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Aims: Biventricular (BiV) pacing was superior to right ventricular apical (RVA) pacing at extended follow-up in the Pacing to Avoid Cardiac Enlargement (PACE) trial. Early pacing-induced systolic dyssynchrony (DYS) might be related to mid-term result. However, it remains unknown whether early pacing-induced DYS can predict long-term reduction of left ventricular (LV) systolic function.Methods and Results: Patients with standard pacing indications and normal LV ejection fraction (LVEF) were randomized either to BiV (n = 89) or RVA (n = 88) pacing. Seventy-four patients in the RVA group and 72 in the BiV pacing group completed follow-up longer than 2 years. Serial echocardiography was performed with DYS assessed by tissue Doppler imaging, and the early pacing-induced DYS was defined as >33 ms by using standard deviation of the time to peak systolic velocity (Dyssynchrony Index) in a 12-segment model of LV at 1 month. There were 46 (32%) patients having early pacing-induced DYS that was more prevalent in the RVA pacing group than that in the BiV pacing group (50.7 vs. 12.3%, χ(2) = 25.1, P < 0.001) despite the similar DYS between the two groups at baseline (30 ± 13 vs. 26 ± 11 ms, P = 0.051). At a median follow-up of 4.8 years, patients developing early DYS had lower LVEF (53.2 ± 9.4 vs. 60.9 ± 8.0%, P < 0.001) and larger LV end-systolic volume (40.3 ± 23.7 vs. 29.3 ± 13.4 mL, P < 0.001) than those without DYS. Significant EF reduction (defined as ≥5%) occurred in 71.7% (33 in 46) of patients with DYS, but only in 30% (30 in 100) in those without DYS (χ(2) = 22.4, P < 0.001). Further analysis showed that both DYS at 1 month [odds ratio (OR): 3.113, P = 0.013] and RVA pacing (OR: 7.873, P < 0.001) independently predicted the deterioration of LV systolic function with pacing period of 4.8 years.Conclusion: Early pacing-induced DYS is a significant predictor of reduction of LV systolic function for long-term pacing, which could be prevented by BiV pacing at relatively long-period follow-up.Clinical Trial Registration: Centre for Clinical Trials number, CUHK_CCT00037 (URL: http://www.cct.cuhk.edu.hk/Registry/publictrialrecord.aspx?trialid=CUHK_CCT00037). [ABSTRACT FROM AUTHOR]

Aims We report the results of long-term follow-up of the Pacing to Avoid Cardiac Enlargement ( PACE) trial, a prospective, double-blinded, randomized, multicentre study that confirmed the superiority of biventricular ( BiV) pacing compared with right ventricular apical ( RVA) pacing in prevention of LV adverse remodelling and deterioration of systolic function at 1 and 2 years. Methods and results Patients with bradycardia and preserved LVEF were randomized to receive RVA ( n = 88) or BiV pacing ( n = 89). Co-primary endpoints were LV end-systolic volume ( LVESV) and LVEF measured by echocardiography. There were 149 patients who had extended follow-up, with a mean duration of 4.8 ± 1.5 years (2.5-7.8 years). The primary endpoint analyses were performed in 146 patients (74 in the RVA group and 72 in the BiV group). In the RVA pacing group, the LVEF decreased while the LVESV increased progressively at follow-up, but remained unchanged in the BiV pacing group. The differences in LVEF between the RVA and BiV groups were -6.3, -9.2, and -10.7% at 1-year, 2-year, and long-term follow-up, respectively (all P < 0.001). The corresponding differences in LVESV were +7.4, +9.9, and +13.1 mL, respectively (all P < 0.001). The deleterious effects of RVA pacing consistently occurred in all the pre-defined subgroups. Furthermore, patients with RVA pacing had a significantly higher prevalence of heart failure hospitalization than the BiV group (23.9% vs. 14.6%, log-rank χ2 = 7.55, P = 0.006). Conclusion Left ventricular adverse remodelling and deterioration of systolic function continued at long-term follow-up in patients with RVA pacing; this deterioration was prevented by the use of BiV pacing. Also, heart failure hospitalization was more prevalent in the RVA pacing group. Trial registration CUHK_CCT00037. [ABSTRACT FROM AUTHOR]

Background: Cardiac contractility modulation (CCM) emerges as a promising device treatment for heart failure (HF). This meta-analysis aimed to systematically review the latest available randomized evidence on the effectiveness and safety of CCM in HF. Methods: The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in November 2011 to identify eligible randomized controlled trials comparing CCM with sham treatment or usual care. Primary outcomes of interest were all-cause mortality, all-cause hospitalizations, and adverse effects. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous data using a random-effects model. Results: Three studies enrolling 641 participants were included. Pooled analysis showed that, compared to control, CCM did not significantly improve all-cause mortality (n = 629, RR 1.19, 95% CI 0.50-2.86, P = 0.69), nor was there a favorable effect in all-cause hospitalizations. No increase in adverse effects with CCM was observed. Conclusions: Meta-analysis of data from small randomized trials suggests that CCM, although with no clear benefits in improving clinical outcomes, is not associated with worsening prognosis. Large, well-designed trials are needed to confirm its role in HF patients for whom cardiac resynchronization therapy is contraindicated or unsuccessful. (PACE 2012; 35:1111-1118) [ABSTRACT FROM AUTHOR]

Background : The acute effects of right ventricular apical (RVA) pacing on left atrial (LA) function in patients with normal ejection fraction are not clear. Methods : A total of 94 patients (age 68.1 ± 11.1 years, 26 men) with implanted RVA-based dual-chamber pacemakers were recruited into this study. Patients who were pacemaker-dependent, in persistent atrial fibrillation or left ventricular ejection fraction <45% were excluded. Echocardiography (iE33, Philips, Andover, MA, USA) was performed during intrinsic ventricular conduction (V-sense) and RVA pacing (V-pace) with 15 minutes between switching modes. The total maximal LA volume (LAVmax), preatrial contraction volume (LAVpre), and minimal volume (LAVmin) were assessed by area-length method. Peak systolic, early diastolic, and peak late diastolic (atrial contractile) velocity (Sm-la, Em-la, and Am-la) and strain (ɛs-la, ɛe-la, and ɛa-la) were measured by color-coded tissue Doppler imaging (TDI) in four mid-LA walls at apical four- and two-chamber views. Results : During V-pace, LA volumes increased significantly compared with V-sense (LAVmax: 52.0 ± 18.8 vs 55.2 ± 21.1 mL, P = 0.005; LAVpre: 39.8 ± 16.4 vs 41.3 ± 16.6 mL, P = 0.014; LAVmin: 27.4 ± 14.0 vs 29.1 ± 15.1 mL, P = 0.001). TDI parameters showed significant reduction in Sm-la and Em-la. Furthermore, ɛs-la, ɛe-la, and ɛa-la decreased significantly, especially in patients with preexisting diastolic dysfunction (all P < 0.01). Conclusions: RVA pacing acutely induced LA enlargement and impaired atrial contractility. Patients with preexisting diastolic dysfunction may be more vulnerable to develop LA dysfunction and remodeling after acute RVA pacing. (PACE 2011;XX:1-7) [ABSTRACT FROM AUTHOR]

Background: Deleterious effect on left ventricular (LV) function was observed with conventional right ventricular apical (RVA) pacing. Preliminary data suggested that biventricular pacing (BiV) may be superior to RVA pacing in patients with LV systolic dysfunction. However, the optimal pacing mode and site(s) for patients with normal LV systolic function remain controversial. Methods: The Pacing to Avoid Cardiac Enlargement (PACE) trial is a prospective, multicenter, randomized, double blinded, parallel, controlled study aiming to determine if BiV pacing is better than conventional RVA pacing in preserving LV systolic function and preventing remodeling in patients with LV ejection fraction (EF) 45% indicated for pacing. This study targets to recruit 200 patients from various centers in Asia, all of whom will receive BiV pacemaker implantation before being randomized to either atrial-based RVA or BiV pacing for 1 year. Their echocardiographic parameters including LV volumes, left ventricular ejection fraction (LVEF), and dyssynchrony index by tissue Doppler imaging, exercise capacity, quality of life assessment, neurohormone levels, and clinical events will be assessed before and after pacing. The primary endpoints are changes in LV end-systolic volume and LVEF 1 year after pacing. It is designed with 90% power to detect a 5% difference in the LVEF after 1 year of pacing. The enrollment began in 2006. It is expected to conclude at the end of 2008. Conclusion: The PACE trial will determine whether atrial-based BiV pacing can preserve LV systolic function and prevent LV adverse remodeling induced by conventional RVA pacing in patients with normal LV systolic function and standard pacing indication. [ABSTRACT FROM AUTHOR]

Prolongation of Atrial Effective Refractory Period. Background: A nonexcitatory, nonpropagating atrial extrastimulus delivered in the refractory period of the preceding cycle can prolong the atrial effective refractory period (AERP) and prevent the induction of atrial fibrillation by another AE introduced in the vulnerable period. Whether the effect of this nonexcitatory stimulation (NE) is confined only to its application site is unknown. Methods and Results: Sixteen consecutive patients were recruited into the study and 2 patients were excluded because of development of more sustained atrial fibrillation. NE was commenced by introduction of a 2.0 msec, 20-mA impulse at 50 msec after the preceding captured pacing impulse. AERP of right atrial septum, a distant site to NE application, was determined at baseline and after 5 minutes of steady pacing at six different protocols: protocol 1, 2, and 3 were conventional pacing at high right atrium, distal coronary sinus, and biatrial sites, respectively, and protocol 4, 5, and 6 were conventional pacing together with NE applied to the same sites as protocol 1, 2, and 3. Biatrial NE (protocol 6 with median AERP = 212.5 msec) significantly prolonged AERP compared with baseline (median AERP = 202.5 msec and P < 0.05), conventional pacing (protocol 1, 2, and 3 with median AERP = 205.0 msec, 205.0 msec, and 205.0 msec, respectively, and all P < 0.05), and single-site NE (protocol 4 and 5 with median AERP = 207.5 msec and 207.5 msec, respectively, and both P < 0.05). Conclusion: Biatrial NE resulted in AERP prolongation even at sites distant to NE application. The study result suggests that by adding NE to multi-sites pacing for atrial fibrillation prevention may have additional benefit. (J Cardiovasc Electrophysiol, Vol. 16, pp. 1-5, August 2005) [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) is currently indicated in patients with moderate to severe heart failure, a wide QRS complex and significant left ventricular dysfunction despite optimal medical therapy. Adoption of these criteria for CRT results in a favorable response in only two thirds of candidates. Methods: "Predictors of response to cardiac resynchronization therapy (PROSPECT)," a prospective, multicenter, nonrandomized study, aims to identify echocardiographic measures of dyssynchrony and evaluate their ability to predict response to CRT. PROSPECT will enroll approximately 300 patients in up to 75 centers in the United States, Asia, and Europe with clinical follow-up for 6 months. We will prospectively and individually test a variety of conventional echocardiographic and tissue Doppler imaging parameters against measures of clinical response. The primary response criteria are improvement in the heart failure Clinical Composite Score and left ventricular reverse remodeling. Enrollment began in March 2004 and is expected to conclude early 2005. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Efficacy of CRT for Mildly Prolonged QRS.. Introduction:Cardiac resynchronization therapy (CRT) has been shown to reverse left ventricular (LV) remodeling and improve symptoms in heart failure patients with wide QRS complexes; however, its role in patients with mildly prolonged QRS complexes is unclear. This study investigated if CRT benefited patients with mildly prolonged QRS complexes>120 to 150 ms and explored if the severity of systolic asynchrony determined such a response.Methods and Results:Fifty-eight patients (age 66± 11 years, 66% male) who had undergone CRT were studied prospectively. Of these patients, 27 had QRS duration between 120 and 150 ms (group A), and 31 had QRS duration>150 ms (group B). Tissue Doppler echocardiography and clinical assessment were performed at baseline and 3 months after CRT. Both groups had significant reduction of LV volume and increased ejection fraction,+dP/dt, and sphericity index (all P<0.05). These improvements were greater in group B and were explained by the higher prevalence of systolic intraventricular asynchrony. Significant reverse remodeling (reduction of LV end-systolic volume>15%) was evident in 46% of group A patients and 68% of group B patients. Improvement in clinical endpoints was observed in both groups (all P<0.01), although the changes in metabolic equivalent and New York Heart Association functional class were greater in group B. In both groups, systolic asynchrony index (TS-SD) was the most important predictor of reverse remodeling (r=−0.78, P<0.001) and was the only independent predictor in the multivariate model (β=−1.80, confidence interval=−2.18 to−1.42, P<0.001); QRS duration was not. A predefined TS-SD value>32.6 ms had a sensitivity of 94% and specificity of 83% to predict reverse remodeling. Improvement of intraventricular asynchrony after CRT was evident only in responders (P= 0.01).Conclusion:Improvement of LV remodeling and clinical status is evident after CRT in heart failure patients with QRS duration>120 to 150 ms. These responders are closely predicted by the severity of prepacing intraventricular asynchrony but not QRS duration.(J Cardiovasc Electrophysiol, Vol. 15, pp. 1-8, September 2004) [ABSTRACT FROM AUTHOR]

The authors discuss the difficult areas for cardiac resynchronization therapy, optimization of the treatment for implanting the left ventricular (LV) lead and the factors that affected the efficacy of LV. They mention about the study by Kristiansen and colleagues that described the role of employing 2-dimensional speckle tracking technology in assessing LV segmental function in heart failure patients. They state the methods to measure the anteroposterior wall delay in LV mid-cavity level.

The article discusses the case of a male patient whose surface electrograms showed two different cycle lengths during left ventricular pacing. The patient has ischemic cardiomyopathy. The electrograms showed pacing cycle of two different cycle lengths and different pacing morphologies. Pacing was predominantly at a longer cycle length with intermittent pacing at a shorter cycle length.

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) >33ms in a 12-segmental model of LV, was measured by tissue Doppler echocardiography at 1month. Results: At 1month, 59 patients (33%) had DYS which was more prevalent in RVA than BiV pacing group (52% vs. 15%, χ2 =28.3, p<0.001), though Dyssynchrony Index was similar at baseline (30±14 vs. 26±11ms, p=0.06). At 12months, 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±10.4ml, 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 (χ2 =40.8, p<0.001). Both DYS at 1month (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 12months. 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). [ABSTRACT FROM AUTHOR]

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±106ms, 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. [ABSTRACT FROM AUTHOR]

Abstract: Background: This prospective study was to examine the impact of right ventricular apical (RVA) pacing on atrial remodeling and function. Methods and results: 103 patients (age 70±11years; 53 men) with preserved left ventricular (LV) ejection fraction (LVEF>45%) who received RVA pacing had Doppler echocardiography performed at baseline and after one year follow up. At one year follow up, left atrial (LA) volumes (pre-atrial contraction volume and the minimal volume) and their indexes were significantly increased with reduction in passive emptying fraction and total emptying fraction (all p<0.05). LA segmental tissue velocities – mean peak systolic (Sm-la), peak early diastolic (Em-la) and late diastolic (Am-la) – were also significantly reduced (all p<0.001). A reduction of Am-la>30% occurred in 24% of patients, and was more prevalent in patients with an elevation of LV filling pressure (E/e''>15) at one year (44.1% vs. 11.7%, χ2 =12.75, p<0.001) as well as those with a reduction of LVEF≥5% (34.0% vs. 14.3%, χ2 =5.140, p=0.023). By multivariate regression analysis, E/e''>15 at one year (odds ratio [OR] 5.213; 95% confidence interval [CI] 1.778–15.281) and reduction of LVEF≥5% (OR 3.181; 95% CI 1.045–9.686) were independent predictors of reduction of Am-la>30%. Conclusions: Chronic RVA pacing results in LA remodeling and reduced atrial function. This is related to elevated filling pressures and impairment of LV systolic function. [Copyright &y& Elsevier]