Early pacing-induced systolic dyssynchrony is a strong predictor of left ventricular adverse remodeling: analysis from the Pacing to Avoid Cardiac Enlargement (PACE) trial.

BACKGROUND: Right ventricular apical (RVA) pacing is associated with adverse left ventricular (LV) remodeling and biventricular (BiV) pacing may prevent it although the mechanisms remain unclear. The current study aimed to assess the role of early pacing-induced systolic dyssynchrony (DYS) to predict adverse LV remodeling. METHODS: Patients with standard pacing indications and normal LV ejection fraction were randomized either to BiV (n=89) or RVA pacing (n=88). Pacing-induced DYS, defined as the standard deviation of the time to peak systolic velocity (Dyssynchrony Index) >33 ms in a 12-segmental model of LV, was measured by tissue Doppler echocardiography at 1 month. RESULTS: At 1 month, 59 patients (33%) had DYS which was more prevalent in RVA than BiV pacing group (52% vs. 15%, χ(2)=28.3, p<0.001), though Dyssynchrony Index was similar at baseline (30 ± 14 vs. 26 ± 11 ms, p=0.06). At 12 months, those developing DYS had significantly lower LV ejection fraction (55.1 ± 9.7 vs. 62.2 ± 7.9%, p<0.001) and larger LV end-systolic volume (35.3 ± 14.3 vs. 27.0 ± 10.4 ml, p<0.001) when compared to those without DYS. Reduction of ejection fraction ≥ 5% occurred in 67% (39 out of 58) of patients with DYS, but only in 18% (21 out of 115) in those without DYS (χ(2)=40.8, p<0.001). Both DYS at 1 month (odds ratio [OR]: 4.725, p=0.001) and RVA pacing (OR: 3.427, p=0.009) were independent predictors for reduction of ejection fraction at 12 months. CONCLUSION: Early pacing-induced DYS is a significant predictor of LV adverse remodeling and the observed benefit of BiV pacing may be related to the prevention of DYS. CLINICAL TRIAL REGISTRATION: Centre for Clinical Trials number, CUHK_CCT00037 (URL: http://www.cct.cuhk.edu.hk/Registry/publictrialrecord.aspx?trialid=CUHK_CCT00037).

Biventricular pacing is superior to right ventricular pacing in bradycardia patients with preserved systolic function: 2-year results of the PACE trial.

AIMS: The Pacing to Avoid Cardiac Enlargement (PACE) trial is a prospective, double-blinded, randomized, multicentre study that reported the superiority of biventricular (BiV) pacing to right ventricular apical (RVA) pacing in the prevention of left ventricular (LV) adverse remodelling and deterioration of systolic function at 1 year. In the current analysis, we report the results at extended 2-year follow-up for changes in LV function and remodelling. METHODS AND RESULTS: Patients (n = 177) with bradycardia and preserved LV ejection fraction (EF ≥45%) were randomized to receive RVA or BiV pacing. The co-primary endpoints were LVEF and LV end-systolic volume (LVESV). Eighty-one (92%) of 88 in the RVA pacing group and 82 (92%) of 89 patients in the BiV pacing group completed 2-year follow-up with a valid echocardiography. In the RVA pacing group, LVEF further decreased from the first to the second year, but it remained unchanged in the BiV pacing group, leading to a significant difference of 9.9 percentage points between groups at 2-year follow-up (P < 0.001). Similarly, LVESV continues to enlarge from the first to the second year in the RVA pacing group, leading to a difference of 13.0 mL (P < 0.001) between groups. Predefined subgroup analysis showed consistent results with the whole study population for both co-primary endpoints, which included patients with pre-existing LV diastolic dysfunction. Eighteen patients in the BiV pacing group (20.2%) and 55 in the RVA pacing group (62.5%) had a significant reduction of LVEF (of ≥5%, P < 0.001). CONCLUSION: Left ventricular adverse remodelling and deterioration of systolic function continues at the second year after RVA pacing. This deterioration is prevented by BiV pacing.

Biventricular pacing in patients with bradycardia and normal ejection fraction.

BACKGROUND: Observational studies suggest that conventional right ventricular apical pacing may have a deleterious effect on left ventricular function. In this study, we examined whether biventricular pacing is superior to right ventricular apical pacing in preventing deterioration of left ventricular systolic function and cardiac remodeling in patients with bradycardia and a normal ejection fraction. METHODS: In this prospective, double-blind, multicenter study, we randomly assigned 177 patients in whom a biventricular pacemaker had been successfully implanted to receive biventricular pacing (89 patients) or right ventricular apical pacing (88 patients). The primary end points were the left ventricular ejection fraction and left ventricular end-systolic volume at 12 months. RESULTS: At 12 months, the mean left ventricular ejection fraction was significantly lower in the right-ventricular-pacing group than in the biventricular-pacing group (54.8+/-9.1% vs. 62.2+/-7.0%, P<0.001), with an absolute difference of 7.4 percentage points, whereas the left ventricular end-systolic volume was significantly higher in the right-ventricular-pacing group than in the biventricular-pacing group (35.7+/-16.3 ml vs. 27.6+/-10.4 ml, P<0.001), with a relative difference between the groups in the change from baseline of 25% (P<0.001). The deleterious effect of right ventricular apical pacing occurred in prespecified subgroups, including patients with and patients without preexisting left ventricular diastolic dysfunction. Eight patients in the right-ventricular-pacing group (9%) and one in the biventricular-pacing group (1%) had ejection fractions of less than 45% (P=0.02). There was one death in the right-ventricular-pacing group, and six patients in the right-ventricular-pacing group and five in the biventricular-pacing group were hospitalized for heart failure (P=0.74). CONCLUSIONS: In patients with normal systolic function, conventional right ventricular apical pacing resulted in adverse left ventricular remodeling and in a reduction in the left ventricular ejection fraction; these effects were prevented by biventricular pacing. (Centre for Clinical Trials number, CUHK_CCT00037.)

The role of repeating optimization of atrioventricular interval during interim and long-term follow-up after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective therapy for heart failure patients with electromechanical delay. Optimization of atrioventricular interval (AVI) is a cardinal component for the benefits. However, it is unknown if the AVI needs to be re-optimized during long-term follow-up. METHODS: Thirty-one patients (66+/-11 years, 20 males) with sinus rhythm who received CRT underwent serial optimization of AVI at day 1, 3-month and during long-term follow-up by pulse Doppler echocardiography (PDE). At long-term follow-up, the optimal AVI and cardiac output (CO) estimated by non-invasive impedance cardiography (ICG) were compared with those by PDE. RESULTS: The follow-up was 16+/-11 months. There was no significant difference in the mean optimal AVI when compared between any 2 time points among day 1 (99+/-30 ms), 3-month (97+/-28 ms) and long-term follow-up (94+/-28 ms). However, in individual patient, the optimal AVI remained unchanged only in 14 patients (44%), and was shortened in 12 (38%) and lengthened in 6 patients (18%). During long-term follow-up, although the mean optimal AVIs obtained by PDE or ICG (94+/-28 vs. 92+/-29 ms) were not different, a discrepancy was found in 14 patients (45%). For the same AVI, the CO measured by ICG was systematically higher than that by PDE (3.5+/-0.8 Vs. 2.7+/-0.6 L/min, p<0.001). CONCLUSION: Optimization of AVI after CRT appears necessary during follow-up as it was readjusted in 55% of patients. Although AVI optimization by ICG was feasible, further studies are needed to confirm its role in optimizing AVI after CRT.

Are left ventricular diastolic function and diastolic asynchrony important determinants of response to cardiac resynchronization therapy?

Cardiac resynchronization therapy (CRT) has been shown to reduce symptoms and reverse left ventricular (LV) remodeling. It is not known, however, whether diastolic function will improve after CRT and diastolic asynchrony will predict LV reverse remodeling. Seventy-six patients (mean age 65 +/- 12 years, 74% men) who received CRT were studied at baseline and after 3 months. Diastolic function was assessed by transmitral Doppler and tissue Doppler imaging. LV systolic and diastolic asynchrony were assessed by the time to peak myocardial contraction (Ts) and early diastolic relaxation (Te) using the 6 basal, 6 mid-segmental model. There were 42 responders (55%) with LV reverse remodeling (defined as a reduction of LV end-systolic volume >or=15%). Parameters of systolic function were significantly improved only in the responders. For diastolic function, there were reductions of transmitral E velocity in the 2 groups, without any change in atrial velocity or the E/A ratio. Tissue Doppler imaging revealed that myocardial early diastolic velocity was unchanged in responders but was significantly worsened in nonresponders. The systolic asynchrony index (the SD of Ts of 12 LV segments) correlated significantly with LV reverse remodeling (r = -0.64, p <0.001) but not the diastolic asynchrony index (the SD of Te of 12 LV segments) (r = -0.10, p = NS). The systolic asynchrony index was the only independent predictor of reverse remodeling (beta = -0.99, 95% confidence interval -1.41 to -0.58, p <0.001). In conclusion, CRT improves systolic function and systolic asynchrony but has a neutral effect on diastolic function and diastolic asynchrony. LV reverse remodeling response is determined by the severity of prepacing systolic asynchrony but not diastolic asynchrony or the diastolic filling pattern.

Effects of cardiac resynchronization therapy on incidence of atrial fibrillation in patients with poor left ventricular systolic function.

Although the beneficial role of cardiac resynchronization therapy (CRT) in selected patients with heart failure is well proven, its effect on the incidence of atrial fibrillation (AF) is unclear. The present study compared the incidence of AF in 36 consecutive patients with chronic heart failure receiving CRT with its incidence in controls matched for age, gender, and left ventricular ejection fraction but not receiving CRT. The findings suggest that patients with CRT had a significantly lower incidence of AF than controls. Further studies to establish the role of CRT in preventing AF and its mechanisms are warranted.

A novel tool to assess systolic asynchrony and identify responders of cardiac resynchronization therapy by tissue synchronization imaging.

OBJECTIVES: This study was designed to investigate if tissue synchronization imaging (TSI) is useful to identify regional wall delay and predict left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). BACKGROUND: Echocardiographic assessment of systolic asynchrony is helpful to predict a positive response to CRT. Tissue synchronization imaging is a new imaging technique that allows quick evaluation of regional systolic delay. METHODS: Tissue synchronization imaging was performed in 56 heart failure patients at baseline and three months after CRT. Regional wall delay was identified on TSI images and the time to regional peak systolic velocity (Ts) in LV was measured by the six-basal-six-mid-segmental model. Eight TSI parameters of systolic asynchrony were computed when Ts was measured in ejection phase or also included postsystolic shortening. RESULTS: Severe lateral wall delay occurred in 17 patients, which predicted LV reverse remodeling (chi-square = 8.13, p = 0.004). Among the eight quantitative parameters of asynchrony, the predictive values were higher for parameters that measured Ts in ejection phase than in postsystolic shortening. The standard deviation of Ts of 12 LV segments in ejection phase (Ts-SD-12-ejection) was most powerful to predict reverse remodeling (r = -0.61, p < 0.001) and gain in ejection fraction (r = 0.53, p < 0.001). The area of the receiver-operating characteristic (ROC) curve was the largest for Ts-SD-12-ejection (0.90, p < 0.001), with a sensitivity of 87% and specificity of 81% at a cutoff of 34.4 ms. The combination of lateral wall delay with Ts-SD-12-ejection gave a sensitivity and specificity of 82% and 87%. CONCLUSIONS: Tissue synchronization imaging allows quick evaluation of regional wall delay, and combined with Ts-SD-12-ejection provides a reliable way of predicting reverse remodeling after CRT.

Assessment of the effect of cardiac resynchronization therapy on intraventricular mechanical synchronicity by regional volumetric changes.

A new echocardiographic technology, the timing of regional volumetric changes by 3-dimensional echocardiography, was applied to assess intraventricular mechanical synchronicity in 13 patients who had received cardiac resynchronization therapy (CRT). When biventricular pacing was withheld, left ventricular (LV) asynchrony occurred as reflected by these echocardiographic parameters, whereas LV volume increased and the ejection fraction decreased. Further studies are needed to explore whether this novel method can be used to select suitable candidates for CRT and to predict a favorable response.