Left Ventricular Sites Research Articles

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms. Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP. A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction (P<0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P=0.018); other outcome measures also indicated benefit with PPoP. In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO. URL: https://clinicaltrials.gov/study; Unique Identifier: NCT03450252.

A porcine large animal model of radiofrequency ablation-induced left bundle branch block

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic Background and Objective ECG features of left bundle branch (LBB) block (LBBB) can be observed in up to 20–30 % of patients that suffer from heart failure with reduced ejection fraction. The resulting mechanical intraventricular asynchrony contributes to the worsening of left ventricular hemodynamics and has a relevant impact on the prognosis of the affected patients. The fact that we still cannot accurately predict which LBBB patients will benefit from cardiac resynchronization therapy (CRT) underscores that our understanding of the pathophysiology of LBBB remains incomplete. Here, a translational animal model of LBBB could be a major contributor to improving our knowledge of the molecular and translational pathomechanisms underlying LBBB. Methods A total of 15 male pigs underwent RF catheter ablation of the LBB, guided by fluoroscopy and intracardiac ECG signals. Before LBBB induction and after a follow-up period of one week or three weeks, a thorough clinical characterization was performed including 12-lead ECG, echocardiography, and electroanatomical mapping. To further test the feasibility of cardiac resynchronization in our model, 3 pigs were implanted with a CRT pacemaker on day seven after LBB ablation. Results Upon LBB ablation, 12-lead ECGs displayed typical characteristics of LBBB like a QRS broadening, a QRS slurring in left lateral leads, and a change of the QRS axis. The QRS width was prolonged from 64.2±4.2 ms to 93,4±7.4 ms and the R wave peak time in V6 was extended from 19.3±3.9 ms to 42.7±4.2 ms. Cardiac electromechanical asynchrony was further confirmed by echocardiography, where the appearance of a septal flash, the prolongation of the septal to posterior wall movement delay and extended left ventricular as well as interventricular electromechanical delays were documented. Electroanatomical mapping demonstrated a shift of the left ventricular breakthrough site. After LBBB-induction, left ventricular activation times, defined as the average of the maximum 10 % of activation times minus the average of the minimum 10 % of activation times were significantly prolonged from 36.3±7.1 ms to 60.8±10.2 ms while right ventricular activation times remained unchanged. Finally, RF-induced LBBB persisted over an observation period of three weeks. The pigs that underwent CRT showed a reduction in QRS duration from 99.1±8.2 ms on day seven after LBBB induction to 75.5±8.2 ms and echocardiography provided additional evidence of successful resynchronization. Conclusions In summary, our porcine large animal model accurately recapitulates the electrical and electromechanical phenotype, observed in LBBB patients. This closed-chest model of LBBB therefore provides an experimental platform to study both, molecular and translational characteristics of cardiac electromechanical asynchrony in a reproducible and clinically relevant setting.

A porcine large animal model of radiofrequency ablation-induced left bundle branch block.

Electrocardiographic (ECG) features of left bundle branch (LBB) block (LBBB) can be observed in up to 20%-30% of patients suffering from heart failure with reduced ejection fraction. However, predicting which LBBB patients will benefit from cardiac resynchronization therapy (CRT) or conduction system pacing remains challenging. This study aimed to establish a translational model of LBBB to enhance our understanding of its pathophysiology and improve therapeutic approaches. Fourteen male pigs underwent radiofrequency catheter ablation of the proximal LBB under fluoroscopy and ECG guidance. Comprehensive clinical assessments (12-lead ECG, bloodsampling, echocardiography, electroanatomical mapping) were conducted before LBBB induction, after 7, and 21days. Three pigs received CRT pacemakers 7days after LBB ablation to assess resynchronization feasibility. Following proximal LBB ablation, ECGs displayed characteristic LBBB features, including QRS widening, slurring in left lateral leads, and QRS axis changes. QRS duration increased from 64.2 ± 4.2ms to 86.6 ± 12.1ms, and R wave peak time in V6 extended from 21.3 ± 3.6ms to 45.7 ± 12.6ms. Echocardiography confirmed cardiac electromechanical dyssynchrony, with septal flash appearance, prolonged septal-to-posterior-wall motion delay, and extended ventricular electromechanical delays. Electroanatomical mapping revealed a left ventricular breakthrough site shift and significantly prolonged left ventricular activation times. RF-induced LBBB persisted for 3weeks. CRT reduced QRS duration to 75.9 ± 8.6ms, demonstrating successful resynchronization. This porcine model accurately replicates the electrical and electromechanical characteristics of LBBB observed in patients. It provides a practical, cost-effective, and reproducible platform to investigate molecular and translational aspects of cardiac electromechanical dyssynchrony in a controlled and clinically relevant setting.

Activation time at left ventricular pacing site (QLV) in relation to actual site of latest activation; effect on response to cardiac resynchronization therapy

Abstract Background Among techniques to improve CRT efficacy, longer QLV (activation time at the left ventricular (LV) pacing site (LVPS)) has been proposed to correlate to response to cardiac resynchronization therapy (CRT), supporting that pacing close to the latest LV electrically activated site (LEAS) improves CRT efficacy. A QLV cut-off of &amp;gt; 95 ms has been proposed, however, predictive value was modest. This may be because LEAS was not identified, and empirically delivered leads may have missed it (described by a longer interval QLEAS (activation time at LEAS) to QLV. Purpose We compared QLEAS to QLV, and assessed effect of the interval QLEAS-QLV, on response to CRT. Methods We studied patients who had received CRT for Class I or Class IIa indications, regardless of CRT response, at 5 European sites. LV lead placement, device programming and follow up (FU) followed physician preference and site protocol. All patients had clinical FU 6-12 months post-implant, including echocardiographic study. CRT non-response was defined as LV end-systolic volume (LVESV) reduction of &amp;lt;15%. Patients underwent noninvasive 3D electrical activation mapping and torso CT 6-24 months post-implant. QLV and QLEAS were assessed from the noninvasive activation map in a blinded core lab. Logistic regression modelling was conducted for QLV and the interval QLEAS-QLV against CRT response, and the optimal cut-off points were calculated. Results Of 111 patients (age 64±11 years (mean±SD), 74% male, 98% LBBB, QRS duration 172±21 ms, baseline LVEF 28±6%, LVESV 183±87 mL, implant duration 12±5 months, 31%/69% NYHA Class II/III, 38% ischemic heart disease), 67% responded at 10±3 months post-implant. QLV overall was 97±23 ms (range 42-148 ms), 103±21 ms for responders and 83±22 for non- responders (p&amp;lt;0.001), QLEAS was 109±19 ms (range 66-150 ms), 109±20 ms for responders and 110±19 ms for non- responders (p=0.74). QLEAS-QLV overall was 13±18 ms (range 0-120 ms), 6±10 ms for responders and 27±22 ms for non-responders (p&amp;lt;0.001) (Figure 1). Optimal cut-off point for QLV was 85 ms with sensitivity 0.89, specificity 0.57 and an AUC of 0.742 (95% CI: 0.637- 0.846). Optimal cut-off point for QLEAS-QLV was 6 ms (sensitivity 0.77, specificity 0.95, AUC 0.901 (95% CI: 0.844-0.957) (Figure 1). The AUC of QLV cut-off and QLEAS-QLV cut-off differed significantly (p&amp;lt;0.001). 18/111 patients (16%) were non-responders despite a QLV≥85 ms, whereas 2 patients (2%) were non-responders despite a QLEAS-QLV≤6 ms. Conclusion QLEAS has greater discriminatory power than a QLV cut-off of 85 ms to separate CRT responders from non-responders in patients with LBBB and long QRS duration. QLV guided LV lead placement without prior knowledge of the latest LV activation in individual patients will miss the ideal LV pacing site in 16% of cases. Using noninvasive 3D global mapping to identify LEAS pre-CRT implant and directing LV lead placement to within 6 ms of this may improve CRT efficacy.Figure 1

Pulsed field ablation and ventricular capture: assessing the need for R-wave gated therapy

Abstract Background Pulsed field ablation (PFA) is a therapy that disrupts cellular homeostasis by applying high intensity and short duration electrical pulses to cardiac tissue, ultimately resulting in cell death. Such stimuli have the potential to initiate ventricular arrhythmias if the therapy is not synchronized with the beginning of ventricular systole (R-wave gating). For the treatment of cardiac arrhythmias, it is important that the candidate therapy locations in the left atrium (e.g., pulmonary veins) are a sufficient distance away from ventricular tissue to avoid ventricular capture. Objective data exploring the need for R wave gating in the context of PFA therapy for pulmonary vein isolation is currently lacking. Purpose To study the effect of electrode distance of the 12-electrode loop catheter from the epicardium on likelihood of ventricular capture. Methods A sternotomy was performed on swine to expose the heart. An incision was then made in the pericardial sac and the edges were lifted and sutured to the surrounding chest cavity to create a cradle. The function of the cradle was to hold a ∼37C saline solution (tuned to match the electrical conductivity of blood) while PFA treatments were performed. Two left ventricular sites (apex and lateral aspect) were selected for treatment, taking care to avoid proximity to the coronary artery. For each PFA therapy trial, the catheter loop was positioned 10mm above the surface of the epicardium and then advanced in 1mm increments until capture was achieved; spacers were used to assure fixed spacing during cardiac activity. For each trial, the maximum distance between the catheter and the epicardium at which the IRE therapy captured the ventricle was recorded. Additionally, CT scans (N=20 human patients) were analyzed to understand distances of interest to ventricular tissue. Results N=12 trials were conducted at each target in each animal (N=48 total ablations). For all trials, the minimum capture distance was found to be 6-8mm (4/48 at 6mm, 28/48 at 7mm and 16/48 at 8mm), with a mean capture distance of 7.25±0.60mm. The mean capture distances for the left ventricular apex and lateral aspect were 7.29±0.55mm and 7.21±0.66mm, respectively (p=0.636). For the CT scan analysis, the minimum distance from pulmonary vein ostia to left ventricular tissue ("nominal case") were 10.6mm and 12.8mm for the left superior and inferior veins, respectively. Considering the use ("worst case") where the catheter is placed just distal to the ostia, the distances to ventricular tissue were 1.6mm and 5.8mm, respectively; 4/20 patients had a vein less than 10mm from ventricular myocardium. Conclusions This study was successful in establishing the distance of ventricular capture via PFA therapy (6-8mm for the considered therapy). Given the described use and CT analysis, there is potential risk in triggering ventricular arrhythmia via PFA therapy unless R-wave triggering is implemented.

Left ventricular anterolateral site is the preferable left ventricular lead position for an upgrade to biventricular pacing

Abstract Background Cardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure with electrical dyssynchrony. The LV lead position in patients with left bundle branch block is usually recommended at the LV posterolateral to the lateral site, which is the latest electrical activation site. In contrast, the preferable LV lead position in patients who plan to upgrade from conventional RV apical pacing to CRT remains unclear. Purpose This study aimed to identify the preferable LV lead position for upgrading to CRT from conventional RV apical pacing. Methods An electrophysiological study was performed on patients who underwent ablation for atrial fibrillation. The electrode catheters were positioned at the RV apex, LV anterolateral, and LV posterolateral sites via the coronary sinus branches. During RV apical pacing, the activation time from the RV apex to the LV anterolateral and posterolateral sites was measured, and the activation time ratio to QRS duration was calculated. Biventricular pacing from both the RV apex and LV anterolateral or LV posterolateral sites was performed, and the difference in QRS duration and LV dP/dt compared to only the RV apical pacing state was measured. Results We enrolled 37 patients who exhibited anterolateral and posterolateral LV coronary sinus branches. During RV apical pacing, the average activation time ratio to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.89±0.07 vs. 0.71±0.11, P &amp;lt;0.001). The shortening ratio of QRS duration during biventricular pacing compared to baseline RV apical pacing was greater at LV anterolateral site than at the LV posterolateral site (45.7±18.0% vs. 32.0±17.6%, P &amp;lt;0.001). The improvement ratio of LV dP/dt during biventricular pacing was also better from the LV anterolateral site than from the LV posterolateral site (12.7±8.9% vs. 3.7±8.2%, P &amp;lt;0.001). Conclusion LV lead position in patients who plan to upgrade to CRT from conventional RV apical pacing is preferably at the LV anterolateral site.

Abstract 17689: Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing

Introduction: Patients with refractory symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM) have extremely limited therapeutic options. Hypothesis: We hypothesized that site-specific-pacing would induce regionalized contractile dyssynchrony to reduce LVMCO gradients and improve symptoms. Methods: Symptomatic-drug-refractory LVMCO patients were recruited for a randomized blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical RV pacing sites were assessed during invasive hemodynamic study. Patient-specific optimal pacing site and atrioventricular (AV) delays were selected on basis of LVMCO gradient reduction and pacing parameters. Patients were randomized to 6 months active or back-up pacing in cross-over design. Primary outcome examined invasive gradient change with PPoP. Secondary outcomes assessed quality of life and exercise. Results: A total of 17 patients were recruited; 16 met primary endpoints. Baseline NYHA was 3±0.6 despite medical therapy. Hemodynamic effects were assessed during pacing at RV apex and a mean of 8 LV sites (range 4-16). Optimal PPoP was achieved via LV pacing in 14 (88%) patients and RV apex in 2. Mean baseline gradient 80±29 mmHg fell to 31±21 mmHg with PPoP (p&lt;0.0001). Cardiac vein perforation occurred in one case, and 15 patients entered into cross-over; 2 withdrawals occurred during cross-over (myocardial infarction, persistent atrial fibrillation). Of the 13 completing cross-over, 9 (69%) chose active pacing as their preferred setting. PPoP was associated with better 6-minute walking test performance (329±100 vs 286±106 meters, p=0.018); other outcome measures also indicated benefit with PPoP. Conclusions: In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic LVMCO patients. A personalized approach to pacing site selection is a key component of this novel therapy.

Acute Hemodynamic Effect of a NovelDual-Vein, Multisite Biventricular Pacing Configuration.

Biventricular pacing (BVP) from multiple left ventricular (LV) sites could enhance the efficacy of cardiac resynchronization therapy (CRT) by engaging a greater myocardial mass. The goal of this study was to evaluate the acute hemodynamic effect of various multisite pacing (MSP) configurations against conventional BVP. Twenty patients with nonischemic dilated cardiomyopathy and left bundle branch block (mean age: 59 ± 14 years; LV ejection fraction: 27% ± 6%; native QRS: 171 ± 16 milliseconds) were investigated during a routine CRT implant procedure. In addition to conventional right atrial and right ventricular leads, 2 quadripolar leads were placed in the distant coronary venous branches. LV hemodynamics was evaluated by using a micromanometer-tipped catheter during atrioventricular BVP with 4 LV lead configurations: single-lead conventional BVP; single-lead multipoint pacing; triventricular pacing from distal dipoles of 2 LV leads; and maximum MSP (MSP-Max) from 4 dipoles of 2 LV leads. Compared with right atrial pacing, any BVP configuration produced a significant increase in the maximal LV diastolic pressure rise (LVdP/dTMax) (amedian relative increase of 28% [IQR: 8%-45%], 25% [IQR: 18%-46%], 36% [IQR: 18%-54%], and 38% [IQR: 28%-58%], respectively; all, P< 0.001). MSP-Max but no other multisite BVP generated a significant increase of the maximal LVdP/dTMax than conventional BVP (P=0.041). Increased LVdP/dTMax during MSP-Max was associated with greater LV diameter and lower LV ejection fraction, independently of the QRS width. The study shows the hemodynamic advantage of a novel dual-vein MSP-Max configuration that could be useful for CRT in patients with advanced LV remodeling.

CRT non-responder to responder conversion rate in the MORE-CRT MPP Trial.

To assess the impact of MultiPoint™ Pacing (MPP) in cardiac resynchronization therapy (CRT) non-responders after six months of standard biventricular pacing (BiVP). The trial enrolled 5,850 patients who planned to receive a CRT device. The echocardiography core laboratory assessed CRT response before implant and after six months of BiVP; non-response to BiVP was defined as < 15% relative reduction in left ventricular end-systolic volume (LVESV). Echocardiographic non-responders were randomized in a 1:1 ratio to receive MPP (541 patients) or continued BiVP (570 patients) for an additional six months and evaluated the conversion rate to the echocardiographic response. The characteristics of both groups at randomization were comparable. The percentage of non-responder patients who became responders to CRT therapy was 29.4% in the MPP arm and 30.4% in the BIVP arm (p=0.743). In patients with > 30 mm spacing between the two left ventricular pacing sites (MPP-AS), identified during the first phase as a potential beneficial subgroup, no significant difference in the conversion rate was observed. Our trial shows that approximately 30% of patients, who do not respond to CRT in the first six months, experience significant reverse remodeling in the following six months. This finding suggests that CRT benefit may be delayed or slowly incremental in a relevant proportion of patients and that the percentage of CRT responders may be higher than what has been described in short/middle-term studies. MPP does not improve CRT response in non-responders to BiVP, even with MPP-AS.

Clinical outcomes of transcatheter mitral valve replacement: two-year results of the CHOICE-MI Registry.

Transcatheter mitral valve replacement (TMVR) using dedicated devices is an alternative therapy for high-risk patients with symptomatic mitral regurgitation (MR). This study aimed to assess the 2-year outcomes and predictors of mortality in patients undergoing TMVR from the multicentre CHOICE-MI Registry. The CHOICE-MI Registry included consecutive patients with symptomatic MR treated with 11different dedicated TMVR devices at 31 international centres. The investigated endpoints included mortality and heart failure hospitalisation rates, procedural complications, residual MR, and functional status. Multivariable Cox regression analysis was applied to identify independent predictors of 2-year mortality. Atotal of 400patients, median age 76 years (interquartile range [IQR] 71, 81), 59.5% male, EuroSCORE II 6.2% (IQR 3.8, 12.0), underwent TMVR. Technical success was achieved in 95.2% of patients. MR reduction to ≤1+ was observed in 95.2% at discharge with durable results at 1 and 2years. New York Heart Association Functional Class had improved significantly at 1 and 2years. All-cause mortality was 9.2% at 30days, 27.9% at 1year and 38.1% at 2years after TMVR. Chronic obstructive pulmonary disease, reduced glomerular filtration rate, and low serum albumin were independent predictors of 2-year mortality. Among the 30-day complications, left ventricular outflow tract obstruction, access site and bleeding complications showed the strongest impact on 2-year mortality. In this real-world registry of patients with symptomatic MR undergoing TMVR, treatment with TMVR was associated with adurable resolution of MR and significant functional improvement at 2years. Two-year mortality was 38.1%. Optimised patient selection and improved access site management are mandatory to improve outcomes.

Preferred left ventricular lead position for upgrade from right ventricular pacing to cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is well-established for treating symptomatic heart failure with electrical dyssynchrony. The left ventricular (LV) lead position is recommended at LV posterolateral to lateral sites in patients with left bundle branch block; however, its preferred region remains unclear in patients being upgraded from right ventricular (RV) apical pacing to CRT. This study aimed to identify the preferred LV lead position for upgrading conventional RV apical pacing to CRT. We used electrode catheters positioned at the RV apex and LV anterolateral and posterolateral sites via the coronary sinus (CS) branches to measure the ratio of activation time to QRS duration from the RV apex to the LV anterolateral and posterolateral sites during RV apical pacing. Simultaneous biventricular pacing was performed at the RV apex and each LV site, and the differences in QRS duration and LV dP/dtmax from those of RV apical pacing were measured. Thirty-seven patients with anterolateral and posterolateral LV CS branches were included. During RV apical pacing, the average ratio of activation time to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.90 ± 0.06 vs. 0.71 ± 0.11, p < .001). The decreasing ratio of QRS duration and the increasing ratio of LV dP/dtmax were higher at the LV anterolateral site than at the posterolateral site (45.7 ± 18.0% vs. 32.0 ± 17.6%, p < .001; 12.7 ± 2.9% vs. 3.7 ± 8.2%, p < .001, respectively) during biventricular pacing compared with RV apical pacing. The LV anterolateral site is the preferred LV lead position in patients being upgraded from conventional RV apical pacing to CRT.

Combination of personalized computational modeling and machine learning for optimization of left ventricular pacing site in cardiac resynchronization therapy.

Introduction: The 30-50% non-response rate to cardiac resynchronization therapy (CRT) calls for improved patient selection and optimized pacing lead placement. The study aimed to develop a novel technique using patient-specific cardiac models and machine learning (ML) to predict an optimal left ventricular (LV) pacing site (ML-PS) that maximizes the likelihood of LV ejection fraction (LVEF) improvement in a given CRT candidate. To validate the approach, we evaluated whether the distance DPS between the clinical LV pacing site (ref-PS) and ML-PS is associated with improved response rate and magnitude. Materials and methods: We reviewed retrospective data for 57 CRT recipients. A positive response was defined as a more than 10% LVEF improvement. Personalized models of ventricular activation and ECG were created from MRI and CT images. The characteristics of ventricular activation during intrinsic rhythm and biventricular (BiV) pacing with ref-PS were derived from the models and used in combination with clinical data to train supervised ML classifiers. The best logistic regression model classified CRT responders with a high accuracy of 0.77 (ROC AUC = 0.84). The LR classifier, model simulations and Bayesian optimization with Gaussian process regression were combined to identify an optimal ML-PS that maximizes the ML-score of CRT response over the LV surface in each patient. Results: The optimal ML-PS improved the ML-score by 17 ± 14% over the ref-PS. Twenty percent of the non-responders were reclassified as positive at ML-PS. Selection of positive patients with a max ML-score >0.5 demonstrated an improved clinical response rate. The distance DPS was shorter in the responders. The max ML-score and DPS were found to be strong predictors of CRT response (ROC AUC = 0.85). In the group with max ML-score > 0.5 and DPS< 30 mm, the response rate was 83% compared to 14% in the rest of the cohort. LVEF improvement in this group was higher than in the other patients (16 ± 8% vs. 7 ± 8%). Conclusion: A new technique combining clinical data, personalized heart modelling and supervised ML demonstrates the potential for use in clinical practice to assist in optimizing patient selection and predicting optimal LV pacing lead position in HF candidates for CRT.

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.

The last shall be the first: the role of combined QLV- and CMR-determined electromechanical concordance in predicting optimal left ventricular stimulation site in cardiac resynchronisation therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background/introduction Optimisation of cardiac resynchronisation therapy (CRT) response still represents a significant challenge to cardiac electrophysiology. In this regard, perhaps the area of greatest uncertainty revolves around optimal left ventricular lead (LVL) position and in particular whether this should be directed at areas of latest electrical or mechanical activation given the equivocal evidence on their precise relationship in heart failure (HF) patients. Furthermore, while echocardiography has demonstrated that LVL aimed at regions of greatest mechanical delay maximises CRT response, cardiac magnetic resonance (CMR) with its greater spatial resolution and tissue definition is yet to demonstrate a role in doing so. Purpose To retrospectively evaluate concordance between latest electrical and CMR-determined mechanical activation in a CRT population and its relationship with reverse remodeling. Methods This is a retrospective single center analysis of 104 CRT patients. All patients had CMR and echocardiography performed before implantation. During implantation, coronary sinus angiogram was performed and electrical delay (QLV time with RV-LV time greater than 80 ms) was mapped on all veins suitable for lead implantation and LVL was positioned in the region of latest electrical activation programming LVL cathode accordingly. LVL cathode position was thus assumed to represent the region of latest electrical delay. A post-hoc analysis was then conducted by means of CART-Tech® software providing radial strain and scar maps on a 36-segment anatomical model. Patients were then stratified based on concordance between LVL cathode position (using 3D heart models superimposed on 2D angiography images) and most mechanically delayed segments (either the three most delayed segments or adjacent ones) or non concordance (one or more segments between LVL cathode and three most mechanically delayed segments). Data from patient follow-up was collected with echocardiography at least 3 months after implant date. CRT response was expressed as reduction in end-systolic volume (ESV) greater than 15%. Results A preliminary analysis of the first 30 patients of our cohort was conducted. Electromechanical concordance and non-concordance were present in 24 and 6 patients, respectively. Baseline patient characteristics including demographics, comorbidities, HF aetiology, ECG and echocardiography features were comparable between groups except for scar burden, which was higher in the non-concordance group. Response to CRT was 80% in the concordant vs. 20% in the non-concordant group. Conclusions While a confounding effect of scar burden cannot be excluded, these preliminary data suggest that electromechanical concordance in LVL cathode placement may represent a predictor of optimal CRT response. The full scope of this study will be fully appreciated in the coming month on completion of analysis of the entire patient cohort.

Changes in myocardial perfusion according to left ventricular pacing site in cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): 1. The Danish Heart Foundation 2. The Health Research Fund of the Central Denmark Region Background/Introduction Changes in left ventricular (LV) myocardial perfusion according to LV pacing site during cardiac resynchronization therapy (CRT) has only been sparsely described. Purpose To assess changes in LV global and regional myocardial perfusion according to LV pacing site after six months CRT. Methods Data from patients enrolled in the randomized controlled trial "Electrically vs. Imaging-guided Left Ventricular Lead Placement in Cardiac Resynchronization Therapy" was evaluated. Global and segmental absolute myocardial perfusion in ml/g/min was assessed by 82Rb-PET the day before CRT implantation and at six-months follow-up (6MFU). The exact LV pacing site was determined by post-implant cardiac CT. Perfusion and pacing site were evaluated using the standard 17’-segment LV model. Echocardiographic assessment of LV ejection fraction (EF) was performed the day before CRT implantation and at 6MFU. Results 93 patients (age 71±9 years; ischemic heart disease 48%; female 25%; median QRS 166±20 ms; mean LVEF 30±7%; NYHA class I/II/III/IV (%) 0/63/33/3) were included. Distribution of LV pacing sites is shown in Figure 1. No change in LV global perfusion was observed from baseline to 6MFU (0.79 to 0.81 ml/g/min, P=0.41; respectively). LV EF increased by 9±10%. Baseline global perfusion was higher in the 39 patients in whom LV EF had increased ≥10% at 6MFU (0.86 vs. 0.74 ml/g/min, P=0.02; respectively). However, no difference in perfusion-change was observed between patients with ≥10% increase in LV EF at 6MFU and patients with &amp;lt;10% increase (0.01 vs. 0.02 ml/g/min, P=0.76; respectively). Baseline perfusion was higher in the segments chosen for LV-pacing than in the non-paced segments (0.96 vs. 0.78 ml/g/min, P=0.00; respectively). Perfusion in the paced segments dropped to 0.86 ml/g/min (P=0.00) at 6MFU. Perfusion in the neighbouring segments also dropped during six months (from 0.91 to 0.86 ml/g/min, P=0.03), while perfusion in the non-paced and non-neighbouring segments increased (from 0.75 to 0.80 ml/g/min, P=0.01). Conclusion Despite a mean increase in LV EF of 9%, global myocardial perfusion remained unchanged. CRT resulted in a homogenous distribution of myocardial perfusion with a decreased perfusion in segments concordant and adjacent to LV pacing site and a corresponding increased perfusion in remote segments.

Does targeted positioning of the left ventricular pacing lead towards the latest local electrical activation in cardiac resynchronization therapy reduce the incidence of death or hospitalization for heart failure?

Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. NCT03280862.

Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia.

Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

Status and Update on Cardiac Resynchronization Therapy Trials.

After decades of clinical use, cardiac resynchronization therapy (CRT) can be considered an established therapy. However, there are multiple open questions to be addressed that shall further improve the proportion of patients responding to CRT. Progress in better understanding the relationship between electrical and mechanical disorder in patients with heart failure with ventricular conduction abnormalities is important. This article presents and discusses ongoing studies in different areas of CRT research, including patient selection by novel diagnostic tools, extension of clinical criteria, left ventricular lead positioning and pacing site selection, optimization of CRT delivery and programming, and selection of device type.

Novel multi-site, multi-point biventricular pacing configuration: acute haemodynamic benefit

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by the research grant of the AZV (Ministry of Health of the Czech Republic) Background Biventricular pacing (BVP) using multiple left ventricular (LV) sites may augment the hemodynamic effect of cardiac resynchronisation therapy (CRT) by engaging a greater mass of the myocardium. Purpose To evaluate the acute hemodynamic effect of a novel multi-site, multi-point BVP configuration. Methods The study investigated 18 patients with idiopathic dilated cardiomyopathy and left bundle-branch block during implantation of a BVP device (age: 59 ± 14 years, female gender: 7 [39%], LVEF: 27 ± 6%, native QRS: 171 ± 16 ms). Conventional leads were placed in the right atrium (RA) and ventricle (RV), one quadripolar LV lead (Quartet, Abbott, Abbott Park, IL, USA) was positioned in the posterolateral and another one in lateral or anterolateral coronary vein. Individual bipoles of all leads were connected through a splitter to separate external cardiac stimulators. Hemodynamics was evaluated using a micromanometer-tipped catheter (Micro-Cath, Millar, Tx, USA) located in the LV during RA pacing above sinus rate and five atrio-ventricular sequential pacing configurations at the same rate: 1.) RA+RV, 2.) RA + RV + distal bipole of the LV lead with greater dP/dT („conventional BVP"), 3.) RA + RV + distal and proximal bipoles of the LV lead with greater dP/dT („single-lead multi-point BVP"), 4.) RA + RV + distal bipoles of both LV leads („two-lead multi-site BVP"), and 5.) sequentional pacing RA + RV + all bipoles of both LV leads interconnected to a mesh („maximum BVP"). Results Compared to RA pacing, LV dP/dT was significantly greater during all BVP pacing configurations (RA pacing: 1940 ± 507 mmHg/s vs. conventional BVP: 2431 ± 855 mmHg/s, single-lead multi-point BVP: 2539 ± 740 mmHg/s, two-lead multisite BVP: 2517 ± 836 mmHg/s, and "maximum BVP": 2685 ± 893 mmHg/s, all p&amp;lt;0.001, Figure 1), but not during RA-RV pacing (2014 ± 721 mmHg/s, p=0.12). In addition, dP/dT was significantly greater during "maximum BVP" compared to conventional BVP (p=0.05). Conclusion Compared to RA pacing and conventional BVP, the greatest increase in LV contractility was achieved with a novel multi-site, multi-point "maximum BVP" configuration. These preliminary findings provide a rationale for designing new approaches to CRT.

Acute hemodynamic impact of atrioventricular delay and left ventricular pacing vector programming in MultiPoint Pacing.

The benefits of cardiac resynchronization therapy (CRT) in heart failure patients have been shown to depend on device programming, particularly atrioventricular delay (AVD) and left ventricular (LV) pacing site selection. This study compared the hemodynamic AVD optimization for commonly used biventricular (BiV) and MultiPoint Pacing(MPP, Abbott) LV vector selection strategies. After de novo CRT-D (Abbott Quadra Assura MP) and quadripolar LV lead (Abbott Quartet) implant, acute LV pressure was measured across a range of AVDs (60-225 ms) in four pacing modes: BiV with most proximal cathode, BiV with most distal cathode, MPP using two cathodes with earliest and latest right ventricle (RV)-LV activation times, and MPP using two cathodes with maximal anatomical separation. Hemodynamic improvement was evaluated by changes in maximum LV pressure first-derivative versus RV pacing (ΔdP/dt). Twenty patients (64 years old, 68% male) completed the acute pacing protocol at six centers in China. Hemodynamic improvement versus RV pacing for BiV (proximal), BiV (Distal), MPP (electrical), and MPP (anatomical) was 22.1% ± 13.6%, 23.7% ± 13.4%, 24.5% ± 13.4%, and 25.1% ± 13.9%, respectively. The best MPP setting was marginally superior to the best BiV across all patients (25.8% ± 13.4% vs. 24.5% ± 13.1%, p = .040) and in the majority of patients (75.0% vs. 25.0%, p = .004). AVD programmed as little as 20 ms from optimum significantly reduced the ΔdP/dt benefit for all modes. The maximal hemodynamic improvement across AV delays in this population was greater with MPP than BiV. Furthermore, patient-specific AVD programming was critical in achieving the full hemodynamic response for all BiV and MPP modes.