Improved Rate Responsive Algorithm in QT Driven Pacemakers—Evaluation of Initial Response to Exercise

The QT pacemaker is a rate modulated pacemaker that uses the evoked QT interval as an indicator to determine its optimal pacing rate. Despite the generally favorable clinical results with this form of pacing, some flaws in the system have been reported, such as the frequently observed rather slow initial response of the pacing rate to physical exercise, and the phenomenon of oscillation of the heart rate. These problems can be attributed to the rate adaptive algorithm used in the current QT pacemaker. Recently, in a reexamination of the relationship between evoked QT interval and pacing rate, a curvilinear relationship between these parameters has been demonstrated. As a result, a new algorithm has been developed for the next generation of the QT pacemaker. Before this new algorithm was implemented in new implantable devices, it was evaluated in a multicenter clinical investigation, with emphasis on the initial response of the pacing rate to exercise. This study was carried out by means of special software in the programmer of the QT pacemaker. By employing real-time bidirectional telemetry, it was possible to submit the study population, consisting of 37 patients with implanted QT pacemakers of the current generation, to identical exercise tests. Comparing these exercise tests, it appears that a considerable gain in speed of response to exercise can be achieved by using the same sensor with a faster reacting, nonlinear rate adaptive algorithm.     

Reliability of the Evoked Response in Determining the Paced Ventricular Rate and Performance of the QT or Rate Responsive (TX) Pacemaker

The TX pacemaker uses a conventional transvenous electrode to sense T-waves of paced ventricular complexes and it adapts the pacing rate to varying physiological demands by responding to changes in the QT or, more correctly, the stimulus artifact-to-T-wave (stimulus-T) interval. This pacing system was assessed in 13 patients. The relation between heart rate and stimulus-T interval and the effect of programming on the performance of this pacemaker were studied on several occasions in each patient. Treadmill exercise performance during TX pacing mode was compared with atrial synchronized ventricular (VAT) and asynchronous ventricular demand (VOO and VVI--70 beats per minute) pacing modes. T-wave sensing problems arose in three patients. In one, this was overcome by reducing the pulse amplitude from 5.0 to 2.5 V. In another patient, spontaneous recovery of T-wave sensing occurred 5 months after pacemaker implantation. T-wave sensing deteriorated with the passage of time in most patients. Satisfactory rate response as assessed by treadmill exercise testing and Holter monitoring was achieved in 12 patients through adjustments of two programmable parameters: the slope that defines the alteration in heart rate in response to a millisecond change in stimulus-T interval and the "sensing window" that is the interval during which T-waves can be sensed and a rate response is possible. Exercise performance was significantly better during rate responsive pacing (TX) mode as compared with VVI pacing but was comparable to that during VAT pacing. The resting heart rate/stimulus-T interval can be described by the following linear regression equation: stimulus-T interval = 466 - 1.68 X paced-rate, r2 = -0.62. This relation, however, was subject to wide inter- and intra-patient variation. Consequently, given identical programmed parameters and exercise protocol, the chronotropic response differed significantly from patient to patient and in the same patient from one occasion to another. Our results show that a physiologically beneficial chronotropic response can be achieved in most patients. However, reprogramming, based on results of exercise tests and Holter monitoring, may be necessary to adjust for changes in T-wave sensing and the heart rate/stimulus-T interval relation and, thus to ensure that the pacemaker continues to function optimally.     

Rate responsive pacing using the evoked QT principle. A physiological alternative to atrial synchronous pacemakers

We have evaluated clinically a rate-responsive pacemaker which uses the evoked QT principle as indicator of physiological demand. This pacemaker is microprocessor-based and fully programmable noninvasively through radiofrequency coupling to an external microcomputer. To date this system has been implanted in 15 patients. With this QT sensing pacemaker the rate response to exercise was smooth and progressive, and gradually returned to the basic paced rate after termination of activity. Physiologic rate responsive pacing resulted in significant improvement in exercise tolerance and a 40% increase in cardiac output when compared to fixed-rate pacing in 8 patients. This initial experience confirms the possibility of obtaining a physiological response to exercise using a pacing system dependent only on a unipolar electrode which is independent of the problems of atrial activity and sensing. Rate responsive pacing might prove to be a useful alternative to atrial synchronous systems, and particularly advantageous in those patients whose sinoatrial function is abnormal or who suffer from atrial arrhythmias.     

Temporal Relationship Between Exercise and QT Shortening in Patients with QT Pacemakers

The present study was undertaken to examine the temporal relationship between exercise and QT interval shortening as one of the principal determinants for the functioning of QT pacemakers. Ten patients (mean age of 72.6 years) with implanted QT pacemakers were subjected to supine bicycle exercise with two different slopes, 90% and 80%. The QT interval as seen by the pacemaker was monitored by telemetry and stored on magnetic tape. After the beginning of exercise QT prolongation of a few msec occurred up to 40 sec in most patients. The earliest QT shortening of 4 msec was noted after 63.4 sec with 90% slope and 75.7 sec with 80% slope. The difference was not significant. The further time course was dependent on slope and pacemaker algorithm. Maximal QT shortening was 65.9 msec with 90% and 69.8 msec with 80% slope. It was seen 29.2 sec after termination of exercise with 90% slope and 69.5 sec with 80% slope (P < 0.05). There was no correlation of the measured delays with age. Earliest rate response in QT driven pacemakers is determined by earliest QT shortening on one hand and by the slope setting of the pacemaker on the other, where the limiting parameter appears to be QT shortening, which occurs after the first minute of exercise.     

Rate Responsive Pacing Using the Evoked QT Principle. A Physiological Alternative to Atrial Synchronous Pacemakers

We have evaluated clinically a rate-responsive pacemaker which uses the evoked QT principle as indicator of physiological demand. This pacemaker is microprocessor-based and fully programmable noninvasively through radiofrequency coupling to an external microcomputer. To date this system has been implanted in 15 patients. With this QTsensing pacemaker the ra te response to exercise was smooth and progressive, and gradually returned to the basic paced rate after termination of activity. Physiologic rate responsive pacing resulted in significant improvement in exercise tolerance and a 40% increase in cardiac output when compared to fixedrate pacing in 8 patients. This initial experience confirms the possibility of obtaining a physiological response to exercise using a pacing system dependent only on a unipolar electrode which is independent of the problems of atrial activity and sensing. Rate responsive pacing might prove to be a useful alternative to atrial synchronous systems, and particularly advantageous in those patients whose sinoatrial function is abnormal or who suffer from atrial arrhythmias.     

Improved Pattern of Rate Responsiveness with Dynamic Slope Setting for the QT Sensing Pacemaker

We have recently described the electrophysiological basis of a new algorithm for the QT (TX) sensing rate responsive pacemaker. By using the new software program running on the standard programmer it has been possible to simulate the new algorithm in ten patients with complete heart block (seven patients had implanted TX units and three were paced with an external TX pacemaker) during routine exercise testing. In this way a single-blind, intra-patient comparison of the pattern of pacing rate change using both the existing and new algorithms was possible. In nine out of the ten cases the time taken to increase the pacing rate from 70 to 80 bpm was reduced significantly when the new algorithm was used (P = 0.037). Additionally, the correlation between the atrial and ventricular rates in those patients with normal sinus node function (seven patients) was determined. In all cases we have observed a significantly improved correlation between the atrial and ventricular paced rates during exercise with the new algorithm (P less than 0.001).     

Initial Experience with a New Single Chamber, Dual Sensor Rate Responsive Pacemaker

In August 1991, a new single chamber pacemaker became available that utilizes information from two sensors, activity and stimulus-to-T wave (QT) interval. We are reporting on the first 90 implants in 21 centers. T wave sensing was adequate at implantation in 88/90 patients, with a safety margin of > 100% in 86/90, Activity sensing was adequate in all patients. The contribution of each sensor fsensor blending) is programmable for each patient. Of 75 patients assessed at 1 month after implant, three have been programmed to "Activity-Only" mode, and 72 to dual sensor mode. Of these, 18 have been programmed to "QT < Activity," 48 to "QT = Activity," and 6 to "QT > Activity." Forty-five patients underwent exercise testing in dual sensor mode and a subgroup of 15 also underwent exercise testing in Activity-Only mode. The dual sensor mode produced a more gradual increase in pacing rate. Sensor Cross Checking^tmsatisfactorily prevented a sustained high pacing rate in tests of false-positive activity sensing (tapping, vibrating pacemaker, or static pressure). The maximum pacing rate on walking downstairs (94.2 ± 7.2 ppm) was similar to that produced by walking upstairs (91.6 ± 5.9 ppm). We conclude that initial assessment of this dual sensor, single chamber, rate responsive pacemaker confirms that the algorithm for combining data from two sensors functions satisfactorily. Dual sensor rate responsive pacing may offer significant advantages over single sensor devices, and further studies of this novel device are indicated.     

Clinical Observations with a Dual Sensor Rate Adaptive Single Chamber Pacemaker

The Topaz model 515 (Vitatron B.V.) is a dual sensor rate responsive pacemaker for single chamber stimulation. It can be driven by activity counts (ACT) and QT interval measurements. Inappropriate rate modulation due to one sensor can be corrected by "sensor cross-checking." It was implanted in ten patients (20-86 years) of whom seven had complete heart block and atrial arrhythmias. After implantation T-wave amplitude ranged from 0.9mV-3.5 mV. T-wave sensing ranged from 88%–99% in 9/10 patients at the follow-up of 3 weeks. Eight patients remained in default setting of the activity threshold, after evaluation with a short walking test. An exercise test was performed on all patients. In one test, QT sensing was marginal because of lead implantation in the right ventricular outflow tract. Therefore, this pacing rate was only modulated by ACT sensing. All others were tested with equal contribution of information from both sensors (ACT = QT). In 7/9, rate response was satisfactory. When the treadmill was repeated with ACT in five of these seven patients, rate generally accelerated too fast. In one patient the setting was adjusted to "QT > ACT," because of inappropriate acceleration due to activity sensing, in another it was adjusted to "QT < ACT" because of delayed response to activity. The pacing rate and the ACT during treadmill tests in "QT = ACT" mode were more closely correlated in the first 3 minutes, compared with the last 3 minutes. We feel that rate modulation with this new pacemaker is adequate. Sensor blending and sensor cross-checking are of clinical importance.     

Usefulness of 1-Hour and 24-Hour Heart Rate Holter Inbuilt in New TX* Rate Adaptive Pacemakers

SERMASI S., ET AL.: Usefulness of 1-Hour and 24-Hour Heart Rate Holter Inbuilt in New TX* Rate Adaptive Pacemakers. The rate adaptive TX* pacemaker uses the evoked QT interval as an indicator of physiological demand. In order to obtain a rate adaptation close to physiological patterns we used in the past, in each patient, on the slope value and/or the T wave sensing window, controlling via exercise stress testing and Holter the results achieved. It was an expensive method, but the system produced effective rate responsive pacing. The new series of TX* pacemakers (Quintech 919 and Rhythmyx), beside the dynamic slope feature, are equipped with a 1-hour heart rate Holter (HRH) that can be used during effort without the need for manually recording the heart rate. In this mode TX* pacemakers calculate the average heart rate over 20-second periods and stores the values continuously for 1 hour. In addition, a 24-hour HRH is available, which calculates the average heart rate over 7.5-minute periods, showing heart rate trend during the last day prior to interrogation. Each HRH can be accessed by the programmer and printed out. Using four Quintech 919* and five Rhythmyx units, the inbuilt HRH proved its utility by making the heart rate adaptation checking procedure easier, faster, and more economic.     

Initial Clinical Experience with a Rate Responsive Pacemaker

Prism-CLR is a new single chamber unipolar pace, bipolar or unipolar sense, rate responsive pacemaker that utilizes a closed-loop system based on the analysis of the evoked potential for rate adjustment. It also has an automatic output regulation feature for capture verification and threshold search. Five patients in whom this pacemaker was implanted exhibited an appropriate rate increase with exercise and psychological stress. Automatic output regulation functioned appropriately in three of five patients. Preliminary data suggest that Prism-ClR is an effective pacemaker for patients who may benefit from rate responsive pacing. The automatic output regulation recognition algorithm may need modification in some patients.     

Rate Responsive Pacing Using a Minute Ventilation Sensor

Minute ventilation, the product of respiratory rate and tidal volume, correlates directly with oxygen consumption, cardiac output, and heart rate. An implantable pacemaker has been developed which allows variation in pacing rate in response to measured changes in minute ventilation. This single chamber system measures transthoracic impedance between the tip electrode of a standard bipolar lead and the pulse generator case. Low amplitude current pulses (1 mA for 15 μsec) are generated each 50 msec between the ring electrode and the case. In the adaptive mode, the pulse generator calculates a rate response factor or slope after maximal exercise. This slope, which describes the relationship between pacing rate and minute ventilation together with the pacing rate limits are the only programmable rate responsive features. Minute ventilation rate responsive systems have been implanted in 12 patients (8/emales, 4 males), of mean age 63 years. Indications were His bundle ablation (6), acquired complete heart block (4), and sick sinus syndrome (2). At post-implant exercise testing, pacing rate rose within the first minute. Peak rate and time to upper rate were dependent on workload. After exercise, pacing rate remained at peak for up to 2 minutes before a gradual fall to resting rate. Comparative studies of the minute ventilation and the activity sensor pacing systems in the same patients confirmed that the minute ventilation system more closely parallels normal sinus response to activity. The minute ventilation rate responsive pacing system is simple to programme, no special lead is required and the system is highly physiologic.     

Beat-To-Beat Behavior of QT Interval During Conducted Supraventricular Rhythm in the Normal Heart

To assess beat-to-beat behavior of QT interval under different conditions, high resolution recordings and computerized beat-to-beat analysis of the electrocardiogram were performed at rest, during recovery after short exercise, and during atrial pacing. Beat-to-beat variations of QT interval during sinus rhythm at rest and after short exercise were measured in ten healthy men. In an additional three patients with supraventricular tachycardia, beat-to-beat QT changes were studied after abrupt sustained acceleration and deceleration of heart rate by atrial pacing. Beat-to-beat changes in RH interval at rest are followed by minimal changes of the QT interval. The measured proportional change of the QT interval compared with the change in HR interval (Δ QT/A BR) was 0.02. This value represents 10% of the value expected for QT changes from Bazett's formula. Following short exercise QT interval did not change for 15 seconds and reached a maximal value 30 seconds later as compared to the RR interval (192 vs 115 sees, P < 0.001). The steady state of the QT interval during sustained atrial pacing was achieved after 132, 135, and 133 seconds for pacing intervals of 600, 500, and 600 msec, respectively. Our data indicate a relatively slow adaptation of the QT interval to changes in heart rate.     

Initial Clinical Experience with Rate Adaptive Cardiac Pacing Using Two Sensors Simultaneously

LANDMAN, M.A.J., ET AL.: Initial Clinical Experience with Rate Adaptive Cardiac Pacing Using Two Sensors Simultaneously. In the rate adaptive pacemakers, all presently available sensors show one or more drawbacks. Combining two sensors in a single pacemaker, we tried to optimize its rate responsive characteristics. In this study, we present the rate adaptive behavior of a two sensor pacemaker system, using both QT interval and activity sensing. In addition, we compared the rate response with that of each sensor alone. Nine patients with an implanted QT interval sensing pacemaker, and an externally attached activity sensing pacemaker performed three exercise stress tests on treadmill. The QT interval, measured by the implanted pacemaker, and the activity level, were transmitted to an external computer. This computer contained the two sensor rate adaptive algorithm, and reprogrammed the implanted pacemaker on beat-to-beat basis. Conclusion: In the two sensor mode the rate increases immediately at the onset of exercise, caused by the prompt response of the activity sensor. Further rate increase is driven by the QT interval sensor and therefore proportional to the level of exercise. Furthermore, the rate decay during the recovery phase is more physiological.     

Changes in QT and Q-aT Intervals Induced by Mental and Physical Stress with Fixed Rate and Atrial Triggered Ventricular Inhibited Cardiac Pacing

We have investigated the influence of mental stress and physical stress, i.e., exercise, on the QT and Q-aT intervals (measured from the pacemaker stimulus to the end or the apex, respectively, of the T wave). The study was made on ten patients with high degree atrioventricular block treated with AV universal (DDD) pacemakers. These were programmed to a fixed rate ventricular (VVI) or an atrial triggered (VDD) function for different parts of the study. An arithmetic mental stress test and a bicycle exercise test were performed with each mode of pacing. In the VVI pacing mode, the atrial rate increased by 11% during mental stress and by 46% during exercise. There was a significant shortening of QT and Q-aT intervals with both types of stress. With VDD pacing, mental stress induced a 12% increase in rate and a significant shortening of QT and Q-aT. The paced rate increased by 50% during the exercise test. This increase in ventricular rate was associated with the most marked changes in QT and Q-aT intervals. Thus, both types of stress cause a significant shortening of the QT and Q-aT interval even in the absence of a simultaneous increase in ventricular rate. When the latter is allowed to increase during VDD pacing, both intervals shorten considerably more. There was a marked inter-individual variability in the response to both types of stress. These findings are of importance with regard to the QT sensing rate responsive pacemaker which can be expected to respond to mental stress in most patients, but that response might be unpredictable in the individual.     

A Randomized Double-Blind, Cross-Over Study of the Linear and Nonlinear Algorithms for the QT Sensing Rate Adaptive Pacemaker

BAIG, M.W., ET AL.: A Randomized Double-Blind, Cross-Over Study of the Linear and Nonlinear Algorithms for the QT Sensing Rate Adaptive Pacemaker. We have compared the pacing rate responses during cardiopulmonary exercise testing in 11 patients (mean 59 years, six female) with implanted QT sensing rate adaptive pacemakers who were randomly programmed to 1-month periods in the linear and nonlinear algorithms using a double-blind, cross-over design. Exercise testing was performed at the end of each month block and symptoms were scored with the MacMaster questionnaire. With exercise, the time to a 10 beats/min increment in rate was significantly less with the nonlinear compared to the linear algorithm (126 sec vs 255 sec, P = 0.02) but there were no significant differences in exercise duration, the peak pacing rate, the peak VO₂, the VO₂ at the anaerobic threshold or the mean correlation coefficients of the pacing rate VO₂ relationship. Rate oscillation occurred in seven patients in the linear algorithm and in two patients in the nonlinear setting. Initial deceleration of the pacing rate at the onset of exercise occurred in seven patients in the linear algorithm and in four patients in the nonlinear setting. The nonlinear algorithm is associated with a faster response time during exercise and fewer instances of rate instability. However, it has not overcome the problem of a dip in the pacing rate at the beginning of exercise. The major difference in the function of the two algorithms is faster initial acceleration with the nonlinear algorithm. This is explained by the significantly higher values of the slope setting at the lower rate limit for the nonlinear versus the linear algorithm (6.3 ms/ms vs 5.1 ms/ms).     

The Ventricular Paced QT Interval—The Effects of Rate and Exercise

Changes in the QT and QTc intervals in 19 patients were studied at a ventricular paced rate difference of 50 beats/min. In all patients the measured QT interval shortened as the pacing rate was increased, from a mean value of 441 ms to 380 ms (p < 0.001), but when correct ed for heart rate the QTc- lengthened from a mean value of 518 ms to 575 ms. In 11 patients the QT in terval was measured at rest and immediately following exercise sufficient to increase the atrial rate by approximately 50 beats/min at identical ventricular paced rates. In all patients exercise-induced QT interval shortening from a mean value of 433 ms to 399 ms (p < 0.001). These results show first that Bazett's formula is unsuitable for correction of QT interval changes induced by ventricular pacing, and second that heart rate and changes in sympathetic tone independently influence the duration of the QT interval. It is suggested that these resuits are relevant to the design of physiological pacemakers in which the duration of the QT interval influences the discharge frequency of the pacemaker and to the consideration of ventricular pacing for the treatment of abnormal repolarization syndromes. (PACE, Vol. 5, May-June, 1982)     

Myopotential Interference in Unipolar Rate Responsive Pacemakers

The effects of myopotential interference on unipolar rate responsive pacemakers were assessed in 22 patients. Six types of pacemakers (from four manufacturers) were studied: five TX2 (QT sensing), seven Biorate (five RDP3 and two MB-1, respiratory rate sensing), seven Activitrax (activity sensing), two Medtronic 2503 (dP/dt sensing), and one Sensolog P703 (activity sensing). Provocative tests using arm exercises were performed in both VVI and rate responsive modes. At nominal sensitivity settings (1.8-2.5 mV), 55% of these patients were myopotential positive for at least 1 provocative test. Pressing the palms together was found to be the most sensitive provocative test. Rate response was achieved with treadmill exercise (all patients), hyperventilation (RDP3 and MB-1) and tapping (Activitrax) or wobbling the pacemaker in its pocket (Sensolog). During continued rate acceleration, myopotential interference was induced by arm exercises. The duration of inhibition was shorter when the provocative tests were performed during rate response compared to that occurred at rest. Short periods of myopotential interference resulted in temporary inhibition of pacing but rate response continued immediately on removal of the interference. In one patient with a RDP3 pacemaker, a prolonged episode of myopotential interference during treadmill exercise resulted in reversion of the pacemaker to the interference mode. Appropriate adjustment of the sensitivity setting effectively controlled the symptoms in most patients. However, one patient with a QT sensing pacemaker and symptomatic myopotential interference required programming to the VVT pacing mode. Two out of five patients with RDP3 required pacemaker replacement because of uncontrolled myopotential interference.(ABSTRACT TRUNCATED AT 250 WORDS)     

Behavior of a Respiratory Driven Pacemaker and Direct Respiratory Measurements

In 10 patients with a mean age of 76 +/- 8 years, a rate responsive pacemaker (Meta-MV, Telectronics) was implanted in the left pectoral site. An exercise test was performed in SSI ("adaptive") mode, allowing the device to measure the changes in thoracic impedance. The "slope number" at maximal exercise was chosen to program the pacemaker for a second exercise test in rate responsive mode. Direct measurements of respiratory rate and minute volume were correlated with the pacing rate. After 1 minute of exercise, pacing rate increased by 6% and it decreased smoothly after maximal exercise. The programmed maximal rate was reached at the maximum exercise level in six patients. During 24-hour Holter recording, the mean maximal pacing rate was 103 +/- 18 beats/min. For individual patients, a good correlation of pacing rate with respiratory rate (r = 0.757), oxygen consumption (r = 0.731), and minute volume (r = 0.800) was observed. The data from the entire group showed a highly significant correlation of changes in pacing rate and in respiratory parameters for different levels of exercise and recovery. In a subgroup of five patients, the slope numbers at maximal exercise were reproducible after 10 months. It was concluded that minute volume and its changes were recognized in a reliable way by the Meta-MV pacemaker.     

Cardiac Output Is a Sensitive Indicator of Difference in Exercise Performance Between Single and Dual Sensor Pacemakers

Although multisensor pacing may compensate the inadequacy of rate adaptation in a single sensor system, the clinical role of multisensor driven rate adaptive pacing remains unclear. We compared the performance between single sensor and dual sensor driven pacemakers using exercise cardiac output (CO) as a marker of cardiac performance. Eight patients with a mean age of 63 ± 3 years implanted with a dual sensor pacemaker driven by combined activity (ACT) and QT interval sensors were studied in the ACT-, QT- only and the dual QT+ACT-VVIR modes. Patients performed submaximal and maximal exercise tests with CO assessed by carbon dioxide rebreathing method. Comparing the HR response based on the change in metabolic workload, the ACT- VVIR “overpaced,” the QT'VVIR “underpaced,” and the QT+ACT-VVlR achieved the best approximation to normal. The percentages of CO increase in ACT-WIR and QT+ACT-VVIR modes over resting CO were higher at 1 minute of exercise (295 ± 85% and 165 ± 49%, respectively) compared to the QT-VVIR mode (81 ± 40%, P ≤ 0.05). During exercise, stroke volume cbanges from baseline were similar between ACT-VVIR and QT + ACT-VVIR modes, but a compensatory increase in stroke volume occurred in the QT-VVIR mode during submaximal exercise (50 ± 11 mL vs 24 ± 17 mL in the QT+ACT-VVlR and 14 ± 4 in ACT-VVIR, P ≤ 0.003). There was no difference in the maximal exercise workload, exercise duration and CO at the submaximal and maximal exercise between the 3 sensor modes. Thus, exercise capacity is a poor indicator of sensor performance while CO measurement is a sensitive indicator of sensor mode differences especially at low workload exercise. The ACT- VVIR gave the fastest increase in CO at start of exercise at the expanse of overpacing, whereas the “under-paced” QT-VVIR compensated for the slower rate increase by utilizing contractility reserve during submaximal exercise. Dual sensor pacing, by achieving the best heart rate to workload relationship, provided a CO response without overpacing or using contractility reserve during exercise.     

Influence of Propranolol on the Ventricular Depolarization Gradient

Sensing of the ventricular depolarization gradient (VDG) has recently been used as The basis of a closed-loop rate responsive pacemaker. Factors influencing this aspect of the evoked response have not been fully evaluated although previous reports have suggested that sympathetic stimulation and circulating catecholamines are primarily responsible for the observed changes during stress and exercise. In five patients (Table I), four males and one female (mean age 60.4 ± 20.1 years) implanted with the Prism pacemaker, the pacing response to exercise and tilting was assessed before and after the infusion of propranolol. There was an increase in the pacing rate in all patients during the infusion of the drug (mean 27 ± 12.9 beats/min) suggestive of a direct drug effect on the VDG. The rate control parameter (RCP) of the pacemaker, the numerical equivalent of the VDG, was significantly different after the administration of propranolol (P < 0.01). However, exercise performance and pacing rate behavior were not different after beta blockade. The pacing rate increase observed when tilting patients to the supine position was not altered by propranolol. Out date suggest that factors other than adrenergic stimulation may be of importance in affecting the ventricular evoked response and accordingly the rate adaptation of the Prism pacemaker.