Author + information
- Received November 30, 2009
- Revision received January 19, 2010
- Accepted January 20, 2010
- Published online November 2, 2010.
- Miriam Shanks, MD,
- Matteo Bertini, MD,
- Victoria Delgado, MD,
- Arnold C.T. Ng, MD,
- Gaetano Nucifora, MD,
- Rutger J. van Bommel, MD,
- C. Jan Willem Borleffs, MD,
- Eduard R. Holman, MD, PhD,
- Nico R.L. van de Veire, MD, PhD,
- Martin J. Schalij, MD, PhD and
- Jeroen J. Bax, MD, PhD⁎ ()
- ↵⁎Reprint requests and correspondence
: Dr. Jeroen J. Bax, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands
Objectives This study sought to examine the changes in diastolic dyssynchrony with cardiac resynchronization therapy (CRT).
Background Little is known about the effect of CRT on diastolic dyssynchrony.
Methods Consecutive heart failure patients (n = 266, age 65.7 ± 10.0 years) underwent color-coded tissue Doppler imaging at baseline, 48 h, and 6 months after CRT. Systolic and diastolic dyssynchrony were defined as maximal time delay in peak systolic and early diastolic velocities, respectively, in 4 basal LV segments. CRT responders were defined as those with ≥15% decrease in LV end-systolic volume at 6 months.
Results Baseline LVEF was 25.2 ± 8.1%; 63.5% patients were CRT responders. Baseline incidence of systolic and diastolic dyssynchrony, and a combination of both was 46.2%, 51.9%, and 28.6%, respectively. Compared to nonresponders, responders had longer baseline systolic (79.2 ± 43.4 ms vs. 45.4 ± 30.4 ms; p < 0.001) and diastolic (78.5 ± 52.0 ms vs. 50.1 ± 38.2 ms; p < 0.001) delays. In follow-up, systolic delays (45.4 ± 31.6 ms at 48 h; 38.9 ± 26.2 ms at 6 months; p < 0.001) and diastolic delays (49.4 ± 36.3 ms at 48 h; 37.7 ± 26.0 ms at 6 months; p < 0.001) improved only in responders.
Conclusions At baseline: 1) diastolic dyssynchrony was more common than systolic dyssynchrony in HF patients; 2) nonresponders had less baseline diastolic dyssynchrony compared to responders. After CRT: 1) diastolic dyssynchrony improved only in responders. Further insight into the pathophysiology of diastolic dyssynchrony and its changes with CRT may provide incremental information on patient-specific treatments.
Systolic dyssynchrony is an independent predictor of clinical outcome and poor survival in heart failure (HF) patients (1–3). Cardiac resynchronization therapy (CRT) is an accepted treatment of patients with drug-refractory HF that improves synchronicity of left ventricular (LV) contraction (4–6), in particular in the responders to this treatment (4,5). Diastolic dyssynchrony is at least as common as systolic dyssynchrony in systolic HF patients, and is often present without a concurrent systolic dyssynchrony in this patient population (5,7–9). Little is known about the effect of biventricular pacing on the diastolic dyssynchrony, in particular about its changes in the responders and the nonresponders to CRT. The present study examined the baseline incidence of the diastolic dyssynchrony and its changes with CRT in the responders and nonresponders to this treatment.
Consecutive end-stage HF patients (n = 266) scheduled for implantation of a CRT device were included in the present study. Patients were selected for CRT implantation according to the European Society of Cardiology guidelines (10), meeting the following criteria: 1) severe HF (New York Heart Association [NYHA] functional class III or IV) despite optimal medical treatment; 2) severely depressed left ventricular ejection fraction (LVEF) (≤35%); and 3) QRS duration >120 ms. Patients with chronic atrial fibrillation were excluded.
All HF patients underwent a clinically indicated transthoracic echocardiogram at baseline, within 48 h, and at 6 months after CRT implantation, for assessment of LV volumes and systolic function, and LV systolic and diastolic dyssynchrony by color-coded tissue Doppler imaging (TDI).
Evaluation of the baseline clinical status included assessment of NYHA functional class, quality-of-life score (using the Minnesota Living with Heart Failure Questionnaire), and evaluation of exercise capacity using the 6-min hall-walk test. A standard 12-lead electrocardiogram was obtained in all subjects before and within 24 h after the pacemaker implantation, and at 6-month follow-up. Responders were defined as showing ≥15% decrease in LV end-systolic volume at 6-month follow-up (11).
To define the normal range of LV diastolic dyssynchrony, color-coded TDI analysis was performed in 38 age-matched controls selected from an echocardiographic database. These individuals were referred to the echocardiography laboratory for evaluation of a cardiac murmur, atypical chest pain, palpitations, or syncope without a murmur and had a normal echocardiogram and no history of cardiovascular disease.
Transthoracic echocardiography was performed with the subjects at rest in the left lateral decubitus position with commercially available ultrasound transducer and equipment (M3S probe, Vivid 7, GE-Vingmed, Horten, Norway). All images were digitally stored for offline analysis (EchoPac version BT07.0.0, GE-Vingmed).
Complete 2-dimensional, color, pulsed and continuous-wave Doppler images were acquired according to standard techniques (12,13). LV end-systolic volume index and end-diastolic volume index were calculated using Simpson's biplane method of discs and indexed to body surface area (14). LVEF was subsequently derived and expressed as a percentage. As previously described, the intraobserver agreement for assessment of LV end-systolic and -diastolic volumes and LVEF were: 7.4 ± 11.2 ml, 7.0 ± 10.1 ml, and 1.9 ± 4.4%, respectively (15). The interobserver agreement for LV end-diastolic volume, LV end-systolic volume, and LVEF were 12.9 ± 14.7 ml, 11.3 ± 13.9 ml, and 2.5 ± 4.9%, respectively (15). Left atrial volumes were calculated using the ellipsoid model as recommended by the American Society of Echocardiography and indexed to body surface area (16). Spectral Doppler velocities were measured from the apical 4-chamber view using a 2-mm sample volume. Diastolic function was evaluated by measuring the transmitral early (E-wave) and late (A-wave) diastolic velocities, and the E-wave deceleration time at the mitral leaflet tips. In addition, TDI early diastolic velocities (E′) were measured at the septal and lateral mitral valve annulus, as previously described. According to current recommendations, diastolic dysfunction was defined by septal E′ ≥8 cm/s or lateral E′ ≥10 cm/s and indexed left atrial volume ≥34 ml/m2(17). Diastolic dysfunction was graded (grade I, II, and III) according to E/A ratio, E-wave deceleration time, and average E/E′ (17). Mitral regurgitation severity was determined semiquantitatively from color Doppler images obtained from the conventional parasternal long-axis and apical views using the regurgitant jet area to left atrial area ratio as previously published (18).
Color-coded TDI of the LV obtained in the apical 2- and 4-chamber views were acquired during end-expiration, with the sector size and depth optimized for the highest frame rates possible (>115 frames/s). Care was taken to keep the incidence angle between the direction of the Doppler beam and the analyzed vector of myocardial motion as small as possible.
Regional myocardial color-coded TDI velocity profiles were analyzed offline by positioning the sample volume (13 × 6 mm) in the middle of the basal portion of 4 different LV wall segments (septal, lateral, anterior, and inferior). Aortic valve opening and closure timing intervals were determined using pulse-wave spectral Doppler with the sample volume placed at the LV outflow tract to define the ejection period. Maximal peak systolic myocardial velocity within this ejection period was selected, and the time interval between the onset of the QRS complex and the peak systolic velocity (maximal systolic electromechanical delay) per region was derived as previously described (4,19,20). Similarly, maximal diastolic electromechanical delay for each region was obtained using the peak early diastolic myocardial velocity (21–23). Intraventricular dyssynchrony was determined using the time difference between the shortest and longest electromechanical delays between any 2 out of 4 basal LV segments during systole and early diastole. Significant systolic intraventricular dyssynchrony was defined as the maximal systolic electromechanical delay of ≥65 ms that was previously shown to predict reverse LV remodeling with CRT (4). Significant diastolic intraventricular dyssynchrony was classified as a maximal diastolic electromechanical delay above that of the mean ± 2 SD of the control group (6,22,23). All TDI recordings were analyzed by an observer who was blinded to the clinical data and outcome results.
All patients received a biventricular pacemaker (Contak Renewal 4RF, TR, or CD, Boston Scientific, St. Paul, Minnesota; InSync Sentry or III, Medtronic Inc. Minneapolis, Minnesota; or Lumax 340 HF-T, Biotronik, Berlin, Germany). When a conventional indication for an internal cardioverter-defibrillator existed, a combined device was implanted. All pacemaker-implantation procedures were performed under local anesthesia. Pacemaker leads were inserted through the right- or left-sided cephalic or subclavian vein. The right atrial and ventricular leads were positioned conventionally. A coronary sinus venogram was obtained using a balloon catheter, followed by the insertion of the LV pacing lead. An 8-F guiding catheter was used to place the LV lead (Easytrak, Boston Scientific; Attain-SD, Medtronic; or Corox OTW, Biotronik) in the coronary sinus. The LV lead position was targeted to the lateral coronary vein; if unavailable, the posterolateral coronary vein or anterior vein was used. One day after implantation, the LV lead position (anterior, lateral, and posterior) was assessed from a chest X-ray, using the lateral views (24). Optimization of the atrioventricular delays was performed in all the patients within 48 h after pacemaker implantation, using an iterative method. The optimal atrioventricular delay was determined by pulsed-wave Doppler recordings of the transmitral inflow as the shortest atrioventricular delay that does not compromise left atrial contribution to the LV diastolic filling (25). The ventricles were paced simultaneously with an interventricular delay set at 0 ms.
Normal distribution of the data was evaluated with the Kolmogorov-Smirnov test. Continuous variables normally distributed are presented as mean and standard deviation, whereas continuous variables non-normally distributed are presented as median and interquartile range (25%, 75%). Categorical data are summarized as frequencies and percentages. The chi-square test with Yates correction was used to compare categorical variables. The Student ttest and Mann-Whitney Utest were used to compare 2 groups of unpaired continuous data, as appropriate. One-way analysis of variance (ANOVA) and Kruskal-Wallis test were used to compare more than 3 groups of continuous variables, as appropriate. Post-hoc analyses for significant results were performed using Bonferroni correction. Linear regression analysis was used to calculate the correlation between electrical and echocardiographic parameters. Changes in the maximal systolic and diastolic delays during follow-up after the pacemaker implantation in the responders and nonresponders were assessed using repeated measures ANOVA test. Changes in mitral regurgitation grade during follow-up were assessed with McNemar test. Univariable and multivariable logistic regression analyses were performed to evaluate the independent determinants of favorable response to CRT. Baseline clinical (age, HF etiology, baseline QRS duration, and serum creatinine level) and baseline echocardiographic (LVEF and systolic and diastolic LV dyssynchrony) characteristics of the patients were evaluated. Only variables with p < 0.05 at univariable analysis were entered as covariates in the multivariable model. The multivariate logistic regression analysis was performed using an enter method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All statistical analyses were performed using SPSS for Windows version 16 (SPSS Inc., Chicago, Illinois).
Clinical and echocardiographic characteristics of the patients and controls
The patient population consisted of 183 male (68.8%) and 83 female (31.2%) patients with a mean age of 65.7 ± 10.0 years. Biventricular pacemaker implantation was successful in all patients, with 256 (96.2%) patients receiving a combined device with an implantable cardioverter-defibrillator. The baseline clinical characteristics of the patients are described in Table 1.Approximately equal numbers of patients had HF of either ischemic or nonischemic etiology. Posterior and lateral lead placements were achieved in 50% and in 43.8% of patients, respectively, whereas the leads were placed anteriorly in 6.2% of patients. Most patients were in NYHA functional class III at the time of CRT implantation (94.4%). The baseline QRS duration was 165.3 ± 21.7 ms.
Clinically indicated echocardiograms were performed at baseline, 48 h, and 6 months after CRT implantation, with the mean color-coded TDI frame rate of 118.5 ± 34.7 frames/s, 123.9 ± 34.3 frames/s, and 128 ± 35.5 frames/s and the mean heart rate of 70.9 ± 14.9 beats/min, 72.1 ± 13.0 beats/min, and 68.7 ± 11.9 beats/min, respectively. The baseline echocardiographic characteristics of the patients are described in Table 1.
Finally, clinical and echocardiographic characteristics of the control population are described in Table 2.Maximal diastolic delay exceeding 55 ms, derived from the mean + 2 SDs (54.6 ms) of the maximal diastolic electromechanical delay in the controls, was used to define diastolic intraventricular dyssynchrony.
Incidence of systolic and diastolic dyssynchrony in HF patients
Overall, dyssynchrony was present in 69.5% patients at baseline (Table 1). The incidence of diastolic dyssynchrony was higher than that of systolic dyssynchrony (51.9% vs. 46.2%, p = 0.002). Both systolic and diastolic dyssynchrony were present in 28.2% patients, whereas isolated systolic dyssynchrony (without concurrent diastolic dyssynchrony) was present in 17.6% patients, and 23.7% patients had isolated diastolic dyssynchrony (Table 1). There were no significant differences in the majority of the baseline clinical and echocardiographic characteristics among patients without LV dyssynchrony, with isolated systolic or isolated diastolic dyssynchrony or with concomitant systolic and diastolic LV dyssynchrony (Table 3).There were only statistically significant differences in the quality-of-life score and in the antiplatelet treatment that was significantly less frequent in patients with isolated diastolic LV dyssynchrony.
Responder versus nonresponder patients
At 6-month follow-up, 63.5% patients were classified as responders based on reverse LV remodeling (≥15% decrease in LV end-systolic volume). No significant differences in the baseline clinical and echocardiographic characteristics were observed between the responders and nonresponders to CRT (Table 4).By definition, the responder patients showed a significant reduction in LV indexed volumes (end-systolic volume index: from 92.4 ± 43.3 ml/m2to 70.5 ± 30.8 ml/m2, p < 0.001; and end-diastolic volume index: from 120.5 ± 47.5 ml/m2to 101.1 ± 34.9 ml/m2, p < 0.001) and a significant increase in LVEF (from 24.7 ± 8.1% to 31.8 ± 10.1%, p < 0.001). In addition, the percentage of patients showing mitral regurgitation severity ≥2+ significantly reduced (from 51.8% to 14.8%, p < 0.001). In contrast, the nonresponder patients did not show significant changes in LV volumes (end-systolic volume index: from 85.0 ± 36.2 ml/m2to 86.3 ± 30.4 ml/m2, p = 0.180; and end-diastolic volume index: from 112.8 ± 40.1 ml/m2to 116.4 ± 37.5 ml/m2, p = 0.064) or LVEF (from 26.2 ± 8.0% to 26.0 ± 8.9%, p = 0.850). Finally, a nonsignificant reduction in the percentage of patients showing mitral regurgitation severity ≥2+ was noted (from 46.9% to 36.1%, p = 0.078).
The responders were more likely to have baseline systolic and/or diastolic dyssynchrony compare to the nonresponders (Fig. 1).In addition, over 80% of those patients who had dyssynchrony of any type at baseline responded to CRT, compared with 23.8% of those without baseline dyssynchrony. Moreover, response to CRT was also seen in over two-thirds of the patients who had isolated diastolic dyssynchrony (71.0%), in 82.6% with isolated dyssynchrony and in 86.7% in patients with concomitant systolic and diastolic dyssynchrony.
Intraventricular electromechanical systolic and diastolic delays after CRT
Baseline intraventricular systolic and diastolic delays were significantly longer in the responders compared with the nonresponders (79.2 ± 43.4 ms vs. 45.4 ± 30.4 ms for systolic delays, and 78.5 ± 52.0 ms vs. 50.1 ± 38.2 ms for diastolic delays; p < 0.001 for both). Figure 2illustrates examples of responder and nonresponder patients. The responder patient showed significant LV isolated diastolic dyssynchrony, whereas the nonresponder patient did not show LV dyssynchrony (Fig. 2). After CRT implantation, a significant improvement in both systolic and diastolic delays was observed in the responders. In contrast, the nonresponders had further worsening of the systolic delays and no change in the diastolic delays after the device implantation. At follow-up, the responder patients showed a significant decrease in systolic LV dyssynchrony (from 79.2 ± 43.4 ms to 45.4 ± 31.6 ms at 48 h, and to 38.9 ± 26.2 ms at 6-month follow-up; ANOVA p value <0.001) and in diastolic dyssynchrony (from 78.5 ± 52.0 ms to 49.4 ± 36.3 ms at 48 h, and to 37.7 ± 26.0 ms at 6-month follow-up; ANOVA p value <0.001). In contrast, the nonresponders showed a significant increase in systolic LV dyssynchrony (from 45.4 ± 30.4 ms to 65.3 ± 45.9 ms at 48 h, and to 62.1 ± 38.3 ms at 6-month follow-up; ANOVA p value <0.001), but diastolic LV dyssynchrony remained unchanged (from 50.7 ± 38.0 ms to 58.6 ± 37.5 ms at 48 h, and to 55.7 ± 42.0 ms at 6-month follow-up; ANOVA p value = 0.206). Interestingly, in the group of patients with isolated diastolic LV dyssynchrony at baseline, there was a slight but significant increase in systolic dyssynchrony measures at 48 h and 6-month follow-up (from 35.6 ± 15.9 ms to 51.5 ± 47.3 ms, and to 46.2 ± 35.1 ms, ANOVA p value = 0.003). Importantly, a significant reduction in diastolic dyssynchrony measures was observed at 48 h and at 6 months after CRT (from 108.9 ± 61.7 ms to 60.0 ± 43.7 ms to 44.8 ± 29.5 ms, ANOVA p value <0.001). Improvement in the systolic and diastolic delays was seen regardless of the etiology of HF (65.3 ± 38.2 ms at baseline, 54.0 ± 40.5 ms at 48 h, and 45.6 ± 37.4 ms at 6 months after CRT for ischemic cardiomyopathy; p < 0.001, and 74.8 ± 60.8 ms at baseline, 50.8 ± 32.1 ms at 48 h, and 42.9 ± 30.5 ms at 6 months for dilated cardiomyopathy; ANOVA p value <0.001).
There was no significant correlation between the QRS duration and the systolic delays (r = 0.072; p = 0.245) and the diastolic delays (r = 0.042; p = 0.500) at baseline. A weak correlation was noted between the shortening of QRS duration and the improvement of the systolic dyssynchrony within 48 h after CRT (0.154; p = 0.022), and at 6 months (r = 0.131; p = 0.038), whereas no correlation was observed in the diastolic dyssynchrony (r = 0.011; p = 0.868 within 48 h after CRT, and r = 0.029; p = 0.649 at 6 months).
Univariable and multivariable determinants of favorable response to CRT
Univariable and multivariable logistic regression analyses demonstrated that the strongest determinants of favorable response to CRT were baseline systolic and diastolic LV dyssynchrony (Table 5).In contrast, any other clinical or echocardiographic parameters were selected in the multivariable model.
The major findings of this study were: 1) baseline incidence of diastolic dyssynchrony in HF patients was higher than that of systolic dyssynchrony; 2) baseline intraventricular systolic and diastolic delays were significantly longer in the CRT responders compared with the nonresponders; and 3) significant improvement in the systolic delays and the diastolic delays post-CRT was observed only in the responders, but not in the nonresponders to CRT.
Incidence of diastolic dyssynchrony in HF patients
The benefits of CRT include improvement in the symptoms and LV systolic function, and promotion of LV reverse remodeling in HF patients who are refractory to medical treatment. Improved synchronicity of systolic contraction explains in part the benefit derived from CRT. Consequently, most studies have focused on the assessment of systolic dyssynchrony in CRT population. However, it has been shown that left bundle branch block is associated with not only systolic, but also diastolic dyssynchrony (26). In addition, cardiac output is dependent not only on systolic emptying, but also on diastolic filling. Therefore, not only systolic, but also diastolic dyssynchrony may contribute to hemodynamic compromise in the failing heart (8). The effect of biventricular pacing on diastolic dyssynchrony is less clear, and whether its improvement plays an important role in the mechanism of response CRT is not known.
In a few recent studies, diastolic dyssynchrony in HF patients with wide QRS complex was found to be at least as common as systolic dyssynchrony, with the prevalence ranging between 40% and 81% for diastolic dyssynchrony and 40% and 73% for systolic dyssynchrony, depending on the echocardiographic definition of dyssynchrony used (6–8). Similar to the previous reports (6–8), the present study showed that diastolic dyssynchrony was more prevalent than systolic dyssynchrony in HF patients scheduled for CRT. Furthermore, the results of the present study supported the previous evidence that systolic and diastolic dyssynchrony do not always coexist despite a wide QRS complex. The relatively low prevalence of concomitant systolic and diastolic dyssynchrony of 28.6% in our study population was similar to the previous reports (25% to 49%) (6,8,27). Although coexistence of systolic and diastolic dyssynchrony has been shown to be more common in patients with a wide QRS complex compared with those with a narrow QRS complex (6), no correlation between the QRS duration and systolic or diastolic dyssynchrony was demonstrated in the present study. In addition, those patients who responded to CRT were much more likely to have not only baseline systolic, but also diastolic dyssynchrony compared with the nonresponders. These findings suggest that the underlying pathophysiology of the 2 conditions may differ, and they may not be regarded as a condition in common (6,27).
Pathophysiology of diastolic dyssynchrony in HF patients
There are several pathophysiological mechanisms that can account for diastolic dyssynchrony in patients with systolic HF. The most obvious explanation for the presence of diastolic dyssynchrony is systolic dyssynchrony: the segments with delayed contraction also show delayed relaxation (23). However, as described earlier, less than one-half of the HF patients have a coexistent systolic and diastolic dyssynchrony.
Another potential reason is the presence of coronary artery disease. In the previous studies using radionuclide angiography, coronary artery disease was associated with asynchronous LV regional diastolic function that improved after coronary revascularization (28–30). Most patients had preserved LV systolic function, and similar data in HF patients are lacking. The present study showed no significant differences in either systolic or diastolic dyssynchrony between the ischemic and nonischemic etiologies of HF, suggesting mechanisms other than myocardial ischemia.
Diastolic function and ventricular filling pattern appear to be important components of the underlying pathophysiology of diastolic dyssynchrony. The degree of diastolic, but not systolic dysfunction, as expressed by the mean myocardial systolic and early diastolic velocity from the 6 basal LV segments using TDI, has been shown to predict diastolic dyssynchrony (8). It also appears that filling abnormalities related to ventricular interaction in diastole are of crucial importance in CRT patients (31). LV filling may be impeded in up to one-half of HF patients due to ventricular interaction from raised right ventricular (RV) diastolic pressure and by external constraint from the pericardium, especially in the patients with increased LV filling pressures (31). This diastolic interaction could explain the delayed onset of mechanical diastolic motion in the LV even in patients without concurrent systolic dyssynchrony (6). In the present study, the effect of ventricular interaction on response to CRT was not addressed, and remains to be determined in further studies.
Effect of CRT on diastolic dyssynchrony
Limited information on the effect of CRT on diastolic dyssynchrony is available. In small cohort studies, either no improvement in diastolic dyssynchrony (20) or less improvement than in systolic dyssynchrony (6) has been demonstrated shortly after the initiation of biventricular pacing, compared with baseline. A mid-term follow-up study showed improvement in diastolic dyssynchrony only in the patients with nonischemic cardiomyopathy, whereas systolic dyssynchrony improved regardless of the HF origin (7).
The present study with a larger cohort of HF patients demonstrated a significant improvement in both systolic and diastolic dyssynchrony acutely and at 6 months after CRT, with no difference between the patients with ischemic and nonischemic HF. In addition, both systolic and diastolic dyssynchrony improved only in the CRT responders, but not in the nonresponders.
Despite a significant shortening of QRS duration with CRT, there was only a weak correlation between the reduction of QRS duration and improvement in the systolic dyssynchrony. No such correlation was observed for the diastolic dyssynchrony, suggesting that the improved coordination of LV myocardial relaxation with CRT is independent of electrical activation.
Considering that only about one-third of HF patients have concurrent systolic and diastolic dyssynchrony, the effect of CRT on diastolic dyssynchrony cannot be entirely explained by systolic resynchronization. CRT may influence favorably on diastolic ventricular interaction (31). Up to one-half of the chronic HF patients have impaired LV diastolic filling due to abnormal interventricular septum mechanics. The increased RV diastolic pressure induces changes in the RV geometry, with a leftward shift and abnormal motion of the interventricular septum. In addition, dilation of the RV and LV chambers increases the external constraint from the pericardium. This diastolic ventricular interdependence may explain the delayed onset of mechanical diastolic motion of the LV, even in patients without systolic dyssynchrony. Acute benefit of CRT on LV filling pressures has been demonstrated, particularly in patients with elevated filling pressures prior to CRT, irrespective of left bundle branch block (32). LV pacing may result in LV filling before RV filling, thus reducing the ventricular interaction from the elevated RV diastolic pressure, and therefore permitting greater LV filling prior to the development of external constraint (32). This could also be translated into a more synchronous relaxation pattern of the LV. Therefore, CRT seems to exert beneficial effects also on LV diastolic performance that may be of importance for the clinical and echocardiographic response at long-term follow-up.
High incidence of the baseline intraventricular diastolic dyssynchrony in the responders to CRT, and its immediate and sustained improvement with biventricular pacing irrespective of the changes in QRS duration are suggestive of a pathophysiology independent of the electromechanical coupling. More comprehensive evaluation of the electrical and mechanical interactions of the LV myocardium throughout the cardiac cycle may provide further information on the more patient-specific therapeutic strategies in HF patients.
Dr. Bax has research grants from GE Healthcare, Medtronic Inc., Boston Scientific, St. Jude Medical, Edwards Lifesciences, Biotronik, and BMS Medical Imaging. Dr. Schalij has research grants from Biotronik, Medtronic Inc., and Boston Scientific. All other authors have reported that they have no relationships to disclose.
- Abbreviations and Acronyms
- cardiac resynchronization therapy
- heart failure
- left ventricle/ventricular
- left ventricular ejection fraction
- New York Heart Association
- right ventricle/ventricular
- tissue Doppler imaging
- Received November 30, 2009.
- Revision received January 19, 2010.
- Accepted January 20, 2010.
- American College of Cardiology Foundation
- Baldasseroni S.,
- Opasich C.,
- Gorini M.,
- et al.
- Duncan A.M.,
- Francis D.P.,
- Gibson D.G.,
- Henein M.Y.
- Bax J.J.,
- Bleeker G.B.,
- Marwick T.H.,
- et al.
- Bleeker G.B.,
- Mollema S.A.,
- Holman E.R.,
- et al.
- Schuster I.,
- Habib G.,
- Jego C.,
- et al.
- Yu C.M.,
- Zhang Q.,
- Yip G.W.,
- et al.
- Vardas P.E.,
- Auricchio A.,
- Blanc J.J.,
- et al.
- Bertini M.,
- Marsan N.A.,
- Delgado V.,
- et al.
- Lang R.M.,
- Bierig M.,
- Devereux R.B.,
- et al.
- Yu C.M.,
- Chau E.,
- Sanderson J.E.,
- et al.
- Yu C.M.,
- Lin H.,
- Fung W.H.,
- Zhang Q.,
- Kong S.L.,
- Sanderson J.E.
- Wang J.,
- Kurrelmeyer K.M.,
- Torre–Amione G.,
- Nagueh S.F.
- Bertini M.,
- Delgado V.,
- Bax J.J.,
- Van de Veire V.
- Yu C.M.,
- Lin H.,
- Zhang Q.,
- Sanderson J.E.
- Bonow R.O.,
- Bacharach S.L.,
- Green M.V.,
- et al.
- Bonow R.O.,
- Vitale D.F.,
- Bacharach S.L.,
- Frederick T.M.,
- Kent K.M.,
- Green M.V.
- Perrone-Filardi P.,
- Bacharach S.L.,
- Dilsizian V.,
- Bonow R.O.
- Morris-Thurgood J.A.,
- Turner M.S.,
- Nightingale A.K.,
- Masani N.,
- Mumford C.,
- Frenneaux M.P.