conventional electrophysiologic test performed before the tilt test was positive in 9 of the 24 patients, revealing arrhythmias that may have caused recurrent syncope, but was negative and thus nondiagnostic in 15 patients. The tilt test alone (i.e., without isoproterenol) induced symptomatic bradycardia or hypotension in 1 of the 9 patients with positive electrophysiologic tests (11 percent), 4 of the 15 patients with negative electrophysiologic tests (27 percent), and none of the controls. When the isoproterenol infusion was administered during the tilt test, 9 of the 11 patients with negative electrophysiologic and tilt tests had syncope, marked slowing of the heart rate, and hypotension. In contrast, isoproterenol was associated with tachycardia and only a slight decline in arterial pressure in the 8 remaining patients with positive electrophysiologic tests and the 18 control subjects, and syncope developed in only 1 of the 8 patients with positive electrophysiologic tests and negative tilt tests (13 percent) and 2 of the 18 control subjects (11 percent). We conclude that an isoproterenol infusion administered in conjunction with the upright-tilt test may be useful for identifying susceptibility to neurally mediated recurrent syncope.

In a 77 year old previously healthy man with mild adult-onset diabetes mellitus, a primary cutaneous Nocardia asteroides infection developed on the hand following inoculation of a traumatic injury. Initially untreated, the infection became locally invasive and resulted in dissemination to the lungs and normal skin. This represents the first known reported case of a N. asteroides actinomycetoma associated with dissemination.

In this study we used transmural multipolar electrodes, sonomicrometers implanted within the left ventricular wall, and cardiac electrical stimulation techniques to examine the effect of transient mechanical posterior papillary muscle traction on local myocardial electrophysiologic characteristics. Nine open-chest dogs were atrially paced (cycle length 400 msec) followed by insertion of timed premature extrastimuli at left ventricular epicardial pacing sites either in the vicinity of (traction zone) or remote from (nontraction zone) the site of papillary muscle traction. Electrophysiologic recordings were made before and during periods of intermittent papillary muscle traction of predetermined timing, application rate (25 cm/sec), and duration (170 msec). Papillary muscle traction was applied in late diastole just before the last beat of each atrial drive train. In seven of nine dogs application of transient papillary muscle traction resulted in significantly earlier local ventricular activation (mean activation advancement 30 +/- 13 msec), altered QRS morphology of the last conducted atrial drive-train beat, and relative prolongation of ventricular functional refractory period in the traction zone. Conversely, in nontraction zones in these seven dogs, early activation did not occur and refractoriness remained unchanged as tested by a locally placed extrastimulus. In two of nine dogs traction failed to induce early activation and changes in refractoriness did not occur. Alterations in regional myocardial blood flow (assessed by radioactive microsphere technique) did not appear responsible for the observed changes, since there was no demonstrable traction-induced difference in regional blood flow between the traction and nontraction zones.(ABSTRACT TRUNCATED AT 250 WORDS)

Flecainide acetate, an investigational class 1 antiarrhythmic agent, undergoes biotransformation in man with production of 2 major metabolites: meta-O-dealkylated flecainide (S-24623) and the meta-O-dealkylated lactam of flecainide (S-26191). This study compared the effects of flecainide, S-24623 and S-26191 on cardiac electrophysiologic characteristics in the anesthetized dog. Each dog received 2 dose levels of 1 of the 3 test compounds after control measurements. Flecainide (2 and 4 mg/kg in 8 dogs), S-24623 (4 and 8 mg/kg in 8 dogs) and S-26191 (4 and 10 mg/kg in 7 dogs) were administered intravenously in dilute solution. Of the 3 compounds, only flecainide significantly prolonged sinus cycle length (p less than 0.01). However, both flecainide and S-24623 significantly prolonged minimum atrial paced cycle length with 1:1 atrioventricular conduction, atrioventricular nodal effective and functional refractory periods, and right ventricular effective refractory period. Metabolite S-26191 exhibited qualitatively similar but much weaker electrophysiologic actions. The maximal electrophysiologic effects of flecainide and S-24623 were approximately equivalent, but the metabolite was about one-half as potent on a milligram-permilligram basis, and lacked marked effects on infranodal (HV interval) conduction. S-26191 was less than one-tenth as potent as flecainide. Therefore, since both flecainide metabolites occur primarily in the conjugated form in plasma (i.e., free metabolite concentrations are low), it is unlikely that these compounds either potentiate flecainide's antiarrhythmic action or increase susceptibility to drug toxicity in the clinical setting.