Joseph Yat-Sun Chan

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.)

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.

Effect of Left Ventricular Endocardial Activation Pattern on Echocardiographic and Clinical Response to Cardiac Resynchronization Therapy

Objective: To explore the left ventricular (LV) electrical activation pattern in heart failure (HF) and its implication to cardiac resynchronization therapy (CRT). Design and setting: Observational study at the University Teaching Hospital. Patients: 23 optimally treated patients with HF with New York Heart Association class III, QRS duration >120 ms and LV ejection fraction <35%. Interventions: The LV endocardial activation pattern and total activation time (Tat) was determined by non-contact mapping and the LV mechanical dys-synchrony was determined by standard deviation (Ts-SD) and maximal difference (Ts-diff) of time to peak systolic contraction (Ts) among 12 LV segments using tissue Doppler imaging before receiving CRT. Main outcome measures: Correlation between electrical and mechanical dys-synchrony; volumetric responder to CRT at 3 months; HF hospitalisation or death by Kaplan–Meier analysis. Results: Homogenous (type I, n = 8) and presence of conduction block (type II, n = 15) patterns were identified. Significant correlation between Tat and Ts-SD/Ts-diff was noted only in type II (r = 0.73/0.56, p = 0.002/0.03). Ts-SD and Ts-diff in type II were significantly longer than type I. 12 patients in type II and 2 in type I were CRT responders (p = 0.01). After 487 (447) days, patients with type II pattern had significantly lower risk of HF hospitalisation or death than those with type I (log rank χ2 = 5.25; p = 0.02). Conclusion: Patients with type II LV endocardial activation pattern had a more favourable echocardiographic and clinical response to CRT than those with type I pattern.

Impact of Cardiac Contractility Modulation on Left Ventricular Global and Regional Function and Remodeling

OBJECTIVES This study aimed to evaluate the impact of cardiac contractility modulation (CCM) on left ventricular (LV) size and myocardial function. BACKGROUND CCM is a device-based therapy for patients with advanced heart failure. Previous studies showed that CCM improved symptoms and exercise capacity; however, comprehensive assessment of LV structure, function, and reverse remodeling is not available. METHODS Thirty patients (60 + or - 11 years, 80% male) with New York Heart Association (NYHA) functional class III heart failure, ejection fraction <35%, and QRS <120 ms were assessed at baseline and 3 months. LV reverse remodeling was measured by real-time 3-dimensional echocardiography. Using tissue Doppler imaging, the peak systolic velocity (Sm) and peak early diastolic velocity (Em) were calculated for LV function, while the standard deviation of the time to peak systolic velocity (Ts-SD) and the time to peak early diastolic velocity (Te-SD) were calculated for mechanical dyssynchrony. RESULTS LV reverse remodeling was evident, with a reduction in LV end-systolic volume by -11.5 + or - 10.5% and a gain in ejection fraction by 4.8 + or - 3.6% (both p < 0.001). Myocardial contraction was improved in all LV walls, including sites remote from CCM delivery (all p < 0.05); hence, the mean Sm of 12 (2.2 + or - 0.6 cm/s vs. 2.5 + or - 0.7 cm/s) or 6 basal LV segments (2.5 + or - 0.6 cm/s vs. 3.0 + or - 0.7 cm/s) were increased significantly (both p < 0.001). In contrast, CCM had no impact on regional or global Em (2.9 + or - 1.3 cm/s vs. 2.9 + or - 1.1 cm/s), whereas Ts-SD (28.2 + or - 11.2 ms vs. 27.9 + or - 12.7 ms) and Te-SD (30.0 + or - 18.3 ms vs. 30.1 + or - 20.7 ms) remained unchanged (all p = NS). Mitral regurgitation was reduced (22 + or - 14% vs. 17 + or - 15%, p = 0.02). Clinically, there was improvement of NYHA functional class (p < 0.001) and 6-min hall walk distance (p = 0.015). A 24-h Holter monitor showed that premature ventricular contractions were not increased during CCM. CONCLUSIONS CCM improves both global and regional LV contractility, including regions remote from the impulse delivery, and may contribute to LV reverse remodeling and gain in systolic function. Such improvement is unrelated to diastolic function or mechanical dyssynchrony.

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).

Effect of Left Ventricular Lead Concordance to the Delayed Contraction Segment on Echocardiographic and Clinical Outcomes after Cardiac Resynchronization Therapy

Introduction: The optimal left ventricular (LV) pacing site for cardiac resynchronization therapy (CRT) is unclear. The current study aims to explore the clinical significance of LV lead concordance to delayed contraction segment in CRT.

Improvement of left atrial function is associated with lower incidence of atrial fibrillation and mortality after cardiac resynchronization therapy

BACKGROUND Left atrial (LA) volume is a predictor of cardiovascular events in patients with heart failure. Improvement of LA function and reverse remodeling was observed after cardiac resynchronization therapy (CRT). OBJECTIVE The purpose of this study was to explore the clinical significance of improvement in LA function after CRT. METHODS Echocardiographic studies were performed before and 3 months after CRT in 97 patients (72 men and 25 women; age 63.8 +/- 13.3 years) with standard CRT indication but no history of atrial fibrillation (AF). LA active emptying fraction based on the change in volumes (LAV-EF) were calculated, and significant improvement in LA function (LA responder) was defined as a relative increase >/=50% from baseline LAV-EF. The primary end-points were newly developed AF detected by ECG or device and all-cause mortality. RESULTS After 1,200 +/- 705 days of follow-up, LA responders (n = 47 [48.5%]) had a significantly lower incidence of AF (12.8% vs 40%, P = .002) and mortality (17% vs 44%, P = .004) than did LA nonresponders. In Cox proportional hazard analysis, LA responders was the only independent predictor of lower risk of new-onset AF (hazard ratio 0.22, 95% confidence interval 0.08-0.61, P = .003), whereas both LA responders (hazard ratio 0.22, 95% confidence interval 0.09-0.53, P <.001) and left ventricular reverse remodeling (>10% reduction in left ventricular end-systolic volume at 3 months; hazard ratio 0.96, 95% confidence interval 0.93-0.99, P = .03) were independent predictors of lower risk of death after CRT. CONCLUSION Improvement of LA function after CRT was associated with a lower incidence of AF and mortality in AF naïve patients with severe heart failure.

Improved coronary artery blood flow following the correction of systolic dyssynchrony with cardiac resynchronization therapy

BACKGROUND Coronary blood flow (CBF) is improved by cardiac resynchronization therapy (CRT) and impaired by right ventricular apical (RVA) pacing in patients with heart failure. However, the underlying mechanism remains unclear. METHODS Twenty-nine non-ischemic heart failure patients who responded to CRT underwent transthoracic echocardiography examination including both left anterior descending (LAD) CBF and tissue Doppler imaging in 3 pacing modes: intrinsic conduction, RVA pacing and biventricular (BiV) pacing. LAD velocity-temporal integral (LAD-VTI) and duration were measured. Systolic dyssynchrony was assessed with the standard deviation of a 12-left ventricular segmental model (Ts-SD). RESULTS BiV pacing improved while RVA pacing reduced CBF compared to intrinsic conduction (all p<0.05). Both Ts-SD and ventricular septal velocity deteriorated during RVA pacing but improved during BiV pacing (all p<0.05). When systolic dyssynchrony was induced, lower LAD-VTI (9.5 ± 3.4 versus 12.7 ± 5.1cm, p=0.001) and shorter LAD diastolic duration (483 ± 92 versus 542 ± 106 ms, p=0.010) were detected than synchronous status. Systolic dyssynchrony was inversely related to septal velocity (r=-0.41), p<0.001 and LAD-VTI (r=-0.30, p=0.007), with the latter found to be moderately correlated to septal velocity (r=0.30, p=0.007). CONCLUSION Regional LAD flow was improved in patients subjected to BiV but worsened in those treated with RVA pacing in non-ischemic heart failure CRT responders. Systolic dyssynchrony was more commonly observed in patients subjected to RVA pacing. Reduction of septal velocity with dyssynchrony may directly lead to reduced LAD flow. Improvement of septal velocity by CRT and hence LAD flow may be an important mechanism in determining the response to CRT.

Prevalence and determinants of left ventricular systolic dyssynchrony in patients with normal ejection fraction received right ventricular apical pacing: a real-time three-dimensional echocardiographic study

AIMS Right ventricular apical (RVA) pacing may induce mechanical dyssynchrony. However, its impact on patients with normal ejection fraction (EF) is not fully understood. This study examined the prevalence and predictors of RVA pacing-induced systolic dyssynchrony by real-time three-dimensional echocardiography (RT3DE), and evaluated its impact on left ventricular (LV) function. METHODS AND RESULTS Ninety-three patients with sinus node dysfunction and normal EF (>50%) received RVA-based dual-chamber pacing were assessed by RT3DE during RVA pacing (V-pace) and intrinsic conduction (V-sense). Systolic dyssynchrony was evaluated using the standard deviation of the time to minimal regional volume of 16 LV segments (Tmsv-16SD), and a cutoff value of 16 ms was determined from 93 normal controls. Systolic dyssynchrony was induced in 49.5% of patients at V-pace with significant increase in LV end-systolic volume (LVESV), decrease in EF, and worsening of Tmsv-16SD (all P < 0.001). Furthermore, patients who developed dyssynchrony had larger LVESV (P < 0.001), lower EF (P < 0.001) at V-pace mode, and higher cumulative percentage of RVA pacing in the past 6 months (P < 0.001) than those without systolic dyssynchrony. In multivariate logistic regression analysis, independent predictors of developing LV systolic dyssynchrony during V-pace included a low normal EF at V-sense, pre-existing LV hypertrophy, and cumulative RVA pacing >40% in the past 6 months. CONCLUSION For patients with preserved EF received RVA pacing, half of them would develop systolic dyssynchrony which was associated with EF deterioration and LV enlargement. A low normal EF, a high cumulative percentage of RVA pacing, and pre-existing LV hypertrophy were predictors of developing dyssynchrony.

Tissue Doppler velocity is superior to strain imaging in predicting long-term cardiovascular events after cardiac resynchronisation therapy

Objective: To examine the predictive value of systolic dyssynchrony measured by tissue Doppler velocity versus tissue Doppler strain imaging on long-term outcome after cardiac resynchronisation therapy (CRT). Design: Cohort study. Setting: Two university hospitals. Patients: Two hundred and thirty-nine patients (65 (SD 12) years, 76% males) who underwent CRT. Interventions: Baseline echocardiography with tissue Doppler imaging (TDI) and clinical follow-up for 37 (20) months. Main outcome measures: The time to peak systolic velocity during ejection phase (Ts) and the time to peak systolic strain (Tϵ) were assessed for dyssynchrony, that is the maximal delay in Ts and the maximal delay in Tϵ among the four left ventricular basal segments. Occurrence of cardiovascular endpoints between patients with and without dyssynchrony was compared by Kaplan–Meier curves, followed by Cox regression analysis for potential predictor(s). Results: There were 78 (33%) deaths, with cardiovascular causes in 64 (27%) patients, while 136 (57%) patients were hospitalised for cardiovascular events, including decompensated heart failure in 87 (36%) patients. Patients with the maximal delay in Ts of ⩾65 ms showed a lower event rate for cardiovascular mortality (19% vs 38%, logrank χ2 = 7.803, p = 0.005) and other prognostic endpoints. In Cox regression analysis, the maximal delay in Ts (hazard ratio (HR) 0.463, 95% CI 0.270 to 0.792, p = 0.005) and ischaemic aetiology (HR 2.716, 95% CI 1.505 to 4.901, p = 0.001) were independent predictors of cardiovascular mortality. In contrast, the maximal delay in Tϵ of ⩾80 ms failed to predict any cardiovascular event. Conclusions: Echocardiographic evidence of prepacing systolic dyssynchrony measured by TDI velocity, but not TDI strain, predicted lower long-term cardiovascular events after CRT.