Author + information
- Received February 11, 2002
- Revision received April 1, 2002
- Accepted April 4, 2002
- Published online August 7, 2002.
- Ole A. Breithardt, MD*,
- Christoph Stellbrink, MD*,* (, )
- Andrew P. Kramer, PhD†,
- Anil M. Sinha, MD*,
- Andreas Franke, MD*,
- Rodney Salo, MSc†,
- Bernhard Schiffgens, BSc*,
- Etienne Huvelle, MD‡,
- Angelo Auricchio, MD, PhD§,
- PATH-CHF Study Group
- ↵*Reprint requests and correspondence:
Dr. Christoph Stellbrink, Medizinische Klinik I der RWTH Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany.
Objectives We sought to determine whether radial left ventricular (LV) asynchrony in patients with heart failure predicts systolic function improvement with cardiac resynchronization therapy (CRT).
Background We quantified LV wall motion by echocardiography to correlate the effects of CRT on LV systolic function with wall motion synchrony.
Methods Thirty-four patients underwent echocardiographic phase analysis of LV septal and lateral wall motion and hemodynamic testing before CRT. Phase relationships were measured by the difference between the lateral (ΦL) and septal (ΦS) wall motion phase angles: ΦLS = ΦL − ΦS. The absolute value of ΦLS was used as an order-independent measure of synchrony: |ΦLS| = |ΦL − ΦS|.
Results Three phase relationships were identified (mean ± SD): type 1 (n = 4; peak positive LV pressure [dP/dtmax] 692 ± 310 mm Hg/s; ΦLS = 5 ± 6°, synchronous wall motion); type 2 (n = 17; dP/dtmax 532 ± 148 mm Hg/s; ΦLS = 77 ± 33°, delayed lateral wall motion); and type 3 (n = 13; dP/dtmax 558 ± 154 mm Hg/s; ΦLS = −115 ± 33°, delayed septal wall motion, triphasic). A large |ΦLS| predicted a larger increase in dP/dtmax with CRT (r = 0.74, p < 0.001). Sixteen patients were studied during right ventricular (RV), LV and biventricular (BV) pacing. Cardiac resynchronization therapy acutely reduced |ΦLS| from 104 ± 41° (OFF) to 86 ± 45° (RV; p = 0.14 vs. OFF), 71 ± 50° (LV; p = 0.001 vs. OFF) and 66 ± 42° (BV; p = 0.001 vs. OFF). A reduction in |ΦLS| predicted an improvement in dP/dtmax in type 2 patients for LV (r = 0.87, p = 0.005) and BV CRT (r = 0.73, p = 0.04).
Conclusions Echocardiographic quantification of LV asynchrony identifies patients likely to have improved systolic function with CRT. Improved synchrony is directly related to improved hemodynamic systolic function in type 2 patients.
QRS prolongation in left bundle branch block (LBBB) is associated with asynchronous ventricular contraction and a depressed ejection fraction (1) and is inversely correlated to global contractile function (2). Cardiac resynchronization therapy (CRT) has been recently introduced as a complementary treatment for patients with heart failure and a ventricular conduction delay, and it has been shown to improve left ventricular (LV) systolic function, as measured by peak positive LV pressure (dP/dtmax) (3) and Doppler echocardiography (4). It improves clinical symptoms and may lead to reversal of LV remodeling (5).
It is assumed that CRT improves systolic ventricular function by restoring more synchronized contraction patterns. However, only a few studies have investigated CRT mechanisms by using direct measures of ventricular asynchrony. Studies using multiple-gated equilibrium blood-pool scintigraphy demonstrated reduced interventricular phase shifts between the LV and right ventricular (RV) contraction sequence with CRT, but had conflicting conclusions about whether CRT reduced intraventricular asynchrony (6,7). Tagged magnetic resonance imaging has been used to quantify baseline mechanical dyssynchrony (8), but this modality is not applicable to patients with a pacemaker. In contrast, echocardiography allows rapid bedside evaluation of cardiac function and ventricular wall motion abnormalities. Abnormal septal wall motion patterns in patients with LBBB undergoing ventricular pacing have been studied by M-mode echocardiography, but these measurements are limited to the evaluation of radial function in the basal LV segments using the parasternal views. Recently, improvement of LV asynchrony was quantified with tissue Doppler imaging from the apical views (9), but this technique is limited to the study of longitudinal axis motion. Two-dimensional Fourier phase imaging may quantify wall motion asynchrony in the radial direction and has been used to assess LV asynergy in coronary artery disease (CAD) (10).
We hypothesized that the degree of radial ventricular asynchrony in patients with heart failure and ventricular conduction delay predicts the magnitude of contractile function improvement with CRT. To that end, we have evaluated a new phase analysis technique to quantify regional wall motion synchrony from endocardial border contours generated semi-automatically from two-dimensional echocardiographic ventricular images.
The PAcing THerapies in Congestive Heart Failure (PATH-CHF) trial is a prospective, multicenter, single-blinded, cross-over study conducted in Europe; it included 42 patients with ischemic and nonischemic cardiomyopathy, with a QRS width >120 ms and PR interval >150 ms. All patients had to be in stable New York Heart Association (NYHA) functional class III or IV, without the need for intravenous inotropic drugs. A detailed study design has been reported elsewhere (11). Because this study was initiated before availability of dedicated CRT systems, all patients received a biventricular (BV) pacing system with two separately implanted dual-chamber (DDD) pacemakers, an apical RV lead and an epicardial LV lead, implanted during a limited thoracotomy of the LV free wall. Biventricular pacing was obtained by programming one device in DDD mode and the second device in a ventricular triggered mode. This configuration enabled noninvasive testing of different pacing sites. The echocardiographic results obtained in the patient group were compared with those of a control group of 10 healthy individuals with a normal PR interval and QRS width.
During implantation, invasive hemodynamic testing was performed using the FLEXSTIM system (Guidant Corp., St. Paul, Minnesota) (11), with repeated measurements of dP/dtmax at various atrioventricular (AV) delays and pacing sites (RV, LV and BV) tested in random order in the VDD mode. The response to pacing was expressed as the percent increase in dP/dtmax (%ΔdP/dtmax), compared with no pacing.
Details of the invasive optimization procedure and pacemaker implantation have been described elsewhere (3). Evaluation of invasive variables was performed with no knowledge of the results of the echocardiographic analysis.
For baseline evaluation, the transthoracic echocardiograms of 34 patients were analyzed if there was sufficient image quality for complete endocardial border delineation. Studies were recorded in the left lateral supine position at rest in the week before implantation of the CRT system. To minimize the influence of relative motion of the heart, only echocardiographic recordings that could be obtained in respiratory hold and with a stable transducer position were included. Fundamental imaging was used in the majority of the baseline examinations (n = 26); harmonic imaging was used whenever it was available to the study center (n = 8). At the first follow-up visit, four weeks after implantation, echocardiographic recordings were made with temporary reprogramming of the CRT system to no pacing (OFF) and to RV, LV, and BV VDD pacing in random order. For each individual, the AV delay was programmed close to the optimal setting, as determined by acute invasive testing during implantation and kept constant for each pacing mode. Valid echocardiographic images from four-week follow-up were available for analysis in 16 patients. Two patients were excluded from the study because of their high pacing thresholds; two patients had sudden cardiac death; and 14 patients were excluded because they had technically inadequate echocardiographic recordings in at least one tested pacing mode. All examinations were recorded on S-VHS videotape and digitized for wall motion analysis with the CMS echo-analysis system (Medis, Leiden, Netherlands) (12) at the responsible core center (University Hospital, Aachen, Germany).
Quantification of ventricular asynchrony.
During the cardiac cycle, each region of the ventricular endocardial wall undergoes a cycle of inward and outward displacement. Each regional displacement cycle can be represented as a curve of displacement plotted over time from the start to the end of a cardiac cycle interval. Because these displacement curves are periodic, they can be analyzed in the frequency domain to quantify the phase relationship between curves independent of the displacement magnitude and heart rate. Each regional displacement curve is modeled as a wave with a period equal to the cardiac cycle interval, which, mathematically, is the fundamental frequency in Fourier analysis. The time at which the center of this wave occurs during the cardiac cycle interval is a function of the fundamental frequency phase angle (Φ). It is near 180° when centered in the middle of the cycle, 0° to 180° if shifted earlier and 180° to 360° if shifted later. Inverted and triphasic displacement curves (e.g., with paradoxical septal wall motion) have phase angles near the end (360°) or start (0°) of the cycle. With this method, the magnitude of synchrony between two regional displacement curves is calculated by the difference between their respective phase angles. Phase differences near 0° indicate near-perfect synchrony, whereas a difference of 180° defines maximal asynchrony.
All wall motion analyses were performed with no knowledge of the invasive hemodynamic test results and the patients’ clinical characteristics. The pacing mode was marked on videotape for identification. The CMS semi-automatic border detection software was used to delineate and track the LV endocardial wall motion in sequential frames of digitized images from the apical four-chamber view. Analysis of the apical two-chamber view was not feasible in the majority of patients because of incomplete border delineation (in most cases, the anterior wall). End diastole was demarcated by the frame in which the mitral valve first began to close; end systole was demarcated by the frame in which the mitral valve first began to open. Wall motion contours (Fig. 1A) were manually drawn in the first systolic and diastolic frames of each cardiac cycle, and the CMS software automatically generated intermediate frame contours, which were manually adjusted as necessary. For each CRT mode, endocardial motion was tracked through three to seven cardiac cycles verified to be in normal sinus rhythm by the concurrent surface electrocardiographic recording. Regional endocardial displacement was calculated for each cardiac cycle automatically by the CMS software, using the centerline method for 100 equally spaced segments on the LV wall motion contours (Fig. 1B). This method has been shown to reduce interobserver variability in the delineation of endocardial boundaries (12).
Forty segments from the basal septum toward the apex and 40 segments from the basal lateral wall toward the apex were averaged for calculation of septal and lateral regional displacement curves (Fig. 1B and 1C). Regional displacement curves were ensemble-averaged over three to seven cardiac cycles using the first systolic frame as the fiducial marker. Each curve was offset to zero displacement at the start of each cycle. Before phase analysis, the average regional displacement curves were smoothed with a three-frame moving-average filter. Septal and lateral displacement phases were defined by the phase angle of the fundamental frequency of the Fourier transform computed over the cardiac cycle regional displacement curve: (): This phase angle was computed with the discrete frame data, using the inner product of the regional displacement curve and orthogonal sine and cosine curves of the cardiac cycle interval length. Septal displacement curves exhibiting paradoxical negative systolic displacement that yielded a very small phase angle (<60°) due to the 360° modulus were adjusted to 360° − ΦS. Lateral and septal (L and S) phase relationships were measured by the difference between the lateral (ΦL) and septal (ΦS) phase angles: ΦLS = ΦL − ΦS. The absolute value of ΦLS was used as an order-independent measure of synchrony: |ΦLS| = |ΦL − ΦS|.
Continuous data are expressed in the text as the mean value ± SD and in the figures as the mean value ± SEM. To evaluate and compare the effects of RV, LV and BV pacing with no pacing treatments on the hemodynamic and echocardiographic measurements of each individual, we used a general linear model (analysis of variance [ANOVA]) accounting for all treatment variations being tested in each patient. To compare measurements among the control and L-S phase type groups, we used independent-samples ANOVA. For both ANOVAs, the Tukey correction was used to correct for type I error inflation introduced by testing multiple hypotheses. An unpaired t test was used to compare characteristics of analyzed and excluded patient groups and to compare measurements from patients with CAD and dilated cardiomyopathy (DCM). Statistical analyses were made with SAS version 8.2 (SAS Institute, Cary, North Carolina). The reproducibility of endocardial border delineation and phase angle measurements was assessed in 10 randomly selected baseline examinations as the mean difference between two independent measurements performed on different occasions by one observer (intraobserver variability) and between two independent observers (interobserver variability). The results were expressed as the percentage of the first measurement (±SD) and also as the percentage of 180° (±SD), based on the fact that two measurements cannot differ by >180° over the 360° cycle.
At baseline, the 34 patients (mean age 59 ± 6 years; 19 men and 15 women) presented, in the majority of cases, with NYHA functional class III (n = 33), LBBB (n = 32) and nonischemic DCM (n = 24). The mean QRS width was 176 ± 34 ms; the mean PR interval was 211 ± 38 ms; and the LV ejection fraction was significantly reduced (mean 21 ± 6%). The mean %ΔdP/dtmax with optimized CRT during invasive testing was 7.6 ± 7.7% with RV pacing, 19.2 ± 15.6% (p < 0.001 vs. RV) with LV pacing and 17.8 ± 14.5% (p < 0.001 vs. RV) with BV pacing. The mean intrinsic AV interval for the patient sample was 221 ± 38 ms, and the average programmed AV interval during follow-up CRT testing and echocardiographic recording was 107 ± 28 ms. All individuals in the control group presented with a normal echocardiographic LV ejection fraction of >60%. The 16 patients studied at the first follow-up visit at four weeks was comparable to the 18 excluded patients in terms of age (59 ± 6 vs. 60 ± 6 years, p = NS), baseline QRS (172 ± 32 vs. 179 ± 36 ms, p = NS), |ΦLS| (82 ± 37° vs. 87 ± 54°), baseline dP/dtmax (600 ± 161 vs. 527 ± 83 mm Hg, p = NS) and %ΔdP/dtmax (21 ± 14% vs. 19 ± 17%, p = NS). All patients were receiving stable pharmacologic therapy from baseline to four-week follow-up, except for one patient who began beta-blocker therapy just before the four-week follow-up.
Baseline L-S phase relationships.
All control subjects were characterized by monophasic lateral and septal displacements with |ΦLS| < 25°, which we defined as near-synchronous phase (Fig. 2A). Three distinct types of L-S phase relationships were retrospectively identified in the 34 patients studied at baseline. A type 1 pattern, similar to the observed pattern in the control group, was apparent in four patients and was characterized by monophasic lateral and septal displacements with |ΦLS| <25° (mean ΦLS 5 ± 6°) (Fig. 2B). A type 2 pattern was defined by a septal phase preceding the lateral phase by >25° with either monophasic or biphasic septal displacement (Fig. 2C), which was observed in 17 patients (mean ΦLS 77 ± 33°). Thirteen patients showed a type 3 pattern (mean ΦLS − 115 ± 33°) with a late septal phase (Fig. 2D). This pattern was usually associated with triphasic or inverted monophasic septal displacement.
Table 1 summarizes the distribution of L-S phase types and the corresponding patient characteristics. The baseline dP/dtmax tended to be highest and the QRS duration shortest in type 1 patients, and this group showed the least benefit from pacing, as measured by mean %ΔdP/dtmax with CRT. Table 2 compares the noninvasive measures of LV asynchrony (QRS width and ΦLS) with the individual hemodynamic responses to CRT. None of the four type 1 patients had improved dP/dtmax with CRT, although one had a QRS duration of 153 ms and baseline dP/dtmax <500 mm Hg/s (patient no. 4). In contrast, although two type 2 patients had a QRS duration ≤130 ms (patient nos. 5 and 6), ventricular preexcitation due to BV CRT led to 11% to 17% increases in dP/dtmax. Three patients did not have improved dP/dtmax with CRT, despite pronounced type 3 asynchrony (patient nos. 22 to 24).
We observed a unimodal relationship between the dP/dtmax response at the best possible CRT setting in each patient and their baseline ΦLS (Fig. 3). Patients who exhibited large increases in dP/dtmax at the best CRT setting tended to have a large positive or negative baseline ΦLS value, corresponding to a large degree of L-S asynchrony. Patients who exhibited small increases in dP/dtmax at the best CRT setting tended to have a small baseline ΦLS value, corresponding to more synchronous L-S displacement.
No significant differences were observed between patients with DCM and CAD, although those with DCM tended to show a slightly larger QRS width at baseline (183 ± 32 vs. 160 ± 34 ms, p = 0.07), a higher |ΦLS| (93 ± 46° vs. 66 ± 43°, p = 0.13) and a larger hemodynamic response to CRT (mean %ΔLVdP/dtmax 22 ± 15 vs. 16 ± 15%, p = 0.07).
Effects of CRT on L-S synchrony.
Sixteen patients were studied four weeks after implantation to test the early effects of CRT on mean L-S synchrony, as measured by the change in |ΦLS| during reprogramming of the pacemakers. During intrinsic conduction (OFF), the mean |ΦLS| was 104 ± 41°, which decreased to 86 ± 45° with RV CRT (p = 0.14 vs. OFF), to 71 ± 50° with LV CRT (mean difference −33°, 95% confidence interval [CI] −54° to −11°, p = 0.001 vs. OFF) and to 66 ± 42° with BV CRT (mean difference −38°, 95% CI −59° to −17°, p = 0.001 vs. OFF). Percent synchrony improvement with each CRT mode was associated with proportional percent increases in dP/dtmax (Fig. 4). Compared with RV pacing, LV and BV pacing resulted in significantly larger increases in dP/dtmax (p < 0.001) and tended to have larger differences in synchrony improvement (p = 0.14 RV vs. LV, and p = 0.12 RV vs. BV).
Type 2 patients (n = 8) exhibited a significant |ΦLS| decrease from 84 ± 26° (OFF) to 36 ± 26° at the best CRT mode (p < 0.001 vs. OFF by the paired t test) (Fig. 5A and 5B). In contrast, type 3 patients (n = 8) showed less change, with a nonsignificant |ΦLS| decrease from 123 ± 46° (OFF) to 105 ± 41° at the best CRT mode (p = NS by the paired t test). However, CRT eliminated or reversed the early septal inward movement in type 3 patients (Fig. 5C and 5D). The correlation between |ΦLS| and dP/dtmax changes with CRT was significant for type 2 patients (n = 8) who had LV and BV CRT, but failed to reach significance for those who had RV CRT (Fig. 6). No significant correlation between |ΦLS| and dP/dtmax was observed in type 3 patients.
We found a good reproducibility of phase angle analysis: 8 ± 11° for repeated measurements (intraobserver variability) (adjusted to 180°: 5 ± 6%) and 15 ± 11° for two independent observers (interobserver variability) (adjusted to 180°: 8 ± 6%).
The study demonstrates a unique echocardiographic method for quantifying LV mechanical wall motion synchrony, which can be used to predict a hemodynamic contractile function benefit from CRT. Increased dP/dtmax due to CRT was directly associated with improved LV mechanical synchrony, as measured by a reduction in the absolute L-S phase angle |ΦLS| in type 2 patients with delayed lateral wall inward movement. Also, this is the first study to noninvasively assess, by two-dimensional echocardiography, the effects of different CRT stimulation sites on LV mechanical synchrony and compare them with invasively measured hemodynamic responses. Both LV and BV CRT significantly improved LV L-S synchrony, whereas less improvement was observed with RV CRT. This is consistent with previous reports that LV and BV CRT increase dP/dtmax to a much greater extent than RV CRT (3,13).
It is well established that basal contractile function is depressed in patients with heart failure with DCM due to alterations in the contractile machinery within each myofibril (14) and in the extracellular matrix (15). Other studies suggest that in addition to altered “molecular contractility,” another cause of lowered contractile function is reduced cooperation among contracting myofibrils due to asynchronous LV contraction (16). “Contractile cooperation,” as we shall call this proposed second dimension of contractile function, may be reduced in patients with heart failure by abnormal ventricular conduction delays (2). Analogously, it can be reduced by RV pacing that advances contraction of the paced region relative to normally synchronous LV regions (16). Early activated regions contract against low chamber pressures but waste energy by prestretching the opposing, nonstimulated regions. Conversely, the late activated, excessively preloaded regions contract against a higher wall stress. This reduced contractile cooperation reduces overall cardiac efficiency and increases myocardial energy demands (17). Our wall motion phase results suggest that LV CRT can advance the start of delayed lateral wall contractions to improve synchrony with early septal wall contractions, and BV CRT can stimulate simultaneous lateral and septal wall contractions, both of which improve contractile cooperation, as indicated by increased dP/dtmax.
Influence of the pacing site.
Experimental data on normal dogs show that RV-only pacing creates early septal and late lateral LV wall contractions; LV-only pacing creates early lateral and late septal LV wall contractions; and simultaneous BV pacing minimizes asynchrony (16,18). The asynchronous contractions with LV-only pacing were observed at very short AV delays that prevented any fusion with intrinsic ventricular activation. In contrast, our results, predominantly in patients with LBBB, demonstrate that L-S wall motion is synchronized nearly as well by LV CRT as by BV CRT. Our hypothesis for this paradox is that resynchronization with LV CRT requires an optimal AV delay, such that the paced lateral wall activation combines with the intrinsic AV-conducted septal wall activation. Even with BV CRT, the resulting wall motion patterns are likely to be a complex function of the two paced wave fronts and intrinsic AV-conducted activation, so that maximal resynchronization depends on an optimal AV delay. This importance of an optimized AV delay might also explain the conflicting results of Kerwin et al. (7), who analyzed multiple-gated blood-pool scintigraphic images and found an increase in left intraventricular dyssynchrony with BV pacing at a fixed AV delay.
Another paradox is that apical RV CRT is able to improve synchrony in patients with delayed LV lateral wall movement, although to a lesser degree than LV and BV CRT. Earlier studies reported that apical RV pacing can improve dP/dtmax and aortic pulse pressure in patients with heart failure and LBBB (3). Xiao et al. (19) showed that the LV electromechanical delay was shorter with apical RV pacing compared with intrinsic activation with LBBB. Thus, apical RV pacing with an optimized AV delay must be able to preexcite at least some areas of the LV, compared with intrinsic activation, but to a lesser extent than LV and BV CRT and, on average, with less hemodynamic benefit.
Predictive value of baseline mechanical asynchrony for hemodynamic improvement.
The multiple L-S phase relationships we observed suggest that patients with heart failure with comparable ventricular conduction delays can have markedly different underlying mechanical abnormalities. Patients with a QRS duration >150 ms could exhibit near-synchronous L-S displacements (type 1), very delayed lateral displacements (type 2) or paradoxical septal motion (type 3). The type 1 pattern with a prolonged QRS complex probably results from a symmetrical conduction delay across the septal and lateral regions. In this group, CRT did not result in improved hemodynamic function, despite the presence of wide QRS complexes and a very low baseline dP/dtmax value. Type 2 patients presented with delayed lateral wall motion and exhibited the most benefit from CRT. The acute reduction in |ΦLS| in type 2 patients correlated well with the rise in dP/dtmax, as documented during invasive testing. This included patients with QRS complexes <155 ms and baseline dP/dtmax >700 mm Hg/s, who, by these criteria, would have been predicted to be acute hemodynamic CRT nonresponders, according to earlier studies (8). Lateral-septal synchrony improved in the majority of type 3 patients, but the change in |ΦLS| was not proportional to the percent increase in dP/dtmax. It is possible that the fundamental frequency phase analysis is not sensitive enough to adequately quantify changes in the complex biphasic and triphasic septal wall motion patterns in type 3 patients; in which case, higher order frequency components might provide additional predictive information. Three patients (Table 2, patient nos. 22 to 24) did not show improved dP/dtmax with CRT, despite pronounced type 3 asynchrony. These exceptions might represent a limitation of our L-S phase measure to predict an acute CRT response for type 3 patients. It might be speculated that in these type 3 patients, the lateral wall does not correspond to the site with the longest electromechanical delay, and that the additional evaluation of anterior-posterior synchrony in the two-chamber view might have improved the results. This group might also represent patients with suboptimal lead locations, who might have benefited from CRT with alternative stimulation sites: in Patient no. 24 the lead was placed near to the LV base in a posterolateral position and in Patient no. 23 the lead was located on the anterior wall. Both positions have been associated with suboptimal acute effects of CRT (20).
Several echocardiographic measures have been proposed to screen or optimize CRT for patients with heart failure, such as transmitral and aortic Doppler echocardiography, three-dimensional echocardiography and tissue Doppler imaging. Sogaard et al. (21) recently demonstrated that assessment of longitudinal function by tissue Doppler echocardiography is able to predict improvement in the LV ejection fraction with CRT, and Yu et al. (9) reported that CRT reduces the regional difference in myocardial peak systolic velocities. However, the new metric |ΦLS| is the first to show a direct relationship between invasively measured hemodynamic improvement with CRT and LV mechanical synchrony assessed by analysis of radial wall motion. We suggest it might provide a noninvasive screening method for patients with heart failure, so that those likely to have increased contractile function with CRT can be selected and so that CRT after implantation can be optimized. Baseline asynchrony indicated by |ΦLS| >25° predicts a contractile function benefit from CRT. For patients with type 2 L-S phase patterns, the magnitude of |ΦLS| reduction with CRT correlates to the invasively measured increase in dP/dtmax.
This study is limited to the echocardiographic prediction of an acute hemodynamic response, and it is unclear how these predictions will extend to long-term clinical benefit. Echocardiographic analysis was limited to the apical four-chamber view. It is possible that although CRT pacing at lateral LV sites resynchronizes L-S wall motion, it may not resynchronize or could delay anteroposterior wall motion. However, previous results with tissue Doppler echocardiography suggest that the effects of CRT are, to a large degree, confined to the interventricular septum and the inferoposterior and lateral walls (21). We were able to identify a subgroup (type 2) in whom the apical four-chamber view provided important information about the associated hemodynamic improvement.
Harmonic imaging was only used in a minority of patients studied; it is expected to improve endocardial border delineation in segments with suboptimal visualization of the endocardium, thereby possibly improving measurement variability and enabling evaluation of additional segments.
The programmed AV delays were defined individually in every patient according to the best invasive hemodynamic results and kept constant in every CRT mode. The effect of AV interaction was not systematically evaluated. Echocardiographic testing with the different CRT modes was performed after four weeks of CRT, which could have altered basal wall motion patterns; a different magnitude of CRT effects might be obtained if measurements are made immediately after device implantation.
Endocardial border displacement methods cannot distinguish between active and passive wall motion and do not take into account changes in myocardial wall thickness. Therefore, changes in L-S phase relationships could be due to changes in RV-LV transseptal pressure gradients, as well as changes in intraventricular synchrony. It should be noted that the same limitation applies to measurement of regional myocardial velocities by tissue Doppler imaging. Strain rate imaging with calculation of regional myocardial velocity gradients might overcome that limitation in the future.
Translational and rotational movement of the heart in relation to the transducer is an inherent problem of all imaging techniques and might influence the regional phase angle values of the walls. However, the opposing walls will be affected to a similar degree, and the relative differences of L-S phase relationships will be less affected (10). We tried to minimize these effects during the examination (respiratory hold, stable transducer position) and during computation of regional phase shifts (averaging of multiple cycles with offset to zero displacement at the start of each cycle). The temporal resolution of wall motion was limited to video recording frame rates of 25 frames/s. Integration on echocardiographic work stations with direct on-line contouration could improve temporal resolution and, thereby, accuracy and reproducibility.
Despite the promising results of CRT on both acute hemodynamic performance and long-term functional status, the selection of suitable patients is still ill defined. A ventricular conduction delay, as measured by the QRS duration, only weakly predicts the expected hemodynamic benefit with CRT (8). Echocardiographic phase analysis of radial endocardial wall motion demonstrates that optimized CRT restores LV synchrony by normalizing septal wall movement and advancing lateral wall activation in relation to the septum. Quantitative echocardiography is able to identify patients likely to have an acute hemodynamic benefit and provides a noninvasive alternative for identification of possible CRT candidates. The magnitude of resynchronization is proportional to the acute contractile function response in a defined subgroup. This may help to optimize CRT during follow-up, particularly in type 2 patients. Further studies are warranted to evaluate the relationship between the degree of LV resynchronization and its long-term benefit on exercise capacity, functional mitral regurgitation and LV reverse remodeling.
We thank Mr. Jeng Mah (Guidant Corp., St. Paul, Minnesota) for assisting with the statistical analysis. The investigators also deeply acknowledge the help and support of all nurses and colleagues at their institutions.
☆ This work was supported by a grant from Guidant Corporation, Brussels, Belgium. The investigators and participating centers of the Pacing Therapies for Congestive Heart Failure (PATH-CHF) Study Group, along with collaborators from the Guidant CHF Research Group, are listed in the Appendix of Circulation 1999;99:2993–3001.
- analysis of variance
- coronary artery disease
- cardiac resynchronization therapy
- dilated (nonischemic) cardiomyopathy
- left bundle branch block
- left ventricular
- peak positive left ventricular pressure
- New York Heart Association
- Pacing Therapies for Congestive Heart Failure study
- right ventricular
- Received February 11, 2002.
- Revision received April 1, 2002.
- Accepted April 4, 2002.
- American College of Cardiology Foundation
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