Pacemaker
F. DORTICÓS1, M.A. QUIÑONES1, F. TORNES1, Y. FAYAD1, R. ZAYAS1, J. CASTRO1, A. BARBETTA2, F. DIGREGORIO2
Introduction
Self-adaptation of the main pacing parameters to changing conditions in daily life is a major challenge in pacemaker technology, which started with the development of devices designed to regulate the stimulation rate accord- ing to the patient’s metabolic needs. A variety of rate-responsive sensors have been applied to this purpose [1]. The most widely used system relies on the detection of body movement by means of an accelerometer mounted in the pacemaker circuit, which is known to ensure high sensitivity and quick rate adaptation to the walking speed. However, the accelerometric sensor cannot discriminate between active and passive motion, thus producing overpacing whenever the patient is shaken or trembling. Furthermore, the accelerometric signal immediately returns to baseline when a physical activi- ty is stopped; in consequence, the pacing rate is not regulated during the recovery period. To prevent such inconveniences, dual-sensor pacemakers have been developed by coupling the accelerometer with a physiological sen- sor, such as the minute ventilation or the Q–T interval [2, 3]. A combined sensing system provides different indications which complement each other and are usually averaged in programmable proportion by a blending algo- rithm to derive the most suitable pacing rate.
In principle, a haemodynamic sensor would be the most appropriate physiological counterpart of the accelerometer. Haemodynamic sensors are designed to record changes in cardiac inotropic regulation, which are expected to be faster and more specific than the modifications in respiratory activity or Q–T duration [4, 5]. In recent years, a new haemodynamic sensor based on transvalvular impedance (TVI) has been proposed to monitor both
1Institute of Cardiology and Cardiovascular Surgery, La Havana, Cuba;2Medico Clinical Research, Rubano (Padua), Italy
stroke volume (SV) and preload at the same time, in order to infer an esti- mate of myocardial contractility devoid of the intrinsic regulation, which is independent of the autonomic nervous system and therefore unrelated to the sinus rate [6–9]. We report the preliminary results of a pilot study which is testing in human patients the general properties and the rate-responsive function of the first implantable pacemaker featuring the TVI sensor.
Materials and Methods
The study was approved by the local Ethical Committee and all enrolled patients gave their written informed consent. Six patients presenting with sick sinus syndrome with marked bradycardia and depressed chronotropic response have been implanted with the Sophòs 100 DDD-R pacemaker (Medico, Padua, Italy), which is equipped with a dual-sensor rate-responsive system including an accelerometer and the TVI recorder. The stimulator was connected with bipolar, passive fixation, atrial and ventricular pacing leads (Medico models 366 and 340, respectively) provided with porous Ti elec- trodes coated with Pt. The atrial lead was positioned in the right appendage and the ventricular lead in the apex.
The patients were checked before discharge and at 1 and 2 months after the implantation. During this initial follow-up period, the TVI sensor was enabled only to collect data to test the response during postural changes and controlled physical activity. The regulation of the rate-responsive function was totally entrusted to the accelerometer, the reliability of which was assessed during fast walking as well as by 24-h Holter monitoring. The rate- response profile of the accelerometric sensor consists in a dual-slope linear increase in pacing rate as a function of the acceleration detected: the first slope is defined by the difference between the programmable ‘snap rate’ and the basic rate, while the second slope results from the difference between the sensor upper rate and the snap rate.
TVI is the electric impedance recorded between right atrium and ventri- cle along the cardiac cycle. The Sophòs 100 pacemaker measures TVI by applying square subthreshold current pulses of 125-µs duration and ampli- tude automatically adapted to the detected impedance, up to a maximum of 45 µA. Although several combinations between current injecting and voltage sampling electrodes are allowed, the present study focused on two alterna- tive TVI configurations: impedance recording between the atrial ring and the ventricular ring (Ar–Vr), or between the atrial ring and the ventricular tip electrodes (Ar–Vt). The minimum (edTVI) and maximum (esTVI) values detected in each cardiac cycle within two rate-adaptive time windows, corre- sponding to the maximum predictable duration of the isometric systole and
the ejection period, respectively, are stored in the memory and processed by the pacemaker in order to derive the inotropic index and the corresponding TVI-indicated pacing rate.
The TVI waveform transmitted by real-time telemetry and the trends of edTVI and esTVI were recorded with the patient resting in the supine posi- tion, right lateral decubitus, left lateral decubitus, and standing upright, as well as during physical exercise of various degrees (slow and fast walking, stair climbing, leg bending), with the aim of evaluating TVI sensitivity and specificity to the cardiovascular challenge induced by common activities of daily living. In addition, the sensitivity of the pacemaker to intrinsic electri- cal activity was assessed in the presence or absence of TVI sampling current.
Mean data are reported ± 1 standard deviation. The significance of differ- ences was evaluated by the paired Student’s t-test and the Wilcoxon signed rank test, respectively, for parametric and non-parametric data.
Results
The implantations were carried out by the standard procedure. Acute atrial and ventricular pacing thresholds were, respectively, 0.46 ± 0.22 V and 0.39
± 0.22 V (0.5-ms pulses, unipolar mode). The corresponding pacing imped- ance at 5 V averaged 695 ± 132 Ω and 768 ± 201 Ω. The A wave amplitude on implantation was 4.4 ± 1.3 mV in unipolar and 4.1 ± 1.9 mV in bipolar mode. The R wave was 8.0 ± 2.6 and 9.3 ± 3.2 mV in unipolar and bipolar mode, respectively.
The first follow-up check was performed within the first 2 days after the implantation. In each patient, TVI was assessed in both the Ar–Vr and the Ar–Vt configuration, after individual tuning of the sampling current. The former TVI configuration was preferred in three cases, while the latter was chosen in the other three patients. An example of the recorded TVI wave- form is illustrated in Figure 1. The TVI signal regularly showed the expected general properties, with minimum and maximum peaks falling within the respective detection windows. In order to check whether the application of the TVI sampling current might affect the pacemaker sensing function, the upper value of bipolar atrial and ventricular sensitivity allowing 100% detec- tion of intrinsic A and R waves was determined with the TVI sensor either enabled or turned off. The upper limit of fully effective atrial sensitivity (averaging 1.12 ± 0.85 mV and 1.13 ± 0.93 mV with the TVI sensor off and on, respectively) was not affected by TVI sensor activation in four out of six cases, while it was decreased by one programming step in one case and increased by one programming step in a second case. Similarly, the upper limit of fully effective ventricular sensitivity (averaging 5.17 ± 2.82 mV and
5.00 ± 2.49 mV with the TVI sensor off and on, respectively) was not affect- ed by the TVI sensor activation in five out of six cases and was decreased by one programming step in one case. Such small differences have no statistical significance.
The TVI signal response to exercise and postural changes was evaluated at 1 and 2 months from the implantation. The absolute values of both edTVI and esTVI could be affected by posture, even in the absence of relevant modifica- tions in the patient’s activity and metabolic demand (Fig. 2). On the other hand, the TVI signal was modulated by the cardiovascular adaptation to physi- cal activity. The inotropic index derived from TVI increased during stress exercise and remained elevated for a while in the recovery phase (Fig. 3). The maximum values of the inotropic index at rest, at peak exercise, and after 5 min recovery averaged 0.14 ± 0.10, 0.85 ± 0.52 and 0.51 ± 0.23, respectively, in the whole patient group. The increase with respect to baseline was statisti- cally significant for both exercise and recovery conditions (P < 0.05).
The pacing rate dynamics indicated by the accelerometric sensor in stan- dard configuration was tested during fast walking (Fig. 4) and proved ade- quate in all the patients, with a maximum rate increase of 38 ± 9 bpm above the basic rate. No episode of sensor-induced tachycardia was noticed in daily life by 24-h Holter recording.
Fig. 1.Pacemaker event markers (upper trace) and TVI waveform (lower trace) trans- mitted in real time by pacemaker telemetry and recorded by the programmer. The markers indicate sequential atrial and ventricular pacing at 60 bpm. TVI was measured in the Ar–Vt configuration; the open and shaded bars correspond to the detection win- dows of the minimum and maximum TVI, which averaged 768 ± 1 and 808 ± 1 Ω, respectively. The TVI sampling is suspended throughout the atrioventricular delay
Fig. 2.Effects of postural changes on end-diastolic (open symbols) and end-systolic TVI (filled symbols), recorded in the Ar–Vt configuration. The patient was resting in the supine position, then moved to right lateral decubitus (rld), left lateral decubitus (lld), supine, right lateral decubitus, left lateral decubitus, supine, standing up, and supine again. The arrows mark the time of each transition
Fig. 3.TVI inotropic index modifications induced by physical exercise. The patient was initially lying in the supine position, then walked slowly on the flat with little or no effort. Thereafter, he was asked to climb and descend the stairs for three storeys twice as fast as he was able, to walk slowly on the flat again in the recovery phase after the stress, and finally to lie down in the supine position. The arrows mark the time of each transi- tion. Note the increase in the inotropic index during exercise, followed by a delayed decrease in the recovery period
time (min)
time (min)
Discussion
A rate-responsive algorithm based upon two complementary sensors is expected to be sensitive to a wider range of physiological conditions and more specific than a single sensor system, as a result of sensor cross-check [3]. All currently available sensors feature advantages and disadvantages. The accelerometer is a sensitive tool, but can be erroneously activated by passive motion imposed on the patient’s body or even on the pacemaker alone.
Physiological sensors are generally more specific, but less sensitive and slow- ly activated [10]. Haemodynamic sensors can be affected by preload and afterload modifications [7, 9] and may require the use of special leads including dedicated hardware, as is the case for the dP/dt and the peak endo- cardial acceleration (PEA) sensors [4, 11]. As an alternative, information on the inotropic state of the heart can be derived from electric impedance mea- surements obtained with standard pacing leads. The heart mechanical activi- ty entails impedance changes at every beat that can reflect the contraction strength [12–14]. Rate-responsive systems based upon impedance recording Fig. 4.Cardiac rate (thicker curve) and accelerometer-indicated rate (lighter curve with open circles) during fast walking. The accelerometric sensor was enabled in passive mode, so the pacemaker worked out the accelerometer-indicated rate and stored it in the memory without actually increasing the pacing rate. This allowed comparison of the sensor-indicated rate and the sinus rate, whenever the latter exceeded the basic rate (60 bpm)
proved generally effective in clinical practice [15, 16], although some cases of overpacing associated with the orthostatic position were reported [17].
The TVI sensor is quite different from the tools used so far to record car- diac impedance. The TVI waveform is a stable periodic signal which allows impedance measurement with DC coupling. The information on the absolute values of edTVI and esTVI, measured independently of each other with respect to zero, is applied to monitor preload changes and protect the system from the influence of the intrinsic heart regulation on the inotropic perfor- mance [7–9]. Our preliminary experience confirms the good sensitivity of TVI to the increased demand for blood supply induced by physical exercise.
The sensor response was also evident in the recovery phase following the stress, when the patient was still or performing minimal activity. However, TVI measurements could be affected by postural changes as well, even in the absence of physiological modifications in either preload or myocardial con- tractility. Although it is conceivable that the postural effects are more pro- nounced in the early post-implant stages than in chronic conditions, when the electrode fixation is expected to improve, a close interaction between TVI and the accelerometer is mandatory to prevent possible false activations caused by any of the two sensors. The Sophòs 100 pacemaker is provided with special algorithms designed for this purpose, which will be tested in the next steps of our study.
In conclusion, our results demonstrate that the Sophòs 100 pacemaker is a reliable device that ensures precise pacing and sensing performance whether the TVI sensor is enabled or not. Suitable rate regulation can be achieved even by means of the accelerometer alone, which is properly tuned for pacemaker patients who show normal motility. The TVI sensor can extend the sensitivity of the rate-responsive system to isometric activities, can drive the pacing rate in the recovery phase, and must integrate the accelerometer in sensor cross-checking. In addition, TVI could play a pivotal role in the autoregulation of a pacing device, providing permanent haemo- dynamic validation of pacing and sensing effectiveness at every beat [18].
References
1. Lau CP (1993) Rate adaptive cardiac pacing: single and dual chamber. Futura Publishing Company, Inc., Mount Kisco, NY
2. Leung SK, Lau CP, Tang MO et al (1996) New integrated sensor pacemaker: compa- rison of rate responses between an integrated minute ventilation and activity sen- sor and single sensor modes during exercise and daily activities and nonphysiolo- gical interference. Pacing Clin Electrophysiol 19[Pt II]:1664–1671
3. Barold SS, Clémenty J (1997) The promise of improved exercise performance by dual sensor rate adaptive pacemakers. Pacing Clin Electrophysiol 20[Pt I]:607–609
4. Bennett T, Sharma A, Sutton R et al (1992) Development of a rate adaptive pace- maker based on the maximum rate-of-rise of right ventricular pressure (RV dP/dtmax). Pacing Clin Electrophysiol 15:219–234
5. Pichlmaier AM, Braile D, Ebner E et al (1992) Autonomic nervous system control- led closed loop cardiac pacing. Pacing Clin Electrophysiol 15:1787–1791
6. Di Gregorio F, Morra A, Finesso M et al (1996) Transvalvular impedance (TVI) recording under electrical and pharmacological cardiac stimulation. Pacing Clin Electrophysiol 19[Pt II]:1689–1693
7. Chirife R, Tentori MC, Mazzetti H et al (2001) Hemodynamic sensors: are they all the same? In: Raviele A (ed) Cardiac arrhythmias 2001. Springer, Milan, pp 566–575 8. Di Gregorio F, Curnis A, Pettini A et al (2002) Trans-valvular impedance (TVI) in the hemodynamic regulation of cardiac pacing. In: Mitro P, Pella D, Rybár R, Valocνik G (eds) Cardiovascular diseases 2002. Monduzzi, Bologna, pp 53–57 9. Chirife R (2003) Hemodynamic assessment with implantable pacemakers. How
feasible and reliable is it? In: Raviele A (ed) Cardiac arrhythmias 2003. Springer, Milan, pp 705–712
10. Barold SS (1993) Limitations and adverse effects of rate-adaptive pacemakers. In:
Benditt DG (ed) Rate-adaptive cardiac pacing. Current technologies and clinical applications. Blackwell, Boston, pp 233–263
11. Rickards AF, Bombardini T, Corbucci G et al (1996) An implantable intracardiac accelerometer for monitoring myocardial contractility. Pacing Clin Electrophysiol 19:2066–2071
12. Chirife R (1991) Acquisition of hemodynamic data and sensor signals for rate con- trol from standard pacing electrodes. Pacing Clin Electrophysiol 14:1563–1565 13. Chirife R, Ortega DF, Salazar A (1993) Feasibility of measuring relative right ventri-
cular volumes and ejection fraction with implantable rhythm control devices.
Pacing Clin Electrophysiol 16:1673–1683
14. Osswald S, Cron T, Gradel C et al (2000) Closed-loop stimulation using intracardiac impedance as a sensor principle: correlation of right ventricular dP/dt max and intracardiac impedance during dobutamine stress test. Pacing Clin Electrophysiol 23:1502–1508
15. Griesbach L, Gestrich B, Wojciechowski D et al (2003) Clinical performance of automatic closed-loop stimulation systems. Pacing Clin Electrophysiol 26[Pt I]:1432–1437
16. Santini M, Ricci R, Pignalberi C et al (2004) Effect of autonomic stressors on rate control in pacemakers using ventricular impedance signal. Pacing Clin Electrophysiol 27:24–32
17. Cron TA, Hilti P, Schächinger H et al (2003) Rate response of a closed-loop stimula- tion pacing system to changing preload and afterload conditions. Pacing Clin Electrophysiol 26[Pt I]:1504–1510
18. Bongiorni MG, Soldati E, Arena G et al (2003) Transvalvular impedance: does it allow automatic capture detection? In: Raviele A (ed) Cardiac arrhythmias 2003.
Springer, Milan, pp 733–739
