EXPEDITED PUBLICATION
Optimizing Hemodynamics in Heart Failure Patients by Systematic Screening of Left Ventricular Pacing SitesThe Lateral Left Ventricular Wall and the Coronary Sinus Are Rarely the Best Sites
Nicolas Derval, MD*,*,
Paul Steendijk, PhD ,
Lorne J. Gula, MD ,
Antoine Deplagne, MD*,
Julien Laborderie, MD*,
Frederic Sacher, MD*,
Sebastien Knecht, MD*,
Matthew Wright, PhD*,
Isabelle Nault, MD*,
Sylvain Ploux, MD*,
Philippe Ritter, MD*,
Pierre Bordachar, MD*,
Stephane Lafitte, MD, PhD*,
Patricia Réant, MD*,
George J. Klein, MD,
Sanjiv M. Narayan, MD ,
Stephane Garrigue, MD*,
Mélèze Hocini, MD*,
Michel Haissaguerre, MD*,
Jacques Clementy, MD* and
Pierre Jaïs, MD*
* Hôpital Cardiologique du Haut Lévêque, CHU Bordeaux, Université Bordeaux 2 Victor Segalen, Pessac, France
Leiden University Medical Center, Leiden, the Netherlands
Arrhythmia Department, University of Western Ontario, London, Ontario, Canada; and the
University of California and Veterans Affairs Medical Center, San Diego, California
Manuscript received April 26, 2009;
revised manuscript received August 17, 2009,
accepted August 26, 2009.
* Reprints and correspondence: Dr. Nicolas Derval, Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, 1, Avenue Magellan, 33600 Pessac, France (Email: dervalnicolas{at}gmail.com).
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Abstract
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Objectives: We sought to evaluate the impact of the left ventricular (LV) pacing site on hemodynamic response to cardiac resynchronization therapy (CRT).
Background: CRT reduces morbidity and mortality in heart failure patients. However, 20% to 40% of eligible patients may not fully benefit from CRT device implantation. We hypothesized that selecting the optimal LV pacing site could be critical in this issue.
Methods: Thirty-five patients with nonischemic dilated cardiomyopathy referred for CRT device implantation were studied. Intraventricular dyssynchrony and latest activated LV wall were defined by tissue Doppler imaging analysis before the study. Eleven predetermined LV pacing sites were systematically assessed in random order: basal and mid-cavity (septal, anterior, lateral, inferior), apex, coronary sinus (CS), and the endocardial site facing the CS pacing site. For each patient, +dP/dTmax, –dP/dTmin, pulse pressure, and end-systolic pressure during baseline (AAI) and DDD LV pacing were compared. Two atrioventricular delays were tested.
Results: Major interindividual and intraindividual variations of hemodynamic response depending on the LV pacing site were observed. Compared with baseline, LV DDD pacing at the best LV position significantly improved +dP/dTmax (+31 ± 26%, p < 0.001) and was superior to pacing the CS (+15 ± 23%, p < 0.001), the lateral LV wall (+18 ± 22%, p < 0.001), or the latest activated LV wall (+11 ± 17%, p < 0.001).
Conclusions: The pacing site is a primary determinant of the hemodynamic response to LV pacing in patients with nonischemic dilated cardiomyopathy. Pacing at the best LV site is associated acutely with fewer nonresponders and twice the improvement in +dP/dTmax observed with CS pacing.
Key Words: heart failure • resynchronization • pacing • hemodynamic
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Abbreviations and Acronyms
| | AVD = atrioventricular delay | | BiV = biventricular | | CRT = cardiac resynchronization therapy | | CS = coronary sinus | | ESP = end-systolic pressure | | LV = left ventricular | | PP = pulse pressure | | TDI = tissue Doppler imaging |
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Despite recent advances in its pharmacologic treatment, congestive heart failure remains a growing health care problem in the Western world (1). Cardiac resynchronization therapy (CRT) was used extensively during the past decade for the management of patients with drug-refractory, end-stage heart failure. Large randomized trials have demonstrated in selected patients that CRT improves quality of life, symptoms, and exercise capacity and reduces all-cause as well as heart failure morbidity and mortality (2–9). However, individual results vary, and 20% to 40% of implanted patients do not respond to CRT according to these studies. Different strategies have been developed to improve the responder rate to CRT such as improving pre-implantation patient selection and optimizing device programming and left ventricular (LV) lead position.
Based on previous studies, the current consensus is to position the LV lead in a lateral or posterolateral branch of the coronary sinus (CS) (10,11). The concept that this site is optimal for all patients has been challenged by hemodynamic studies suggesting that the actual pacing site is of critical importance to CRT (12,13). However, such studies have been limited by the number of LV pacing sites compared, either due to the constraints of CS anatomy or the LV sites that are accessible by thoracotomy. To date, no study has systematically investigated whether optimal LV pacing sites, selected individually from sites throughout the LV wall, might decrease the rate of nonresponders or optimize the benefit of CRT among responders.
We hypothesized that LV hemodynamics may be optimized by pacing at sites that do not coincide with conventional CS pacing sites and that the optimal site may lie remote from the lateral LV wall or from sites of maximal mechanical LV delay. We tested this hypothesis by comparing the quantitative hemodynamic response to pacing at each of 10 transseptally accessed endocardial sites with the response at the conventional CS site in patients with nonischemic cardiomyopathy and clinical indications for CRT.
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Methods
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Patients.
Thirty-five consecutive patients (mean age 63 ± 12 years; 28 men) with New York Heart Association functional class III or IV heart failure despite optimal medical therapy, echocardiographic LV ejection fraction <35%, and a left bundle branch block pattern on the surface electrocardiogram with a QRS duration of >140 ms, scheduled for implantation of a CRT device were included in this single-center prospective study. The protocol was approved by the CHU Bordeaux ethics committee, and all patients gave informed consent. All patients included in this study had appropriate investigations to exclude reversible causes of dilated cardiomyopathy and ischemic disease. They were on an optimal medical regimen, including angiotensin-converting enzyme inhibitors and beta-blockers. Patients with ischemic or valvular cardiomyopathy were excluded from participation.
LV pressure and volume measurements.
To acquire real-time pressure-volume loops during the study, a 7-F combined pressure-conductance catheter (CD Leycom, Zoetermeer, the Netherlands) was inserted through a femoral artery and advanced to the LV apex through a 0.025-inch flexible guidewire via the retroaortic route. The catheter was connected to a cardiac function analyzer (Leycom CFL512, CD Leycom) that recorded and displayed online pressure and 7 segmental volumes delineated by the electrodes at a sample frequency of 250 Hz. For the purpose of the present study, the volume data were not used.
The pigtail of the conductance catheter was positioned in the apex and was adjusted to the long heart axis under fluoroscopic guidance. Temporary pacing leads were placed in the right atrium (Josephson, Bard Electrophysiology, Lowell, Massachusetts) and in a lateral branch of the coronary sinus (Xtrem catheter, ELA Medical, Le Plessis-Robinson, France) via the femoral vein. A deflectable-tip catheter (Celsius 4 mm, Biosense Webster Inc., Diamond Bar, California) was placed in the left ventricle via the transseptal route and used for pacing the predetermined LV endocardial sites. Pulsatile arterial pressure was measured continuously.
Echocardiographic assessment.
In addition to the invasive hemodynamic study described in detail in the following, patients underwent echocardiography with intraventricular dyssynchrony assessment. Recordings were performed using a GE Vingmed Ultrasound system (System 7, GE Vingmed Ultrasound AS, Horten, Norway) equipped with a 2.5- to 5-MHz imaging probe and offline cine loop analysis software. All images were recorded digitally and analyzed by the same operator. Mitral regurgitation was quantified and graded by the proximal isovelocity surface area method. Intra-LV dyssynchrony was determined using tissue Doppler imaging (TDI) to assess segmental wall motion, as previously described (14–16). In brief, TDI was performed by placing the sample volume in the middle of the basal and mid-segmental portion of the septal, lateral, inferior, anterior, posterior, and anteroseptal walls. Gain and filter settings were adjusted as needed to eliminate background noises and to allow a clear tissue signal. The TDI velocities were recorded and measured at a sweep speed of 100 mm/s using online calipers. The intra-LV delaypeak was then calculated as the difference between the shortest and longest of the 12 segmental electromechanical delaypeak values, and the latest activated LV wall was defined as the wall with the longest electromechanical delaypeak (14–17).
Experimental protocol.
All measurements during baseline and LV pacing were performed at a constant atrial pacing rate of 10 beats on the resting heart rate (Table 1). Two atrioventricular delays (AVDs) were tested; a short AVD was set as the longest AVD that allowed complete ventricular capture, whereas the long AVD was 50 ms longer. Eleven predetermined LV pacing sites were assessed in a randomized order during the protocol: 9 endocardial LV sites basal and mid-cavity (septal, anterior, lateral, inferior); apex; CS; and 1 endocardial site facing the CS pacing site (Fig. 1).
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Figure 1 Distribution of LV Pacing Sites and Catheter Position
(A) Predetermined left ventricular (LV) pacing site used during the study. The LV cavity was divided into 9 zones: 4 basal, 4 mid-cavity (inferior, lateral, anterior, and septal aspects), and 1 apex. One site was epicardial in a lateral branch of the coronary sinus (CS), and 1 site was endocardial just facing the CS pacing site. (B) Catheter position during the study.
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For each pacing site, 3 pacing modes were successively applied: AAI, then DDD (i.e., not BiV) with long and short AVDs. Hemodynamic data were acquired consecutively 60 s after any change in the pacing mode or site, and periods of at least 20 s of steady state were selected for offline analysis. Twelve-lead electrocardiography at 100 mm/s was performed, and arterial pressure measurements were collected at each pacing site and mode.
Hemodynamic data analysis.
Analysis of the pressure-volume loops was performed with custom software (Circlab, Leiden University Medical Center, Leiden, the Netherlands) as described previously (18). For each patient, pacing mode, and site, hemodynamic indexes were calculated as the mean of all beats during a 20-s steady-state period. LV function was quantified by maximal and minimal rates of LV pressure change (+dP/dTmax, –dP/dTmin), end-systolic pressure (ESP), and arterial pulse pressure (PP).
Hemodynamic results at each pacing site and mode were expressed as a percentage of variation from the control that was defined as data from AAI pacing. Notably, these AAI pacing data were remeasured immediately before each ventricular pacing site was tested to account for hemodynamic alterations over time. We arbitrarily defined the best and worst sites as the best and worst improvement of the considered hemodynamic parameter by LV DDD pacing compared with baseline (AAI pacing) among the 11 tested sites.
Comparison of lead placement strategies.
Four different strategies to select the optimal LV pacing site were compared: 1) individually based strategy in which the LV pacing site was defined for each patient as the site associated with the greatest improvement of +dP/dTmax; 2) conventional strategy in which the LV pacing site was defined as the CS pacing site using traditional clinical criteria; 3) echo-guided strategy in which the LV pacing site was defined as the latest mechanically activated LV wall; and 4) lateral area strategy in which the endocardial LV pacing site was defined as the lateral LV wall, with the basal and mid-lateral sites being pooled and considered as a single site.
Randomization and statistical analysis.
Each patient was randomized independently according to an 11 x 11 Latin square (11 different sequences of 11 pacing sites). Briefly, the Latin square was generated by random permutations of a basic sequence of 11 pacing sites. Each sequence was applied to 3 patients. Statistical analysis was performed using SAS software version 9.1 (SAS Institute, Cary, North Carolina). Values of p < 0.05 were considered significant. All results are expressed as mean ± SD. Parametric tests were used as appropriate for normally distributed data. Paired t tests were performed to compare values obtained for individual subjects at paired pacing locations and to compare values at single sites while pacing with a long versus short AVD. Comparison of multiple pacing sites was performed using simple 1-way analysis of variance testing.
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Results
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Patients.
Between 2004 and 2008, 35 eligible consecutive patients were enrolled in the study (28 men, mean age 63 ± 12 years); their baseline characteristics are summarized in Table 1. Two patients were excluded from final analysis due to the pressure-volume loop computer failure before the beginning of the procedure. All patients had nonischemic dilated cardiomyopathy with severely depressed LV function (mean LV ejection fraction 28 ± 7%). Mean LV end-diastolic diameter was 71 ± 10 mm. Severe mechanical intra-LV dyssynchrony was present at baseline (mean maximal delay 81 ± 20 ms). Of 27 patients with usable TDI data, the most delayed site was the lateral wall in 48% (n = 13), the inferior wall in 22% (n = 6), the inferolateral wall in 22% (n = 6), and the inferoseptal wall in 7% (n = 2) of patients. The CS catheter was positioned at the mid-lateral LV wall in 77% of the patients, at the mid-anterolateral LV wall in 17% of the patients, and at the mid-posterolateral LV wall in 6% of the patients.
General results in the population.
In total, 1,155 pacing conditions were tested in the entire study; of these, 1,034 (90%) were usable.
intraindividual variations.
Within individual patients, substantial variations of hemodynamic response depending on the LV pacing site were found. An example is shown in Figure 2
(Patient #20): +dP/dTmax (compared with baseline), during pacing at the mid-lateral site, was associated with a +93% improvement, whereas pacing at the basal anterior site was associated with a +19% increase (long AVD).
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Figure 2 Patient #20: Best and Worst Sites
Patient #20: +dP/dTmax recorded at the worst and best left ventricular pacing sites. AAI pacing and DDD pacing mode, long atrioventricular delay.
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interindividual variations.
The hemodynamic response to LV pacing varied significantly among individuals in the study. When all the tested LV pacing sites are taken into consideration, the maximal range of hemodynamic response between patients was +dP/dTmax from –31% to +93% and –32% to +81%; –dP/dTmin from –29% to +67% and –32% to +68%; PP from –51% to +133% and –61% to +140%; ESP from –23% to +48% and –40% to +42%, for long and short AVDs, respectively.
The mean improvements in +dP/dTmax by pacing at the best compared with the worst LV sites were +31 ± 26% versus 2 ± 12% and +26 ± 23% versus 1 ± 13% for long and short AVDs, respectively (Fig. 3).
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Figure 3 Best and Worst Sites for Each Individual (+dP/dTmax)
Percentage of change in +dP/dTmax for each individual patient at best (open bars) and worst (solid bars) left ventricular pacing location (long atrioventricular delay).
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comparison of long and short avds.
Pacing with a long AVD was associated with a significantly shorter QRS duration than pacing with a short AVD (p < 0.001). Pacing with a long versus a short AVD was associated with significantly greater hemodynamic improvement in +dP/dTmax (31 ± 26% vs. 26 ± 23% [p = 0.005]); –dP/dTmin (19 ± 17% vs. 17 ± 16% [p = 0.002]), and ESP (14 ± 11% vs. 12 ± 10% [p = 0.03]). No significant change was observed for PP (36 ± 30% vs. 32 ± 28% [p = 0.09]) (Fig. 4).
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Figure 4 Comparison of Hemodynamic Change for Both AV Delays at Best Location
AV = atrioventricular; ESP = end-systolic pressure; LAV = long atrioventricular delay; PP = pulse pressure; SAV = short atrioventricular delay.
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Impact of LV pacing site on hemodynamic response..
Comparison of the 11 pacing sites demonstrated that none of the tested sites was consistently associated with the best hemodynamic improvement (Fig. 5). The distribution of the best pacing site for each individual was uniformly spread among the 11 tested sites (+dP/dTmax, long AVD) (Fig. 6). Similar results were found with the other hemodynamic parameters (data not shown).
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Figure 5 Site by Site, Mean Percentage of Change in +dP/dTmax
Mean percentage of change in +dP/dTmax for each pacing site compared with best and worst left ventricular pacing sites, long atrioventricular delay. ant = anterior; endo CS = endocardial coronary sinus; inf = inferior; lat = lateral; sept = septal.
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For individual patients, pacing at the best location resulted in a significant improvement of all hemodynamic parameters (+dP/dTmax, –dP/dTmin, PP, and ESP) compared with CS pacing, whereas pacing at the worst site altered all hemodynamic parameters compared with CS pacing (Fig. 7, Table 2). When the LV pacing site was chosen according to the best improvement of +dP/dTmax, pacing at this site was associated with a significant improvement of the other hemodynamic parameters (Fig. 8, Table 2).
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Figure 7 Average Hemodynamic Change at Best Site, Worst Site, and CS Site, Long AVD
Comparison of the magnitude of change of +dP/dtmax, –dP/dtmin, pulse pressure, and end-systolic pressure (ESP) at best site, worst site, and coronary sinus (CS) site, long atrioventricular delay (AVD). *p < 0.01.
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Table 2 Hemodynamic Results at Baseline and During Left Ventricular Pacing at the CS Site, Best Site, Worst Site, and the Left Ventricular Pacing Site Associated With the Best Improvement of +dP/dTmax (at Best +dP/dTmax)
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Figure 8 Impact of Left Ventricular Pacing at the Best +dP/dTmax Location
Comparison of hemodynamic change when the pacing site is defined by the site associated with the greatest improvement of +dP/dTmax. AV = atrioventricular; CS = coronary sinus; ESP = end-systolic pressure; PP = pulse pressure.
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comparison of endocardial and epicardial pacing..
Pacing at an endocardial site just facing the epicardial CS pacing site was not associated with a significantly greater improvement of +dP/dTmax, PP, or ESP with both AVDs. However, –dP/dTmin increased from +0.4 ± 13% to 8.5 ± 16% with long AVDs (p = 0.001) and from –0.9 ± 14% to 5.8 ± 18% with short AVDs (p = 0.01) when pacing the CS and the equivalent endocardial site, respectively.
Comparison of lead placement strategies.
- 1 Pacing at the best site (individually-based approach) was associated with a mean improvement of +dP/dTmax of +31 ± 26%. LV pacing at the best position was associated with >20% improvement in 19 patients (54%), between 10% and 20% improvement in 9 patients (26%), between 0% and 10% improvement in 2 patients (6%), and <0% in 3 patients (9%) (long AVD, +dP/dTmax).
- 2 Pacing from within the CS (conventional strategy) was associated with a mean improvement of +dP/dTmax of +15 ± 23% (p < 0.001 vs. best site) (Table 3). It was associated with the best improvement of +dP/dTmax (long AVD) in only 3 patients (9%) and was the worst position in 6 patients (17%). LV pacing from the CS was associated with >20% improvement in 10 patients (29%), between 10% and 20% improvement in 4 patients (11%), between 0% and 10% improvement in 9 patients (26%), and <0% in 8 patients (23%) (+dP/dTmax, long AVD).
- 3 Pacing the lateral LV wall (lateral area strategy) was associated with a mean improvement of 18 ± 22% (p < 0.001 vs. best site). The lateral area was the best site in 8 patients (23%) and at the worst position in 9 patients (26%). LV pacing at the lateral area was associated with >20% improvement in 13 patients (37%), between 10% and 20% improvement in 5 patients (14%), between 0% and 10% improvement in 11 patients (31%), and <0% in 4 patients (11%) (+dP/dTmax, long AVD).
- 4 Pacing the latest activated LV wall (echo-guided strategy) was associated with a mean improvement of 11 ± 17% (p < 0.001 vs. best site). The latest site was the best site for +dP/dTmax in 2 patients (6%) and at the worst in 3 patients (9%). LV pacing at the latest site was associated with >20% improvement in 8 patients (23%), between 10% and 20% improvement in 4 patients (11%), between 0% and 10% improvement in 9 patients (26%), and <0% in 6 patients (17%) (+dP/dTmax, long AVD).
Comparison of the 3 current strategies (conventional CS pacing, lateral area, and echo guided) demonstrated no significant change in acute +dP/dTmax (p > 0.05). LV pacing using an individually based approach was associated with a delta (absolute value) of hemodynamic improvement of 16% compared with conventional CS pacing, 13% compared with LV pacing at the lateral area, and 20% compared with LV pacing at the latest wall (echo-guided).
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Discussion
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The present study demonstrates that acutely: 1) the LV pacing site is a major determinant of the hemodynamic response; 2) major interindividual and intraindividual variations in response to LV pacing are observed; 3) an optimal LV pacing site cannot be defined a priori and is specific to each individual; 4) an individually-based approach to pacing at the best possible location is superior to the other pacing strategies: pacing from within the CS, at the lateral, or at the most delayed wall; 5) endocardial pacing may improve the diastolic function compared with epicardial pacing; and 6) in LV pacing, a long AVD is consistently superior to a short AVD.
Role of the LV pacing site.
This study demonstrates the importance of the LV pacing site as a primary determinant of the short-term hemodynamic response. There were significant variations in the hemodynamic response to LV pacing among patients and within each individual. In some patients, there was as much as an 81% difference in +dP/dTmax change between the best and worst locations. Importantly, we observed that the best site is not a predetermined area of the LV but is specific to each patient. These results are consistent with those of a previous study by Dekker et al. (12), who found that the hemodynamic response to biventricular (BiV) pacing varies widely with the LV sites. In 11 patients with heart failure eligible for CRT, they showed that pacing at the optimal epicardial LV site acutely increased LV stroke volume, +dP/dTmax, and ejection fraction compared with baseline, whereas suboptimal sites did not change or worsened LV function. In their study, patients included were those in whom conventional CRT had failed and were mainly patients with ischemic cardiomyopathy. Importantly, only the LV sites that were accessible by mini-invasive surgery were tested in that study. Our study confirms those results in a larger group of nonischemic patients with unrestricted access to LV sites that were systematically assessed in a random order.
The limited number of pacing sites that are accessible via the CS were associated with important hemodynamic consequences in our study: 1) pacing at the best LV site was associated with twice the increase of +dP/dTmax compared with CS pacing; 2) pacing the CS was the best location in only 3 patients (9%); and 3) in 8 patients (23%), CS pacing had either no effect or a detrimental effect on +dP/dTmax (nonresponders), whereas this was observed in only 3 patients (9%) with LV pacing when all sites were tested (true nonresponders). These data suggest that some of the clinical nonresponders with CS pacing would benefit from LV pacing using an individually-based approach.
Strategy to define the LV pacing site.
To date, there is no clear consensus as to the optimal strategy regarding LV lead placement. Current practice for CRT is to place the LV lead at the lateral wall by either a percutaneous (CS) or surgical approach. This is based on a previous study suggesting that positioning the LV pacing lead at the lateral wall resulted in a greater improvement of +dP/dTmax compared with the anterior wall (10); however, in that study, only 2 LV sites were assessed. The present study demonstrates that only a minority of patients had the best site along the lateral LV wall. The classic basal lateral site was the best site in terms of +dP/dTmax in only 9% of patients and the mid-lateral site in 14% (long AVD), with similar results in all other measured hemodynamic parameters.
It has been shown that echocardiography reproducibly identifies the latest LV wall to be activated and accurately quantifies the intraventricular delay. Ansalone et al. (11) studied 31 patients eligible for CRT and showed that the greatest improvement of LV performance was found in patients paced at the most delayed site. Recently published data demonstrated that pacing the site of latest mechanical activation was associated with a better long-term prognosis and reverse LV remodeling after 6 months of CRT (19). However, only 3 different LV pacing sites accessible via the CS were tested (all basal sites, lateral [45%], posterior [49%], and anterior [5%]). In our study, there were no differences among CS pacing, lateral wall pacing, and echo-guided strategy. In contrast, the individually-based approach significantly improved hemodynamic parameters. The large number of sites systematically tested in the present protocol in all patients may explain why our results are in disagreement with those of previous studies.
The reason that such important variations of hemodynamic response between LV sites are observed is unclear. The selected population was comparable to previous trials of CRT in terms of QRS duration (165 ± 28 ms), LV function (ejection fraction 28 ± 7%), and mitral regurgitation (4 patients with grade III) (3,4,6,7). In the present study, only patients with nonischemic cardiomyopathy were selected, and large areas of ischemic necrosis or scar cannot explain those variations. However, it has been demonstrated that severe nonischemic cardiomyopathy with left bundle branch block is a complex electrical disease resulting from conduction delay located at several anatomic levels (20–22). Auricchio et al. (23) performed endocardial 3-dimensional mapping on 24 patients with nonischemic cardiomyopathy and described the presence of a transmural functional line of block resulting in atypical LV activation sequence around these lines (U-shaped pattern). It may be that the presence of a line of electrical block in the left ventricle may contribute to regional, and hence interindividual, variation in hemodynamic response to the LV pacing site.
Clinical implications: which parameter to choose?.
The definition of the best or worst site for an individual patient may vary according to the parameter considered. Discordant responses at a single LV pacing site were sometimes observed, but no studies have demonstrated the superiority of a single parameter to predict long-term clinical response. Nelson et al. (24) showed that LV +dP/dTmax is a more sensitive parameter than LV and aortic PP in the evaluation of CRT effects. In our study, the best site was selected on LV +dP/dTmax and was associated with a significant improvement of all the other measured parameters for both AVDs. In addition, LV +dP/dTmax has been the most extensively used parameter and is relatively easy to obtain.
Endocardial versus epicardial pacing.
In this study, we tested endocardial and epicardial pacing at the exact same location to investigate whether endocardial pacing was better, as has been suggested by a previous study (25). The results on +dP/dTmax, PP, and ESP were not significantly different, but endocardial pacing was significantly superior to epicardial pacing on –dP/dTmin at both AVDs. In 2001, Garrigue et al. (25) compared 15 patients who underwent implantation of a conventional BiV pacing (epicardial pacing) device with 8 patients with a BiV implantable cardioverter-defibrillator where the LV lead was inserted endocardially in the LV cavity via the transseptal route. They showed that endocardial BiV pacing was associated with better LV filling and systolic performance. The reason that –dP/dTmin is notably improved by endocardial pacing is not clear. The impact of CRT on diastolic dysfunction is still a matter of debate, and further studies are needed to confirm our results (12,26,27).
Impact of AVD.
Two different AVDs were tested in our study. By allowing some degree of fusion between intrinsic LV activation by the right bundle and LV pacing, the long AVD was associated with a shorter QRS complex compared with a short AVD. In all but 1 parameter, pacing with a long AVD had a greater impact on hemodynamic improvement. Van Gelder et al. (28) reported similar results. They showed that LV pacing with optimal AVD allowing fusion with intrinsic activation was associated with higher LV +dP/dTmax than BiV pacing.
Study limitations.
The main limitation of this study is the relative complexity of the protocol. Data acquisition and analysis are lengthy and would be difficult to use routinely to define the best site before implantation. However, we demonstrated that selecting the optimal site has an important role in the response to LV pacing. This should promote studies of alternative approaches to the conventional CRT using the CS.
A second limitation of this study is that to keep the pacing protocol relatively simple, DDD LV pacing was chosen instead of BiV pacing. However, several previous studies demonstrated the noninferiority of LV pacing compared with BiV pacing (28–31), but further studies of BiV pacing are needed to confirm our results. We acknowledge that VDD pacing would have been closer to the usual resynchronization pacing strategy, but DDD LV pacing was the only option to ensure a steady rate for accurate hemodynamics throughout the study and therefore a fair comparison of the pacing sites and modalities.
It is unlikely that our results were limited by the use of endocardial pacing because the results did not significantly differ for pacing at endocardial and epicardial (CS) sites. Moreover, some of these sites were located away from the lateral wall, lessening concerns that differences between endocardial and epicardial pacing sites may be regional.
This study was also limited to short-term hemodynamic changes, and their relationship to clinical improvement was not evaluated. However, Steendijk et al. (32) studied 22 patients implanted with a CRT device based on conventional criteria. They showed that short-term improvement of invasive hemodynamic parameters (including +dP/dTmax, –dP/dTmin, and ESP) was maintained at 6-month follow-up after CRT device implantation.
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Conclusions
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This hemodynamic study shows that the LV pacing site is a primary determinant of the response to LV pacing in patients with nonischemic dilated cardiomyopathy. Pacing at the best LV site is associated acutely with fewer nonresponders and twice the improvement in dP/dTmax observed with CS pacing. These results suggest that new approaches allowing unrestricted access to LV pacing sites need to be assessed because conventional pacing from the CS is rarely optimal.
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Acknowledgments
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The authors thank Dr. David Massel (University of Western Ontario, London, Ontario, Canada), Dr. Paul Perez, and Dr. Christine Germain (Clinical Epidemiology Unit, University Hospital, Bordeaux, France) for their advice and assistance with the statistical analysis, and Maïder Piquet-Bessouet for assistance.
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Footnotes
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Dr. Derval is supported by grants from Medtronic Corporation, Boston Scientific Corporation, and St. Jude Medical, Inc. This study was supported by the Programme Hospitalier de Recherche Clinique 2001 (www.clinicaltrials.gov: NCT00221780) from CHU Bordeaux, France. Dr. Deplagne is supported by a grant from Biotronik, Inc. Dr. Laborderie is supported by grants from Medtronic Corporation, Boston Scientific Corporation, and St. Jude Medical, Inc. Dr. Nault is supported by a grant from St. Jude Medical, Inc. Dr. Ritter is a consultant for the research and development departments of Sorin Corporation and Biotronik, Inc. Dr. Klein is a consultant for Medtronic Corporation. Dr. Narayan is a member of the Speakers' Bureaus of and has fellowship funding from St. Jude Medical, Inc., Boston Scientific Corporation, and Medtronic Corporation. Dr. Jaïs is a speaker for St. Jude Medical, Inc. Steven E. Nissen, MD, MACC, served as Guest Editor for this article.
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References
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Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD trial JAMA 2003;289:2685-2694.[Abstract/Free Full Text] 6 Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure N Engl J Med 2004;350:2140-2150.[CrossRef][Web of Science][Medline] 7 Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure N Engl J Med 2005;352:1539-1549.[CrossRef][Web of Science][Medline] 8 Auricchio A, Stellbrink C, Butter C, et al. Clinical efficacy of cardiac resynchronization therapy using left ventricular pacing in heart failure patients stratified by severity of ventricular conduction delay J Am Coll Cardiol 2003;42:2109-2116.[Abstract/Free Full Text] 9 Lozano I, Bocchiardo M, Achtelik M, et al. Impact of biventricular pacing on mortality in a randomized crossover study of patients with heart failure and ventricular arrhythmias Pacing Clin Electrophysiol 2000;23:1711-1712.[Medline] 10 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] 11 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] 12 Dekker AL, Phelps B, Dijkman B, et al. Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops J Thorac Cardiovasc Surg 2004;127:1641-1647.[Abstract/Free Full Text] 13 Helm RH, Byrne M, Helm PA, et al. Three-dimensional mapping of optimal left ventricular pacing site for cardiac resynchronization Circulation 2007;115:953-961.[Abstract/Free Full Text] 14 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] 15 Yu CM, Fung WH, Lin H, Zhang Q, Sanderson JE, Lau CP. Predictors of left ventricular reverse remodeling after cardiac resynchronization therapy for heart failure secondary to idiopathic dilated or ischemic cardiomyopathy Am J Cardiol 2003;91:684-688.[CrossRef][Web of Science][Medline] 16 Yu CM, Lin H, Yang H, Kong SL, Zhang Q, Lee SW. Progression of systolic abnormalities in patients with "isolated" diastolic heart failure and diastolic dysfunction Circulation 2002;105:1195-1201.[Abstract/Free Full Text] 17 Bax JJ, Marwick TH, Molhoek SG, et al. 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Initial ventricular activation in left-sided intraventricular conduction defects Circulation 1980;62:621-631.[Abstract/Free Full Text] 22 Rodriguez LM, Timmermans C, Nabar A, Beatty G, Wellens HJ. Variable patterns of septal activation in patients with left bundle branch block and heart failure J Cardiovasc Electrophysiol 2003;14:135-141.[Web of Science][Medline] 23 Auricchio A, Fantoni C, Regoli F, et al. Characterization of left ventricular activation in patients with heart failure and left bundle-branch block Circulation 2004;109:1133-1139.[Abstract/Free Full Text] 24 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] 25 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][Web of Science][Medline] 26 de Cock CC, Vos DH, Jessurun E, Allaart CP, Visser CA. Effects of stimulation site on diastolic function in cardiac resynchronization therapy Pacing Clin Electrophysiol 2007;30Suppl 1:S40–42. 27 Waggoner AD, Faddis MN, Gleva MJ, de las Fuentes L, Davila-Roman VG. Improvements in left ventricular diastolic function after cardiac resynchronization therapy are coupled to response in systolic performance J Am Coll Cardiol 2005;46:2244-2249.[Abstract/Free Full Text] 28 van Gelder BM, Bracke FA, Meijer A, Pijls NH. The hemodynamic effect of intrinsic conduction during left ventricular pacing as compared to biventricular pacing J Am Coll Cardiol 2005;46:2305-2310.[Abstract/Free Full Text] 29 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] 30 Touiza A, Etienne Y, Gilard M, Fatemi M, Mansourati J, Blanc JJ. Long-term left ventricular pacing: assessment and comparison with biventricular pacing in patients with severe congestive heart failure J Am Coll Cardiol 2001;38:1966-1970.[Abstract/Free Full Text] 31 Garrigue S, Bordachar P, Reuter S, et al. Comparison of permanent left ventricular and biventricular pacing in patients with heart failure and chronic atrial fibrillation: prospective haemodynamic study Heart 2002;87:529-534.[Abstract/Free Full Text] 32 Steendijk P, Tulner SA, Bax JJ, et al. Hemodynamic effects of long-term cardiac resynchronization therapy: analysis by pressure-volume loops Circulation 2006;113:1295-1304.[Abstract/Free Full Text]
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