Europace Advance Access originally published online on November 23, 2007
Europace 2008 10(1):53-58; doi:10.1093/europace/eum257
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CARDIAC RESYNCHRONISATION THERAPY
Should we use the rate-adaptive AV delay in cardiac resynchronization therapy-pacing?
1 The Medical Division, Charité University Medical Centre, Berlin, Germany; 2 The Rostock University Hospital, Clinic for Internal Medicine, Rostock, Germany
Manuscript submitted 11 June 2007. Revision received 29 October 2007. Accepted after revision 29 October 2007.
* Corresponding author: Charité—Campus Mitte Medizinische Klinik mit Schwerpunkt Kardiologie, Angiologie, Pneumologie Schumannstraße 20/21, D—10117 Berlin, Germany. Tel: +49 30 450 613 145 ; fax: +49 30 450 513 904.E-mail address: christoph.melzer{at}charite.de
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Abstract |
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Aims: Recommendations for programming the rate-adaptive AV delay in CRT.
Methods and results: In cases of continual biventricular pacing, the optimal AV delay in CRT (AVDopt) is the net effect of the pacemaker-related interatrial conduction time (IACT), duration of the left-atrial electromechanical action (LA-EAClong), and the duration of the left-ventricular latency period (SV-EACshort). It can be calculated by AVDopt = IACT+LA-EAClong–SV-EACshort. We measured these three components in 20 CRT–ICD patients during rest and submaximal ergo metric exercise (71 ± 9 W) resulting in a 22.5 ± 9.6 bpm rate increase. IACT and SV-EACshort did not reveal significant differences. LA-EAClong, however, varied significantly by –10.7 ± 16.1 ms (P = 0.008) during exercise. In contrast to AVDoptVDD, there was a significant difference in AVDoptDDD of –8.8 ± 14.5 ms (P = 0.014) between the resting and submaximal exercise conditions. In DDD pacing, AVDopt was shortened by 2.6 ms/10 bpm.
Conclusion: In consideration of the findings of the studies performed to date, the rate-adaptive AV delay should be deactivated.
Key Words: Rate-adaptive AV delay, CRT, AV delay optimization
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Introduction |
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In patients with CRT and congestive heart failure, the AV delay must be programmed to allow for continual biventricular stimulation. Consequently, the AV delay in CRT is usually programmed to be shorter than the AV delay in normal DDD pacing (100–120 ms).1
–4
Clinical studies have shown that the principles of the haemodynamic optimization of the AV delay used in anti-bradycardia pacemaker systems for resting conditions can also be used under specific conditions for CRT.5–11
Modern CRT devices, such as the standard DDD pacemakers, are designed to integrate rate-adaptive AV delay programming because such programming has proven benefits.12–16 However, there is a lack of clear recommendations for effective programming of this parameter in DDD pacing as well in CRT.17,18 This is assumedly the reason why the recommendations for the programming of the rate-adaptive AV delay for CRT devices varies among the different manufacturers (Table 1).
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Studies in healthy subjects have shown that the natural AV delay decreases with increasing heart rate (4 ms/10 bpm).19
,20
Melzer et al.21 came to a similar finding in a study of DDD pacemaker patients with an EF > 45%, although this finding was not statistically significant.
Scharf et al.22 published the first results of a study of the rate-adaptive optimal AV delay in patients with CRT. Astonishingly, the optimal AV delay increased with increasing heart rate (20 ms/10 bpm).
In consideration of these studies, our goal in this study was to determine the AVDopt using the method described by Ismer et al.23 to establish a clear recommendation for the programming of the rate-adaptive AV delay in CRT.
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Methods |
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Inclusion criteria
All patients had been treated with a CRT-ICD according to the current guidelines.17
In order to carry out the multiple complex measurements under controlled exercise conditions, it was necessary for the patients to be in relatively good physical condition. Consequently, the study was restricted to CRT-responders.
Exclusion criteria
Exclusion criteria were heart failure categorized as NYHA class III–IV, unstable angina pectoris, atrial fibrillation, and device malfunction. Furthermore, patients were excluded with any type of disorder of the esophagus because in such cases an esophageal electrode could be harmful to the patient and therefore cannot be used.
Study equipment
We performed simultaneous recordings of transmitral flow, the left-atrial esophageal electrogram, and the real-time sense-event markers as proposed by Ismer et al.23 and Melzer et al.24 This approach required the placement of a bi-polar esophageal electrode to provide a filtered left-atrial electrogram (LAE). Therefore, we applied a 5F esophagus electrode (Osypka TO2/5F) in the position of maximal left-atrial deflection and connected it to a filter amplifier (Fiab Rostockfilter, by Vicchio-Firence, Italy). The filtered esophageal electrogram along with telemetric real-time pacemaker markers provided by the programmers analogue output were superimposed into the display of transmitral flow velocity on the Doppler-echo system (Sonolayer SSH-140A/Toshiba®). Therefore, telemetric output of the programmer and output of the Rostockfilter were connected to the DC inputs of the echo device.
Cardiac resynchronization therapy–implantable cardioverter-defibrillator programming during exercise
We programmed all the devices to turn the rate responsive mode off. The AV delay was optimized in atrial sense mode at a heart rate of 60–70 bpm. In order to determine the AVDopt in atrial paced mode, the right atrial heart rate was set 
10 bpm above the sinus rate.
Components and calculation of the optimal AV delay in cardiac resynchronization therapy
Ritter et al.5 and Ismer et al.25 define the optimal AV delay for any heart rate, based on diastolic optimization, as the net effect of the individual pacemaker-related interatrial conduction time (IACT: MA-LA or SA-LA.) and the left-atrial electromechanical action (LA-EAClong) reduced by the left-ventricular latency period (SV-EACshort). The four determinants of the optimal AV delay were measured as follows using two screenshots (Figure 1).
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Left-atrial electromechanical action (LA-EAClong) and pacemaker-related interatrial conduction time (IACT) in VDD pacing
To determine the left-atrial electromechanical action (LA-EAClong), we programmed a maximally long AV delay defined as IACT+150 ms (averaging 220 ± 34 ms) during which proper biventricular stimulation still occurs in VDD pacing and measured the time between the beginning of left-atrial deflection (LA) in the esophageal electrogram and the end of undisturbed left-atrial contribution (EAClong) in transmitral flow.
In the same screenshot, pacemaker-related IACT in VDD pacing was measured between right-atrial sense-event marker (MA) and the beginning of left-atrial deflection (LA) in the esophageal electrogram (IACT = MA-LA).
Left-ventricular electromechanical latency period (SV-EACshort) and pacemaker-related interatrial conduction time (IACT) in DDD pacing
To determine the left-ventricular electromechanical latency period (SV-EACshort), we programmed an unphysiologically short AV delay defined as IACT –20 ms (averaging 80.5 ± 19.6 ms) measured during DDD pacing (rate 10 bpm above sinus rate) and measured the duration between ventricular pacing stimulus (SV) and the end of the truncated left-atrial contribution (EAC) in transmitral flow.
In the same screenshot, IACT in DDD pacing was measured between right-atrial pacing stimulus (SA) and the beginning of left-atrial deflection (LA) in the esophageal electrogram (IACT = SA-LA).
Based on these measurements, optimal AV delays were calculated for VDD (atrial-triggered, AVDoptVDD) and DDD (atrial-paced, AVDoptDDD) modes using the following formulas:
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Programming of VV delays
Since the VV delay could not be optimized in all of the devices, we did not optimize this component in any of the cases. The VV delay was left as programmed without any alterations (0–5 ms).
Exercise test
In order to enable echo measurements immediately after exercise, this study had to be performed in a supine position on a bicycle ergometer. We began with 25 W and increased the workload by 25 W every 2 min until the individually determined submaximal exercise level was reached. The patients were asked to aim for an intensity of exercise, which they could maintain steadily for 3 min in order to have enough time during the exercise period to carry out the complex measurements. For this reason, the measurement of the components of the AV delay was taken under conditions of submaximal and not maximal exercise.
Statistical analysis
The data are expressed as mean ± standard deviation. Individual differences between resting and exercise conditions were statistically analysed by the Student’s t-test using SPSS 12.0 Base System and Professional Statistics for Windows® (SPSS, Inc., San Rafael, CA, USA). P < 0.05 was considered statistically significant.
Ethics
The study was conducted in accordance with Helsinki guidelines and was approved by the local ethics committee. Patients provided written informed consent prior to inclusion in the study.
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Results |
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Patients
Twenty patients were included in our study, 6 women and 14 men with mean age of 64.04 ± 10.66 years. Table 2 shows the clinical characteristics of the patients. The mean interval between CRT implantation and inclusion in the study was 1.3 ± 2.7 years. Before CRT implantation 17 patients were NYHA III (85%) and 3 patients were NYHA IV (15%). At the beginning of the study, 19 patients were NYHA II (95%) and 1 patient was NYHA I (5%).
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The following types of CRT–ICDs had been used: 6 Kronos LV-T (Biotronik® Inc; Berlin, Germany), 2 Tupos LV (Biotronik® Inc; Berlin, Germany), 4 Lumax 300 HF-T (Biotronik® Inc; Berlin, Germany), 3 Insync III Marquis (Medtronic® Inc; Minneapolis, USA), and 5 Insync Sentry (Medtronic® Inc; Minneapolis, USA).
Exercise test
All 20 patients fulfilled the criteria of the study protocol. Their resting rate was 73.4 ± 10.0 bpm. A submaximal exercise load of 50 and 75 W (71 ± 9 W) resulted in a significant rate increase (P = 0.000) between 7 and 43 bpm with a mean increase of 22.5 ± 9.6 bpm which correlates to an exercise heart rate of 95.8 ± 10.8 bpm. Seven of the patients reached a subjective submaximal exercise level at 75 W, 13 of them at 50 W.
Components and total duration of the optimal AV delay
In all 20 subjects, it was possible to measure the components of the optimal AV delay in rest as well as during exercise.
Pacemaker-related interatrial conduction time
Comparing exercise with rest, changes of IACT were not significant. The right-atrial sense event marker (MA), beginning of left-atrial deflection in the esophageal electrogram (LA) in VDD mode, and right atrial pacing stimulus (SA), beginning of left-atrial deflection in the esophageal electrogram (LA) in DDD mode, varied by 3.2 ± 12.0 ms (P = 0.254) and 0.6 ± 4.9 ms (P = 0.594), respectively.
Left-atrial electromechanical action (LA-EAClong) and left-ventricular electromechanical latency period (SV-EACshort)
The most significant exercise-related changes concerned the left-atrial electromechanical action (LA-EAClong). During exercise, this interval varied significantly by –10.7 ± 16.1 ms (P = 0.008). In comparison, the left-ventricular latency period (SV-EACshort) varied only by –1.3 ± 15.1 ms (P = 0.705). The difference between these intervals represents the electromechanical component of the optimal AV delay.
Calculation of the optimal AV delay
We succeeded in defining the optimal AV delays for each patient for rest and submaximal exercise in both modes. The results are shown in Table 3.
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As a consequence of the above results, compared to the resting values (AVDoptVDD = 101.9 ± 33.0 ms and AVDoptDDD = 172.4 ± 48.3 ms), the mean value of the optimal AV delay during submaximal exercise conditions in VDD mode was found to be 6.2 ± 16.1 ms shorter (AVDoptVDD = 95.7 ± 39.2 ms, P = 0.101) without statistical significance. In DDD operation however, the optimal AV delay of –8.8 ± 14.5 ms during submaximal exercise conditions was significantly shorter (AVDoptDDD = 163.7 ± 48.3 ms, P = 0.014). In DDD pacing, AVDopt was shortened by 2.6 ms/10 bpm.
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Discussion |
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In order to determine whether it makes sense to activate the rate adaptive AV delay in CRT, we determined the AVDopt in resting as well as exercise conditions. We are the first to implement the method described by Ismer et al.23
to calculate AVDopt in 20 patients with CRT. The findings regarding the electrical component of the optimal AV-interval were in accordance with formerly published data. These studies showed that the pacemaker related IACT in VDD and DDD pacing can be seen as a constant for each individual.16,21,23 Consequently, only the electromechanical component of the AV delay can be responsible for the heart rate dependent changes in AVDopt. The electromechanical component of AVDopt is the difference between the two electromechanical intervals: left-atrial electromechanical action (LA-EAClong) and left-ventricular electromechanical latency period (SV-EACshort). We found a significant reduction of the interval LA-EAClong (left-atrial electromechanical action) by –10.7 ± 16.1 ms (P = 0.008) during exercise, while the interval of SV-EACshort (left-ventricular electromechanical latency period) was only shortened by –1.3 ± 15.1 ms (P = 0.705), which lacks statistical significance.
The only other study to date of LA-EAClong and SV-EACshort during exercise was performed in patients with AV block and a normal EF (55 ± 8%), and in accordance with our findings resulted in a non-significant shortening of SV-EACshort (–2.6 ± 21.8 ms; P = 0.604).21
The same study found that the left-atrial electromechanical action (LA-EAClong) varied the most of all the various components of AVDopt, although statistical significance was not achieved (–8.4 ± 32.7 ms; P = 0.277).21 A review of all of the published findings on the electromechanical component of AV delay to date suggests that LA-EAClong is the component which is most influenced by the heart rate, especially in CRT patients as we show here for the first time. A definitive statement, however, cannot be given because some of the findings were not statistically significant.
Fittingly, Ismer et al.,26 found that the electromechanical component of AVDopt correlated to the ejection fraction, which would explain the differences in the findings in patients with heart failure compared to patients with almost normal ejection fractions.
Consideration of the AVDopt reveals that the adaptations under exercise with DDD-stimulation, in contrast to VDD-pacing, are significant, with a change in AVDopt of –8.8 ± 14.5 ms with an increase in heart rate of 22.5 ± 9.6 bpm which translates into a shortening by 2.6 ms per 10 bpm.
Two primary reasons for the lack of significant findings regarding the changes in AVDopt under VDD-stimulation could be: (i) the reduced accuracy in the measurements of the interatrial intervals, which depend on the exact triggering of the right-atrial deflection; (ii) the relatively small increases in heart rate because of the reduced capacity for exercise in our patient collective with heart failure which results, subsequently, in only small changes in the various measured parameters.
In healthy subjects, the duration of the natural atrioventricular conduction interval has been reported to decrease with exercise-increased heart rate.19,20 Daubert et al.19 observed a physiological shortening of the atrioventricular conduction delay in 10 healthy subjects with a decrease of 4 ± 2.1 ms per 10 bpm, at mean. Hence, our results are congruent with those of Daubert et al.19 regarding the shortening of AVDopt during exercise.
To our knowledge, the only other study of rate-adaptive AV delay in CRT patients is a study by Scharf et al.22 In this study, the AV delay optimization was performed in 36 patients using the maximum LVOT-VTI determined by echocardiography. In the investigation, the authors came to the conclusion that the optimal AV delay increased during exercise (20 ms per 10 bpm). The authors suggest that the improvement of diastolic filling under the conditions of a longer AV-interval is a possible explanation for this unexpected result, although diastolic parameters were not examined in the study. Furthermore, it has been speculated that a progressive fusion at longer AVDs might increase ventricular resynchronization during exercise.
The results of Scharf et al.22 and our findings cannot be brought into congruence, but our results are in congruence with the other to date published findings regarding the rate-adaptive AV delay showing a shortening of optimal AV delay with increased heart rate. The shortcoming of our investigation is that significant changes were only found for AVDoptDDD, while no significant change in AVDoptVDD between rest and exercise was established. Consequently, the shortening of AVDopt by 2.6 ms/10 bpm can only be applied to DDD pacing.
According to our results, the recommendation by Scharf et al.22 to set the rate adaptive AV delay to + 20 ms/10 bpm in CRT patients should be followed only with extreme caution.
Until further investigations have been performed, for example ones using the myocardial performance index,27 to clarify whether AVDopt in CRT patients is shortened or lengthened under exercise conditions, the rate-adaptive AV delay parameter in CRT patients should be turned off.
Study limitations
In order to carry out the multiple complex measurements under controlled exercise conditions, it was necessary to carry out this study under submaximal, instead of maximal, exercise conditions. Maximal exercise conditions with greater increases in heart rate would potentially result in larger changes in AVDopt. A further limitation is that in the method we used, only an optimization of the diastolic function was considered, the systolic function was not examined.
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Conclusions |
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Our study of CRT patients with an average heart rate increase of 22 bpm under submaximal exercise conditions did not reveal significant difference in pacemaker-related IACT and left-ventricular electromechanical latency period (SV-EACshort). However, the left-atrial electromechanical action (LA-EAClong) significantly varied by –10.7 ± 16.1 ms (P = 0.008) during exercise. Consequently, the whole electromechanical component of AVDopt (LA-EAClong–SV-EACshort) was shortened significantly (P = 0.008) between 60.3 ± 36.9 ms and 51.0 ± 33 ms.
In contrast to AVDoptVDD, AVDoptDDD revealed a significant change between rest and submaximal exercise conditions of –8.8 ± 14.5 ms (P = 0.014). Therefore, for DDD pacing, the resulting shortening of AVDopt is 2.6 ms/10 bpm.
Considering the studies performed to date, the rate-adaptive AV delay parameter should be deactivated in CRT.
Conflict of interest: none declared.
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References |
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