Optimized standby rate reduces the ventricular rate variability in pacemaker patients with atrial fibrillation.

Patients with chronic atrial fibrillation (AF) and symptomatic bradycardia often receive ventricular-based pacemakers. However, many of these patients continue to have symptoms of palpitations, which may be due to ventricular rate variability. It has previously been shown that continuous ventricular pacing during AF has a stabilizing effect on the ventricular rate. Hence, a study was initiated to determine whether a patient-specific optimal ventricular standby rate that reduces the ventricular rate variability, without over-pacing, could be predicted. A ventricular rate stabilization (VRS) pacing algorithm that increases the pacing rate until instability is reduced below a threshold was developed. The VRS algorithm was utilized to determine a patient-specific standby rate in 15 patients with chronic AF, intact AV nodal conduction, and implanted pacemakers. The computer algorithm controlled a pacemaker programmer to automatically change the pacemaker's ventricular pacing rate via telemetry. Patients were studied for 15 minutes with VRS and for 15 minutes with 50 ppm fixed rate pacing (control). The results were as follows: (1) VRS versus control = P < 0.05; (2) mean ventricular pacing rate (ppm): 77 +/- 13 versus 50 +/- 0; (3) mean ventricular rate (beats/min): 82 +/- 13 versus 79 +/- 12; (4) ventricular rate coefficient of variation (%): 11 +/- 1 versus 22 +/- 5; (5) percent pacing: 75 +/- 8 versus 6 +/- 8; (6) percent of RR intervals less than minimum pacing interval eliminated: 58 +/- 12; (8) regression analysis: mean VRS pacing rate (beats/min) = 0.96 x mean control ventricular rate + 2.3, r2 = 0.85. We concluded that: (1) a moderate increase in the ventricular pacing rate was required to substantially stabilize the ventricular rate; (2) the resulting mean ventricular rate increased marginally; (3) a majority of RR cycles less than each patient's minimum pacing interval were eliminated; and (4) there was a linear relationship between the mean ventricular rate during control and the optimal ventricular pacing rate. Thus, a ventricular pacing rate close to the mean ventricular rate during control consistently reduced the ventricular variability. Although pacing at an increased ventricular standby rate reduces variability at rest, the optimal solution would likely be an adaptive rate algorithm that changes the ventricular standby rate as the mean intrinsic rate varies.

Clinical significance of a new P wave lead vector for pacemaker follow-up of atrial functions.

Patient welfare requires routine follow-up procedures of implantable pacemakers. However, the assessment of atrial sensing and pacing functions in implantable pacemakers is often a challenge due to difficult identification of low amplitude P waves on surface electrocardiograms (ECGs). A previous body surface mapping study suggested that a novel P wave lead vector (P lead) had larger root mean square values than other standard leads. However, for pacemaker follow-up procedures, peak-to-peak amplitudes are more relevant than root mean square values. In this study, the peak-to-peak amplitudes of intrinsic and paced P waves recorded from surface ECG standard lead II and the P lead were compared. In addition, intrinsic and paced R waves were also compared. Data recorded from 15 patients undergoing electrophysiological studies indicated that peak-to-peak amplitudes of the P lead were significantly larger than standard lead II: 24% for intrinsic P waves, 30% for paced P waves, and 72% for intrinsic R waves. In addition, the P lead amplitude of paced R waves showed a nonsignificant increase of 24% compared with standard lead II. Therefore, the use of this new lead vector may improve the clinical ease-of-use and reduce the time required for follow-up procedures of implantable pacemakers for atrial sensing and pacing assessments.

The evolution of the implanted pacemaker's window to the world.

An implanted pacemaker can only communicate with the outside world through its window, i.e., the clinical programmer. Since its inception, the pacemaker has evolved from a non-programmable device to a complex device. Therefore, programming a modern implantable pacemaker could be very challenging for non-experienced or infrequent users. Various programmer-based automatic functions have been developed to reduce programming time and complexity and to obtain accurate measurements. With increasing interests in the telecommunications and information exchange, these programmer-based automatic functions are pushing forward a future vision that automatic pacemaker follow-up procedures via telecommunications are possible for patients located in any corner of the globe.

A rate responsive pacemaker that physiologically reduces pacing rates at rest.

Current rate responsive pacemakers incorporate sensors such as minute ventilation (MV) for adapting to changing patient conditions during exercise and periods of exertion. However, for sleep and/or rest periods, the only pacemakers currently on the market that slow the pacing rate utilize an internal timer to determine a decrease in pacing rate. It would be advantageous if the pacing rate could be automatically lowered during periods of sleep or rest. This study utilized a rate responsive sensor, MV, to track the patient's sleeping and resting periods and to decrease the pacing rate at such times. A total of eight patients implanted with Sentri 1210 single chamber MV sensor pacemakers were studied. A sleep rate (SR) of 45 beats/min was selected. A sleep rate response function, which indicated the relationship between changes in MV and corresponding heart rate, was initially set at a value of 16 and continually and automatically updated in a 3-month study. Adaptation was based on the premise that 3 hours per day should be spent at the SR. The average decrease in pacing rates from onset to 3 month for the eight patients was 12.4% +/- 5.3%. Correspondingly, the histograms of the lowest datalog histogram (40-59 beats/min) increased from 0% to 15.4% +/- 0.9% of paced beats. Correlation between the patients' 24-hour diary and Holter recordings showed that the pacing rates during sleep were consistently lower than when the patients were awake and active. This was also the case with a patient whose nocturnal and daily routine was intentionally altered.(ABSTRACT TRUNCATED AT 250 WORDS)

A simple digital filter to remove line-frequency noise in implantable pulse generators.

This study investigated computer simulations and animal studies of a simple digital notch filter to remove 50-and 60-Hz line-frequency-noise interference. The digital notch filter was achieved by computing running subtraction of the intracardiac electrogram and the electrogram recorded one notch-sample period previously. Simultaneous rejection of the two worldwide line frequencies was obtained by computation of the minimum of two separate notch-filter outputs. Power consumption of this numerical algorithm was reduced for applications in implantable devices by operating the notch filters only from 20 msec to 50 msec after a sense event. A sense event was classified as a noise sense if the sum of notch-filter output during this window was less than a preset threshold of the sum of the raw data during the same time window. Otherwise, the sense event was classified as a true sense. The computer simulations determined an optimum threshold value of 33%. The filter was tested in five animal studies using a signal generator to inject additive noise interference. The results indicated that this simple filter could be implemented in an implantable pulse generator and could effectively exclude incorrect line-frequency-noise senses at the notched frequencies.

Separation of ventricular tachycardia from sinus rhythm using a practical, real-time template matching computer system.

Template matching morphology analysis of the intraventricular electrogram (IVEG) has been proposed for inclusion in implantable cardioverter defibrillators (ICDs) to reduce the number of false ventricular tachyarrhythmia detections caused by rate overlap between ventricular tachycardia (VT) and sinus tachycardia and/or supraventricular tachycardia. Template matching techniques have been developed that reduce the computational complexity while preserving the perceived important aspects of electrogram amplitude and baseline independence found in such computationally unsolved methods as correlation waveform analysis (CWA). These methods have been shown to work as well as CWA for separation of VT, however, they have not been proven in real-time on a system that incorporates many of the constraints of present day ICDs. The present study was undertaken with two purposes: (1) to determine if real-time IVEG template matching analysis on an ICD sensing emulator was accurate in separating VT from sinus rhythm (SR) electrograms; and (2) to compare amplitude normalized area of difference (NAD) with signature analysis (SIG), a new, computationally less expensive technique that normalizes for amplitude variation within the expected physiological level of variability. In this study, IVEGs, obtained from 16 patients who underwent electrophysiological study (EPS) for evaluation of sustained ventricular arrhythmia, were digitized to 250 Hz with 6-bit quantization after filtering (16-44 Hz) and differentiation. After an SR template was selected and periodically updated, it was compared to subsequent IVEGs using NAD and SIG. In general, SIG calculates the fraction of samples occurring outside template window boundaries. Eleven-beat running medians from beat-by-beat NAD and SIG results were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Template matching techniques for electrophysiologic signals: a practical, real-time system for detection of ventricular tachycardia.

Time domain template matching morphology techniques have been proposed for inclusion in implantable cardioverter defibrillators (ICDs) for the detection of ventricular arrhythmias from intraventricular electrograms (IVEGs). However, ICDs have limited battery capacity which necessitate the use of low current drain algorithms. Although more computationally efficient template matching algorithms have been developed, none have incorporated the limitations inherent in current ICDs. An external ICD sensing prototype system was developed which filters, digitizes, and analyzes IVEGs during electrophysiology studies. Two template matching IVEG metrics, amplitude normalized area of difference and signature analysis, are calculated. These metrics are being tested clinically for their accuracy in differentiating ventricular tachycardia and sinus rhythm IVEGs.

Effects of stress and beta 1 blockade on the ventricular depolarization gradient of the rate modulating pacemaker.

Prism-CLR is a closed loop, rate modulating pacemaker that uses ventricular depolarization gradient (Gd) to continuously adjust heart rate. Heart rate response to a formal mental stress protocol, esmolol (500 mcg/kg bolus, 75-125 mcg/kg/min infusion), and mental stress during esmolol infusion were studied in six patients to investigate if Gd and paced heart rate response are under direct beta-adrenergic control. Paced heart rates increased in response to mental stress in a physiological manner (P less than 0.001). Response to esmolol infusion was paradoxical, with increased paced heart rates during esmolol bolus and infusion (P less than 0.05). There was no significant alteration in either systolic or diastolic blood pressure during mental stress or esmolol infusion (P greater than 0.05). Paradoxical increase in paced heart rates during esmolol administration suggests a primary or secondary effect of esmolol to decrease the ventricular depolarization gradient. This hypothesis was supported in four dog studies in which direct Gd measurements were made during esmolol infusion. Mental stress during esmolol infusion resulted in significantly increased paced heart rates (esmolol effect) with blunted changes in heart rate in response to the mental stress. The results of this study suggest that the physiological rate response during mental stress is attributable to sympathetic autonomic response.

Modulation of collision-induced changes in canine heart repolarization by cycle length.

The possibility that cycle length modulates the electronic effect of activation sequence on repolarization was investigated in experiments using isolated canine cardiac Purkinje strands, in situ canine ventricular myocardium, and computer simulations. Action potential durations and refractory periods during one-way propagation were compared to those obtained during action potential collision. In both the computer simulations and the Purkinje strand experiments, collision decreased action potential duration more at long cycle lengths than at short cycle lengths. Comparably, collision of activation fronts in ventricular myocardium was associated with greater reductions in refractory period during pacing at long cycle lengths than at short cycle lengths. Theoretic considerations indicate that the magnitude of electrotonic effects of activation sequence on repolarization are directly related to action potential height and the square root of membrane resistance during repolarization and are inversely related to conduction velocity. In computer simulations and Purkinje strand experiments, changes in conduction velocity and action potential height elicited by decreasing cycle length could not fully account for the cycle length dependence of collision-induced changes in repolarization. Time-varying membrane resistance of a single cell was calculated in the simulations by briefly hyperpolarizing the membrane and determining the change in total ionic current. Membrane resistance during repolarization was less at short cycle lengths than at long cycle lengths. The results suggest the cycle length dependence of collision-induced changes in repolarization results largely from the effect of cycle length on membrane resistance during action potential repolarization, with changes in action potential height and conduction velocity playing a lesser role.

Detection of ventricular tachycardia using scanning correlation analysis.

Cross correlation is an accurate method for distinguishing normal sinus rhythm (NSR) from ventricular arrhythmias. The computational demands of the method, however, have prohibited development of an implantable device using correlation. In this study, temporal data compression prior to correlation analysis was used to reduce the total number of computations. Unipolar and bipolar intracardiac electrograms of NSR and 23 episodes of ventricular tachycardia (VT) from 23 patients were obtained from a right ventricular apex electrode catheter during routine electrophysiology studies. The data were filtered (1-11 Hz), digitized (250 samples/sec) and temporally compressed to 50 samples/sec. Data compression removed four out of every five samples by only saving the sample with the maximum excursion from the last saved sample. The average squared correlation coefficient (r2) was computed for the NSR and VT episodes using each patient's NSR waveform as a template. In all 23 patients, the r2 values showed large separation between NSR versus VT in both unipolar (0.93 +/- 0.05 vs 0.20 +/- 0.16, P less than 0.005) and bipolar (0.91 +/- 0.07 vs 0.17 +/- 0.11, P less than 0.005) electrode configurations using template lengths of 80% the intrinsic interval (avg +/- SD). Narrow templates (40% intrinsic interval or less) often resulted in multiple r2 peaks during each heart cycle and degraded the r2 separation (n = 10, P less than 0.005). High pass filtering at 3 Hz also degraded the r2 separation (n = 10, P less than 0.05). Standard noncompressed correlations indicated that data compression had negligible effects on the results. Thus, a computationally efficient cross correlation method was found to be a reliable detector of VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Directional differences in excitability and margin of safety for propagation in sheep ventricular epicardial muscle.

Computer simulations and isolated tissue experiments were used to characterize the relation between excitability and margin of safety for propagation in anisotropic ventricular myocardium. Longitudinal, uniform transverse, and nonuniform transverse tissue directions were modeled in a one-dimensional Beeler-Reuter based cable. Stimulation threshold was smallest in the nonuniform transverse direction. The safety factor for propagation was determined in the model as the total axial charge that was available for depolarizing downstream tissue divided by the threshold charge that was just sufficient for continued propagation and was largest in the longitudinal direction. The strength-interval plot for the junction between simulated longitudinal and nonuniform transverse directions identified a range of stimulus strengths and intervals that resulted in nonuniform transverse but not longitudinal propagation. When high values of transverse resistance were used, higher stimulus strengths during premature stimulation resulted in longitudinal but not nonuniform transverse propagation. The experimental strength interval plots from 17 L-shaped preparations of isolated sheep epicardial muscles had similar characteristics. In nine additional L-shaped tissue experiments, changing extracellular K+ concentrations from 4 to 20 mM resulted in progressive membrane depolarization and conduction impairment in both directions. However, in eight of nine experiments, complete block occurred first in the transverse direction. In one experiment, block was simultaneous in both directions. We conclude that, under normal conditions, threshold requirements for active propagation are lower for transverse than for longitudinal propagation. In addition, when active membrane properties are impaired, the safety factor for propagation is larger in the direction along the longitudinal axis of the cells.

Estimating cardiac transmembrane activation and recovery times from unipolar and bipolar extracellular electrograms: a simulation study.

A model of one-dimensional action potential propagation was used to compare activation times and recovery times measured from simulated unipolar and bipolar electrograms with the activation and recovery times measured from simulated transmembrane action potentials. Theory predicts that the intrinsic deflection--the time of the maximum negative slope of the unipolar electrogram QRS complex--corresponds to the time of maximum positive slope of action potential depolarization. Similarly, the time of the maximum positive slope of the unipolar electrogram T wave corresponds to the time of maximum negative slope of action potential repolarization. This study showed that the difference between the unipolar electrogram activation time and the action potential activation time and the difference between the unipolar electrogram recovery time and the action potential recovery time were small during ideal conditions of uniform propagation in a long cable. Nonideal conditions, however, were associated with activation time differences in excess of 1.8 msec and recovery time differences in excess of 30 msec (243 msec in certain conditions). Nonideal conditions that had a major influence were changes in activation sequence, propagation in a short cable, and propagation through regions of nonuniform coupling resistance and/or nonuniform membrane properties. Nonideal conditions that had a smaller influence were variations in distance from the measurement site to the simulated tissue surface, nonzero reference potentials, and the addition of distant events. Recovery time differences were more sensitive to the nonideal conditions than were activation time differences, and both depended on the action potential shape. When distant events significantly contributed to the unipolar electrogram waveform, the time differences when bipolar electrograms were used were less than those when unipolar electrograms were used; however, under other conditions, the time differences were comparable. Results showed that activation times and especially recovery times measured from electrograms can be greatly affected by conditions independent of changes in the underlying action potential waveforms.

Nonuniform epicardial activation and repolarization properties of in vivo canine pulmonary conus.

The relation between nonuniform epicardial activation and ventricular repolarization properties was studied in 14 pentobarbital anesthetized dogs and with a computer model. In 11 dogs, isochrone maps of epicardial activation sequence were constructed from electrograms recorded from the pulmonary conus with 64 electrodes on an 8 X 8 grid with 2-mm electrode separation. The heart was paced from multiple sites on the periphery of the array. Uniformity of epicardial activation was estimated from activation times at test sites and their eight neighboring sites. Acceleration shortened and deceleration prolonged refractory periods. The locations of acceleration and deceleration sites of activation differed during drives from various sites, and differences in uniformity of activation during pairs of drives were correlated to differences in refractory periods (r = 0.76, range 0.59-0.93). In three additional experiments, transmural activation sequence maps were constructed from electrograms recorded from needle-mounted electrodes placed upstream and downstream to epicardial activation delays. Activation proceeded from epicardium to endocardium upstream to the delays and from endocardium to epicardium downstream to the delays. A computer simulation of two-dimensional action potential propagation based on the Beeler-Reuter myocardial membrane model provided insights to the mechanism for the results of the animal experiments. The two-dimensional sheet modeled the transmural anisotropic histology of the canine pulmonary conus and corresponded to previous reports and histology of specimens from five experiments. Simulated activation patterns were similar to those found in the experimental animals. In addition, action potentials were electronically prolonged at sites of deceleration and shortened at sites of acceleration, results comparable to the animal experiments. Our findings demonstrate that the location of areas of nonuniform epicardial activation is dependent on drive site and that nonuniform activation electronically modulates repolarization properties. Therefore it seems likely that the site of origin of ectopic ventricular complexes, especially in ischemic myocardium where activation is nonuniform, could be an important determinant of whether ectopic activity initiates sustained tachyarrhythmias.

Effects of activation sequence on ventricular refractory periods of ischemic canine myocardium.

Refractory periods were measured in pentobarbital-anesthetized dogs during control periods and one to one and a half hours after distal left anterior descending coronary artery occlusion. The refractory period test site was on the anterior surface of the left ventricle in the distribution of the artery to be occluded. Measurements were made during drive of the refractory period test site, drive of a distant site on the pulmonary conus and during fusion drive in which drive of the test site was delayed with respect to drive of the pulmonary conus. Refractory periods were longer during test site drive than during pulmonary conus or fusion drives in both the control periods and following coronary occlusion. However, the effects of driving mode on refractory periods were greater following coronary occlusion than in the control periods. The findings are likely secondary to different magnitudes of change in electrotonic interactions associated with changes in activation sequence in ischemic and nonischemic myocardium. The greater dependence of repolarization properties in ischemic than nonischemic tissue suggests that inhomogeneity of these properties could be modified considerably by the site of origin of ectopic ventricular complexes.