© 2005 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
Effect of pacemaker rate-adaptation on 24 h beat-to-beat heart rate and blood pressure profiles
aInstitute of the Heart and Great Vessels, University La Sapienza Rome, Italy; bDepartment of Technologies and Health, Istituto Superiore di Sanità Viale Regina Elena 299, 00161 Roma, Italy; cBiotronik Seda Milano, Italy
Manuscript submitted 15 December 2004. Accepted after revision 6 March 2005.
*Corresponding author. Tel.: +390649902862; fax: +390649387079. E-mail address: giovanni.calcagnini{at}iss.it (G. Calcagnini).
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Abstract |
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AIMS: The aims of the study were to evaluate the 24-h beat-to-beat heart rate (RR) and blood pressure changes during closed loop stimulation (DDD-CLS) pacing and conventional fixed rate DDD pacing with respect to spontaneous activity.
METHODS: We simultaneously and continuously measured beat-to-beat heart rate and blood pressure for 24 h in patients implanted with Inos2+ (Biotronik GmbH, Berlin, Germany). A randomised cross-over comparison of DDD-CLS and DDD pacing was performed by short- and long-term analyses.
RESULTS: Seventeen patients (10 males, aged 46–85 years) were enroled in the study: 11 completed the protocol. The percentage of atrial stimulation was 72.87% during DDD-CLS and 38.36% in DDD (P = 0.003). All patients were 100% stimulated in the ventricle. On average, the percentage increase of paced RR intervals with respect to spontaneous beats was only 7.4% in DDD-CLS but 20.1% in DDD (P = 0.0001). A significant correlation between spontaneous and paced RR profiles was obtained only during DDD-CLS (rDDD-CLS = 0.77, rDDD = 0.23, P = 0.01). Short-term analysis revealed a 3.79% reduction of the escape interval in DDD-CLS and 8.19% in DDD, and the relative fall in diastolic blood pressure was 1.14% in DDD-CLS and 3.81% in DDD.
CONCLUSION: DDD-CLS provided physiological heart rate fluctuations throughout the 24-h test. The blood pressure profiles of paced and spontaneous beats were comparable. The onset of paced rhythm in DDD-CLS resulted in a less pronounced decrease in heart rate and fall in diastolic pressure than in DDD.
Key Words: Heart rate, Blood pressure, Rate-responsive pacing
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Introduction |
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Dual chamber pacing (DDD) has been shown to have better haemodynamic function and effort tolerance with respect to single chamber pacing (VVI). Several studies have demonstrated that DDD pacing gives better control of blood pressure with fewer episodes of hypotension (pacemaker syndrome). These advantages are the result of atrioventricular (AV) synchrony and rate-responsiveness due to P wave tracking [1
–5].
In further studies the loss of AV synchrony was observed to result in the lowering of arterial blood pressure and in increase in beat-to-beat blood pressure fluctuations [6–8]. Moreover, dual chamber pacing seems to influence sympathetic nervous activity: in fact DDD pacing shows lower sympathetic nerve activity and higher arterial pressure with respect to VVI, indicating that pacing mode may influence sympathetic outflow through arterial baroreflex mechanisms [9].
Other mechanisms contribute to the short- and long-term regulation and adaptation of blood pressure: heart rate, peripheral resistance, body fluid control, to name a few.
The new generation of physiological pacemakers adapt the pacing rate according to an indirect measure of ventricular contractility (closed loop stimulation, DDD-CLS) [10,11]. This method has been described to respond to provoked changes of sympathetic activity [12,13]. The potential benefit of this rate-responsive pacing has also been investigated in patients prone to neuromediated syncope [14] and to atrial fibrillation [15].
Data on the impact of rate-responsive pacing on cardiovascular parameters during daily activity are scarce, because of the need for non-invasive, continuous monitoring of blood pressure and for discrimination between spontaneous and paced beats.
Twenty-four-hour continuous monitoring of blood pressure is now possible with the non-invasive photoplethysmographic measurement of beat-to-beat systolic and diastolic blood pressure in the finger, as measured with Portapres (TNO, Amsterdam, The Netherlands). In spite of the technique's limitation, its tracking accuracy is considered sufficiently good to study blood pressure changes induced by orthostatis and other simple manoeuvres [16]. It has been previously used as a clinical tool for assessing the relative changes in haemodynamic response also in pacemaker patients [17].
The aims of the study were to evaluate the beat-to-beat heart rate and blood pressure changes during DDD-CLS pacing with respect to atrial spontaneous activity, and to compare these changes with those observed during conventional fixed rate DDD pacing, in patients undertaking daily activities.
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Methods |
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Patient selection and study protocol
We simultaneously and continuously measured surface ECG and blood pressure waveforms in patients who had indications for dual-chamber rate-responsive pacing. The selected population required permanent ventricular stimulation. Exclusion criteria were angina, chronic atrial fibrillation, congestive heart failure, total sinus node block or severe chronotropic incompetence, life expectancy less than one year, pregnancy. All patients in the study received their first implant.
Patients underwent two 24-h ECG and blood pressure recordings, in a randomised cross-over comparison of DDD-CLS with DDD pacing. Informed consent was obtained, and the study was approved by the local ethics committee.
Enroled patients were implanted with Inos2+ pacemakers (Biotronik GmbH, Germany) and randomly assigned to DDD-CLS or DDD pacing mode. The first recording was made 3 months after the implant. Then, the pacing mode was reprogrammed to the alternative mode and the cross-over was recorded approximately 3 months later.
Pacemaker description
Inos2+ is a dual-chamber, rate-responsive pacemaker which uses an indirect measure of ventricular contractility to modulate the stimulation rate. This measure is obtained from each ventricular paced beat, via a permanent sampling of the intraventricular impedance signal by a high-frequency sub-threshold pulse train (pulse amplitude = 600 µV; pulse duration = 30.5 µs and pulse frequency = 128 Hz). The pacemaker records the impedance values under resting conditions (reference curve), then compares the instantaneous impedance values for each ventricular paced beat with the reference curve: an increase in the impedance curve slope is an indication of increased contractility and this value is used to modulate the pacing rate [18,19]. In addition, the system updates the reference curve continuously, to adapt it to the patient's condition. In this study, Inos2+ was programmed according to patient's age, weight and clinical conditions as follows: lower rate = 60 bpm; upper DDD-CLS rate = 130; AV interval = 150–180 ms; atrial and ventricular sensing polarity = bipolar; atrial and ventricular pacing polarity = unipolar.
Signal processing
Twenty-four-hour ECGs were acquired by a three-lead digital Holter system (PRIMA Holter, Remco, Italy). Arterial pressure waveform was non-invasively acquired for 24 h from the finger by Portapres. Two cuffs were used; cuffs were mounted on the non-dominant hand and the switching interval was set at 15 min. The accuracy of the measures was checked at the beginning of each recording by a conventional sphygmomanometer, on the opposite arm. The two monitoring systems were synchronised at the beginning of the recording. Synchronisation was obtained by injecting the marker event signal of the Portapres into one ECG lead, temporarily disconnected from the patient electrodes. For each patient, this synchronisation procedure was repeated twice (1 min apart). Based on these markers, the recordings were realigned offline.
An algorithm was developed to classify atrial events using LabView (National Instruments, US). ECG signals were sampled at 500 Hz to have a reliable identification of the PM spikes. The classification of the beat as atrial paced or atrial sensed proceeded as follows. First, the PM spikes were filtered out by using a non-linear procedure. The R-wave was recognised in the spike-free signal according to a modified version of the algorithm by Pan and Tompkins [20]. Then, for each detected beat, sensed or paced atrial events were classified according to the presence, if any, of pacemaker spikes. Since all our patients were always stimulated in the ventricle, we referred to atrial beats as paced (Ap), preceded by a spike, or spontaneous (As).
For each beat we estimated the heart rate (RR interval) and the systolic and diastolic pressure values (SS and DD, respectively). The conventions and the labelling of the beats are illustrated in Fig. 1. To increase the robustness of the procedure against artefacts and errors, the RR, SS and DD series were then visually scanned and corrected according to the following exclusion criteria: RR intervals longer than 1 s or shorter than 0.4 s; systolic values higher than 170 mmHg or lower than 90 mmHg; diastolic values higher than 110 mmHg or lower than 40 mmHg.
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Long-term statistical analysis
Since the RR, SS and DD spontaneous and paced series did not differ from a normal distribution, the mean values and standard deviations over the entire recording were calculated for each patient. The one-way t-test for paired samples was used to compare paced with spontaneous values. A type I error level was set to 0.05 for statistical significance.
In order to compare the long-term heart rate and blood pressure profiles of spontaneous with paced atrial beats, we proceeded as follows: each 24 h recording was segmented into 5-min non-overlapping epochs; for each epoch, we extracted the RR intervals, SS and DD values of paced and spontaneous beats; finally, the average over each group of beats was calculated. We thus obtained two series (i.e. spontaneous and paced atrial events) of values for each parameter (RR, SS and DD), for the entire recording. The similarity in the 5-min profiles was assessed by calculating the Pearson cross-correlation between the series. Mean values and one-way t-test for paired samples were used to compare the cross-correlation values of RR, SS and DD.
Short-term statistical analysis
The short-term analysis aimed at evaluating the changes in heart rate and blood pressure induced by a single atrial paced beat occurring after a period of spontaneous activity lasting at least two beats (AsAsAp sequence). The changes in heart rate and blood pressure induced by the rise in the spontaneous activity after a period of pacing lasting at least two beats (ApApAs sequence) were also evaluated. These evaluations were carried out by computing the median value of the RR, SS and DD percentage changes with respect to the previous beat, for each patient. Statistical differences were analysed by the Wilcoxon test.
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Results |
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From November 2002 to March 2004, 17 patients (10 male) were enroled in the study. Eleven completed the protocol; after the first recording five did not accept repetition of the second 24-h monitoring (discomfort from wearing of Portapres); and one did not tolerate the DDD-CLS mode. Population characteristics are summarised in Table 1. The electrical values at implant and follow-up were: mean atrial sensing 3.7 (1.6–9.7) mV; mean ventricular sensing 10.2 (3.4–17.5) mV; mean atrial impedance 587 (422–803) Ohm; mean ventricular impedance 649 (422–863) Ohm; mean atrial threshold 0.7 (0.2–1.2) V; mean ventricular threshold 0.7 (0.5–1.7) V at 0.5 ms pulse duration.
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Long-term analysis
Regardless of the pacing mode (DDD-CLS or DDD), patients were always stimulated in ventricle.
On average the percentage of atrial stimulation was significantly higher in DDD-CLS than in DDD (DDD-CLS 72.87 ± 29.84%, DDD 38.36 ± 36.32%, P = 0.003). Only in one patient we observed an increase in paced beats in DDD compared with DDD-CLS.
During DDD-CLS stimulation, paced RR intervals were significantly longer than spontaneous RR intervals (0.797 ± 0.113 s vs. 0.744 ± 0.098 s, P = 0.02, mean values ± standard deviation over the population). No significant difference was observed for systolic blood pressure (SSCLSs = 129.8 ± 19.1 mmHg, SSCLSp = 127.5 ± 21.5 mmHg, P = 0.5), while a significant difference was obtained for diastolic pressure (DDCLSs = 69.5 ± 12.9 mmHg, DDCLSp = 66.7 ± 11.3 mmHg, P = 0.03).
DDD pacing mode resulted in significant differences in all the parameters with respect to spontaneous activity. Paced RR intervals increased, as expected, from 0.789 ± 0.064 s to 1.000 s (P = 0.001), while both systolic and diastolic blood pressure decreased (SSDDDs = 137.8 ± 22.0 mmHg, SSDDDp = 129.7 ± 21.9 mmHg, P = 0.001; DDDDDs = 74.4 ± 14.3 mmHg, DDDDDp = 69.7 ± 15.2 mmHg, P = 0.01).
RR intervals, SS and DD values mean percentage changes of paced beats with respect to spontaneous beats were calculated for each patient. Table 2 summarises these percentage changes averaged over the population.
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A significantly higher value of cross-correlation between spontaneous and paced RR intervals was obtained in DDD-CLS pacing mode, compared with the correlation observed in DDD (rDDD-CLS = 0.77, rDDD = 0.23, P = 0.01).
An example of the correlation between paced and spontaneous heart rates during DDD-CLS with respect to DDD is shown in Fig. 2.
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As for blood pressure profiles, cross-correlation between spontaneous and paced series showed no differences in either DDD or DDD-CLS pacing mode: rDDD = 0.82 vs. rDDD-CLS = 0.88 for systolic pressure (P = 0.32) and rDDD = 0.83 vs. rDDD-CLS = 0.86 for diastolic pressure (P = 0.66).
An example of systolic and diastolic blood pressure profiles for both pacing modalities is shown in Fig. 2.
Short-term analysis
The results of the short-term analysis are summarised in Table 3. The escape interval (i.e. RR interval of a paced beat following a spontaneous beat – AsAsAp) was shorter in DDD-CLS than in DDD (3.79% longer than spontaneous rhythm in DDD-CLS, vs. 8.19% in DDD). This delay resulted in an average fall in diastolic pressure of 1.14% in DDD-CLS vs. 3.81% in DDD. On average, spontaneous activity takes over with comparable interval reductions between DDD-CLS and DDD (6.82% in DDD-CLS and of 5.71% in DDD). This interval reduction caused a minor effect on systolic pressure both in DDD-CLS and in DDD (–0.85% and 0.98%) and a comparable increase in diastolic pressures (3.15% in DDD-CLS and 3.52% in DDD).
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Discussion |
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This is the first study that analyses the 24-h beat-to-beat heart rate and blood pressure profiles during daily activity in patients implanted with dual-chamber rate-responsive pacemaker. The careful selection of the study population allowed us to compare the paced beats with spontaneous activity and their mutual interactions.
We compared the heart rate and blood pressure changes with respect to spontaneous activity, resulting from atrial paced beats occurring either at fixed rate (DDD) or at a physiological-like rate (DDD-CLS). The changes in the cardiovascular parameters were analysed both on a long-term basis (i.e. average values over 24 h and over 5-min epochs) and on a short-term basis (i.e. effects of a single atrial beat).
Long-term changes in heart rate and blood pressure
We observed that during DDD-CLS the number of paced beats was greater than during DDD; the mean heart rate of DDD-CLS paced beats was slightly lower than the spontaneous rate, showing no signs that DDD-CLS may overdrive spontaneous activity, if any. The analysis of the cross-correlation profiles further confirms the good tracking of sinus node activity achievable by this pacing mode. It should also be noted that our results were obtained using mean values over 24 h and over 5-min epochs, and thus carry information on the long-term control of heart rate [21], rather than on the short-term control investigated in previous studies [12,13].
The DDD-CLS pacing mode had no influence on systolic pressure, while it resulted in lower diastolic pressures (3.7%), probably an expression of the longer RR intervals of the paced beats. This behaviour was observed also in the comparison between DDD paced and spontaneous beats, where a 9.6% decrease in diastolic pressure was obtained. During DDD pacing mode, systolic pressures of spontaneous beats were higher (7.9%) than paced values, which were instead comparable with the values measured during DDD-CLS. Baroreflex activation due to artificial pacing was observed by Taylor et al. [9], who investigated the differences between DDD and VVI pacing. They concluded that the sympathetic outflow may be influenced by the pacing mode. Chiladakis et al. [22] investigated the autonomic effect of short-term single and dual chamber pacing, using HRV spectral analysis; they observed an overall shift of the sympathovagal balance toward sympathetic predominance after VVI pacing and to a minor extent during DDD and VDD. Similarly, our finding of an increased spontaneous systolic pressure during DDD could be an expression of a shift toward sympathetic predominance.
Both DDD-CLS and DDD produced 5 min blood pressure profiles highly correlated with those arising from spontaneous beats. These results are consistent with previous findings on pacemaker patients showing that pacing rate plays a minor role in the long-term regulation [23] of blood pressure.
Short-term changes in heart rate and blood pressure
To asses the short-term haemodynamic impact of the two pacing modalities, we used a short-term analysis based on the computation of the percentage differences between consecutive paced and spontaneous beats. As expected, when applied to beats of the same type (i.e. AsAsAs or ApApAp) this method gave negligible differences both in heart rate and blood pressure values.
The average escape interval in DDD-CLS was shorter than in DDD, showing that DDD-CLS makes the pacemaker stimulate at rates closer to the spontaneous rate. DDD-CLS continuously updates the escape interval according to the sympathetic tone, whereas in DDD the interval has always the same value. The recovery of spontaneous activity occurs with a similar RR interval reduction in both pacing modalities. This result further confirms that DDD-CLS behaves similar to a DDD pacemaker whose escape interval is continuously updated.
The shorter RR interval associated with the pacemaker activation in DDD-CLS may explain the lower fall in diastolic values with respect to DDD pacing. We may speculate that DDD-CLS helps in maintaining better coronary perfusion than DDD, particularly during moderate physical activity. However, this study was not designed to address this issue.
Limitation of the study
The number of paced and spontaneous beats available for the short-term analysis varied greatly among the patients. In some patients we were unable to find enough sequences to obtain reliable measurements and statistical evaluation of the data. If overcome, this limitation would result in a severe bias of the population.
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Conclusion |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionAcknowledgementsReferences |
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The present study investigated the effects of rate-responsive pacing in patients implanted with dual chamber pacemakers, comparing the 24-h beat-to-beat heart rate and blood pressure profiles of paced and spontaneous beats. The long-term analysis showed that the DDD-CLS pacing mode resulted in a higher percentage of atrial pacing than DDD, and in higher paced heart rates (but always lower than spontaneous rhythms, if any). The fluctuations of DDD-CLS paced heart rates were similar to the spontaneous rates throughout the 24 h. The analysis of blood pressure profiles of paced and spontaneous beats showed a lower fall in diastolic pressure during paced beats in DDD-CLS with respect to DDD. Short-term analysis showed that upon a change from spontaneous to paced rhythm, DDD-CLS results in a less pronounced fall in heart rate and diastolic pressure than DDD. Although this study did not aim to assess the sympathovagal balance during different pacing modalities, we observed changes in the long-term systolic values which may be an expression of autonomic adaptation to fixed-rate cardiac pacing. Further work is needed to evaluate the impact of rate-responsive pacing on short- and long-term autonomic balance. In conclusion, our data confirm the possibility that CLS might exert a more favourable effect on haemodynamic function and, in particular, on RR intervals and arterial pressure values.
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Acknowledgements |
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The authors thank Maddalena D'Alessandro for the implementation of the algorithms for atrial event classification and Monica Brocco for the linguistic revision of the manuscript.
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References |
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