Rate-Responsive Pacing Controlled by Transvalvular Impedance: Preliminary Clinical Experience

Impedance: Preliminary Clinical Experience

E. O

, G. G

, A. C

, M. G

, M. B

, A. M

, A. C

, L. B

, G. M

, G.M. F

, F. D

G

, A. B

, A. R

Introduction

All the different sensors used to assess the patient’s metabolic demand in rate-responsive pacing feature well-known advantages and disadvantages.

Activity sensors are usually quick and highly sensitive, but lack specificity since they can be activated by either active or passive motion. Physiological sensors are more specific, but can be slow and only sensitive to intensive exercise conditions [1]. Haemodynamic sensors, aimed at regulating the pac- ing rate according to the inotropic tone [2–8], can be affected by preload modifications independently of the influence exerted by the autonomic ner- vous system on the cardiac function [9–12]. Preload monitoring is thus advisable to take into account the contribution of the intrinsic heart regula- tion to the actual haemodynamic performance.

A new haemodynamic sensor based on transvalvular impedance (TVI) has been proposed to assess relative preload and stroke volume (SV) changes at the same time, by using standard pacing leads [13–15]. TVI is recorded without high-pass filtering and impedance data are processed on the assumption of an inverse relationship with right-ventricular volume: an increase in the absolute TVI value in telediastole (edTVI) represents a decrease in diastolic ventricular volume (EDV), while a decrease in edTVI indicates an increase in EDV. Peak-to-peak TVI excursion from diastole to end-systole is proportional to SV, which is a function of EDV, according to Starling’s law. The relationship between TVI-derived SV and EDV at any time defines the current inotropic index, which can be applied to drive a rate- responsive system following the modifications in ventricular contractility induced by the autonomic nervous system [9, 10, 16, 17].

1Division of Cardiology, School of Medicine, Università degli Studi del Piemonte Orientale, Novara;²Cardiology O.U., Ospedale Umberto I, Mestre (Venice);³Cardiology O.U. Spedali Civili, Brescia, Italy;⁴Cardiology O.U, Ospedale S. Luigi - S. Currò, Catania;

5Medico Clinical Research, Rubano (Padua), Italy

The TVI sensor has been implemented in an external cardiac pacemaker, which automatically adapts the pacing rate according to the inotropic index.

The aim of the present study was to check and evaluate the rate-responsive function of this device under pharmacological adrenergic stimulation.

Materials and Methods

Tests were performed in 30 patients, during the implantation of bipolar dual- chamber pacing systems for conventional indications. Permanent pacing leads from any manufacturer were temporarily connected with an external DDD-R pacemaker (Ext Sophòs, Medico, Padua, Italy), equipped for TVI recording. The TVI signal was sampled at 64 Hz with DC coupling, in order to work out the minimum diastolic and maximum systolic impedance in each cycle (edTVI and esTVI, respectively). Diastolic and systolic intervals were rate-adaptive time windows, triggered by each pacing or sensing ven- tricular event. EdTVI and esTVI were filtered for possible outliers, averaged over a programmable number of cycles, and converted into the correspond- ing inotropic index, which specified the TVI-indicated pacing rate (TVI rate) according to the relation:

TVI rate = basic rate + resting rate x inotropic index x rate gain,

where the rate gain is a programmable factor used for individual tuning of the rate-responsive system. The actual pacing rate applied by the stimula- tor corresponded to the current TVI rate after a smoothing process. The trends of cardiac rate (either intrinsic or paced) and TVI rate, as well as the TVI waveform and the associated event markers, were stored in the stimula- tor memory and optionally transmitted to a PC through an optically isolated serial cable, for real-time display.

The TVI recording configuration was chosen between two possible alter- natives, i.e. using the ring atrial electrode and either the tip or the ring ven- tricular electrode. The ring-tip configuration usually provided higher sig- nals, which could be sensitive, however, to possible artefacts generated by cardiac contraction at the electrode–myocardium interface. The ring–ring configuration provided smaller signals with the advantage of lower noise, since both the electrodes were directly in contact with the blood conducting volume. In both configurations, TVI was derived from the voltage generated by the application of subthreshold current pulses with amplitude program- mable from 15 to 45 µA. The same electrodes were used for both current injection and voltage sampling.

After TVI signal acquisition in resting conditions, β-adrenergic stimula-

tion was induced by intravenous administration of 2 µg/min isoproterenol (IPN), which was continued until the cardiac rate exceeded 90 bpm.

Whenever possible, the stimulator basic rate and the rate gain were pro- grammed so as to keep the TVI rate below the sinus rate, in order to avoid overdrive pacing and allow the comparison of TVI rate and sinus rate trends.

The relationship between TVI inotropic index and sinus rate changes with respect to the resting rate in each patient was evaluated by linear regression analysis and expressed by the squared Pearson correlation coefficient.

Results

At the time of testing, stable intrinsic atrial activity was present in 28 cases at rest, while 2 patients received atrial pacing throughout the procedure.

Sequential ventricular pacing was performed in 57% of the patients, while the remaining exhibited intrinsic AV conduction. The ring–ring and ring–tip TVI configurations were chosen, respectively in 67% and 33% of the cases. A representative example of the recorded TVI signal is shown in Fig. 1. The minimum impedance was recorded within 200 ms following the electrical ventricular activation, which was indicated by either R wave detection or pacing spike emission. Thereafter the impedance increased, reaching the maximum value at a time compatible with the end of the systole.

Fig. 1.Upper trace: transvalvular impedance (TVI) recorded by the Ext Sophòs stimulator in a patient at rest. Ring–tip TVI configuration; end-diastolic TVI = 482 ± 5 Ω, end-sys- tolic TVI = 577 ± 3 Ω. Lower trace: pacemaker event markers, demonstrating intrinsic atri- al (upward spike) and ventricular activity (downward spike). The sinus rate was 66 ± 1 bpm

All patients provided with intrinsic atrial activity showed positive chronotropic response to IPN. In addition, β-adrenergic stimulation enhanced myocardial contractility, as suggested by the trend of TVI-derived inotropic index, which increased from about 0 in resting conditions up to maximum values ranging from 0.4 to 3.4 in the patient group (mean ± SD

= 1.2 ± 1.0). In 27 out of 28 patients, the time course of the inotropic index reflected the sinus rate trend, so that a linear correlation between the two parameters was demonstrated. The squared Pearson correlation coefficient averaged 0.81 ± 0.12, being higher than 0.7 in 93% of the cases. The recipro- cal of the individual regression slope corresponded to the optimal rate gain to be applied in each patient, which ranged from 0.1 to 2 with a mean of 0.8

± 0.6. The product of current inotropic index times the individual rate gain proved a good approximation of relative sinus rate changes observed during IPN-induced stimulation (Fig. 2). As a consequence, the TVI rate closely reproduced the sinus rate trend, as well as the maximum extent of the intrin- sic chronotropic response. The highest sinus rate value reached in each patient is compared with the TVI rate derived at the same time in Fig. 3. Very

Fig. 2.Fractional change in sinus rate (defined as: (current rate – resting rate)/resting rate; heavy line) and product TVI inotropic index x rate gain (light line), during intra- venous administration of 2 µg/ml isoproterenol. The rate gain was equal to the slope of the individual linear regression of fractional sinus rate on inotropic index. Positive chronotropic and inotropic effects started simultaneously and showed similar time courses, until the sinus rhythm was temporarily suppressed by overdrive pacing.

Consequently, the TVI-indicated rate (given by: basic rate + resting rate x inotropic index x rate gain) paralleled the sinus rate trend

x

good correspondence was demonstrated by a regression line featuring slope and squared correlation coefficient both close to 1.

The relationship between inotropic index and sinus response could not be assessed in the patients undergoing atrial pacing throughout the test.

Nevertheless, in these cases as well IPN administration entailed a substantial increase in the inotropic index and a corresponding acceleration in the pac- ing rate.

Conclusions

The present study demonstrates that TVI data processing based on the inverse relationship with right ventricular volume provides an index of cardiac con- tractility that correlates closely with the simultaneous sinus rate modifications induced by adrenergic challenge. Similar progressive changes in the inotropic index are noticed even when the chronotropic adaptation is prevented. In con- trast, a rate increase produced by overdrive pacing in the absence of contrac- tility modifications does not affect the inotropic index [18].

TVI is sensitive to myocardial properties controlled by the sympathetic nervous system, is capable of discriminating the haemodynamic effects of intrinsic and extrinsic heart regulation, and is totally free of positive feed- backs from the cardiac rate. Therefore, this new sensor can be proposed as an advanced tool in the physiological regulation of rate-responsive pacing.

Fig. 3.Relationship between the maximum increase in sinus rate induced by β-adrenergic stimulation in each patient and the corre- sponding rate increase in- dicated by TVI at the same time. The regression line is described by the equation:

y = 0.96x – 0.56, w ith r²= 0.94

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