Estimation of conduction velocity vector fields from epicardial mapping data.

An automated method to estimate vector fields of propagation velocity from observed epicardial extracellular potentials is introduced. The method relies on fitting polynomial surfaces T(x, y) to the space-time (x, y, t) coordinates of activity. Both speed and direction of propagation are computed from the gradient of the local polynomial surface. The components of velocity, which are total derivatives, are expressed in terms of the partial derivatives which comprise the gradient of T. The method was validated on two-dimensional (2-D) simulations of propagation and then applied to cardiac mapping data. Conduction velocity was estimated at multiple epicardial locations during sinus rhythm, pacing, and ventricular fibrillation (VF) in pigs. Data were obtained via a 528-channel mapping system from 23 x 22 and 24 x 21 arrays of unipolar electrodes sutured to the right ventricular epicardium. Velocity estimates are displayed as vector fields and are used to characterize propagation qualitatively and quantitatively during both simple and complex rhythms.

Implantable atrial defibrillators.

Due to the limited efficacy of antiarrhythmic drugs for atrial fibrillation, several nonpharmacologic therapeutic options have evolved. One of these is an implantable atrial defibrillator. Recent studies have shown that internal atrial defibrillation is feasible with relatively low energies. To date, the optimal electrode configuration involves large surface area catheters in the right atrium and coronary sinus. In humans, atrial defibrillation can generally be achieved with < 2 J using this electrode configuration and a biphasic shock waveform. For shocks < 5 J, there is no significant pathological damage to the atria or coronary sinus. Further investigation is needed to guarantee that atrial defibrillation shocks do not provoke ventricular arrhythmias. Preliminary data suggest that atrial defibrillation shocks synchronized to R waves that are not closely coupled are safe. In addition, the shocks are well tolerated if the shock energy is < 1.5 J. With additional studies to confirm the safety of implantable atrial defibrillators, further reduce shock energy, and improve patient tolerance, an implantable atrial defibrillator can become an acceptable therapy for patients with symptomatic, paroxysmal atrial fibrillation.

Alteration of ventricular fibrillation by propranolol and isoproterenol detected by epicardial mapping with 506 electrodes.

INTRODUCTION: We hypothesized that drugs which alter ventricular refractoriness or excitability produce quantifiable changes in ventricular fibrillation. METHODS AND RESULTS: We used a 528-channel mapping system to quantify the effects of the beta-antagonist, propranolol, and the beta-agonist, isoproterenol, on activation patterns in ventricular fibrillation. A plaque of 506 (22 x 23) electrodes spaced 1.12 mm apart and covering about 5% of the ventricular epicardium was sewn to the anterior right ventricle in 18 pigs (30 kg). Propranolol (0.25 to 0.4 mg/kg) increased the refractory period at a right ventricular epicardial site while isoproterenol (3 to 5 micrograms/min) shortened it. Ventricular fibrillation was induced by programmed stimulation, and unipolar electrograms were recorded from the 506 plaque electrodes for 2 seconds beginning 1, 15, and 30 seconds after the onset of fibrillation. Active epicardial recording sites were identified from the first derivative of the unipolar potentials (dV/dt) detected at each electrode. Then, neighboring active sites were grouped into activation fronts by computer analysis. In six pigs the effect of repeated inductions of ventricular fibrillation was assessed by comparing ventricular fibrillation after saline with a preceding control episode of fibrillation. Each activation front excited 40% +/- 46% of the mapped region before blocking. No changes were observed with saline and multiple inductions of fibrillation. In another six pigs, ventricular fibrillation after propranolol was compared with a preceding control episode of fibrillation. Ventricular fibrillation after propranolol exhibited a decreased activation rate per epicardial recording site and fewer activation fronts per second. There was no change in the amount of tissue excited by each activation front or the number of reentry cycles per activation front compared with control. In addition, there was no change in the maximum negative dV/dt detected per activation at an epicardial site. In six pigs ventricular fibrillation during isoproterenol was compared with control episodes of ventricular fibrillation before and 45 minutes after washout of the drug. The control episodes of fibrillation were not different from each other. Compared with control, ventricular fibrillation during isoproterenol exhibited an increased activation rate per epicardial site, an increased amount of tissue excited by each activation front, and an increased maximum negative dV/dt for each activation. There was no change in the number of activation fronts per second or the number of reentry cycles per activation front compared with control. CONCLUSION: Quantitative analysis revealed that propranolol and isoproterenol do not have symmetrically opposite effects on ventricular fibrillation. Propranolol decreased the number of activation fronts while isoproterenol increased the amount of tissue excited by each activation front. Thus, drugs that alter ventricular refractoriness or excitability alter ventricular fibrillation.

The probability of defibrillation success and the incidence of postshock arrhythmia as a function of shock strength.

The effects of high voltage defibrillation shocks given to six swine were studied to determine if there is a limit to the advantage gained from increasing the shock strength. An endocardial electrode was placed in the right ventricle, and a 114-cm2 cutaneous patch was placed on the left lateral thorax. Monophasic (10 msec) and single capacitor biphasic (5/5 msec) shocks with leading edge voltages of 200, 400, 600, 800, and 990 volts (approximately 2.3-59 J) were tested. For monophasic shocks, the probability of successful defibrillation ranged from 0% at 200 V to 90% at 990 V. The incidence of postshock arrhythmia increased from 0% for successful shocks at 600 V to 67% for successful shocks at 990 V. For biphasic shocks, the probability of success peaked at 97% for the 600-, 800-, and 990-V shocks. The incidence of postshock arrhythmia increased from 8% at 400 V to 55% at 990 V. Although more postshock arrhythmias occurred at lower strengths for biphasic than for monophasic shocks, an efficacy criterion, quantifying the probability of defibrillation success and the probability that a postshock arrhythmia will not occur, was always higher for biphasic shocks. The probability of success never reached 100% for either waveform while the incidence of postshock arrhythmia increased as the shock strength increased. In conclusion, for the catheter-patch electrode configuration, increasing the shock strength does not always improve the probability of success and may increase the incidence of postshock arrhythmia.

An automated technique for identification and analysis of activation fronts in a two-dimensional electrogram array.

Cardiac activation sequences are normally determined by (i) the detection and timing of local activations in cardiac electrograms, (ii) the grouping together of activations in different electrodes that are generated by the same activation fronts, and (iii) the construction by interpolation of isochronal maps showing the pathways of the activation fronts. This process is typically carried out by manual or semiautomated methods. These methods are usually adequate for stable, repeatable rhythms in normal hearts. However, in situations in which the electrograms are distorted, as in those recorded from abnormal myocardium, or the mapped rhythms are rapidly changing, as in ventricular fibrillation, they are tedious and time-consuming and yield results that are subjective and not repeatable from one investigator to another. Therefore, we developed a computer-based method for automating the identification and analysis of activation fronts recorded from a large array of electrodes. The electrodes are closely spaced (1 mm) so that interpolation is not required. Electrodes are identified as recording an activation when the temporal derivative of the potential is more negative than a user-specified value. Activations occurring less than a user-specified distance apart in time and space are identified as part of the same activation front. Characteristics of the activation fronts, such as their number, size, and the presence of reentry or collision, are then quantified. The differences between the results obtained by this automated method and those obtained by four human investigators was no greater than the differences in results among the four investigators themselves. Because the method is automated and algorithmic, it is both rapid and repeatable.

Paroxysmal cold hemoglobinuria associated with non-Hodgkin's lymphoma.

This report describes a patient with severe unexplained recurrent hemolytic anemia and congestive heart failure. Donath-Landsteiner antibodies, suggestive of paroxysmal cold hemoglobinuria (PCH), were detected. On postmortem examination, a diagnosis of non-Hodgkin's lymphoma, primarily involving the heart, was made. This previously undescribed association expands on the clinical and serologic spectrum of non-Hodgkin's lymphoma and PCH. Unexplained hemolytic anemia in the elderly should raise the suspicion of an underlying lymphoproliferative disorder.

Why do some patients have high defibrillation thresholds at defibrillator implantation? Answers from basic research.

Implantable cardioverter defibrillators reduce the risk of sudden cardiac death in patients with ventricular tachyarrhythmias. However, for the few patients with unacceptably high defibrillation thresholds at implantation the risk of sudden death may remain high. If a small number of defibrillation attempts are used to determine a defibrillation threshold, then a high defibrillation threshold may occur in some patients due to the probabilistic nature of defibrillation: a small percentage of shocks will fail even at optimal shock strengths. Basic investigations have suggested mechanisms for high defibrillation thresholds in other patients. The extracellular potential gradients produced by a shock correlate with ability to defibrillate and may be used to classify mechanisms for high defibrillation thresholds. Computerized mapping studies have demonstrated that extracellular potential gradient fields produced by defibrillation shocks are uneven with high gradient areas close to the electrodes and low gradient areas distant from the electrodes. A high defibrillation threshold may occur because: (1) a shock creates a subthreshold potential gradient in the low gradient areas; (2) a patient has a higher minimum potential gradient threshold than other patients; or (3) a shock leads to refibrillation in the high gradient areas. This article reviews experimental evidence to support each of these three possibilities then suggests experimental and clinical investigations that may clarify the causes of high defibrillation thresholds in patients.

Is the second phase of a biphasic defibrillation waveform the defibrillating phase?

Why some biphasic waveforms defibrillate with lower energies than monophasic waveforms of similar duration is unknown. One hypothesis is that the first phase of a biphasic waveform acts as a conditioning, hyperpolarizing prepulse to prepare for defibrillation by a second depolarizing phase. To test whether the second phase of a biphasic waveform is the defibrillating phase, three monophasic waveforms, an ascending ramp (A), a square wave (S), and a descending ramp (D), were compared to three biphasic waveforms with A, S, or D in the first phase (biphasic first phase) and three biphasic waveforms with A, S, or D in the second phase (biphasic second phase). Two defibrillation thresholds for each waveform were performed in 18 open chest pigs and mean defibrillation thresholds were compared. In nine pigs 16-msec monophasic and 16/16-msec biphasic waveforms were ranked by mean current and energy at defibrillation threshold. The ranks were the same for monophasic and biphasic second phase waveforms: for mean current A < S = D and for energy A < S < D. The ranks were different for the biphasic first phase waveforms: for mean current S < A = D and for energy S < A = D. Although ranks for the 16-msec monophasic waveforms matched those for the 16/16-msec biphasic second phase waveforms, the biphasic waveforms had higher mean currents and energies at defibrillation threshold. In nine pigs defibrillation thresholds for 6-msec monophasic and 6/6-msec biphasic waveforms were ranked. For mean current the ranks were monophasic: A < S = D; biphasic first phase: A = S = D; and biphasic second phase: S = D < A. For energy the ranks were monophasic: A = S < D; biphasic first phase: A = S = D; and biphasic second phase: S = D < A. Thus, ranks for the 6-msec monophasic waveforms differed from those for the 6/6-msec biphasic second phase waveforms. For 16/16-msec biphasic waveforms, less effective for defibrillation than corresponding 16-msec monophasic waveforms, these results support the hypothesis that the second phase of a biphasic waveform defibrillates since the defibrillation efficacy of a 16/16-msec biphasic waveform is related to the defibrillation efficacy of its second phase waveshape. However, for clinically useful 6/6-msec biphasic waveforms, more effective for defibrillation than 6-msec monophasic waveforms, the hypothesis is not supported because the ability of a 6/6-msec biphasic waveform to defibrillate is unrelated to the defibrillation efficacy of its second phase waveshape.