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Shortening of paced QRS duration after electrocardiographic optimization of left ventricular pacing vector in patients treated with Cardiac Resynchronization Therapy
Accepted Manuscript Shortening of paced QRS duration after electrocardiographic optimization of left ventricular pacing vector in patients treated with Cardiac Resynchronization Therapy
Casper Lund-Andersen, Helen H. Petersen, Christian Jøns, Berit T. Philbert, Michael Vinther, Jesper H. Svendsen PII: DOI: Reference:
S0022-0736(18)30085-2 doi:10.1016/j.jelectrocard.2018.04.016 YJELC 52618
To appear in: Please cite this article as: Casper Lund-Andersen, Helen H. Petersen, Christian Jøns, Berit T. Philbert, Michael Vinther, Jesper H. Svendsen , Shortening of paced QRS duration after electrocardiographic optimization of left ventricular pacing vector in patients treated with Cardiac Resynchronization Therapy. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Yjelc(2017), doi:10.1016/j.jelectrocard.2018.04.016
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Shortening of paced QRS duration after electrocardiographic optimization of Left Ventricular Pacing Vector in patients treated with Cardiac Resynchronization Therapy.
Casper Lund-Andersen1, Helen H. Petersen1†, , Christian Jøns1, Berit T. Philbert1, Michael Vinther1,
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Jesper H. Svendsen1.
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(1) Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen,
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Blegdamsvej 9, DK-2100 Copenhagen East, Denmark
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(†) Deceased
Corresponding author: Casper Lund-Andersen, Department of Cardiology, Section 9441, The Heart
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Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen East,
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[email protected]
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Denmark. Tel: +45 2613 2757, Fax: +45 3445 7705 E-mail address: casper.lund-
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Abstract Backgroud: Choice of left ventricular pacing vector (LVPV) affects the QRS-duration (QRSd) in patients with Cardiac Resynchronization Therapy (CRT). It is not known whether testing all LVPVs reduces QRSd compared to device-based “standard-programming”.
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Methods:
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In patients implanted with CRT several ECGs were recorded for each usable LVPV (no phrenic nerve stimulation and threshold <3.5 V) and during “standard-programming” after device-based optimization of AV/VV delays.
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Results:
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22 consecutive patients were included. Average QRSd reduction after CRT + ”standardprogramming” was 27.3±22 ms . Additional QRSd-reduction was possible in 4 patients by changing the LVPV, and in 5 other patients after optimization of AV- and VV delays without changing LVPV. Conclusions:
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Shortening of QRSd compared to “standard-programming” was possible approximately 40% of these patients treated with CRT by testing all LVPVs and re-optimizing AV/VV delays during follow-up. Studies of clinical effects are needed.
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Introduction Cardiac resynchronization therapy (CRT) is an established therapy for patients with reduced left ventricular (LV) function and electromechanical dyssynchrony [1, 2]. Shortening of the QRS-duration (QRSd) after implantation is associated with favorable clinical outcome and is often used in clinical practice as a surrogate marker of successful resynchronization [3, 4]. The use of quadripolar LV leads
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increases the number of potential pacing vectors. Recent evidence shows that the paced QRSd as
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well as hemodynamics are affected by choice of left ventricular pacing vector (LVPV) offered by the
addition to programming of the AV- and VV-delay.
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quadripolar LV lead [5, 6]. This suggests that selection of LVPV could be used to optimize therapy in
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After implantation a ”standard-programming” is often chosen by device based algorithms without the use of 12-lead ECG and without testing all possible LVPVs. In this study we investigated whether
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it was possible to shorten the paced QRSd compared to “standard-programming” by systematically
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testing all available LVPVs.
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After implantation device reconfiguration/optimization is often required, but current guidelines do not provide recommendations for this process [1]. Easy and widely available options for optimization
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are therefore warranted.
Several small retrospective studies suggest favorable outcome in patients with shortening of QRSd
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(∆QRSd) after implantation [3]. Whether this can be used as an optimization parameter is however without consensus due to ambiguous results from larger datasets and lack of randomized trials of specific optimization protocols [7, 8]. Current left ventricular (LV) leads offer 10-16 left ventricular pacing vectors (LVPVs) and recent studies show that pacing from individual LVPVs results in large variation in hemodynamics correlated with changes in QRSd [5, 6]. It has therefore been proposed that utilizing all LVPVs and choosing the LVPV that results in the shortest paced QRSd could provide therapeutic benefit. This would be an
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easy, non-invasive and readily available optimization method and should be investigated in future prospective trials. Other factors, however, such as phrenic nerve stimulation (PNS) and capture threshold also influence the choice of LVPV. This might limit the number of available LVPVs. In this study we therefore
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practice by testing all available LVPVs in patients implanted with CRT.
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wanted to investigate to what extend it was possible to reduce the paced QRSd compared to current
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We hypothesized that in a substantial fraction of patients with a CRT-device it was possible to reduce
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the QRS-duration by utilizing all pacing vectors.
Methods
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Study population
This was a single center study at a tertiary referral hospital, Copenhagen University Hospital,
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Rigshospitalet. Consecutive patients implanted with a CRT system were approached for recruitment
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after implantation or during routine follow-up in our outpatient clinic. Only patients with class I indication for CRT in European Society of Cardiology Guidelines 2013 were considered for inclusion: LBBB and QRS>150 ms (Class Ia), LBBB 120 ms < QRSd < 150 ms (Class Ib) and upgrade from
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pacemaker (PM) to CRT (Class Ib)
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Specifically the main criteria for inclusion were: De novo implantation of a CRT-system or upgrade with a quadripolar lead (Quartet – St. Jude Medical, USA or Attain Performa – Medtronic, Minneapolis, USA) for heart failure indication, sinus rhythm, stable ischemic or non-ischemic dilated cardiomyopathy on optimal medical therapy, native left bundle branch block (LBBB), QRSd > 120 ms, ≥ 18 years of age and able to give informed consent. Exclusion criteria were: atrial fibrillation on day of study, implantation due to bradycardia with expected high percentage of right ventricular pacing.
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CRT implantation Patients underwent routine CRT- implantation at our institution. During implantation the CRT device was programmed with “standard-programming” at the discretion of the implanting physician and pacemaker technician using the interval from the first deflection of the surface ECG to the bipolar left ventricular electrocardiogram (QLV) and onboard device based algorithms , which is current practice
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at our institution.
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Study procedure
Patients were planned for participation in this study approximately one month after implantation
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and “standard-programming”. On the day of study, patients were placed in the supine position and
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ECG electrodes were attached according to standard practice. As described in the following, participants underwent recording of ECGs during: “standard-programming”, “standard-programming
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QRSd with standard-programming
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+ optimization of AV- and VV-delays” and during each available LVPV.
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QRSd with standard-programming First a series of ten 12-lead ECGs were recorded without making any changes to device settings. These were considered ECGs with “standard-programming” (programmed during initial
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implantation), and used to calculate the QRSd during “standard-programming”. This high number
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was chosen since the ECGs were also used to estimate the variance of ECG measurement. Hereafter AV- and VV-delays were re-optimized using standard device based algorithms (Adaptive CRT, Medtronic and QuickOpt, St.Jude Medical) before recording of three ECGs. These three ECGs were considered as ECGs for “standard-programming + AV/VV-optimization”.
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QRSd after re-optimization of AV- and VV-delays After recording of ECGs during “standard-programming” AV- and VV-delays were re-optimized using standard device based algorithms (Adaptive CRT, Medtronic and QuickOpt, St.Jude Medical). Optimization was done without changing the LVPV. After optimization three ECGs were recorded and used to calculate QRSd for “standard-programming + AV/VV-optimization”.
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ECGs with each available pacing vector
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QRSd with each available pacing vector Each available LVPV was hereafter examined in random order by device based algorithms. Ten, 14
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and 16 LVPVs were available for patients implanted with St. Jude Medical CRT-P, St. Jude Medical
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CRT-D and Medtronic CRT-D, respectively. LVPVs with threshold <3.5V and without phrenic nerve stimulation (PNS) were classified as usable. For each usable LVPV AV- and VV-delays were optimized
before recording of at least three ECGs.
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using standard device based algorithms (Adaptive CRT, Medtronic and QuickOpt, St.Jude Medical)
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ECG recordings All ECGs were recorded by the same examiner (CLA) using the same electrocardiograph, GE MAC1600 (GE Healthcare, Chalfont, St. Giles, UK), and the QRSd calculated automatically by the onboard algorithm (Marquette 12SL, GE Healthcare) was used for further analysis. All ECGs were recorded
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with patients in the supine position and at rest. A minimum of 15 seconds was allowed between
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successive recordings. ECGs were inspected on screen at time of recording and ECGs with gross noise, more than one premature ventricular complex or more than one type of QRS morphology was discarded during recording. During this on-screen inspection the examiner (CLA) was unaware of the measured value of QRSd. Measurement of intra-cardiac electrical delays In patients implanted with a St. Jude Device we recorded the values of time of electrical delay from RV sensing to sensing in each of the four LV poles (RV-D1, RV-M2, RV-M3, RV-P4) recorded by the programmer (Merlin®, St. Jude Medical). These values were chosen as they are used by the device
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algorithm to calculate the optimal LVPV and have been shown to be correlated with outcome[9]. A mean electrical delay was calculated for each patient as a mean of the four recorded delays. For each patient the electrical delay along the LV lead (intrapole-delay) was calculated as the difference between the maximal recorded delay and the minimal recorded delay.
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Statistics Continuous variables are expressed as mean ±SD or median (Quartile1 – Quartile3) for non-normally
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distributed variables as appropriate. Differences between groups were calculated with one-sided
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ANOVA or Kruskal-Wallis rank test for continuous variables and with Chi-squarred test or Fisher’s
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exact test for proportions as appropriate.
A shared variance for all recordings was calculated using a linear mixed model with random intercept
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for each examined LVPC.
The mean QRSd was calculated during “standard-programming”, “standard-programming + AV/VV
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optimization” and during each usable LVPV. The mean QRSd for each tested configurations was
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compared to the mean QRSd with “standard-programming” using a Student’s t-test for non-paired data with equal variance. The shared variance found for all recordings was used for these tests. In
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each test the level of significance was adjusted with Bonferroni adjustment for multiple comparisons with an overall one-sided level of significance at the 5% level. In all other statistical tests the level of
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significance was two-sided at the 5% level. Confidence intervals were calculated at the 95% limit. The correlation between electrical delay of pacing cathode and paced QRSd was calculated using a linear mixed model with fixed effect of electrical delay and patient specific random effects. All calculations were made using SAS (Version 9.4, SAS Institute) and R-software and all models were validated by visual inspection of residual plots.
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In this study we wanted to investigate in what fraction of patients a reduction of QRSd is possible. The number of included patients affects the confidence limits for our estimate. If 15, 24, 45, 90 patients were included in the study, the fraction (ranging from 0 to 1) can be estimated with 95% confidence limits of ±0.2, ±0.17, ±0.15, ±0.09. (Confidence limits are calculated for an expected
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fraction of 0.33). Due to the exploratory nature of our study we aimed at including 20-25 patients.
Ethical considerations
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The study complies with the Declaration of Helsinki. All participants received oral and written
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information about the study and signed informed consent documents upon inclusion in the study. The study has been approved by the Ethics Committee of the Capital Region of Denmark and by
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Danish data safety authorities.
Results
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From April 2016 to February 2017 a total of 22 patients (16 males, age 65.7±9.6, five with ischemic
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heart disease, 17 with non-ischemic dilated cardiomyopathy) were included and studied at a median of 86 (38-115) days after CRT implantation. (Patient characteristics are shown in table 1).
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After implantation and “Standard programming” the most frequent LVPVs were D1-M2 in 12 patients
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and M3-M2 in 5 patients. The average paced AV-delay was 165.5ms, sensed AV-delay 123ms, and interventricular delay 20ms (indicating left ventricle pacing before right). Implantation of CRT and “standard-programming” had resulted in mean paced QRSd reduction of 27.3±21.9ms (p<0.001) compared to before CRT implantation. Prior to implantation the mean QRSd was 169.9±22ms with QRSd>150ms in 21 (95%) of patients. Implantation of CRT and “standard-programming” had resulted in an average reduction of QRSd of 27.3±21.9ms (p<0.001). During “standard-programming” the most frequent LVPVs were D1-M2 in 12
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patients and M3-M2 in 5 patients. The average paced AV-delay was 165.5ms, sensed AV-delay 123ms, and interventricular delay 20ms (indicating left ventricle pacing before right). A total of 270 LVPVs were available in the 22 patients. Due to high pacing thresholds and PNS only 139 LVPVs, a median of 6 (4-9) per patient were considered usable. 3 ECGs were also recorded for
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“standard-programming + AV/VV-optimization”, as described in the methods section.., why a median of 7 (5-10) configurations were tested per patient. In total 632 ECGs (median of 3 per LVPV) were
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analyzed in this study.
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Reduction of QRS-duration
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In 4 out of 22 patients (18%, CI:6-41%) it was possible to obtain a statistical significant reduction of paced QRSd compared to “standard-programming” by changing the LVPV (see figure 1). In these 4
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patients changes in LVPV were: D1-M2 to D1-P4, D1-M2 to M3-M2, D1-RV to M3-P4 and M3-P4 to M2-P4. The electrical differences between the used cathodes were 0ms, 1ms, 13ms, respectively (For
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one patient the data were not complete).
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In 5 out of the 22 patients (23% CI: 9-46%) renewed AV-/VV-optimization with a device-based algorithm resulted in shorter QRSd, with no additional benefit of optimizing the LVPV. In these
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patients the changes in AV-paced delay, AV-sensed delay and VV-delay were a median of -5,-5 and 13 ms respectively (negative numbers indicating in increased delay).
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Device settings and changes during optimization are seen in table 2. We found no significant differences between the patients with and without significant QRSd shortening with respect to clinical characteristics or pacemaker settings. There was a tendency that patients without significant QRSd shortening had the largest reduction in paced QRSd after implant of CRT, but this was not significant.
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Correlation between native electrical delay and paced QRSd Complete recordings of the time delay between sensing in RV and sensing in each of the four LV poles were available in 19 patients. The mean time delay (averaged over all four poles in all patients) was 131.8 ms (±27.8) with no statistical difference between patients with and without possible QRS shortening (p=0.76). Intra-pole delay (measured as maximal electrical delay – minimal electrical
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delay) for each patient was 14.9 ±7.3 ms with no difference between response groups (p=0.74)
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We found no association between the electrical delay at a particular cathode and the corresponding
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paced QRSd for individual patients (p=0.95).
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Discussion
The main finding of the present study is that in 18% of patients with CRT systematic testing of all
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LVPVs resulted in significant reduction of the paced QRSd compared to “standard-programming”. Furthermore shortening of the paced QRSd after re-optimization of AV/VV-delay without changing
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LVPV was seen in 23% of patients.
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Accumulating evidence shows that the choice of LVPV affects paced QRSd as well as acute hemodynamics [5, 6]. Because narrowing of the QRSd after implantation of CRT is shown to be
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associated with favorable clinical outcome adequately choosing LVPV has been suggested as a way to
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optimize treatment in addition to programming of AV and VV-delay [3, 5]. Most patients in our study had already experienced significant symptomatic improvement and reduction of QRSd after routine implantation of CRT and device-programming by standard algorithms. Additional testing of all available LVPVs resulted in further shortening of QRSd in 18% of patients. We found no differences between patients with and without significant QRSd shortening with respect to clinical characteristics or pacemaker settings. There was a tendency that patients with the largest reductions in paced QRSd after implantation of CRT were less likely to benefit from further optimization of AV/VV-delays and/or changing of LVPV. Although this observation was not
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statistically significant it may suggest that that these patients had already reached their maximal potential for electrical modulation as reflected by shortening of QRSd. Patients in our study were implanted with CRT-devices from St. Jude Medical and Medtronic that are all equipped with onboard algorithms that select LVPV based on the cathode with the latest electrical
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activation during native conduction. This strategy was questioned in a recent study by Trolese et al. where only 3 out of 16 patients achieved the best possible hemodynamics by selecting LVPV with the
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latest electrical activation [5]. In our study onboard algorithms selected the best possible pacing
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vector in 80% of patients, but we did not find any correlation between the time of electrical
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activation and paced QRSd.
Time of electrical activation during native conduction varies considerably between target veins of the
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coronary sinus within individual patients (often up to 100 ms) and targeting the vein with the latest electrical activation yields superior response to CRT [10-12]. Changes in hemodynamics are also
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found to be large when pacing in different target veins but only small using different LVPVs within
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the same vein [11]. In our study the electrical difference between the four cathodes along the quadripolar lead was only 14.9±7.3 ms; similar to 20.4 ±12.3 ms found by Trolese et al., and thus
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much smaller than electrical delays between individual veins. The electromechanical changes during selection of LVPV can therefore be expected to be small in most patients. This probably explains
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some of the contrasting results using the onboard algorithms. Adequate physical placement of the LV lead seems to offer much greater possibilities for electromechanical improvements. Interestingly small changes in AV and VV-delays (5-10 ms), during renewed AV and VV-optimization, resulted in significant reduction of paced QRSd in about 25% of patients in our study. The effect of AV and VV-optimization is much debated, and whether frequent optimization by onboard algorithms has any clinical benefit is currently being investigated [1, 13, 14].
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Despite the small differences of 10 ms between LVPVs and despite small changes in AV and VVdelays during optimization we still observed significant QRSd shortening in a proportion of patients. This suggests that there may be mechanisms during pacing that we are not aware of. For example anodal stimulation is possible during bipolar LV pacing since all poles are in contact with the vessel
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wall simultaneously. Reports show that this occurs frequently and could potentially be beneficial [15]. It is also possible that certain LVPVs and/or in combination with AV/VV delays cause favorable
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electromechanical activation such as fusion or other phenomena that are yet to be discovered[16].
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Clinical implications
Changing the LVPV has been suggested as an optimization parameter for patients treated with CRT.
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Systematic testing of all LVPVs can result in a significant reduction of paced QRSd in a small fraction of patients but whether this translates into a clinical effect needs investigation in large prospective
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clinical trials. Systematic testing is cumbersome and may not be feasible in all patients with heart failure. Until clinical benefit is demonstrated we therefore do not recommend routine use of LVPV
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optimization, but it could be tried in patients without initial response to CRT.
Limitations
This study included relatively few patients. We settled on a lower number of patients due to the
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exploratory nature of the study since many more patients were needed in order to increase the precision of our estimate considerably. The limited sample size did not allow further subgroup
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analysis and it is likely that stronger associations can be found in larger studies. We used automated measurement of QRSd with the GE Mac1600. We did not find previous studies of the precision of this particular electrocardiograph, but data from other electrocardiographs suggest that measurements can vary considerably [17]. To reduce the impact of measurement variability we included automated QRSd measurements from at least three independent ECGs for each tested configuration. We did not include manual measurement of QRSd since this also shows similar large inter and intra-observer variability [18]. Furthermore manual measurement is very
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cumbersome and we do not believe it is realistic to implement manual measurement during optimization in a clinical setting. The ECGs discarded during recording were not stored and bias is possible. The examiner (CLA) was unaware of the value of QRSd during recording and we consider this reason of bias to be minor.
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Patients in our study primarily had devices from St. Jude Medical, which reflects the current implant
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practice at our institution. The results may therefore not necessarily apply to patients with CRT
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devices from other manufacturers.
Conclusion:
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Compared to “standard-programming” chosen by device based algorithms a significant reduction of paced QRSd was possible in 18% of these 22 patients treated with CRT by changing the left ventricular pacing vector. Furthermore shortening of the paced QRSd after re-optimization of AV/VV-
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delay without changing LVPV was seen in other 23% of patients. This has possible implications for optimizing patients with CRT, but whether these changes can be translated to clinical effects remains
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to be investigated in future clinical trials.
Acknowledgements
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Funding This work was supported by ‘Innovationsfonden’ (grant #72-2014-1) Conflicts of interest: C. Lund-Andersen has received congress fees from Medtronic and St. Jude Medical. Jesper H. Svendsen has received grants from Medtronic, Biotronik, Gilead, St. Jude Medical; speaker fees from Medtronic, Biotronik, Astra Zeneca, Boehringer Ingelheim, Bayer. C. Jønz has received consultant fees from Biotronik.
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Abraham WT, Gras D, Yu CM, Guzzo L, Gupta MS, and Committee FS. Rationale and design of a randomized clinical trial to assess the safety and efficacy of frequent optimization of cardiac resynchronization therapy: the Frequent Optimization Study Using the QuickOpt Method (FREEDOM) trial. Am Heart J 2010;159:944-48 e1.
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Tables Table 1: Baseline characteristics
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0/15/7/0 20 (90%)
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5/17 21.6±8.5 11/11
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21/1 21/1 169.8±21.9 21 (95%)
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Male sex, n (%) Age at implant, mean ± SD Heart failure etiology IHD/DCM, n/n Pre implant LVEF, mean ±SD CRTD/CRTP NYHA class, before implant I/II/III/IV Improvement of symptoms after implant of CRT, n(%) Device manufactorer, St. Jude/Medtronic De novo implantation / upgrade Pre-implant QRSd, mean ±SD Patients with QRSd>150 ms, n (%)
Patients n=22 16 (72) 65.7 ± 9.6
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SD – Standard Deviation. LVEF – Left Ventricular Ejection Fraction. CRTD – Cardiac Resynchronization Therapy with defibrillator. CRTP – Cardiac Resynchronization Therapy pacemaker. NYHA – New York Heart Association function class. QRSd – QRS duration. IHD – ischemic heart disease. DCM – nonischemic dilated cardiomyopathy.
ACCEPTED MANUSCRIPT Tabel 2. Patient characteristics, pacemaker settings and recorded intra-cardiac delays grouped according the possibility of QRSd shortening. No significant QRSd shortening
QRSd shortening due to AV/VV optimization
QRSd shortening due to change of LVPV
(n=13)
(n=5)
(n=4)
Pre implant LVEF, mean±SD
22±10
Pre implant NYHA class, median (Q1-Q3)
2 (2-2)
Pre implant QRSd, mean±SD, ms
170±24
QRS reduction after CRT implant, mean±SD, ms
33±20
Paced AV-delay at "standard-programming", median (Q1-Q3), ms VV-delay at "standard-programming", median (Q1-Q3), ms
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Sensed AV-delay at optimal programming, median (Q1-Q3), ms Paced AV-delay at optimal programming, median (Q1-Q3), ms
2 (2-3)
3 (3-3)
173±26
165±13
0.87
18±27
0.40 0.38
120 (110-130)
125 (120-130)
120 (100-150)
0.76
160 (150-180)
165 (150-170)
150 (140-200)
0.85
28 (15-50)
00 (00-15)
30 (-20-35)
0.18
130 (120-150)
120 (110-120)
175 (150-200)
170 (160-170)
20 (00-35)
45 (35-50)
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VV-delay at optimal programming, median (Q1-Q3), ms
0.96
3 (75%)
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23±06
20±32
12 (92%)
Pacemaker settings
21±04
5 (100%)
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Response after CRT-implant and "standard-programming" §§, n (%)
Sensd AV-delay at "standard-programming", median (Q1-Q3), ms
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p§
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Change in AV-dealy from "standard" to optimal programming, median (Q1-Q3), ms
-05 (-20-00)
00 (-10-30)
Change in paced AV-delay from "standard" to optimal programming, median (Q1-Q3), ms
-05 (-20-00)
-10 (-30-30)
Change in VV-delay from "standard" to optimal programming, median (Q1-Q3), ms
-13 (-40--03)
-15 (-65--05)
31±08
39±13
14±08
17±07
14±06
0.76
137±28
128±33
125±18
0.74
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Reduction in QRSd from "standard" to optimal programming, mean±SD , ms Electrical delays Intralead delay§§§, mean±SD, ms Electrical delay RV->LV cathode
§§§§
, mean±SD, ms
ACCEPTED MANUSCRIPT LVEF – left ventricular ejection fraction. NYHA – New York Heart Association class. QRSd – QRS duration. CRT – Cardiac Resynchronization Therapy. AV – atrioventricular. SD – standard deviation. VV – inter-ventricular. § P-values for equality among groups. §§ Response defined as patient-reported improvement of symptoms. §§§ Intralead delay measured for each patient as the pole with the longest electrical delay minus the pole with the shortest delay. §§§§ For each patient calculated as an average of time of electrical delay from RV sensing to sensing in each of the four LV poles.
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Figures
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Figure 1. QRS-durations with ”standard-programming” and ”optimal-programming” for each patient. One column represents one patient. The top of each bar represents the QRS-duration during ”standardprogramming”; the horizontal line below represents the QRS-duration with “optimal-programming”. Patients with significant reduction due to change of left ventricular pacing vector are colored green. Patients with significant reduction due to re-optimization of AV/VV-delays, but with no effect of change of pacing vector are colored red. Patients without significant shortening of the QRS-duration are colored white.
Casper Lund-Andersen, Helen H. Petersen, Christian Jøns, Berit T. Philbert, Michael Vinther, Jesper H. Svendsen PII: DOI: Reference:
S0022-0736(18)30085-2 doi:10.1016/j.jelectrocard.2018.04.016 YJELC 52618
To appear in: Please cite this article as: Casper Lund-Andersen, Helen H. Petersen, Christian Jøns, Berit T. Philbert, Michael Vinther, Jesper H. Svendsen , Shortening of paced QRS duration after electrocardiographic optimization of left ventricular pacing vector in patients treated with Cardiac Resynchronization Therapy. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Yjelc(2017), doi:10.1016/j.jelectrocard.2018.04.016
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Shortening of paced QRS duration after electrocardiographic optimization of Left Ventricular Pacing Vector in patients treated with Cardiac Resynchronization Therapy.
Casper Lund-Andersen1, Helen H. Petersen1†, , Christian Jøns1, Berit T. Philbert1, Michael Vinther1,
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Jesper H. Svendsen1.
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(1) Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen,
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Blegdamsvej 9, DK-2100 Copenhagen East, Denmark
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(†) Deceased
Corresponding author: Casper Lund-Andersen, Department of Cardiology, Section 9441, The Heart
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Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen East,
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[email protected]
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Denmark. Tel: +45 2613 2757, Fax: +45 3445 7705 E-mail address: casper.lund-
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Abstract Backgroud: Choice of left ventricular pacing vector (LVPV) affects the QRS-duration (QRSd) in patients with Cardiac Resynchronization Therapy (CRT). It is not known whether testing all LVPVs reduces QRSd compared to device-based “standard-programming”.
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Methods:
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In patients implanted with CRT several ECGs were recorded for each usable LVPV (no phrenic nerve stimulation and threshold <3.5 V) and during “standard-programming” after device-based optimization of AV/VV delays.
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Results:
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22 consecutive patients were included. Average QRSd reduction after CRT + ”standardprogramming” was 27.3±22 ms . Additional QRSd-reduction was possible in 4 patients by changing the LVPV, and in 5 other patients after optimization of AV- and VV delays without changing LVPV. Conclusions:
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Shortening of QRSd compared to “standard-programming” was possible approximately 40% of these patients treated with CRT by testing all LVPVs and re-optimizing AV/VV delays during follow-up. Studies of clinical effects are needed.
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Introduction Cardiac resynchronization therapy (CRT) is an established therapy for patients with reduced left ventricular (LV) function and electromechanical dyssynchrony [1, 2]. Shortening of the QRS-duration (QRSd) after implantation is associated with favorable clinical outcome and is often used in clinical practice as a surrogate marker of successful resynchronization [3, 4]. The use of quadripolar LV leads
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increases the number of potential pacing vectors. Recent evidence shows that the paced QRSd as
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well as hemodynamics are affected by choice of left ventricular pacing vector (LVPV) offered by the
addition to programming of the AV- and VV-delay.
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quadripolar LV lead [5, 6]. This suggests that selection of LVPV could be used to optimize therapy in
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After implantation a ”standard-programming” is often chosen by device based algorithms without the use of 12-lead ECG and without testing all possible LVPVs. In this study we investigated whether
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it was possible to shorten the paced QRSd compared to “standard-programming” by systematically
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testing all available LVPVs.
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After implantation device reconfiguration/optimization is often required, but current guidelines do not provide recommendations for this process [1]. Easy and widely available options for optimization
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are therefore warranted.
Several small retrospective studies suggest favorable outcome in patients with shortening of QRSd
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(∆QRSd) after implantation [3]. Whether this can be used as an optimization parameter is however without consensus due to ambiguous results from larger datasets and lack of randomized trials of specific optimization protocols [7, 8]. Current left ventricular (LV) leads offer 10-16 left ventricular pacing vectors (LVPVs) and recent studies show that pacing from individual LVPVs results in large variation in hemodynamics correlated with changes in QRSd [5, 6]. It has therefore been proposed that utilizing all LVPVs and choosing the LVPV that results in the shortest paced QRSd could provide therapeutic benefit. This would be an
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easy, non-invasive and readily available optimization method and should be investigated in future prospective trials. Other factors, however, such as phrenic nerve stimulation (PNS) and capture threshold also influence the choice of LVPV. This might limit the number of available LVPVs. In this study we therefore
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practice by testing all available LVPVs in patients implanted with CRT.
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wanted to investigate to what extend it was possible to reduce the paced QRSd compared to current
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We hypothesized that in a substantial fraction of patients with a CRT-device it was possible to reduce
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the QRS-duration by utilizing all pacing vectors.
Methods
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Study population
This was a single center study at a tertiary referral hospital, Copenhagen University Hospital,
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Rigshospitalet. Consecutive patients implanted with a CRT system were approached for recruitment
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after implantation or during routine follow-up in our outpatient clinic. Only patients with class I indication for CRT in European Society of Cardiology Guidelines 2013 were considered for inclusion: LBBB and QRS>150 ms (Class Ia), LBBB 120 ms < QRSd < 150 ms (Class Ib) and upgrade from
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pacemaker (PM) to CRT (Class Ib)
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Specifically the main criteria for inclusion were: De novo implantation of a CRT-system or upgrade with a quadripolar lead (Quartet – St. Jude Medical, USA or Attain Performa – Medtronic, Minneapolis, USA) for heart failure indication, sinus rhythm, stable ischemic or non-ischemic dilated cardiomyopathy on optimal medical therapy, native left bundle branch block (LBBB), QRSd > 120 ms, ≥ 18 years of age and able to give informed consent. Exclusion criteria were: atrial fibrillation on day of study, implantation due to bradycardia with expected high percentage of right ventricular pacing.
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CRT implantation Patients underwent routine CRT- implantation at our institution. During implantation the CRT device was programmed with “standard-programming” at the discretion of the implanting physician and pacemaker technician using the interval from the first deflection of the surface ECG to the bipolar left ventricular electrocardiogram (QLV) and onboard device based algorithms , which is current practice
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at our institution.
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Study procedure
Patients were planned for participation in this study approximately one month after implantation
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and “standard-programming”. On the day of study, patients were placed in the supine position and
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ECG electrodes were attached according to standard practice. As described in the following, participants underwent recording of ECGs during: “standard-programming”, “standard-programming
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QRSd with standard-programming
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+ optimization of AV- and VV-delays” and during each available LVPV.
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QRSd with standard-programming First a series of ten 12-lead ECGs were recorded without making any changes to device settings. These were considered ECGs with “standard-programming” (programmed during initial
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implantation), and used to calculate the QRSd during “standard-programming”. This high number
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was chosen since the ECGs were also used to estimate the variance of ECG measurement. Hereafter AV- and VV-delays were re-optimized using standard device based algorithms (Adaptive CRT, Medtronic and QuickOpt, St.Jude Medical) before recording of three ECGs. These three ECGs were considered as ECGs for “standard-programming + AV/VV-optimization”.
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QRSd after re-optimization of AV- and VV-delays After recording of ECGs during “standard-programming” AV- and VV-delays were re-optimized using standard device based algorithms (Adaptive CRT, Medtronic and QuickOpt, St.Jude Medical). Optimization was done without changing the LVPV. After optimization three ECGs were recorded and used to calculate QRSd for “standard-programming + AV/VV-optimization”.
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ECGs with each available pacing vector
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QRSd with each available pacing vector Each available LVPV was hereafter examined in random order by device based algorithms. Ten, 14
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and 16 LVPVs were available for patients implanted with St. Jude Medical CRT-P, St. Jude Medical
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CRT-D and Medtronic CRT-D, respectively. LVPVs with threshold <3.5V and without phrenic nerve stimulation (PNS) were classified as usable. For each usable LVPV AV- and VV-delays were optimized
before recording of at least three ECGs.
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using standard device based algorithms (Adaptive CRT, Medtronic and QuickOpt, St.Jude Medical)
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ECG recordings All ECGs were recorded by the same examiner (CLA) using the same electrocardiograph, GE MAC1600 (GE Healthcare, Chalfont, St. Giles, UK), and the QRSd calculated automatically by the onboard algorithm (Marquette 12SL, GE Healthcare) was used for further analysis. All ECGs were recorded
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with patients in the supine position and at rest. A minimum of 15 seconds was allowed between
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successive recordings. ECGs were inspected on screen at time of recording and ECGs with gross noise, more than one premature ventricular complex or more than one type of QRS morphology was discarded during recording. During this on-screen inspection the examiner (CLA) was unaware of the measured value of QRSd. Measurement of intra-cardiac electrical delays In patients implanted with a St. Jude Device we recorded the values of time of electrical delay from RV sensing to sensing in each of the four LV poles (RV-D1, RV-M2, RV-M3, RV-P4) recorded by the programmer (Merlin®, St. Jude Medical). These values were chosen as they are used by the device
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algorithm to calculate the optimal LVPV and have been shown to be correlated with outcome[9]. A mean electrical delay was calculated for each patient as a mean of the four recorded delays. For each patient the electrical delay along the LV lead (intrapole-delay) was calculated as the difference between the maximal recorded delay and the minimal recorded delay.
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Statistics Continuous variables are expressed as mean ±SD or median (Quartile1 – Quartile3) for non-normally
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distributed variables as appropriate. Differences between groups were calculated with one-sided
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ANOVA or Kruskal-Wallis rank test for continuous variables and with Chi-squarred test or Fisher’s
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exact test for proportions as appropriate.
A shared variance for all recordings was calculated using a linear mixed model with random intercept
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for each examined LVPC.
The mean QRSd was calculated during “standard-programming”, “standard-programming + AV/VV
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optimization” and during each usable LVPV. The mean QRSd for each tested configurations was
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compared to the mean QRSd with “standard-programming” using a Student’s t-test for non-paired data with equal variance. The shared variance found for all recordings was used for these tests. In
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each test the level of significance was adjusted with Bonferroni adjustment for multiple comparisons with an overall one-sided level of significance at the 5% level. In all other statistical tests the level of
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significance was two-sided at the 5% level. Confidence intervals were calculated at the 95% limit. The correlation between electrical delay of pacing cathode and paced QRSd was calculated using a linear mixed model with fixed effect of electrical delay and patient specific random effects. All calculations were made using SAS (Version 9.4, SAS Institute) and R-software and all models were validated by visual inspection of residual plots.
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In this study we wanted to investigate in what fraction of patients a reduction of QRSd is possible. The number of included patients affects the confidence limits for our estimate. If 15, 24, 45, 90 patients were included in the study, the fraction (ranging from 0 to 1) can be estimated with 95% confidence limits of ±0.2, ±0.17, ±0.15, ±0.09. (Confidence limits are calculated for an expected
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fraction of 0.33). Due to the exploratory nature of our study we aimed at including 20-25 patients.
Ethical considerations
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The study complies with the Declaration of Helsinki. All participants received oral and written
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information about the study and signed informed consent documents upon inclusion in the study. The study has been approved by the Ethics Committee of the Capital Region of Denmark and by
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Danish data safety authorities.
Results
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From April 2016 to February 2017 a total of 22 patients (16 males, age 65.7±9.6, five with ischemic
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heart disease, 17 with non-ischemic dilated cardiomyopathy) were included and studied at a median of 86 (38-115) days after CRT implantation. (Patient characteristics are shown in table 1).
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After implantation and “Standard programming” the most frequent LVPVs were D1-M2 in 12 patients
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and M3-M2 in 5 patients. The average paced AV-delay was 165.5ms, sensed AV-delay 123ms, and interventricular delay 20ms (indicating left ventricle pacing before right). Implantation of CRT and “standard-programming” had resulted in mean paced QRSd reduction of 27.3±21.9ms (p<0.001) compared to before CRT implantation. Prior to implantation the mean QRSd was 169.9±22ms with QRSd>150ms in 21 (95%) of patients. Implantation of CRT and “standard-programming” had resulted in an average reduction of QRSd of 27.3±21.9ms (p<0.001). During “standard-programming” the most frequent LVPVs were D1-M2 in 12
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patients and M3-M2 in 5 patients. The average paced AV-delay was 165.5ms, sensed AV-delay 123ms, and interventricular delay 20ms (indicating left ventricle pacing before right). A total of 270 LVPVs were available in the 22 patients. Due to high pacing thresholds and PNS only 139 LVPVs, a median of 6 (4-9) per patient were considered usable. 3 ECGs were also recorded for
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“standard-programming + AV/VV-optimization”, as described in the methods section.., why a median of 7 (5-10) configurations were tested per patient. In total 632 ECGs (median of 3 per LVPV) were
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analyzed in this study.
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Reduction of QRS-duration
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In 4 out of 22 patients (18%, CI:6-41%) it was possible to obtain a statistical significant reduction of paced QRSd compared to “standard-programming” by changing the LVPV (see figure 1). In these 4
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patients changes in LVPV were: D1-M2 to D1-P4, D1-M2 to M3-M2, D1-RV to M3-P4 and M3-P4 to M2-P4. The electrical differences between the used cathodes were 0ms, 1ms, 13ms, respectively (For
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one patient the data were not complete).
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In 5 out of the 22 patients (23% CI: 9-46%) renewed AV-/VV-optimization with a device-based algorithm resulted in shorter QRSd, with no additional benefit of optimizing the LVPV. In these
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patients the changes in AV-paced delay, AV-sensed delay and VV-delay were a median of -5,-5 and 13 ms respectively (negative numbers indicating in increased delay).
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Device settings and changes during optimization are seen in table 2. We found no significant differences between the patients with and without significant QRSd shortening with respect to clinical characteristics or pacemaker settings. There was a tendency that patients without significant QRSd shortening had the largest reduction in paced QRSd after implant of CRT, but this was not significant.
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Correlation between native electrical delay and paced QRSd Complete recordings of the time delay between sensing in RV and sensing in each of the four LV poles were available in 19 patients. The mean time delay (averaged over all four poles in all patients) was 131.8 ms (±27.8) with no statistical difference between patients with and without possible QRS shortening (p=0.76). Intra-pole delay (measured as maximal electrical delay – minimal electrical
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delay) for each patient was 14.9 ±7.3 ms with no difference between response groups (p=0.74)
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We found no association between the electrical delay at a particular cathode and the corresponding
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paced QRSd for individual patients (p=0.95).
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Discussion
The main finding of the present study is that in 18% of patients with CRT systematic testing of all
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LVPVs resulted in significant reduction of the paced QRSd compared to “standard-programming”. Furthermore shortening of the paced QRSd after re-optimization of AV/VV-delay without changing
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LVPV was seen in 23% of patients.
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Accumulating evidence shows that the choice of LVPV affects paced QRSd as well as acute hemodynamics [5, 6]. Because narrowing of the QRSd after implantation of CRT is shown to be
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associated with favorable clinical outcome adequately choosing LVPV has been suggested as a way to
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optimize treatment in addition to programming of AV and VV-delay [3, 5]. Most patients in our study had already experienced significant symptomatic improvement and reduction of QRSd after routine implantation of CRT and device-programming by standard algorithms. Additional testing of all available LVPVs resulted in further shortening of QRSd in 18% of patients. We found no differences between patients with and without significant QRSd shortening with respect to clinical characteristics or pacemaker settings. There was a tendency that patients with the largest reductions in paced QRSd after implantation of CRT were less likely to benefit from further optimization of AV/VV-delays and/or changing of LVPV. Although this observation was not
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statistically significant it may suggest that that these patients had already reached their maximal potential for electrical modulation as reflected by shortening of QRSd. Patients in our study were implanted with CRT-devices from St. Jude Medical and Medtronic that are all equipped with onboard algorithms that select LVPV based on the cathode with the latest electrical
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activation during native conduction. This strategy was questioned in a recent study by Trolese et al. where only 3 out of 16 patients achieved the best possible hemodynamics by selecting LVPV with the
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latest electrical activation [5]. In our study onboard algorithms selected the best possible pacing
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vector in 80% of patients, but we did not find any correlation between the time of electrical
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activation and paced QRSd.
Time of electrical activation during native conduction varies considerably between target veins of the
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coronary sinus within individual patients (often up to 100 ms) and targeting the vein with the latest electrical activation yields superior response to CRT [10-12]. Changes in hemodynamics are also
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found to be large when pacing in different target veins but only small using different LVPVs within
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the same vein [11]. In our study the electrical difference between the four cathodes along the quadripolar lead was only 14.9±7.3 ms; similar to 20.4 ±12.3 ms found by Trolese et al., and thus
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much smaller than electrical delays between individual veins. The electromechanical changes during selection of LVPV can therefore be expected to be small in most patients. This probably explains
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some of the contrasting results using the onboard algorithms. Adequate physical placement of the LV lead seems to offer much greater possibilities for electromechanical improvements. Interestingly small changes in AV and VV-delays (5-10 ms), during renewed AV and VV-optimization, resulted in significant reduction of paced QRSd in about 25% of patients in our study. The effect of AV and VV-optimization is much debated, and whether frequent optimization by onboard algorithms has any clinical benefit is currently being investigated [1, 13, 14].
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Despite the small differences of 10 ms between LVPVs and despite small changes in AV and VVdelays during optimization we still observed significant QRSd shortening in a proportion of patients. This suggests that there may be mechanisms during pacing that we are not aware of. For example anodal stimulation is possible during bipolar LV pacing since all poles are in contact with the vessel
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wall simultaneously. Reports show that this occurs frequently and could potentially be beneficial [15]. It is also possible that certain LVPVs and/or in combination with AV/VV delays cause favorable
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electromechanical activation such as fusion or other phenomena that are yet to be discovered[16].
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Clinical implications
Changing the LVPV has been suggested as an optimization parameter for patients treated with CRT.
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Systematic testing of all LVPVs can result in a significant reduction of paced QRSd in a small fraction of patients but whether this translates into a clinical effect needs investigation in large prospective
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clinical trials. Systematic testing is cumbersome and may not be feasible in all patients with heart failure. Until clinical benefit is demonstrated we therefore do not recommend routine use of LVPV
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optimization, but it could be tried in patients without initial response to CRT.
Limitations
This study included relatively few patients. We settled on a lower number of patients due to the
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exploratory nature of the study since many more patients were needed in order to increase the precision of our estimate considerably. The limited sample size did not allow further subgroup
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analysis and it is likely that stronger associations can be found in larger studies. We used automated measurement of QRSd with the GE Mac1600. We did not find previous studies of the precision of this particular electrocardiograph, but data from other electrocardiographs suggest that measurements can vary considerably [17]. To reduce the impact of measurement variability we included automated QRSd measurements from at least three independent ECGs for each tested configuration. We did not include manual measurement of QRSd since this also shows similar large inter and intra-observer variability [18]. Furthermore manual measurement is very
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cumbersome and we do not believe it is realistic to implement manual measurement during optimization in a clinical setting. The ECGs discarded during recording were not stored and bias is possible. The examiner (CLA) was unaware of the value of QRSd during recording and we consider this reason of bias to be minor.
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Patients in our study primarily had devices from St. Jude Medical, which reflects the current implant
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practice at our institution. The results may therefore not necessarily apply to patients with CRT
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devices from other manufacturers.
Conclusion:
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Compared to “standard-programming” chosen by device based algorithms a significant reduction of paced QRSd was possible in 18% of these 22 patients treated with CRT by changing the left ventricular pacing vector. Furthermore shortening of the paced QRSd after re-optimization of AV/VV-
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delay without changing LVPV was seen in other 23% of patients. This has possible implications for optimizing patients with CRT, but whether these changes can be translated to clinical effects remains
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to be investigated in future clinical trials.
Acknowledgements
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Funding This work was supported by ‘Innovationsfonden’ (grant #72-2014-1) Conflicts of interest: C. Lund-Andersen has received congress fees from Medtronic and St. Jude Medical. Jesper H. Svendsen has received grants from Medtronic, Biotronik, Gilead, St. Jude Medical; speaker fees from Medtronic, Biotronik, Astra Zeneca, Boehringer Ingelheim, Bayer. C. Jønz has received consultant fees from Biotronik.
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References Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013;34:2281-329.
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Liang Y, Yu H, Zhou W, Xu G, Sun YI, Liu R, et al. Left Ventricular Lead Placement Targeted at the Latest Activated Site Guided by Electrophysiological Mapping in Coronary Sinus Branches Improves Response to Cardiac Resynchronization Therapy. J Cardiovasc Electrophysiol 2015;26:1333-9.
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Abraham WT, Gras D, Yu CM, Guzzo L, Gupta MS, and Committee FS. Rationale and design of a randomized clinical trial to assess the safety and efficacy of frequent optimization of cardiac resynchronization therapy: the Frequent Optimization Study Using the QuickOpt Method (FREEDOM) trial. Am Heart J 2010;159:944-48 e1.
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Auger D, Hoke U, Bax JJ, Boersma E, and Delgado V. Effect of atrioventricular and ventriculoventricular delay optimization on clinical and echocardiographic outcomes of patients treated with cardiac resynchronization therapy: a meta-analysis. Am Heart J 2013;166:20-9.
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Occhetta E, Dell'era G, Giubertoni A, Magnani A, Rametta F, Blandino A, et al. Occurrence of simultaneous cathodal-anodal capture with left ventricular quadripolar leads for cardiac resynchronization therapy: an electrocardiogram evaluation. Europace 2017;19:596-601.
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Ter Horst IaH, Bogaard MD, Tuinenburg AE, Mast TP, De Boer TP, Doevendans P, et al. The concept of triple wavefront fusion during biventricular pacing: Using the EGM to produce the best acute hemodynamic improvement in CRT. Pacing Clin Electrophysiol 2017;40:873-82.
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Vancura V, Wichterle D, Ulc I, Smid J, Brabec M, Zarybnicka M, et al. The variability of automated QRS duration measurement. Europace 2017;19:636-43.
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De Guillebon M, Thambo JB, Ploux S, Deplagne A, Sacher F, Jais P, et al. Reliability and reproducibility of QRS duration in the selection of candidates for cardiac resynchronization therapy. J Cardiovasc Electrophysiol 2010;21:890-2.
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Tables Table 1: Baseline characteristics
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0/15/7/0 20 (90%)
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5/17 21.6±8.5 11/11
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21/1 21/1 169.8±21.9 21 (95%)
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Male sex, n (%) Age at implant, mean ± SD Heart failure etiology IHD/DCM, n/n Pre implant LVEF, mean ±SD CRTD/CRTP NYHA class, before implant I/II/III/IV Improvement of symptoms after implant of CRT, n(%) Device manufactorer, St. Jude/Medtronic De novo implantation / upgrade Pre-implant QRSd, mean ±SD Patients with QRSd>150 ms, n (%)
Patients n=22 16 (72) 65.7 ± 9.6
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SD – Standard Deviation. LVEF – Left Ventricular Ejection Fraction. CRTD – Cardiac Resynchronization Therapy with defibrillator. CRTP – Cardiac Resynchronization Therapy pacemaker. NYHA – New York Heart Association function class. QRSd – QRS duration. IHD – ischemic heart disease. DCM – nonischemic dilated cardiomyopathy.
ACCEPTED MANUSCRIPT Tabel 2. Patient characteristics, pacemaker settings and recorded intra-cardiac delays grouped according the possibility of QRSd shortening. No significant QRSd shortening
QRSd shortening due to AV/VV optimization
QRSd shortening due to change of LVPV
(n=13)
(n=5)
(n=4)
Pre implant LVEF, mean±SD
22±10
Pre implant NYHA class, median (Q1-Q3)
2 (2-2)
Pre implant QRSd, mean±SD, ms
170±24
QRS reduction after CRT implant, mean±SD, ms
33±20
Paced AV-delay at "standard-programming", median (Q1-Q3), ms VV-delay at "standard-programming", median (Q1-Q3), ms
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Sensed AV-delay at optimal programming, median (Q1-Q3), ms Paced AV-delay at optimal programming, median (Q1-Q3), ms
2 (2-3)
3 (3-3)
173±26
165±13
0.87
18±27
0.40 0.38
120 (110-130)
125 (120-130)
120 (100-150)
0.76
160 (150-180)
165 (150-170)
150 (140-200)
0.85
28 (15-50)
00 (00-15)
30 (-20-35)
0.18
130 (120-150)
120 (110-120)
175 (150-200)
170 (160-170)
20 (00-35)
45 (35-50)
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VV-delay at optimal programming, median (Q1-Q3), ms
0.96
3 (75%)
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23±06
20±32
12 (92%)
Pacemaker settings
21±04
5 (100%)
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Response after CRT-implant and "standard-programming" §§, n (%)
Sensd AV-delay at "standard-programming", median (Q1-Q3), ms
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Change in AV-dealy from "standard" to optimal programming, median (Q1-Q3), ms
-05 (-20-00)
00 (-10-30)
Change in paced AV-delay from "standard" to optimal programming, median (Q1-Q3), ms
-05 (-20-00)
-10 (-30-30)
Change in VV-delay from "standard" to optimal programming, median (Q1-Q3), ms
-13 (-40--03)
-15 (-65--05)
31±08
39±13
14±08
17±07
14±06
0.76
137±28
128±33
125±18
0.74
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Reduction in QRSd from "standard" to optimal programming, mean±SD , ms Electrical delays Intralead delay§§§, mean±SD, ms Electrical delay RV->LV cathode
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, mean±SD, ms
ACCEPTED MANUSCRIPT LVEF – left ventricular ejection fraction. NYHA – New York Heart Association class. QRSd – QRS duration. CRT – Cardiac Resynchronization Therapy. AV – atrioventricular. SD – standard deviation. VV – inter-ventricular. § P-values for equality among groups. §§ Response defined as patient-reported improvement of symptoms. §§§ Intralead delay measured for each patient as the pole with the longest electrical delay minus the pole with the shortest delay. §§§§ For each patient calculated as an average of time of electrical delay from RV sensing to sensing in each of the four LV poles.
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Figures
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Figure 1. QRS-durations with ”standard-programming” and ”optimal-programming” for each patient. One column represents one patient. The top of each bar represents the QRS-duration during ”standardprogramming”; the horizontal line below represents the QRS-duration with “optimal-programming”. Patients with significant reduction due to change of left ventricular pacing vector are colored green. Patients with significant reduction due to re-optimization of AV/VV-delays, but with no effect of change of pacing vector are colored red. Patients without significant shortening of the QRS-duration are colored white.