Endocardial Biventricular Pacing Research Articles

Left bundle branch area pacing reduces epicardial dispersion of repolarization compared with biventricular cardiac resynchronization therapy

Biventricular endocardial pacing (BiV-endo) and left bundle branch area pacing (LBBAP) are novel methods of delivering cardiac resynchronization therapy. These techniques are associated with improved activation times and acute hemodynamic response compared with conventional biventricular epicardial pacing (BiV-epi); however, the effects on repolarization and arrhythmic risk are unknown. The purpose of this study was to compare the effects of temporary BiV-epi, BiV-endo, and LBBAP on epicardial left ventricular (LV) repolarization using electrocardiographic imaging (ECGi). Eleven patients indicated for cardiac resynchronization therapy underwent a temporary pacing protocol with ECGi. BiV-endo was delivered via endocardial stimulation of the LV lateral wall. LBBAP was delivered by pacing the LV septum. Epicardial LV repolarization time (LVRT-95; time taken for 95% of the LV to repolarize), LV RT dispersion, mean LV activation recovery interval (ARI), LV ARI dispersion, and RT gradients were calculated. The protocol was completed in 10 patients. During LBBAP, there were significant reductions in LVRT-95 (94.9 ± 17.4 ms vs 125.0 ± 29.4 ms; P=.03) and LV RT dispersion (29.4 ± 6.3 ms vs 40.8 ± 11.4 ms; P = .015) compared with BiV-epi. In contrast, there were no significant differences between baseline, BiV-epi, or BiV-endo. There was a nonsignificant reduction in mean RT gradients between LBBAP and baseline rhythm (0.74 ± 0.22 ms/mm vs 1.01 ± 0.31 ms/mm; P = .07). There were no significant differences in mean LV ARI or LV ARI dispersion between groups. Temporary LBBAP reduces epicardial dispersion of repolarization compared with conventional BiV-epi. Further study is required to determine whether these repolarization changes on ECGi translate into a reduced risk of ventricular arrhythmia in clinical practice.

Variation in optimal hemodynamic atrio-ventricular delay of biventricular pacing with different endocardial left ventricular lead locations using precision hemodynamics.

It is not known whether the optimal atrioventricular (AVopt ) delay varies between left ventricular (LV) pacing site during endocardial biventricular pacing (BiVP) and may therefore needs consideration. We assessed the hemodynamic AVopt in patients with chronic heart failure undergoing endocardial LV lead implantation. AVopt was assessed during atrio-BiVPwith a "roving LV lead."Up to four locations were studied: mid-lateral wall, mid-septum (or a close alternative), site of greatest hemodynamic improvement, and LV lead implant site. The AVopt was compared to a fixed AV delay of 180 ms. Seventeen patients were included (12 male, aged 66.5 ± 12.8 years, ejection fraction 26 ± 7%, 16 left bundle branch block or high percentage of right ventricular pacing [RVP], QRS duration 167 ± 27 ms). In most locations (62/63), AVopt increased systolic blood pressure during BiVP compared with RVP (relative improvement 6 mmHg,interquartile range [IQR] 4-9 mmHg). Compared to a fixed AV delay, the hemodynamic improvement at AVopt was higher (1 mmHg, IQR 0.2-2.6 mmHg, p < .001). Within most patients (16/17), we observed a difference in AVopt between pacing sites (median paced AVopt 209 ms, IQR 117-250). Within this range, the hemodynamic impact of these differences was small (median loss 0.6 mmHg, IQR 0.1-2.6 mmHg). Within a patient, different endocardial LV lead locations have slightly different hemodynamic AVopt which are superior to a fixed AV delay. The hemodynamic consequence of applying an optimum from a different lead location is small.

Biventricular endocardial pacing and left bundle branch area pacing for cardiac resynchronization: Mechanistic insights from electrocardiographic imaging, acute hemodynamic response, and magnetic resonance imaging

Biventricular endocardial pacing (BiV-endo) has demonstrated superior cardiac resynchronization compared to conventional biventricular epicardial pacing (BiV-epi). Left bundle branch area pacing (LBBAP) may also achieve effective cardiac resynchronization therapy (CRT). The purpose of this study was to compare the acute electrical and hemodynamic effects of BiV-epi, BiV-endo, and LBBAP delivered from the LV endocardium and to assess how myocardial scar affects response. Eleven patients with heart failure and indications for CRT underwent a temporary pacing study with electrocardiographic imaging (ECGi) and hemodynamic assessment. BiV-endo was delivered by stimulation of the left ventricular (LV) lateral wall, and LBBAP was delivered by stimulation of the LV septum, at the site of a Purkinje potential. LV activation time (LVAT-95), LV dyssynchrony index (LVDI), biventricular activation time (BIVAT-90), and biventricular dyssynchrony index (BIVDI) were calculated. Myocardial scar was assessed using magnetic resonance imaging (MRI). The protocol was completed in 10 patients. Compared to BiV-epi (LVAT-95: 79.2 ± 13.1 ms; LVDI: 26.6 ± 3.4 ms) LV resynchronization was superior during BiV-endo (LVAT-95: 48.5 ± 14.9 ms; P = .001; LVDI: 16.6 ± 6.4 ms; P = .002) and LBBAP (LVAT-95: 48.9 ± 12.5 ms; P = .001; LVDI: 15.3 ± 3.4 ms; P = .001). Biventricular resynchronization was similarly superior during BiV-endo and LBBAP vs BiV-epi (BIVAT-90 and BIVDI; P <.05). The rate of acute hemodynamic responders was higher during BiV-endo (90%) and LBBAP (70%) vs BiV-epi (50%). The benefits of LBBAP (but not BiV-endo) on LV resynchronization were attenuated when septal scar was present in a subset of 8 patients who underwent MRI. Our findings suggest superior electrical resynchronization and a higher proportion of acute hemodynamic responders during BiV-endo and LBBAP compared to BiV-epi. Electrical resynchronization was similar between BiV-endo and LBBAP; however, septal scar seemed to attenuate response to LBBAP.

The acute haemodynamic response with endocardial biventricular pacing: comparing RV paced and LBBB patients

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boston Scientific Background A third of patients that receive cardiac resynchronisation (CRT) are non-responders. Predictors of positive response include broader QRS duration, non-ischaemic aetiology and sinus rhythm, but it is still unclear whether lead placement site determines a positive responder. Purpose We assessed the acute haemodynamic response of endocardial biventricular pacing in patients with intrinsic left bundle brunch block (LBBB) versus LBBB due to pre-existing right ventricular pacing (RVP). Methods Patients who fulfilled standard criteria for CRT implantation but had failed conventional (coronary sinus) left ventricular (LV) lead placement (primary or revision) or were deemed clinical ‘non-responders after &amp;gt; 6 months of conventional CRT were enrolled. The acute haemodynamic response during endocardial biventricular pacing was assessed with a roving LV lead at 9 different locations (basal and mid: septal, anterior, posterior and lateral walls and apex). Acute changes in beat-to-beat systolic blood pressure (SBP) in the left ventricle were recorded and analysed. Results We recruited 23 patients across 10 UK centres: 14 intrinsic LBBB and 9 dependent on RVP. Patient characteristics were comparable: age (mean 67 + 10.6 years vs. 62 + 15.4 years), ischaemic (63% vs 50%), QRS (160 + 18ms vs. 190 + 36ms, p =0.07). Of the RVP group 5/9 had septal RV leads (the remainder apically positioned). There was no difference in the SBP improvement between the groups: change in SBP ranged from -5.25 – 19.91mmHg (median 3mmHg) in RVP patients vs -5.92 – 23.03mmHg (median 3mmHg) for intrinsic LBBB. However, the improvement in SBP was more consistent across the different segments in the patients with RVP (group A), as compared to intrinsic LBBB (group B), where the lateral wall and then non-septal walls provided the greatest haemodynamic improvement. Figure 1: depicts SBP improvement (in mmHg) during endocardial biventricular pacing in different positions within the LV for patients with RVP (A) vs underlying intrinsic LBBB (B): 9 segment model of the LV: Ant (anterior wall), Lat (lateral wall), Post (posterior wall), Sept (septum). Outer ring represents the four basal LV locations, middle ring the mid LV locations and centre ring the apex. Scale depicts mmHg improvement in SBP. Conclusion When implanting an LV lead for patients who are RV pacing dependent any position within the LV provides an acute haemodynamic improvement, compared with those with intrinsic LBBB, where a targeted lateral wall approach is more important. This finding corroborates the key differences in LV activation patterns for induced versus intrinsic LBBB.

Leadless left ventricular endocardial pacing in nonresponders to conventional cardiac resynchronization therapy.

Endocardial pacing may be beneficial in patients who fail to improve following conventional epicardial cardiac resynchronization therapy (CRT). The potential to pace anywhere inside the left ventricle thus avoiding myocardial scar and targeting the latest activating segments may be particularly important. The WiSE-CRT system (EBR systems, Sunnyvale, CA) reliably produces wireless, endocardial left ventricular (LV) pacing. The purpose of this analysis was to determine whether this system improved symptoms or led to LV remodeling in patients who were nonresponders to conventional CRT. An international, multicenter registry of patients who were nonresponders to conventional CRT and underwent implantation with the WiSE-CRT system was collected. Twenty-two patients were included; 20 patients underwent successful implantation with confirmation of endocardial biventricular pacing and in 2 patients, there was a failure of electrode capture. Eighteen patients proceeded to 6-month follow-up; endocardial pacing resulted in a significant reduction in QRS duration compared with intrinsic QRS duration (26.6 ± 24.4ms; P=.002) and improvement in left ventricular ejection fraction (LVEF) (4.7 ± 7.9%; P=.021). The mean reduction in left ventricular end-diastolic volume was 8.3 ± 42.3 cm3 (P=.458) and left ventricular end-systolic volume (LVESV) was 13.1 ± 44.3 cm3 (P=.271), which were statistically nonsignificant. Overall, 55.6% of patients had improvement in their clinical composite score and 66.7% had a reduction in LVESV ≥15% and/or absolute improvement in LVEF ≥5%. Nonresponders to conventional CRT have few remaining treatment options. We have shown in this high-risk patient group that the WiSE-CRT system results in improvement in their clinical composite scores and leads to LV remodeling.

Endocardial biventricular pacing for chronic heart failure patients: Effect on transmural dispersion of repolarization.

Background and AimConventional epicardial cardiac resynchronization therapy (CRT) can cause fatal arrhythmia associated with increased transmural dispersion of repolarization (TDR). It is unknown whether endocardial biventricular pacing in various locations will decrease TDR and hence the occurrence of fatal arrhythmia. This study aimed to find out the most effective location of endocardial biventricular pacing resulting in the shortest homogenous TDR.MethodsA before‐and‐after study on adult chronic heart failure (CHF) patients undergoing endocardial biventricular pacing in several defined locations. The changes in TDR from baseline were compared among various pacing locations.ResultsFourteen subjects were included with age ranged 36‐74 years old, of which 10 were males. Location revealed the highest post biventricular pacing TDR (113.4 (SD 13.8) ms) was the outlet septum of right ventricle in combination with lateral wall of left ventricle (RVOTseptum‐LVlateral) while the lowest one (106.1 (SD 11.6) ms) was of the right ventricular apex and posterolateral left ventricle (RVapex‐LVposterolateral). Two CRT locations resulted in the most homogenous TDR, that is the right ventricular apex ‐ left ventricular lateral wall (RVapex‐LVlateral, mean difference −9.43; 95% CI (−19.72;0.87) ms, P = 0.07) and right ventricular apex ‐ left ventricle posterolateral wall (RVapex‐LVposterolateral, mean difference −6.85; 95% CI (−13.93;0.22) ms, P = 0.056).ConclusionEndocardial biventricular pacing on right ventricular apex and left ventricular lateral/posterolateral walls results in the most homogenous TDR.

Real World Experience of Leadless LV Endocardial CRT with the WiSE CRT Pacing System; An International Study

IntroductionBiventricular endocardial pacing (BiV ENDO) is a potential therapy for heart failure patients who either cannot receive transvenous, epicardial CRT (BiV EPI) or who have failed to respond. BiV ENDO is traditionally delivered via trans-septal pacing leads, mandating lifelong anti-coagulation due to thromboembolic complications. The introduction of a new wireless LV endocardial pacing system (WiSE-CRT System, EBR Systems, Sunnyvale, California) avoids the need for long-term anticoagulation.ObjectiveWe sought to assess the safety & efficacy of the WiSE-CRT system during real world clinical use in an international registry.MethodsRegistry of centres implanting the WiSE-CRT system as part of the WICS Post Market Surveillance Registry (Clinical trial study number NCT02610673)ResultsA total of 68 patients across the 12 centers underwent implantation with the WiSE-CRT system, the largest series of leadless LV endocardial CRT yet reported. Patients were predominantly male with a mean age of 68.3± 10.4 years, a mean LVEF of 31% ± 9.1 and a mean QRS duration of 195.8 ± 120.0ms. Ischemic etiology was present in 37.5% of patients. Successful implantation and chronic delivery of BiV ENDO pacing via the WiSE-CRT system was achieved in 97% of patients. Acute (<24hrs) and 30 day complications rates were 5.9% and 23.5% respectively.ConclusionThis is the largest international series of the WiSE-CRT pacing system to date. In a real-world setting, leadless LV endocardial CRT proved technically feasible with a high success rate and similar complication rate to that previously described. BiV ENDO is a safe and effective therapeutic option for patients who fail to improve following transvenous, epicardial CRT. Biventricular endocardial pacing (BiV ENDO) is a potential therapy for heart failure patients who either cannot receive transvenous, epicardial CRT (BiV EPI) or who have failed to respond. BiV ENDO is traditionally delivered via trans-septal pacing leads, mandating lifelong anti-coagulation due to thromboembolic complications. The introduction of a new wireless LV endocardial pacing system (WiSE-CRT System, EBR Systems, Sunnyvale, California) avoids the need for long-term anticoagulation. We sought to assess the safety & efficacy of the WiSE-CRT system during real world clinical use in an international registry. Registry of centres implanting the WiSE-CRT system as part of the WICS Post Market Surveillance Registry (Clinical trial study number NCT02610673) A total of 68 patients across the 12 centers underwent implantation with the WiSE-CRT system, the largest series of leadless LV endocardial CRT yet reported. Patients were predominantly male with a mean age of 68.3± 10.4 years, a mean LVEF of 31% ± 9.1 and a mean QRS duration of 195.8 ± 120.0ms. Ischemic etiology was present in 37.5% of patients. Successful implantation and chronic delivery of BiV ENDO pacing via the WiSE-CRT system was achieved in 97% of patients. Acute (<24hrs) and 30 day complications rates were 5.9% and 23.5% respectively. This is the largest international series of the WiSE-CRT pacing system to date. In a real-world setting, leadless LV endocardial CRT proved technically feasible with a high success rate and similar complication rate to that previously described. BiV ENDO is a safe and effective therapeutic option for patients who fail to improve following transvenous, epicardial CRT.

Guidance for Optimal Site Selection of a Leadless Left Ventricular Endocardial Electrode Improves Acute Hemodynamic Response and Chronic Remodeling.

This study hypothesized that guided implants, in which the optimal left ventricular endocardial (LVENDO) pacing location was identified and targeted, would improve acute markers of contractility and chronic markers of cardiac resynchronization (CRT) response. Biventricular endocardial (BiVENDO) pacing may offer a potential benefit over standard CRT; however, the optimal LVENDO pacing site is highly variable. Indiscriminately delivered BiVENDO pacing is associated with a reverse remodeling response rate of between 40% and 60%. Registry of centers implanting a wireless, LVENDO pacing system (WiSE-CRT System, EBR Systems, Sunnyvale, California); John Radcliffe Hospital (Oxford, United Kingdom), Guy's and St. Thomas' Hospital (London, United Kingdom), and The James Cook University Hospital (Middlesbrough, United Kingdom). Centers used a combination of preprocedural imaging and electroanatomical mapping the identify the optimal LVENDO site. A total of 26 patients across the 3 centers underwent a guided implant. Patients were predominantly male with a mean age of 68.8 ± 8.4 years, the mean LV ejection fraction was 34.2 ± 7.8%. The mean QRS duration was 163.8 ± 26.7 ms, and 30.8% of patients had an ischemic etiology. It proved technically feasible to selectively target and deploy the pacing electrode in a chosen endocardial segment in almost all cases, with a similar complication rate to that observed during indiscriminate BiVENDO. Ninety percent of patients met the definition of echocardiographic responder. Reverse remodeling was observed in 71%. Guided endocardial implants were associated with a higher degree of chronic LV remodeling compared with historical nonguided approaches.

Electrical latency predicts the optimal left ventricular endocardial pacing site: results from a multicentre international registry

The optimal site for biventricular endocardial (BIVENDO) pacing remains undefined. Acute haemodynamic response (AHR) is reproducible marker of left ventricular (LV) contractility, best expressed as the change in the maximum rate of LV pressure (LV-dp/dtmax), from a baseline state. We examined the relationship between factors known to impact LV contractility, whilst delivering BIVENDO pacing at a variety of LV endocardial (LVENDO) locations. We compiled a registry of acute LVENDO pacing studies from five international centres: Johns Hopkins-USA, Bordeaux-France, Eindhoven-The Netherlands, Oxford-United Kingdom, and Guys and St Thomas' NHS Foundation Trust, London-UK. In all, 104 patients incorporating 687 endocardial and 93 epicardial pacing locations were studied. Mean age was 66 ± 11 years, mean left ventricular ejection fraction 24.6 ± 7.7% and mean QRS duration of 163 ± 30 ms. In all, 50% were ischaemic [ischaemic cardiomyopathy (ICM)]. Scarred segments were associated with worse haemodynamics (dp/dtmax; 890 mmHg/s vs. 982 mmHg/s, P < 0.01). Delivering BiVENDO pacing in areas of electrical latency was associated with greater improvements in AHR (P < 0.01). Stimulating late activating tissue (LVLED >50%) achieved greater increases in AHR than non-late activating tissue (LVLED < 50%) (8.6 ± 9.6% vs. 16.1 ± 16.2%, P = 0.002). However, the LVENDO pacing location with the latest Q-LV, was associated with the optimal AHR in just 62% of cases. Identifying viable LVENDO tissue which displays late electrical activation is crucial to identifying the optimal BiVENDO pacing site. Stimulating late activating tissue (LVLED >50%) yields greater improvements in AHR however, the optimal location is frequently not the site of latest activation.

Systematic review and meta-analysis of left ventricular endocardial pacing in advanced heart failure: Clinically efficacious but at what cost?

Cardiac resynchronization using a left ventricular (LV) epicardial lead placed in the coronary sinus is now routinely used in the management of heart failure patients. LV endocardial pacing is an alternative when this is not feasible, with outcomes data sparse. To review the available evidence on the efficacy and safety of endocardial LV pacing via meta-analysis. EMBASE, MEDLINE, and COCHRANE databases with the search term "endocardial biventricular pacing" or "endocardial cardiac resynchronization" or "left ventricular endocardial" or "endocardial left ventricular." Comparisons of pre-and post-QRS width, LV ejection fraction (LVEF), and New York Heart Association (NYHA) functional classification was performed, and mean differences (and respective 95% confidence interval [CI]) applied as a measurement of treatment effect. Fifteen studies, including 362 patients, were selected. During a mean follow-up of 40 ± 24.5 months, death occurred in 72 patients (11 per 100 patient-years). Significant improvements in LVEF (mean difference 7.9%, 95% CI 5-10%, P<0.0001; I2 =73%), QRS width (mean difference: -41% 95% -75 to -7%; P<0.0001; I2 =94%), and NYHA class (mean difference: -1.06, 95% CI -1.2 to -0.9, P<0.0001; I2 =60%), (all P<0.0001) occurred. Stroke rate was 3.3-4.2 per 100 patient-years, which is higher than equivalent heart failure trial populations and recent meta-analysis that included small case series. LV endocardial lead implantation is a potentially efficacious alternative to CS lead placement, but preliminary data suggest a potentially higher risk of stroke during follow-up when compared to the expected incidence of stroke in similar cohorts of patients.

Optimized Left Ventricular Endocardial StimulationIs Superior to Optimized EpicardialStimulation in Ischemic Patients WithPoor Response to Cardiac ResynchronizationTherapy: ACombined Magnetic Resonance Imaging, ElectroanatomicContact Mapping, and Hemodynamic Study toTarget Endocardial Lead Placement.

ObjectivesThe purpose of this study was to identify the optimal pacing site for the left ventricular (LV) lead in ischemic patients with poor response to cardiac resynchronization therapy (CRT).BackgroundLV endocardial pacing may offer benefit over conventional CRT in ischemic patients.MethodsWe performed cardiac magnetic resonance, invasive electroanatomic mapping (EAM), and measured the acute hemodynamic response (AHR) in patients with existing CRT systems.ResultsIn all, 135 epicardial and endocardial pacing sites were tested in 8 patients. Endocardial pacing was superior to epicardial pacing with respect to mean AHR (% change in dP/dtmax vs. baseline) (11.81 [-7.2 to 44.6] vs. 6.55 [-11.0 to 19.7]; p = 0.025). This was associated with a similar first ventricular depolarization (Q-LV) (75 ms [13 to 161 ms] vs. 75 ms [25 to 129 ms]; p = 0.354), shorter stimulation–QRS duration (15 ms [7 to 43 ms] vs. 19 ms [5 to 66 ms]; p = 0.010) and shorter paced QRS duration (149 ms [95 to 218 ms] vs. 171 ms [120 to 235 ms]; p < 0.001). The mean best achievable AHR was higher with endocardial pacing (25.64 ± 14.74% vs. 12.64 ± 6.76%; p = 0.044). Furthermore, AHR was significantly greater pacing the same site endocardially versus epicardially (15.2 ± 10.7% vs. 7.6 ± 6.3%; p = 0.014) with a shorter paced QRS duration (137 ± 22 ms vs. 166 ± 30 ms; p < 0.001) despite a similar Q-LV (70 ± 38 ms vs. 79 ± 34 ms; p = 0.512). Lack of capture due to areas of scar (corroborated by EAM and cardiac magnetic resonance) was associated with a poor AHR.ConclusionsIn ischemic patients with poor CRT response, biventricular endocardial pacing is superior to epicardial pacing. This may reflect accessibility to sites that cannot be reached via coronary sinus anatomy and/or by access to more rapidly conducting tissue. Furthermore, guidance to the optimal LV pacing site may be aided by modalities such as cardiac magnetic resonance to target delayed activating sites while avoiding scar.

Delayed Trans-Septal Activation Results in Comparable Hemodynamic Effect of Left Ventricular and Biventricular Endocardial Pacing

Background— We sought to compare left ventricular (LV epi ) and biventricular epicardial pacing (BIV epi ) with LV (LV endo ) and BIV endocardial pacing (BIV endo ) in patients with chronic heart failure with an emphasis on the underlying electrophysiological mechanisms and hemodynamic effects. Methods and Results— Ten patients with chronically implanted cardiac resynchronization devices underwent temporary LV endo and BIV endo pacing with an LV endocardial roving catheter. A pressure wire and noncontact mapping array were placed to the LV cavity to measure LVdP/dt max and perform electroanatomical mapping. At the optimal endocardial position, the acute hemodynamic response (AHR) was superior to epicardial stimulation, the AHR to BIV endo pacing and LV endo pacing being comparable (21±15% versus 22±17%; P =NS). During intrinsic conduction, QRS duration was 185±30 ms, endocardial LV total activation time 92±27 ms, and trans-septal activation time 60±21 ms. With LV endo pacing, QRS duration (187±29 ms; P =NS) and endocardial LV total activation time (91±23 ms; P =NS) were comparable with intrinsic conduction. There was no significant difference in endocardial LV total activation time between LV endo and BIV endo pacing (91±23 versus 85±15 ms; P =NS). Assessment of isochronal maps identified slow trans-septal conduction with both LV endo and BIV endo pacing resulting in activation of almost the entire LV endocardium prior to septal breakout, thereby limiting any possible fusion with either pacing mode. Conclusions— The equivalent AHR to LV endo and BIV endo pacing may be explained by prolonged trans-septal conduction limiting fusion of electrical wavefronts. The optimal AHR was associated with predominantly LV pre-excitation and depolarization. Our results suggest that LV pacing alone may offer a viable endocardial stimulation strategy to achieve cardiac resynchronization.

A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study

Alternative forms of cardiac resynchronization therapy (CRT), including biventricular endocardial (BV-Endo) and multisite epicardial pacing (MSP), have been developed to improve response. It is unclear which form of stimulation is optimal. We aimed to compare the acute haemodynamic response (AHR) and electrophysiological effects of BV-Endo with MSP via two separate coronary sinus (CS) leads or a single-quadripolar CS lead. Fifteen patients with a previously implanted CRT system received a second temporary CS lead and left ventricular (LV) endocardial catheter. A pressure wire and non-contact mapping array were placed into the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. Conventional CRT, BV-Endo, and MSP were then performed (MSP-1 via two epicardial leads and MSP-2 via a single-quadripolar lead). The best overall AHR was found using BV-Endo pacing with a 19.6 ± 13.6% increase in AHR at the optimal endocardial site over baseline (P < 0.001). There was an increase in LVdP/dtmax with MSP-1 and MSP-2 compared with conventional CRT, but this was not statistically significant. Biventricular endocardial pacing from the optimal site was significantly superior to conventional CRT (P = 0.039). The AHR achieved when BV-Endo pacing was highly site specific. Within individuals, the best pacing modality varied and was affected by the underlying substrate. Left ventricular activation times did not predict the optimal haemodynamic configuration. Biventricular endocardial pacing and not MSP was superior to conventional CRT, but was highly site specific. Within individuals, however, different methods of stimulation are optimal and may need to be tailored to the underlying substrate.

Left ventricular endocardial or triventricular pacing to optimize cardiac resynchronization therapy in a chronic canine model of ischemic heart failure

Cardiac resynchronization therapy (CRT) is a proven treatment for heart failure but ~30% of patients appear to not benefit from the therapy. Left ventricular (LV) endocardial and multisite epicardial [triventricular (TriV)] pacing have been proposed as alternatives to traditional LV transvenous epicardial pacing, but no study has directly compared the hemodynamic effects of these approaches. Left bundle branch block ablation and repeated microembolizations were performed in dogs to induce electrical dysynchrony and to reduce LV ejection fraction to <35%. LVdP/dt(max) and other hemodynamic indexes were measured with a conductance catheter during LV epicardial, LV endocardial, biventricular (BiV) epicardial, BiV endocardial, and TriV pacing performed at three atrioventricular delays. LV endocardial pacing was obtained with a clinically available pacing system. The optimal site was defined as the site that increased dP/dt(max) by the largest percentage. Implantation of the endocardial lead was feasible in all canines (n = 8) without increased mitral regurgitation seen with transesophageal echocardiography and with full access to the different LV endocardial pacing sites. BiV endocardial pacing increased dP/dt(max) more than BiV epicardial and TriV pacing on average (P < 0.01) and at the optimal site (P < 0.01). There were no significant differences between BiV epicardial and TriV pacing. BiV endocardial pacing was superior to BiV epicardial and to TriV pacing in terms of acute hemodynamic response. Further investigation is needed to confirm the chronic benefit of this approach in humans.

Improvement in pump function with endocardial biventricular pacing increases with activation time at the left ventricular pacing site in failing canine hearts

Recently, attention has been focused on comparing left ventricular (LV) endocardial (ENDO) with epicardial (EPI) pacing for cardiac resynchronization therapy. However, the effects of ENDO and EPI lead placement at multiple sites have not been studied in failing hearts. We hypothesized that differences in the improvement of ventricular function due to ENDO vs. EPI pacing in dyssynchronous (DYSS) heart failure may depend on the position of the LV lead in relation to the original activation pattern. In six nonfailing and six failing dogs, electrical DYSS was created by atrioventricular sequential pacing of the right ventricular apex. ENDO was compared with EPI biventricular pacing at five LV sites. In failing hearts, increases in the maximum rate of LV pressure change (dP/dt; r = 0.64), ejection fraction (r = 0.49), and minimum dP/dt (r = 0.51), relative to DYSS, were positively correlated (P < 0.01) with activation time at the LV pacing site during ENDO but not EPI pacing. ENDO pacing at sites with longer activation delays led to greater improvements in hemodynamic parameters and was associated with an overall reduction in electrical DYSS compared with EPI pacing (P < 0.05). These findings were qualitatively similar for nonfailing hearts. Improvement in hemodynamic function increased with activation time at the LV pacing site during ENDO but not EPI pacing. At the anterolateral wall, end-systolic transmural function was greater with local ENDO compared with EPI pacing. ENDO pacing and intrinsic activation delay may have important implications for management of DYSS heart failure.

Transmural Repolarization Dispersion of Endocardial Biventricular Pacing Sites in Patients for Cardiac Resynchronization Therapy

Objectives: We sought to investigate the transmural repolarization dispersion (TRD) of endocardial biventricular pacing sites in patients for cardiac resynchronization therapy. Background: CRT reduces morbidity and mortality in patients with dyssynchronous LV failure; however epicardial pacing of LV and endocardial pacing of RV reverses the normal sequence of transmural repolarization and enhances TRD which facilitate fatal arrhythmia. Endocardial biventricular pacing yield natural transmural activation pattern and minimize TRD and reduce the incidence of ventricular arrhythmia. Methods: TRD was measured at precordial and limb leads at baseline and post pacing in CRT group (n=15), and in normal subjects (n=15). Endocardial biventricular pacing was performed at nine locations. Results: In CRT group, areas with enhanced TDR are RVapex-LVanterolateral (108±19, 68 ms, p<0.02), RVseptum-LVposterolateral (103±9 ms, p<0.023), RVOTseptum-LVanterolateral (92±19.12 ms), p<0.00), and RVOTseptum-LVposterolateral (105±14, 23 ms, p<0.001). In the control group, locations with increased TDR are RVapex-LVanteroateral (108±19.60 ms, p<0.02), RVOTseptum-LVposterolateral (104±13.35 ms, p<0.001), and RVOTseptum-LVanterolateral (92±19.52 ms, p<0.000). Conclusions: CRT delivered at both LV and RV endocardial gives less transmural repolarization dispersion (TRD). The location of optimal TRD are RVapex-LVposterolateral, RVapex-LVlateral, RVseptum-LVanterolateral, RVseptum-LVlateral, and RVOTseptum-LVlateral.

Comparison of chronic biventricular pacing between epicardial and endocardial left ventricular stimulation using Doppler tissue imaging in patients with heart failure

In patients with a wide QRS, drug-resistant heart failure, and a coronary sinus that is unsuitable for transvenous biventricular pacing (BVP), a transseptal approach from the right to left atrium can allow endocardial left ventricular (LV) pacing (with permanent anticoagulant therapy) instead of epicardial pacing via the coronary sinus branches. We sought to compare the effects of endocardial pacing with those of epicardial LV pacing on regional LV electromechanical delay (EMD) and contractility. Twenty-three patients (68 ± 8 years) with severe heart failure and QRS ≥130 ms received a pacemaker for BVP. Fifteen patients underwent epicardial LV pacing, and 8 underwent endocardial LV pacing because of an unsuitable coronary sinus. All LV leads were placed at the anterolateral LV wall. Six months after implant, echocardiography and Doppler tissue imaging were performed. LV wall velocities and regional EMDs (time interval between the onset of the QRS and local ventricular systolic motion) were calculated for the 4 LV walls and compared for each patient between right ventricular (RV) and BVP. The amplitude of regional LV contractility was also assessed. Epicardial BVP reduced the septal wall EMD by 11% versus RV pacing (p = 0.05) and the lateral wall EMD by 41% versus RV pacing (p <0.01). With endocardial BVP, the septal and lateral EMDs were 21.3% and 54%, respectively (p <0.01, compared with epicardial BVP). The mitral time-velocity integral increased by 40% with endocardial BVP versus 2% with epicardial BVP (p <0.01). The amplitude of the lateral LV wall systolic motion increased by 14% with epicardial BVP versus 31% with endocardial BVP (p = 0.01). This resulted in a LV shorterning fraction increase of 25% in patients with endocardial BVP (p = 0.05). However, all patients were clinically improved at the end of follow-up. Thus, in heart failure patients with BVP, endocardial BVP provides more homogenous intraventricular resynchronization than epicardial BVP and is associated with better LV filling and systolic performance.