Mapping of atrial activation with a noncontact, multielectrode catheter in dogs.

BACKGROUND: Endocardial mapping of sustained arrhythmias has traditionally been performed with a roving diagnostic catheter. Although this approach is adequate for many tachyarrhythmias, it has limitations. The purpose of this study was to evaluate a novel noncontact mapping system for assessing atrial tachyarrhythmias. METHODS AND RESULTS: The mapping system consists of a 9F multielectrode-array balloon catheter that has 64 active electrodes and ring electrodes for emitting a locator signal. The locator signal was used to construct a 3-dimensional right atrial map; it was independently validated and was highly accurate. Virtual electrograms were calculated at 3360 endocardial sites in the right atrium. We evaluated right atrial activation by positioning the balloon catheter in the mid right atrium via a femoral venous approach. Experiments were performed on 12 normal mongrel dogs. The mean correlation coefficient between contact and virtual electrograms was 0.80+/-0.12 during sinus rhythm. Fifty episodes of atrial flutter induced in 11 animals were evaluated. In the majority of experiments, complete or almost complete reentrant circuits could be identified within the right atrium. Mean correlation coefficient between virtual and contact electrograms was 0.85+/-0.17 in atrial flutter. One hundred fifty-six episodes of pacing-induced atrial fibrillation were evaluated in 11 animals. Several distinct patterns of right atrial activation were seen, including single-activation wave fronts and multiple simultaneous-activation wave fronts. Mean correlation coefficient between virtual and contact electrograms during atrial fibrillation was 0.81+/-0.18. The accuracy of electrogram reconstruction was lower at sites >4.0 cm from the balloon center and at sites with a high spatial complexity of electrical activation. CONCLUSIONS: This novel noncontact mapping system can evaluate conduction patterns during sinus rhythm, demonstrate reentry during atrial flutter, and describe right atrial activation during atrial fibrillation. The accuracy of electrogram reconstruction was good at sites <4.0 cm from the balloon center, and thus the system has the ability to perform high-resolution multisite mapping of atrial tachyarrhythmias in vivo.

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.

Cardiac asystole: a manifestation of neurally mediated hypotension-bradycardia.

It has been proposed that prolonged cardiac asystole mimicking an episode of sudden cardiac death may occur as a manifestation of neurally mediated hypotension-bradycardia syndrome. To assess this possibility, electrocardiographic and hemodynamic findings during upright tilt testing were evaluated in six survivors of suspected asystolic sudden cardiac arrest with normal conventional electrophysiologic evaluation (Group I). These observations were compared with findings in two control groups: six patients with syncope but without evident asystole and with normal conventional electrophysiologic evaluation but demonstrable neurally mediated hypotension-bradycardia (Group II), and six patients with syncope in whom conventional electrophysiologic evaluation provided a presumptive diagnosis (Group III). Patients in all three groups ranged in age from 16 to 59 years. During head-up tilt testing (either alone or with isoproterenol infusion), patients in both Groups I and II developed syncope in less than or equal to 5 min, whereas patients in Group III remained asymptomatic. Patients in Groups I and II exhibited a similar tilt-induced decrease in mean arterial pressure (-46 +/- 9 and -40 +/- 9 mm Hg, respectively, p = NS) and heart rate (-44 +/- 28 and -49 +/- 12 beats/min, respectively, p = NS). In contrast, patients in Group III manifested only a moderate decrease in mean arterial pressure (-14 +/- 5 mm Hg) and had an increase in heart rate (+14 +/- 8 beats/min). Both mean arterial pressure and heart rate changes in Group I and Group II patients differed significantly (p less than 0.001) from values in Group III patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelium dependent vasodilatation following brief ischaemia and reperfusion in anaesthetised swine.

STUDY OBJECTIVE: The aim as to compare the responses of intracoronary infusions of ATP, an endothelium dependent vasodilator, with adenosine following brief ischaemia (10 min) and reperfusion in a model of myocardial stunning. DESIGN: In group 1 (n = 6), coronary blood flow and endocardial (endo) and epicardial (epi) percent segment length shortening were measured in the distribution of the left anterior descending coronary artery before and during maximal intracoronary infusions of either adenosine or ATP (20 micrograms.kg-1.min-1). Measurements were obtained before and after myocardial stunning both at control heart rate and during atrial pacing (150 beats.min-1). In group 2 (n = 6), myocardial blood flows by microspheres and arterial-venous lactate and oxygen differences were determined following the same ischaemia-reperfusion protocol to characterise transmural changes in blood flow and metabolism in this model of stunning. EXPERIMENTAL MATERIAL: The experiments were done on 12 anaesthetised swine, weight 25-39 kg. MEASUREMENTS AND MAIN RESULTS: In group 1, baseline endo and epi segment length shortening were 16(SD 3)% and 14(6)% and following reperfusion were reduced to 10(4)% and 8(6)% respectively (p less than 0.05). Prior to stunning, minimal coronary resistances during adenosine and ATP were 0.81(0.40) and 0.76(0.25) mm Hg.min.ml-1 respectively and following reperfusion were 0.86(0.31) (NS) and 0.85(0.23) (NS) mm Hg.min.ml-1 respectively. Infusion of either vasodilator enhanced function by 30% following reperfusion whereas no such effect was observed prior to ischaemia. In group 2, no maldistribution of blood flow was observed following the same ischaemia-reperfusion protocol to account for this vasodilator enhancement in function. Percent lactate extraction values were 29(11)% and 25(14)% at preischaemic control and paced heart rates respectively, and following reperfusion were lowered to 0(12)% without pacing (p less than 0.05) and -1(34)% during pacing (p less than 0.05). CONCLUSIONS: Brief ischaemia and reperfusion in swine induces myocardial stunning without altering the vasodilator responses of either ATP, an endothelium dependent vasodilator, or adenosine. Recruitment in postischaemic segment length shortening was observed during infusions of both vasodilators at a time when maldistribution of flow was not observed. Possible mechanisms include either enhanced washout of lactate from the reperfused myocardium or greater utilisation of substrates during higher blood flows.

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.

Exercise thallium testing in ventricular preexcitation.

Ventricular preexcitation, as seen in Wolff-Parkinson-White syndrome, results in a high frequency of positive exercise electrocardiographic responses. Why this occurs is unknown but is not believed to reflect myocardial ischemia. Exercise thallium testing is often used for noninvasive assessment of coronary artery disease in patients with conditions known to result in false-positive electrocardiographic responses. To assess the effects of ventricular preexcitation on exercise thallium testing, 8 men (aged 42 +/- 4 years) with this finding were studied. No subject had signs or symptoms of coronary artery disease. Subjects exercised on a bicycle ergometer to a double product of 26,000 +/- 2,000 (+/- standard error of mean). All but one of the subjects had at least 1 mm of ST-segment depression. Tests were terminated because of fatigue or dyspnea and no patient had chest pain. Thallium test results were abnormal in 5 patients, 2 of whom had stress defects as well as abnormally delayed thallium washout. One of these subjects had normal coronary arteries on angiography with a negative ergonovine challenge, and both had normal exercise radionuclide ventriculographic studies. Delayed thallium washout was noted in 3 of the subjects with ventricular preexcitation and normal stress images. This study suggests that exercise thallium testing is frequently abnormal in subjects with ventricular preexcitation. Ventricular preexcitation may cause dyssynergy of ventricular activation, which could alter myocardial thallium handling, much as occurs with left bundle branch block. Exercise radionuclide ventriculography may be a better test for noninvasive assessment of coronary artery disease in patients with ventricular preexcitation.

Usefulness of disopyramide for prevention of upright tilt-induced hypotension-bradycardia.

Susceptibility to transient hypotension-bradycardia of neurally mediated origin has been attributed in part to accentuated afferent neural traffic arising from cardiopulmonary mechanoreceptors, and consequently, may be diminished by agents with anticholinergic and negative inotropic effects, such as disopyramide phosphate. This study assessed electrocardiographic and hemodynamic responses to upright tilt testing (alone or during isoproterenol infusion) before and after disopyramide therapy in 10 patients (age range 16 to 74 years) with recurrent syncopal episodes of neurally mediated origin. Untreated, syncope occurred at less than or equal to 7 minutes of tilt alone (6 patients) or tilt plus isoproterenol at less than or equal to 3 micrograms/min (4 patients) and was associated with hypotension (mean arterial pressure, 40 +/- 16 mm Hg vs baseline 76 +/- 10 mm Hg, p less than 0.001) and inappropriate heart rate slowing (mean heart rate, 59 +/- 39 beats/min vs baseline 88 +/- 18 beats/min, p less than 0.005). After oral disopyramide 150 mg 3 times daily (mean plasma level, 3.0 +/- 0.64 micrograms/ml), all patients tolerated 10 minutes of both tilt and tilt plus isoproterenol (maximum dose, 3 micrograms/min) without symptoms, hypotension (mean arterial pressure; tilt 1 min, 79 +/- 7 mm Hg vs tilt 10 min, 77 +/- 8 mm Hg, difference not significant) or bradycardia (mean heart rate; tilt 1 min, 81 +/- 12 beats/min vs tilt 10 min, 83 +/- 11 beats/min, difference not significant). Furthermore, during subsequent 20 +/- 5 months of disopyramide therapy, all but 1 patient remain asymptomatic. Thus, oral disopyramide may be effective for preventing inducible and spontaneous neurally mediated syncope.

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.

Recovery from acute renal failure.

Acute tubular necrosis is the most common cause of acute renal failure making up two-thirds of such cases. Mortality is best correlated to basic disease. Surgery, particularly in the abdomen, carries an unusually sinister prognosis. The influence of age on outcome is controversial. Intensified dialysis, early reoperations, hyperalimentation, and possibly continuous dialysis and antibiotic barrage deserves close investigation as tools of improving survival. Almost all surviving patients recover renal function within 30 days and beyond two months recovery almost never occurs. Approximately 3% of the patients initially suspected of having acute tubular necrosis will need chronic hemodialysis indefinitely or have a transplant to regain renal function. The older patient seems to be more susceptible to this problem. Delayed recovery and chronic renal failure is unusual. High dose loop diuretic therapy and hyperalimentation with intravenous amino acids may shorten the time for recovery, although considerable controversy exists.

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.