BASIC SCIENCE
Intra-ventricular resynchronization for optimal left ventricular function during pacing in experimental left bundle branch block
Xander A. A. M. Verbeek, PhD*,*,
Kevin Vernooy, MD*,
Maaike Peschar, PhD*,
Richard N. M. Cornelussen, PhD* and
Frits W. Prinzen, PhD*
* Department of Physiology, Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
Manuscript received February 7, 2003;
revised manuscript received March 27, 2003,
accepted April 4, 2003.
* Reprint requests and correspondence: Dr. Xander Verbeek, Department of Physiology, Cardiovascular Research Institute, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
x.verbeek{at}fys.unimaas.nl
 |
Abstract
|
|---|
OBJECTIVES: We sought to investigate to what extent intra-ventricular asynchrony (intraVA) and inter-ventricular asynchrony (interVA) determine left ventricular (LV) function in canine hearts with left bundle branch block (LBBB) during ventricular pacing.
BACKGROUND: Pacing therapy improves LV pump function in patients with heart failure and abnormal ventricular conduction supposedly due to resynchronization. However, the relationship between LV pump function and measures of asynchrony is not well established.
METHODS: In 15 experiments, LV (various sites) and biventricular (BiV) pacing was performed at atrioventricular (AV) delays of 20 to 140 ms. Measured were the maximum rate of increase (dP/dtmax) of LV pressure and LV stroke work (SW) (conductance catheter), interVA (time delay between the upslope of LV and RV pressures), and intraVA (from endocardial electrical activation maps).
RESULTS: Induction of LBBB increased interVA (–6.4 ± 8.6 to –28.4 ± 8.5 ms [RV earlier]) and intraVA (4.9 ± 2.4 to 18.0 ± 3.3 ms), whereas LV dP/dtmax and SW decreased (–13 ± 18% and –39 ± 24%, respectively). During LBBB, LV and BiV pacing increased LV dP/dtmax and SW (mean increases 14% to 21% and 11% to 15%, respectively) without changing diastolic function or preload. Optimal improvement in LV function was obtained consistently when intraVA returned to pre-LBBB values, while interVA remained elevated. Normalization of intraVA required AV delays shorter than the baseline PQ time during LV apex and BiV pacing, thus excluding endogenous LV activation, but AV delays virtually equal to the baseline PQ time (difference 4 ± 9 ms, p = NS) during pacing at (mid)lateral LV sites to obtain fusion between pacing-induced and endogenous activation.
CONCLUSIONS: In LBBB hearts, optimal restoration of LV systolic function by pacing requires intra-ventricular resynchronization. The optimal AV delay to achieve this depends on both the site of pacing and baseline PQ time.
|
Abbreviations and Acronyms
| | ADV | | activation delay vector | | AV | | atrioventricular | | BiV | | biventricular | | dP/dtmax | | maximum rate of increase in pressure | | dP/dtmin | | maximum rate of decrease in pressure | | ECG | | electrocardiogram or electrocardiographic | | interVA | | inter-ventricular asynchrony | | intraVA | | intra-ventricular asynchrony | | LBBB | | left bundle branch block | | LV | | left ventricle/ventricular | | RV | | right ventricle/ventricular | | SW | | stroke work | | TVV | | excitation time difference between LV and RV |
|
Recent clinical studies have shown that left ventricular (LV) and biventricular (BiV) pacing improves LV pump function in patients with heart failure and conduction defects (1–5). The majority of the patients responding to this pacing therapy have left bundle branch block (LBBB). Also, experiments in dogs with isolated LBBB have shown that LV and BiV pacing can improve LV function, indicating that proper modes of pacing can restore part of the LBBB-induced impairment in LV pump function (6,7).
The positive impact of pacing therapy on LV pump function has been attributed to "resynchronization" of ventricular activation. To optimize pacing therapy, some studies focused on minimizing the QRS duration, which is considered a measure of total ventricular asynchrony. Although improved LV pump function has been associated with a reduced QRS duration (8,9), others revealed that optimal improvement of LV function occurs at an unchanged or even increased QRS duration (3,10). Alternatively, intra-ventricular asynchrony (intraVA) and inter-ventricular asynchrony (interVA) have been proposed as determinants of pump function, but conflicting results have been reported as to which of these parameters requires resynchronization (10–15). Furthermore, simultaneous BiV pacing has been applied in order to resynchronize activation of the ventricles, but some studies show that LV pacing alone results in a similar hemodynamic benefit (1,2). Thus, it is still unknown which property of ventricular activation should be normalized. As a consequence, it is also not clear what the best strategy of pacing is in failing hearts with LBBB.
The aim of the present study was to explore the mechanism of improvement in LV pump function during LV-based pacing of hearts with LBBB and the role of total (QRS duration), inter- or intra-ventricular resynchronization. Moreover, we investigated how the mechanism of hemodynamic improvement determines the pacing strategy (pacing site[s] and atrioventricular [AV] delay). To this purpose, pacing was performed in canine hearts with experimental LBBB (7) at four LV sites, the right ventricular (RV) apex, and simultaneously at the RV and LV apex (BiV pacing), using a large number of AV delays. Changes in LV systolic function parameters (pressure–volume relationships) were correlated to direct, accurate measures of interVA and intraVA.
|
Methods
|
|---|
Animal handling was performed according to the Dutch Law on Animal Experimentation and the European Directive for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes (86/609/EU). The protocol was approved by the Experimental Animal Committee of the Maastricht University.
Preparation.
Fifteen dogs were premedicated and anesthetized as described previously (7). The electrocardiogram (ECG) was recorded from the limb leads. Left ventricular pressure and volume were measured using a 7F combined catheter-tip manometer and conductance catheter, and RV pressure with a 7F catheter-tip manometer (CD-Leycom, Zoetermeer, the Netherlands). For assessment of LV endocardial activation maps, a basket catheter (EPT Constellation, Boston Scientific, San Jose, California) consisting of eight flexible splines with eight electrodes each (inter electrode distance of 7 mm) was unfolded in the LV. After opening the chest, temporary pacing leads (type 6500, Medtronic, Minneapolis, Minnesota) were attached to the right atrium and the epicardium of the LV apex, anterior, lateral, and posterior wall, while another lead was positioned transvenously into the RV apex. Pacing was performed with an external pacemaker (Medtronic AV Pacing System Analyzer, model 5311B) connected to the RV apex electrode and to a four-channel external pulse stimulator (Medtronic, model 2883). The four LV electrodes were connected to the external pulse stimulator. The external pacemaker was programmed in the VDD mode so that atrial sensing was used to govern the rate of ventricular pacing. The pacing electrodes served as a cathode and an indifferent electrode as an anode.
Protocol.
After completion of the preparation and after a stabilization period, measurements of hemodynamics and ECG and endocardial activation mapping were performed. Subsequently, LBBB was induced with the use of radiofrequency ablation. To this purpose, a Medtronic MarinR ablation catheter was introduced into the carotid artery and, under fluoroscopic guidance, advanced through the aortic valve until its tip was positioned against the basal septum. Guided by the electrogram, derived from the tip, the left bundle branch was located (as evidenced by a sharp spike preceding the Q-wave) and subsequently ablated using a Medtronic AtakR ablation unit. After a 15 to 30 min stabilization period, measurements were performed during VDD pacing at the five ventricular sites alone and during simultaneous biventricular (RV apex + LV apex = BiV) pacing at AV delays ranging from 20 to 140 ms, alternated with baseline LBBB measurements.
Successful pre- and post-LBBB measurements were acquired in 11 dogs, and successful pacing measurements in 12 dogs. Endocardial mapping was performed directly after hemodynamic measurements to exclude interference of the basket catheter with LV function measurements. Because of contact problems, good endocardial maps before and after the creation of LBBB were acquired in seven dogs, and during pacing with a sufficient range of AV delays in five animals.
Data analysis.
Pressures and ECG signals were digitized at 200 Hz and stored on a disk for off-line analysis. Measurements were performed on all heartbeats within one ventilation cycle. The conductance catheter was connected with a Leycom Sigma 5DF signal conditioner processor (CD-Leycom) (16). Calibration of absolute LV volume was performed by correcting for parallel conductance (using hypertonic saline injection) and calibrating stroke volume using thermodilution cardiac output. Data were analyzed using the CIRCLAB software package developed by Dr. P. Steendijk, Leiden University Medical Center.
In addition to paced AV delays, true AV delays were calculated as the timing difference between the onset of the P wave and the pacing stimulus on the ECG in order to account for differences in the location of the atrial sensing lead between experiments (7).
Excitation time difference between the RV and LV (TVV) during LV pacing was calculated as the difference between baseline LBBB PQ time and the true AV delay (onset of LV excitation) (7). During BiV pacing, TVV was assumed to be zero, except for the long AV delays when endogenous activation (Q-wave) preceded the pacing stimulus.
InterVA was calculated as the timing difference between the upslopes of simultaneously recorded LV and RV pressure curves, estimated by cross correlation (7). Positive timing differences indicate an earlier LV than RV pressure rise.
Endocardial electrical activation maps were determined from unipolar endocardial electrograms recorded from the basket electrodes. Because of contact problems, the basal three electrodes on each spline were discarded, thus providing activation maps of two-thirds of the LV long axis. From these maps, the two-dimensional activation delay vector (ADV) was determined as a measure of intraVA in the circumferential direction (17). The ADV amplitude was used as a measure of intraVA, and the ADV angle expresses the main direction of conduction.
Trans-septal conduction delay was calculated during LBBB as the timing difference between the Q-wave (onset of RV activation during LBBB) and the first LV endocardial activation, which was always on the septum, as used by Vassallo et al. (18) in human LBBB hearts. The transmural LV conduction delay was calculated as the first endocardial activation during epicardial LV pacing.
Statistical analysis.
Statistical significance of the effect of induction of LBBB and pacing in LBBB was evaluated using one-way analysis of variance for repeated measurements, followed by Tukey post hoc testing for a comparison between pacing sites. A p value <0.05 was considered significant. Data are presented as the mean value ± SD.
|
Results
|
|---|
Creation of LBBB.
Induction of LBBB increased the QRS duration as well as interVA and intraVA (Fig. 1, Table 1). During LBBB, LV endocardial activation started at the septum and moved toward the lateral wall. The increased asynchrony consistently reduced stroke volume and stroke work (SW) as well as the maximum rate of increase (dP/dtmax) and decrease (dP/dtmin) of LV pressure, but did not significantly affect LV and RV end-systolic and end-diastolic pressures, LV end-diastolic volume, or diastolic filling time (Fig. 1, Table 1).
View larger version (29K):
[in this window]
[in a new window]
|
Figure 1 Examples of (A) left ventricular (LV) endocardial activation maps with the activation delay vector indicated by arrows, (B) electrocardiographic tracings, (C) right ventricular (RV) and LV pressure signals, and (D) pressure–volume loops, before and after creation of left bundle branch block. In (B), the earliest and latest LV endocardial activation are indicated by dotted lines. In (C), right ventricular (RV) and LV pressures are normalized to reveal timing differences. The LV endocardial activation maps are presented as bull's-eye plots, with the inner disc representing the LV apex and the outer circle disc representing the LV base (S, A, L, and P indicate the septum and anterior, lateral, and posterior walls, respectively).
|
|
Inter- and intra-ventricular resynchronization during pacing.
Figure 2 shows interVA as a function of the AV delay and TVV during LV apex, lateral wall, and BiV pacing in one experiment. The results for LV anterior and posterior wall pacing were similar to those of LV lateral wall pacing. During LV pacing with a decreasing AV delay, interVA increased linearly to positive values (LV earlier than RV) (r = 0.95 ± 0.04 for all experiments and LV sites). Inter-ventricular resynchronization (interVA = 0 ms) was possible during pacing at all LV sites. Pacing the LV simultaneously with endogenous RV excitation (TVV = 0 ms) resulted in negative interVA values (Fig. 2B). Similarly, BiV pacing resulted in a fixed negative interVA per experiment, which was reached at AV delays shorter than the baseline PQ time (Fig. 2A, dotted line), guaranteeing simultaneous LV and RV activation before endogenous activation.
View larger version (23K):
[in this window]
[in a new window]
|
Figure 2 Inter-ventricular asynchrony as a function of (A) the paced atrioventricular (AV) delay and (B) the left ventricular–right ventricular (LV–RV) excitation time difference (TVV) during LV apex, biventricular (BiV), and LV lateral wall pacing. The results for anterior and posterior wall pacing were comparable to those for lateral wall pacing.
|
|
Endocardial activation maps showed that during LV pacing at short AV delays (TVV > 0 ms), the electrical impulse propagated away from the pacing site (Fig. 3, left panels). For LV anterior, lateral, and posterior wall pacing, this caused a large intraVA. Intra-ventricular resynchronization (intraVA = 0 ms) occurred when the endogenous activation wave merged with the pacing-induced activation wave (TVV  0 ms) (Fig. 3, middle panels). The fact that this occurred at TVV 0 ms during epicardial pacing could be explained by nearly identical trans-septal and transmural conduction delays (34 ± 7 and 37 ± 7 ms, respectively). During LV apex and BiV pacing, intra-ventricular resynchronization was obtained at short AV delays, while intraVA increased with an increasing AV delay (Fig. 3, upper and lower rows). For all pacing conditions, asynchrony in the longitudinal direction (radial direction on polar plots) was smaller than that in the circumferential direction.
View larger version (65K):
[in this window]
[in a new window]
|
Figure 3 Examples of left ventricular (LV) endocardial activation maps during left bundle branch block (LBBB) and pacing at various LV sites and excitation time difference between LV and RV (TVVs) smaller than, equal to, and larger than zero. Also presented is an example of LV endocardial activation during right ventricular (RV) pacing at a short AV delay. The black arrows denote the activation delay vectors, the amplitude of which reflects the degree of intra-ventricular asynchrony.
|
|
For all pacing sites, intraVA correlated linearly to interVA (r = 0.94 ± 0.05), with a significant intercept of –19 ± 10 ms, indicating that intra-ventricular resynchronization did not coincide with inter-ventricular resynchronization.
Hemodynamic changes during pacing and as a function of the AV delay.
Typical examples of pressure–volume loops during LV pacing in LBBB hearts illustrate that pacing from various sites increased SW at essentially unchanged end-diastolic volume (Fig. 4). This figure illustrates that the optimal AV delay varied between pacing sites.
View larger version (21K):
[in this window]
[in a new window]
|
Figure 4 Pressure–volume loops measured with the conductance catheter, showing the short-term effect of pacing during left bundle branch block (LBBB) for left ventricular (LV) apex (left panel) and LV lateral pacing (right panel) at paced atrioventricular delays of 40 and 90 ms. The results for anterior and posterior wall pacing were comparable to those for lateral wall pacing.
|
|
Figure 5 shows the changes in LV dP/dtmax as a function of the paced AV delay (left panels) and TVV (right panels) during LV apex pacing and LV lateral wall pacing for two experiments. During LV apex pacing the largest hemodynamic improvement occurred at short paced-AV delays, but during LV lateral wall pacing at intermediate paced-AV delays. During LV lateral wall pacing, large differences in optimal paced AV delay were observed between the two experiments, but this was due to differences in the PQ time, because optimal LV dP/dtmax was found consistently at TVV = 0 ms (Fig. 5, right panels).
View larger version (38K):
[in this window]
[in a new window]
|
Figure 5 Changes in left ventricular (LV) maximum rate of increase in pressure (dP/dtmax) relative to baseline left bundle branch block (LBBB) as a function of the (A and C) paced atrioventricular (AV) delay and (B and D) excitation time difference between LV and right ventricular (TVV) for two experiments during LV apex and LV lateral wall pacing. The results for anterior and posterior wall pacing were comparable to those for lateral wall pacing.
|
|
For the whole group of experiments, LV dP/dtmax and SW increased significantly by LV and BiV pacing (mean increases ranging from 14% to 21% and from 11% to 15% for LV dP/dtmax and SW, respectively), with no significant differences between pacing sites, except for a significantly larger LV dP/dtmax during LV apex pacing (Table 2). Right ventricular apex pacing did not significantly increase LV dP/dtmax and SW. None of the pacing modes introduced significant changes in LV systolic or end-diastolic pressure, end-diastolic volume, LV dP/dtmin, diastolic filling times, or heart rate at maximal LV dP/dtmax, except for a significant decrease in diastolic filling time at maximal LV dP/dtmax during LV apex and RV apex pacing (Table 2). During LV apex pacing, optimal hemodynamic improvement occurred at TVV >0, whereas for all other LV pacing sites, optimal hemodynamic improvement occurred at TVV not significantly different from zero.
Relationship between hemodynamic changes and asynchrony values.
Figure 6 shows changes in LV dP/dtmax versus interVA (Fig. 6A) and intraVA (Fig. 6B) measured at different AV delays during LV apex, lateral wall, and BiV pacing in one experiment. During LV apex pacing, LV dP/dtmax reached a plateau around interVA = 0 ms, which extended to the most positive interVA values (approximately short AV delays), whereas during BiV pacing, the highest LV dP/dtmax values were found at fixed interVA values, and during pacing of the LV lateral wall, a relatively sharp peak LV dP/dtmax peak occurred at negative interVA values (Fig. 6A). For all pacing sites, interVA at peak LV dP/dtmax varied between experiments but was always negative; however, the highest LV dP/dtmax values were observed at intraVA values close to zero (Fig. 6B).
View larger version (26K):
[in this window]
[in a new window]
|
Figure 6 Typical example of the relationship between changes in left ventricular (LV) maximum rate of increase in pressure (dP/dtmax) and inter-ventricular asynchrony (interVA) (A) and intra-ventricular asynchrony (intraVA) (B) during LV apex, LV lateral wall, and biventricular (BiV) pacing with atrioventricular (AV) delays ranging from 20 to 200 ms. The dotted arrows indicate shortening of the AV delay. Data points most remote from baseline left bundle branch block (LBBB) denote the shortest AV delay (20 ms); subsequent points were obtained at a 10-ms increase, except for intraVA. The sign given to intraVA values indicates the direction of the wave front, as indicated above the graphs. The results for anterior and posterior wall pacing were comparable to those for lateral wall pacing.
|
|
For the whole group of experiments and all pacing sites except the RV apex, maximum hemodynamic improvement was obtained at intraVA values not significantly different from pre-LBBB values, while interVA was incompletely restored (range –2 to –32 ms), and the QRS duration did not change significantly from LBBB values (Fig. 7). The results for anterior and posterior wall pacing (data not shown) were similar to those for lateral wall pacing.
View larger version (53K):
[in this window]
[in a new window]
|
Figure 7 Values of intra-ventricular asynchrony (intraVA) (n = 5), inter-ventricular asynchrony (interVA) (n = 12), and QRS duration (n = 12) at a maximum increase of left ventricular (LV) maximum rate of increase in pressure (dP/dtmax) (left column) and stroke work (SW) (right column). The mean ± SD of pre-left bundle branch block (LBBB) (C) and post-LBBB (LBBB) values are indicated by the patterned bars (one-way analysis of variance followed by Tukey post hoc testing for C vs. LBBB; * p < 0.05 vs. LBBB and C, respectively). The results for anterior and posterior wall pacing were comparable to those for lateral wall pacing.
|
|
|
Discussion
|
|---|
The findings of the present study indicate that in canine hearts with experimental LBBB, LV based pacing can recover LV function in terms of LV dP/dtmax and SW. Relative improvements in LV dP/dtmax (20% to 23%) were in the same range as those observed in patients (1,3) and occurred in the absence of changes in diastolic function parameters. Maximum improvement of LV function is consistently obtained at intra-ventricular resynchronization of activation. This requires pacing with AV delays equal to baseline PQ time for all LV sites, except for LV apex and BiV pacing, which require AV delays shorter than PQ time during baseline LBBB.
Hemodynamic effects of pacing during LBBB.
The present study extends the insights in effects of resynchronization therapy by providing data on the improvement of LV dP/dtmax and SW in LBBB hearts during pacing at different sites and at a large range of AV delays. Improvements in LV dP/dtmax and SW were obtained at unchanged diastolic function, indicating increased ventricular contractility.
Because asynchronous electrical activation induces opposing contraction patterns within the LV wall (19,20), it is most likely that electrical resynchronization increases contractility by improving coherence of contraction of the various myocardial regions. This idea is supported by more uniform strain patterns observed during BiV pacing than during RV pacing in canine hearts without conduction abnormalities (17). The important role of better coherence of LV contraction is further emphasized by the lack of mitral regurgitation in our experimental LBBB model, as determined using both color Doppler imaging and left atrial pressure measurements. As a consequence, reduction of mitral regurgitation, mentioned to contribute to the beneficial effect of resynchronization therapy in patients, does not contribute to the improvement of LV function in experimental LBBB.
Intra-ventricular resynchronization.
The importance of intraVA for LV function is emphasized by the finding that for different degrees of interVA the same optimal LV function is obtained as long as intraVA is close to zero. This result is independent from the pacing site and strategy required to achieve intra-ventricular resynchronization (exclusion of endogenous activation (LV apex and BiV pacing) or fusion of endogenous and pacing induced activation (LV anterior, lateral, and posterior wall pacing). Asynchrony around the LV circumference appears especially relevant, probably because it is considerably larger than asynchrony in the longitudinal direction, an observation in agreement with MRI tagging studies during ventricular pacing (17).
Observations on LV wall motion and velocity using echocardiography and Tissue Doppler imaging in patients suggest improved LV synchrony during biventricular pacing (12,15,21). The requirement of intra-ventricular resynchronization for optimal LV function is supported by MRI tagging measurements of mechanical asynchrony in canine hearts with pacing induced heart failure and experimental LBBB (22). These investigators concluded, however, that during optimal LV pacing electrical asynchrony persists, but this is based mainly on extrapolation of electrical activation measured during LV pacing with short AV delay. Endocardial mapping data from the present study, with similar PQ time (100 ms) and optimal paced AV delay (70 ms), demonstrate that electrical asynchrony differs significantly between short and intermediate AV delays (Fig. 3). Therefore, their conclusion that fusion is absent during pacing at optimal AV delay, based on electrical activation determined during pacing at short AV delays, does not seem justified.
The discrepancy between our finding that the QRS duration and inter-ventricular resynchronization are poor predictors of optimal LV function and the value attributed to these parameters in other studies can be explained by the use of a small range of AV delays in those studies (8,9,13,23) and by the fact that hemodynamics improve over a range of interVA and QRS duration (1,3,6,24).
Optimization of the AV delay.
Our results show that the paced AV delay modulates interVA and intraVA besides AV timing. In the present study the latter does not seem to be crucial for improving LV systolic function, because none of the diastolic function parameters changed when LV systolic function was optimized. The insensitivity of systolic function to changes in diastolic function has also been observed in patients receiving resynchronization therapy (25). Together, these findings suggest that optimizing AV delay should be based on assessment of systolic rather than diastolic function, as suggested elsewhere (26,27).
Possible limitations of the experimental design.
The present study was meant to unravel the mechanism of pacing therapy. The animal model allowed detailed measurements of electrical activation and LV function during a large number of pacing strategies. Before extrapolating the data from this animal study to patients with heart failure, several aspects have to be kept in mind.
First of all, in the present study only short-term hemodynamic changes are studied. In patients receiving resynchronization therapy, short-term hemodynamic improvements were associated with long-term clinical benefit (28), but it is not clear if the degree of short-term improvement predicts the degree of clinical improvement on an individual basis. Furthermore, patient hearts are often pathologically enlarged as a result of which endocardial activation takes longer (60 ms [18]) than in our healthy dog hearts (30 ms). Moreover, due to the potential presence of fibrotic and thus poorly conducting regions, the pacing site is a more determinative factor, which may explain why some studies in patients show that hemodynamic effects of pacing depend on the pacing site (21,24). Also, failing hearts may differ from healthy dog hearts with respect to filling pressure, electromechanical delay (see preceding text), and other potential adaptational changes.
We created proximal LBBB using radiofrequency ablation resulting in a more localized lesion than the diffuse fibrosis observed in patients (29). However, even in our animal model, electrical and mechanical activation maps (17) indicate that impulse conduction in the LV wall occurs mainly through muscle conduction without signs of retrograde entry into the Purkinje system. The observation that the relative difference in the QRS duration and interVA between normal and LBBB individuals is similar in our dogs and in patients (30) suggests that sequelae of experimental LBBB are at least comparable to those in patients. Also the hemodynamic effect of resynchronization appears to be quantitatively comparable. Therefore, it appears worthwhile to investigate whether the main findings of the present study also apply to patients with dilated and dysfunctional ventricles.
Conclusions.
Intra-ventricular asynchrony around the LV circumference is an important determinant of LV pump function during LBBB and ventricular pacing. Pacing strategy for intra-ventricular resynchronization depends on the site of pacing and on the baseline LBBB PQ time.
|
Acknowledgments
|
|---|
The authors are indebted to Sabine Eysbouts and Arne van Hunnik for their assistance with the mapping system and animal experiments, respectively.
|
Footnotes
|
|---|
Dr. Prinzen is an advisor for Medtronic. This study was supported by grants from the Netherlands Heart Foundation (NHS2000.189 to Dr. Verbeek and NHS 2000.227 to Dr. Cornelussen).
|
References
|
|---|
1. Auricchio A, Stellbrink C, Block M, et al. Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation. 1999;99:2993–3001[Abstract/Free Full Text]
2. Blanc JJ, Etienne Y, Gilard M, et al. Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study. Circulation. 1997;96:3273–3277[Abstract/Free Full Text]
3. Kass DA, Chen CH, Curry C, et al. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation. 1999;99:1567–1573[Abstract/Free Full Text]
4. Nelson GS, Berger RD, Fetics BJ, et al. Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block. Circulation. 2000;102:3053–3059[Abstract/Free Full Text]
5. Saxon LA, Kerwin WF, Cahalan MK, et al. Acute effects of intraoperative multisite ventricular pacing on left ventricular function and activation/contraction sequence in patients with depressed ventricular function. J Cardiovasc Electrophysiol. 1998;9:13–21[Medline]
6. Liu L, Tockman B, Girouard S, et al. Left ventricular resynchronization therapy in a canine model of left bundle branch block. Am J Physiol (Heart Circ Physiol). 2002;282:H2238–H2244[Abstract/Free Full Text]
7. Verbeek XAAM, Vernooy K, Peschar M, van der Nagel T, van Hunnik A, Prinzen FW. Quantification of interventricular asynchrony during LBBB and ventricular pacing. Am J Physiol Heart Circ Physiol. 2002;283:H1370–H1378[Abstract/Free Full Text]
8. Alonso C, Leclerq C, Victor F, et al. Electrocardiographic predictive factors of long-term clinical improvement with multisite biventricular pacing in advanced heart failure. Am J Cardiol. 1999;84:1417–1421[CrossRef][Medline]
9. Janousek J, Vojtovic P, Hucin B, et al. Resynchronization pacing is a useful adjunct to the management of acute heart failure after surgery for congenital heart defects. Am J Cardiol. 2001;88:145–152[CrossRef][Medline]
10. Nelson GS, Curry CW, Wyman BT, et al. Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay. Circulation. 2000;101:2703–2709[Abstract/Free Full Text]
11. Garrigue S, Jais P, Espil G, et al. Comparison of chronic biventricular pacing between epicardial and endocardial left ventricular stimulation using Doppler tissue imaging in patients with heart failure. Am J Cardiol. 2001;88:858–862[CrossRef][Medline]
12. Yu CM, Chau E, Sanderson JE, et al. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation. 2002;105:438–445[Abstract/Free Full Text]
13. Kerwin WF, Botvinick EH, O'Connell JW, et al. Ventricular contraction abnormalities in dilated cardiomyopathy: effect of biventricular pacing to correct interventricular dyssynchrony. J Am Coll Cardiol. 2000;35:1221–1227[Abstract/Free Full Text]
14. Toussaint JF, Lavergne T, Kerrou K, et al. Ventricular coupling of electrical and mechanical dyssynchronization in heart failure patients. Pacing Clin Electrophysiol. 2002;25:178–182[CrossRef][Medline]
15. Sogaard P, Kim WY, Jensen HK, et al. Impact of acute biventricular pacing on left ventricular performance and volumes in patients with severe heart failure: a tissue Doppler and three-dimensional echocardiographic study. Cardiology. 2001;95:173–182[CrossRef][Medline]
16. Baan J, van der Velde ET, de Bruin HG, et al. Continuous measurement of left ventricular volume in animals and humans by conductance catheter. Circulation. 1984;70:812–823[Abstract/Free Full Text]
17. Wyman BT, Hunter WC, Prinzen FW, Faris OP, McVeigh ER. Effects of single- and biventricular pacing on temporal and spatial dynamics of ventricular contraction. Am J Physiol (Heart Circ Physiol). 2002;282:H372–H379[Abstract/Free Full Text]
18. Vassallo JA, Cassidy DM, Marchlinski FE, et al. Endocardial activation of left bundle branch block. Circulation. 1984;69:914–923[Abstract/Free Full Text]
19. Prinzen FW, Augustijn CH, Arts T, Allessie MA, Reneman RS. Redistribution of myocardial fiber strain and blood flow by asynchronous activation. Am J Physiol. 1990;259:H300–H308
20. Prinzen FW, Hunter WC, Wyman BT, McVeigh ER. Mapping of regional myocardial strain and work during ventricular pacing: experimental study using magnetic resonance imaging tagging. J Am Coll Cardiol. 1999;33:1735–1742[Abstract/Free Full Text]
21. Ansalone G, Giannantoni P, Ricci R, Trambaiolo P, Fedele F, Santini M. Doppler myocardial imaging to evaluate the effectiveness of pacing sites in patients receiving biventricular pacing. J Am Coll Cardiol. 2002;39:489–499[Abstract/Free Full Text]
22. Leclercq C, Faris O, Tunin R, et al. Systolic improvement and mechanical resynchronization does not require electrical synchrony in the dilated failing heart with left bundle-branch block. Circulation. 2002;106:1760–1763[Abstract/Free Full Text]
23. Leclercq C, Cazeau S, Le Breton H, et al. Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure. J Am Coll Cardiol. 1998;32:1825–1831[Abstract/Free Full Text]
24. Butter C, Auricchio A, Stellbrink C, et al. Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients. Circulation. 2001;104:3026–3029[Abstract/Free Full Text]
25. Auricchio A, Ding J, Spinelli JC, et al. Cardiac resynchronization therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay. J Am Coll Cardiol. 2002;39:1163–1169[Abstract/Free Full Text]
26. Kindermann M, Frohlig G, Doerr T, Schieffer H. Optimizing the AV delay in DDD pacemaker patients with high degree AV block: mitral valve Doppler versus impedance cardiography. Pacing Clin Electrophysiol. 1997;20:2453–2462[CrossRef][Medline]
27. Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med. 2001;344:873–880[Abstract/Free Full Text]
28. Auricchio A, Stellbrink C, Sack S, et al. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol. 2002;39:2026–2033[Abstract/Free Full Text]
29. Demoulin JC, Simar LJ, Kulbertus HE. Quantitative study of left bundle branch fibrosis in left anterior hemiblock: a stereologic approach. Am J Cardiol. 1975;36:751–756[CrossRef][Medline]
30. Verbeek XAAM, Auricchio A, Yu Y, et al. Interventricular asynchrony determines improvement of left ventricular function during resynchronization therapy. Pacing Clin Electrophysiol. 2002;25:557 (abstr)
This article has been cited by other articles:
|
|
|
|
 
C. van Deursen, I. E. van Geldorp, L. M. Rademakers, A. van Hunnik, M. Kuiper, C. Klersy, A. Auricchio, and F. W. Prinzen
Left Ventricular Endocardial Pacing Improves Resynchronization Therapy in Canine Left Bundle-Branch Hearts
Circ Arrhythm Electrophysiol,
October 1, 2009;
2(5):
580 - 587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Mills, R. N. Cornelussen, L. J. Mulligan, M. Strik, L. M. Rademakers, N. D. Skadsberg, A. van Hunnik, M. Kuiper, A. Lampert, T. Delhaas, et al.
Left Ventricular Septal and Left Ventricular Apical Pacing Chronically Maintain Cardiac Contractile Coordination, Pump Function and Efficiency
Circ Arrhythm Electrophysiol,
October 1, 2009;
2(5):
571 - 579.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. B. Popovic and J. D. Thomas
In Search of a Holy Grail: Predicting Cardiac Resynchronization Therapy Outcomes by Echocardiography
Circ Cardiovasc Imaging,
July 1, 2008;
1(1):
3 - 5.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. W. Prinzen and A. Auricchio
Is echocardiographic assessment of dyssynchrony useful to select candidates for cardiac resynchronization therapy?: Echocardiography Is Not Useful Before Cardiac Resynchronization Therapy if QRS Duration Is Available
Circ Cardiovasc Imaging,
July 1, 2008;
1(1):
70 - 78.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. O. Sweeney and F. W. Prinzen
Ventricular Pump Function and Pacing: Physiological and Clinical Integration
Circ Arrhythm Electrophysiol,
June 1, 2008;
1(2):
127 - 139.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Yoshida, Y. Yokoyama, Y. Seo, Y. Sekiguchi, and K. Aonuma
Triangle ventricular pacing in a non-responder to conventional bi-ventricular pacing
Europace,
April 1, 2008;
10(4):
502 - 504.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Butter and G. Hindricks
Cardiac resynchronization therapy: haemodynamic background and perspectives
Eur. Heart J. Suppl.,
December 1, 2007;
9(suppl_I):
I87 - I93.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Kimmel, N. D. Skadsberg, C. L. Byrd, D. J. Wright, T. G. Laske, and P. A. Iaizzo
Single-site ventricular and biventricular pacing: investigation of latest depolarization strategy
Europace,
December 1, 2007;
9(12):
1163 - 1170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Johnson, H. K. Kim, M. Tanabe, J. Gorcsan, D. Schwartzman, S. G. Shroff, and M. R. Pinsky
Differential effects of left ventricular pacing sites in an acute canine model of contraction dyssynchrony
Am J Physiol Heart Circ Physiol,
November 1, 2007;
293(5):
H3046 - H3055.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Authors/Task Force Members, P. E. Vardas, A. Auricchio, J.-J. Blanc, J.-C. Daubert, H. Drexler, H. Ector, M. Gasparini, C. Linde, F. B. Morgado, et al.
Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association
Europace,
October 1, 2007;
9(10):
959 - 998.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Authors/Task Force Members, P. E. Vardas, A. Auricchio, J.-J. Blanc, J.-C. Daubert, H. Drexler, H. Ector, M. Gasparini, C. Linde, F. B. Morgado, et al.
Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association
Eur. Heart J.,
September 2, 2007;
28(18):
2256 - 2295.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Vernooy, R. N.M. Cornelussen, X. A.A.M. Verbeek, W. Y.R. Vanagt, A. van Hunnik, M. Kuiper, T. Arts, H. J.G.M. Crijns, and F. W. Prinzen
Cardiac resynchronization therapy cures dyssynchronopathy in canine left bundle-branch block hearts
Eur. Heart J.,
September 1, 2007;
28(17):
2148 - 2155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Zannad, E. Huvelle, K. Dickstein, D. J. van Veldhuisen, C. Stellbrink, L. Kober, S. Cazeau, P. Ritter, A. P. Maggioni, R. Ferrari, et al.
Left bundle branch block as a risk factor for progression to heart failure
Eur J Heart Fail,
January 1, 2007;
9(1):
7 - 14.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. A. A. M. Verbeek, A. Auricchio, Y. Yu, J. Ding, T. Pochet, K. Vernooy, A. Kramer, J. Spinelli, and F. W. Prinzen
Tailoring cardiac resynchronization therapy using interventricular asynchrony. Validation of a simple model
Am J Physiol Heart Circ Physiol,
March 1, 2006;
290(3):
H968 - H977.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. M. van Gelder, F. A. Bracke, A. Meijer, and N. H.J. Pijls
The Hemodynamic Effect of Intrinsic Conduction During Left Ventricular Pacing as Compared to Biventricular Pacing
J. Am. Coll. Cardiol.,
December 20, 2005;
46(12):
2305 - 2310.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. C. P. Kerckhoffs, O. P. Faris, P. H. M. Bovendeerd, F. W. Prinzen, K. Smits, E. R. McVeigh, and T. Arts
Electromechanics of paced left ventricle simulated by straightforward mathematical model: comparison with experiments
Am J Physiol Heart Circ Physiol,
November 1, 2005;
289(5):
H1889 - H1897.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Brignole, M. Gammage, E. Puggioni, P. Alboni, A. Raviele, R. Sutton, P. Vardas, M.G. Bongiorni, L. Bergfeldt, C. Menozzi, et al.
Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fibrillation
Eur. Heart J.,
April 1, 2005;
26(7):
712 - 722.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Vernooy, X. A.A.M. Verbeek, M. Peschar, H. J.G.M. Crijns, T. Arts, R. N.M. Cornelussen, and F. W. Prinzen
Left bundle branch block induces ventricular remodelling and functional septal hypoperfusion
Eur. Heart J.,
January 1, 2005;
26(1):
91 - 98.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Hay, V. Melenovsky, B. J. Fetics, D. P. Judge, A. Kramer, J. Spinelli, C. Reister, D. A. Kass, and R. D. Berger
Short-Term Effects of Right-Left Heart Sequential Cardiac Resynchronization in Patients With Heart Failure, Chronic Atrial Fibrillation, and Atrioventricular Nodal Block
Circulation,
November 30, 2004;
110(22):
3404 - 3410.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Steendijk, S. A.F. Tulner, M. Wiemer, R. A. Bleasdale, J. J. Bax, E. E. van der Wall, J. Vogt, and M. J. Schalij
Pressure-volume measurements by conductance catheter during cardiac resynchronization therapy
Eur. Heart J. Suppl.,
August 1, 2004;
6(suppl_D):
D35 - D42.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Peschar, K. Vernooy, R. N Cornelussen, X. A.A.M Verbeek, R. S Reneman, M. A Vos, and F. W Prinzen
Structural, electrical and mechanical remodeling of the canine heart in AV-block and LBBB
Eur. Heart J. Suppl.,
August 1, 2004;
6(suppl_D):
D61 - D65.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. G. Stevenson and M. O. Sweeney
Single Site Left Ventricular Pacing for Cardiac Resynchronization
Circulation,
April 13, 2004;
109(14):
1694 - 1696.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Auricchio
Pacing the left ventricle: does underlying rhythm matter?
J. Am. Coll. Cardiol.,
January 21, 2004;
43(2):
239 - 240.
[Full Text]
[PDF]
|
|
|
|
Top
Abstract
Methods