Intracavitary electrode catheter cardioversion of atrial tachyarrhythmias in the dog.

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.

Primary cutaneous Nocardia asteroides infection with dissemination.

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.

Electrophysiologic effects of flecainide acetate and its major metabolites in the canine heart.

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.

Mildly symptomatic pulmonary emboli associated with electrophysiologic procedures. Indications for anticoagulant use.

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.

Cardiopulmonary support mitigates the effects of experimental myocardial ischemia.

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.

Electrophysiologic properties of the myocardial infarction border zone: effects of transient aortic occlusion.

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.

Atrial flutter, atrial fibrillation, and other primary atrial tachycardias.

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.

Timing and magnitude of serum creatine kinase-MB after transcatheter cardiac tissue fulguration in man.

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.

Cellular electrophysiologic effects of dexamethasone sodium phosphate: implications for cardiac stimulation with steroid-eluting electrodes.

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.

Anticoagulant use in nonvalvular atrial fibrillation. Determining risk and choosing the safest course.

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.

Heart rate recovery post-exercise as an index of parasympathetic activity.

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.

Endocardial activation during ventricular fibrillation in normal and failing canine hearts.

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.

Sensor-triggered, rate-variable cardiac pacing. Current technologies and clinical implications.

Conventional implantable dual-chamber cardiac pacemakers adjust heart rate and maintain normal atrial and ventricular contraction by tracking "native" atrial electrical activity and pacing the ventricles after a predetermined programmable atrioventricular delay. However, in patients with symptomatic bradyarrhythmias, optimal function of "atrial-tracking" devices may be limited by concomitant sinoatrial disease. Provision of chronotropic response during physical exertion or emotional stress may be achieved by using physiologic sensors to alter pacing rate independently of atrial activity. Additional systems using sensor technologies are being developed. Future pacing systems will have dual-chamber pacing capability and may use several sensors coupled synergistically in order to take advantage of particular strengths of each. Physiologic sensor technology may be of diagnostic value in both antitachycardia devices and implantable cardioverter and defibrillator systems.

Electrophysiologic characteristics of a pulsed iontophoretic drug-delivery system in coronary arteries.

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).

Validation of a new noncontact catheter system for electroanatomic mapping of left ventricular endocardium.

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.

The utility of ultrasound to determine ventricular capture in external cardiac pacing.

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.

Electrophysiological effects of left ventricular free wall traction in intact hearts.

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.

Electrophysiologic effects of papillary muscle traction in the intact heart.

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)

Role of transesophageal echocardiography in the detection of left atrial thrombus in patients with chronic nonrheumatic atrial fibrillation.

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.