Multipoint Pacing Research Articles

43Dynamic atrioventricular delay achieves superior electrical synchrony when pacing both ventricles rather than left ventricle alone

Abstract Funding Acknowledgements Abbott Introduction Automatic adjustment of atrioventricular delay (AVD) with SyncAV has been shown to improve electrical synchronization when pacing one or two sites in the left ventricle together with the right ventricle. However, it is unknown if the same benefit can be gained by using SyncAV while pacing only the left ventricle without right ventricular pacing. Purpose Evaluate the acute improvement in electrical synchrony provided by SyncAV with and without MultiPoint Pacing (MPP) during biventricular (BiV) and LV only pacing. Methods Patients with LBBB and QRS duration (QRSd) ≥ 150 ms scheduled for CRT-P/D device implantation with quadripolar LV lead were enrolled in this prospective study. QRSd was measured post-implant from 12-lead surface electrograms by blinded experts during the following pacing configurations: intrinsic conduction, conventional BiV (BiV = RV + LV1), MPP (MPP = RV + LV1 + LV2), LV-only single-site (LVSS = LV1 only), and LV-only MPP (LVMPP = LV1 + LV2). For each pacing mode, SyncAV was enabled (e.g. BiV + SyncAV) with the patient-tailored SyncAV offset that minimized QRSd. As an additional reference, QRSd during BiV was also measured using the nominal static AVD (paced/sensed AVD = 140/110 ms). BiV and LVSS pacing used the latest activating LV cathode, whereas MPP and LVMPP used the two LV cathodes with the widest possible separation (>30mm). All configurations used the minimum programmable RV-LV and LV1-LV2 delays. Results Thirty-five patients (78% male, 33% ischemic, 26% ejection fraction, 165 ms intrinsic QRSd) completed device implant and QRSd assessment. Relative to intrinsic conduction, BiV with nominal AVD reduced the QRSd by 17.5% (p < 0.001 vs intrinsic). Enabling SyncAV with a patient-optimized offset significantly improved QRSd reduction. BiV + SyncAV reduced QRSd by 25.2% (p < 0.001 vs. BiV). The greatest QRSd reduction of 28.9% was achieved by MPP + SyncAV (p < 0.01 vs. BiV + SyncAV). Single- and multi-site LV-only pacing reduced QRSd significantly less than corresponding biventricular modes. LVSS + SyncAV reduced QRSd by 22.5% (p < 0.05 vs. BiV + SyncAV), and LVMPP + SyncAV reduced QRSd by 24.3% (p < 0.05 vs. MPP + SyncAV). As a percent of PR interval, optimal SyncAV offsets were similar for BiV + SyncAV (median: 13%, mean: 17%) vs. MPP + SyncAV (median: 13%, mean 16%, p = 0.35 vs. BiV + SyncAV), and similar for LVSS + SyncAV (median: 20%, mean: 28%) and LVMPP + SyncAV (median: 23%, mean: 26%, p = 0.35 vs. LVSS + SyncAV), but were significantly higher for LV-only settings vs. corresponding BiV/MPP settings (p < 0.01 for both pairs). Conclusion: Greater improvement in electrical synchrony using SyncAV was observed when right ventricular pacing was included with left ventricular pacing. Additional benefit was gained by the addition of a second left ventricular pacing site with MPP in combination with SyncAV in both biventricular and LV only pacing modes. Abstract Figure.

Evaluating multisite pacing strategies in cardiac resynchronization therapy in the preclinical setting.

BackgroundMultisite pacing strategies that improve response to cardiac resynchronization therapy (CRT) have been proposed. Current available options are pacing 2 electrodes in a multipolar lead in a single vein (multipoint pacing [MPP]) and pacing using 2 leads in separate veins (multizone pacing [MZP]).ObjectiveThe purpose of this study was to compare in a systematic manner the acute hemodynamic response (AHR) and electrophysiological effects of MPP and MZP and compare them with conventional biventricular pacing (BiVP).MethodsHemodynamic and electrophysiological effects were evaluated in a porcine model of acute left bundle branch block (LBBB) (n = 8). AHR was assessed as LVdP/dtmax. Activation times were measured using >100 electrodes around the epicardium, measuring total activation time (TAT) and left ventricular activation time (LVAT).ResultsCompared to LBBB, BiVP, MZP, and MPP reduced TAT by 26% ± 10%, 32% ± 13%, and 32% ± 14%, respectively (P = NS between modes) and LVAT by 4% ± 5%, 11% ± 5%, and 12% ± 5%, respectively (P <.05 BiVP vs MPP and MZP). On average, BiVP increased LVdP/dtmax by 8% ± 4%, and optimal BiVP increased LVdP/dtmax by 13% ± 4%. The additional improvement in LVdP/dtmax by MZP and MPP was significant only when its increase during BiVP and decrease in TAT were poor (lower 25% of all sites in 1 subject). The increase in LVdP/dtmax was larger when large interelectrode distances (>5 cm vs <2.2 cm) were used.ConclusionIn this animal model of acute LBBB, MPP and MZP create similar degrees of electrical resynchronization and hemodynamic effect, which are larger if interelectrode distance is large. MPP and MZP increase the benefit of CRT only if the left ventricular lead used for BiVP provides poor response.

Delay optimization of multipoint pacing increases the cardiac index and narrows the QRS width

IntroductionThe benefits of MPP delay optimization on hemodynamics and ventricular contraction synchronicity can be quantified with cardiac index (CI) and QRS width. A delay with the maximum CI and minimum QRS width may be the optimized settings for multipoint pacing (MPP). MethodsTwelve patients with advanced heart failure who received cardiac resynchronization therapy defibrillation with MPP at the Third People's Hospital of Chengdu from March 2016 to April 2019 were included. Interventricular and intraventricular delays were optimized through noninvasive cardiac output monitoring and a 12 lead ECG. ResultsAccording to CI, the optimized left ventricular- left ventricular - right ventricular delay setting was mainly 25 ms–25 ms and 40 ms–40 ms. And the delay with the minimum QRS width was mainly in 5 ms–5 ms, 25 ms–25 ms, and 40 ms–25 ms. The optimal MPP configuration increased CI compared to the MPP setting that produced the minimum CI (4.5 ± 1.3 vs. 2.8 ± 1.0 L/min/m2, P < 0.001). The QRS width of the optimized MPP was narrower than the MPP setting that produced the maximum QRS width (127 ± 20 vs. 160 ± 29 ms, P < 0.001). ConclusionDelay optimization improves hemodynamic response and ventricular contraction synchronicity. The delay of 25 ms–25 ms may be the optimal setting for most MPP patients.

Clinical and economic impact of multipoint left ventricular pacing: A comparative analysis from the Italian registry on multipoint pacing in cardiac resynchronization therapy (IRON-MPP).

Early evidence suggests that multipoint left ventricular pacing (MPP) may improve response to cardiac resynchronization therapy (CRT). It is unknown whether this benefit is sustained and cost-effective. We used real-world data to evaluate long-term impact of MPP-ON clinical status, heart failure hospitalizations (HFH) and costs. The Italian registry on multipoint left ventricular pacing is a prospective, multicenter registry of patients implanted with MPP-enabled CRT devices. For this analysis, clinical and echocardiographic data were collected through 24 months and compared between patients with (MPP-ON) or without (MPP-OFF) early MPP activation at implant. The total cost of each HFH was estimated with national Italian reimbursement rates. The study included 190 MPP-OFF and 128 MPP-ON patients with similar baseline characteristics. At 1 and 2 years, the MPP-ON group had lower rates of HFH vs MPP-OFF (1-year hazard ratio [HR]: 0.14, P = .0014; 2-year HR: 0.38, P = .009). The finding persisted in a subgroup of patients with consistent MPP activation through follow-up (1-year HR: 0.19; P = .0061; 2-year HR: 0.39, P = .022). Total HFH per-patient costs were lower in the MPP-ON vs the MPP-OFF group at 1 year (€101 ± 50 vs €698 ± 195, P < .001) and 2 years (€366 ± 149 vs €801 ± 203, P = .038). More MPP-ON patients had ≥5% improvement in ejection fraction (76.8% vs 65.4%, P = .025) and clinical composite score (66.7% vs 47.5%, P = .01). In this multicenter clinical study, early MPP activation was associated with a significant reduction in cumulative HFH and related costs after 1 and 2 years of follow-up.

Comparison of Multi-point Pacing and Conventional CRT Through Non-invasive Hemodynamics Measurement and Global Longitudinal Strain Assessment

Comparison of Multi-point Pacing and Conventional CRT Through Non-invasive Hemodynamics Measurement and Global Longitudinal Strain Assessment

Design and rationale of the Impact of MultiPoint pacing in CRT patients with reduced RV-to-LV delay (IMAGE-CRT) study.

Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration. A biventricular device is implanted to achieve faster activation and more synchronous contraction of the ventricles. Despite the convincing effect of CRT, 30-40% of patients do not respond. We decided to investigate the role of multipoint pacing (MPP) in a selected group of patients with right ventricle (RV)-to-left ventricle (LV) intervals less than 80 ms that do not respond to traditional CRT. We will enrol 248 patients in this patient-blinded, observational, clinical study aiming to investigate if MPP could decrease LV end-systolic volume (ESV) in patients with RV-to-LV interval less than 80 ms. MPP will be activated ON at implant in patients with RV-to-LV delay less than 80 ms and OFF in RV-to-LV at least 80 ms. At follow-up the activation of MPP will be related to CRT response. The primary study endpoint will be the responder rate at 6 months, defined as a decrease in LV ejection fraction, LV end-diastolic volume, LV end-systolic volume (LVESV) at least 15% from baseline. Secondary outcomes include 12 months relative percentage reduction in LVESV and a combined clinical outcome measure of response to CRT defined as the patient being alive, no hospitalization due to heart failure, and experiencing an improvement in New York Heart Association functional class (Composite-Score). Reducing the nonresponder rate continues to be an important goal for CRT.If an increase in reverse remodelling can be achieved by MPP, this study supports the conduct of larger trials investigating the role of MPP on clinical outcomes in selected patients treated, right now, only with traditional CRT. ClinicalTrials.gov, NCT02713308. Registered on 18 March 2016.

P4529Atrioventricular optimization in cardiac resynchronization therapy with quadripolarleads, improves energy handling and quality of life in heart failure patients: HUMVEE Trial

Abstract Background Cardiac resynchronization therapy (CRT) is a well-established technique for symptomatic heart failure (HF) patients, producing significant clinical benefits. Recent studies have revealed the potential role of multipoint pacing (MPP) in improving response and clinical outcomes. The aim of Heart failUre study of Multisite pacing effects on VEntriculoartErial coupling (HUMVEE) trial was to evaluate the association between MPP of the left ventricle vs those of standard biventricular pacing (BVP) on: a) ventriculoarterial coupling (VAC) and energy efficiency of the failing heart, b) diastolic function, c) quality of life, and d) NT-proBNP levels. Methods HUMVEE is a single-center, prospective (13 months) trial (clinicaltrials.gov identifier NCT03189368), of 54 NYHA III patients (69±9 years; 79% men; 50% dilated cardiomyopathy), under optimal tolerated medical therapy, with standard BVP indication, having being implanted with a CRT system able to deliver both modes of pacing. Creatinine and NT-proBNP levels and echocardiographic measurements (VAC calculation, strain rate, diastolic function assessment), as well as 6-min-walking-test and quality of life (MLHF questionnaire) were measured at baseline, 6 months post BVP optimization (right before MPP activation) and at the end of follow-up (6 months post MPP optimization). Cardiac power (CP) was calculated according the equation: CP=Cardiac Output x Mean Aortic Pressure/451. Results Both CRT and MPP improved 6-min-walk (differences at baseline/6 mo/end of FU: 277±27 vs. 345±27 vs 363±27 m, p=0.07); left ventricular ejection fraction (24,2% vs 30,6%vs, 32%, p=0.05); end -diastolic diameters of left ventricle (65±1,4 vs. 63±1.7 vs. 61±1.1, p=0.03); end-systolic volume (150±15 vs. 140±10 vs. 131±13, p=0.08); stroke volume (41.6±9 vs. 53.6±14 vs. 62±9, p=0.0001 for MPP); left atrial volume (76±5 vs. 74±10 vs 61±6, p=0.001 for MPP), E/Emv (14±5 vs. 12±4 vs. 11±3, p=0.05 for MPP); NtproBNP (2782±1000 vs. 2080±2500 vs. 2000±1000, p=0.05 for MPP). VAC was reduced from 1.14±0.27 to 1.1±0.17 (p=0.1) while CP increased from 564.2±142 to 768±103 (p=0.009). Quality of life score (the lower the better) improved from 23.75±17 at baseline to 17.25±10 at end of FU (p=0.05). Conclusions MPP is a new, promising pacing modality with the potential to improve HF patients' outcome, offering additive effects on myocardial energy balance, cardiac power, systolic and diastolic ventricular function and aortoventricular coupling, especially in ischemic patients. HUMVEE trial illustrates those clinical, imaging and biochemical divergences of MPP from standard BVP that reflect significant improvement in quality of life in patients with advanced HF and cardiac dysychronization.

Scar Location and Acute Haemodynamic Response to MultiPoint Pacing Study in Patients With Ischemic Cardiomyopathy

Scar Location and Acute Haemodynamic Response to MultiPoint Pacing Study in Patients With Ischemic Cardiomyopathy

Multipoint Pacing with Septal Fusion Using an Adaptive AV Algorithm to Optimize CRT Patients

Background Adaptive AV shortening algorithms have demonstrated QRS duration (QRd) narrowing in traditional cardiac resynchronization therapy (CRT) patients. Multipoint pacing (MP) has also demonstrated benefit in these patients. An additional site of activation via intrinsic conduction of the septum may further contribute to CRT response, however incorporation of all of these strategies together has yet to be developed or investigated. Objective We developed and tested a method combining MP-CRT and controlled septal contribution to create MP-Fusion encouraging 4 ventricular activation sites for CRT patients utilizing measurements from intracardiac electrograms and incorporation of an AV delay shortening algorithm (Sync-AVTM Abbott laboratories, Sylmar Ca.) Methods Patients with intact AV conduction Results 13 (N=17) patients were analyzed 65.5 +/- 8.3 years. (M:F /Age/) Mean baseline QRSd was 148ms (+/-22.14). Programming utilizing the MP-fusion algorithm yielded a QRSd of 113.23ms (+/-17.14) (P Conclusion The simple use of MP-fusion demonstrated significant QRSd narrowing in all patients tested. A randomized trial with larger sample size and outcome measures in addition to QRSd is warranted.

BENEFICIAL EFFECT OF MULTIPOINT PACING IN CRT PATIENTS BASED ON NON-INVASIVE HEMODYNAMIC ASSESSMENT: DATA OF THE COMPACT-MPP STUDY

Cardiac resynchronization therapy (CRT) associated with multi-point pacing (MPP) has demonstrated improvement cardiac function improvements through hemodynamic assessment. However, invasive measurement of dP/dtmax is unfeasible in clinical practice and thus cannot be used as a method to optimize the

Benefits of Multisite/Multipoint Pacing to Improve Cardiac Resynchronization Therapy Response.

This article provides a general overview of the underlying mechanisms that support pacing from more discrete points and/or a wider vector (multisite and multipoint pacing) to improve left ventricular resynchronization. We performed a critical overview of the current literature and to identify some remaining knowledge gaps to spur further research. It was not our goal to provide a systematic review with a comprehensive bibliography, but rather to focus on selected publications that, in our opinion, have either expertly reviewed a specific aspect of cardiac resynchronization therapy or have been landmark studies in the field.

Optimization of CRT programming using non-invasive electrocardiographic imaging to assess the acute electrical effects of multipoint pacing.

AimQuadripolar lead technology and multi‐point pacing (MPP) are important clinical adjuncts in cardiac resynchronization therapy (CRT) pacing aimed at reducing the rate of non‐response to therapy. Mixed results have been achieved using MPP and it is critical to identify which patients require this approach and how to configure their MPP stimulation, in order to achieve optimal electrical resynchronization.Methods & ResultsWe sought to investigate whether electrocardiographic imaging (ECGi), using the CARDIOINSIGHT ™ inverse ECG mapping system, could identify alterations in electrical resynchronization during different methods of device optimization. In no patient did a single form of programming optimization provide the best electrical response. The effects of utilizing MPP were idiosyncratic and highly patient specific. ECGi activation maps were clearly able to discern changes in bulk LV activation during differing MPP programming. In two of the five subjects, MPP resulted in more rapid activation of the left ventricle compared to standard CRT; however, in the remaining three patients, the use of MPP did not appear to acutely improve electrical resynchronization. Crucially, this cohort showed evidence of extensive LV scarring which was well visualized using both CMR and ECGi voltage mapping.ConclusionsOur work suggests a potential role for ECGi in the optimization of non‐responders to CRT, as it allows the fusion of activation maps and scar analysis above and beyond interrogation of the 12 lead ECG.

Left ventricular global longitudinal strain and mechanical dispersion predict response to multipoint pacing for cardiac resynchronization therapy

To evaluate the acute effect of multipoint pacing (MPP) and search for the better baseline predictors of response to MPP for guiding patient selection. We enrolled 46 heart failure patients scheduled for implantation of MPP-enabled cardiac resynchronization therapy (CRT) devices. An acute pacing protocol including conventional CRT and MPP pacing configurations was performed after implantation. Echocardiography was used at baseline and during pacing test, and response was defined as left ventricular (LV) end-systolic volume (ESV) reduction ≥ 15% at 6-month follow-up. MPP response was present in 32 (69%) patients. Responders showed significantly superior LV ejection fraction, global longitudinal peak strain (GLPS), and mechanical dispersion (MD) with MPP than with conventional CRT (all P < 0.05). Baseline GLPS (OR 1.524; 95% CI 1.031-2.251; P = 0.034) and MD (OR 1.048; 95% CI 1.016-1.081; P = 0.003) were independent predictors of MPP response in multivariate regression analysis. Both |GLPS| and MD were significantly correlated with percentage change in LVESV (▵LVESV%) at 6-month follow-up (r = 0.731 and r = 0.696, respectively; all P < 0.001). |GLPS| ≥ 5.0% combined with MD ≥ 120 ms predicted MPP response with the optimal sensitivity of 91% and specificity of 71% (AUC = 0.848, P < 0.001). MPP tends to be superior to conventional CRT in improving acute response. |GLPS| and MD can successfully predict response to MPP, and their combination can further improve the prediction accuracy of response.

Rationale and design of a randomized clinical trial to assess the safety and efficacy of multipoint pacing therapy: MOre REsponse on Cardiac Resynchronization Therapy with MultiPoint Pacing (MORE-CRT MPP–PHASE II)

Although cardiac resynchronization therapy (CRT) is beneficial in most heart failure patients, up to 40% do not respond to CRT. Data from the MultiPoint Pacing (MPP) IDE trial and MORE-CRT MPP-PHASE I study suggest improved response in subjects in the MPP arm-programmed with wide left ventricular (LV) electrode anatomical separation (≥30 mm) and shortest timing delays of 5 milliseconds (MPP-AS)-compared with quadripolar biventricular (BiV) pacing. The MORE-CRT MPP-PHASE II trial is a prospective, randomized, multicenter study to assess the 6-month impact of MPP programmed to mandated MPP-AS settings in subjects who do not respond to 6 months of BiV pacing (MPP OFF). Approximately 5,000 subjects with a standard CRT indication will be enrolled and implanted with a quadripolar CRT system (Abbott) capable of delivering MPP. Only BiV pacing is activated at implant. At 6 months, subjects classified as CRT nonresponders (<15% reduction in LV end-systolic volume) are randomized (1:1) to MPP or continued BiV pacing. The mandated MPP parameters (eg, MPP-AS) are programmed to subjects randomized to the MPP arm. At 12 months, the 2 groups will be compared to determine if there is a difference in CRT response rate. This trial will evaluate whether MPP programmed to mandated MPP-AS settings improves LV reverse remodeling and clinical response to CRT in patients who fail to respond to 6 months of BiV pacing (www.clinicaltrials.gov identifier NCT02006069).

Multipoint pacing-more CRT or awaste of battery power?

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with broad QRS complex ≥130 ms and heart failure with reduced ejection fraction despite optimal guideline-directed medical therapy. However, approximately 30% of the patients implanted with aCRT system do not show clinical benefit. Reasons for nonresponse are complex and some aspects can be addressed during follow-up. Based on quadripolar lead technology, multipoint pacing (MPP) allows left ventricular stimulation at two different sites along the lead. In particular, in scarred and fibrotic ventricular myocardium stimulation at two different sites may overcome conduction barriers and lead to homogeneous ventricular depolarization. Especially for patients that do not respond to conventional CRT, activation of MPP may present an option to increase clinical response. On the other hand, MPP may significantly decrease battery longevity.This review offers an overview of the current knowledge and data on MPP balancing the potential clinical benefit and the possible disadvantages of this therapy.

Clinical outcome of left ventricular multipoint pacing versus conventional biventricular pacing in cardiac resynchronization therapy: a systematic review and meta-analysis.

Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with systolic heart failure. Unlike conventional biventricular pacing (BIP), the left ventricular multipoint pacing (MPP) can increase the number of left ventricular pacing sites via a quadripolar lead positioned in the coronary sinus. This synthetic study was conducted to integratively and quantitatively evaluate the clinical outcome of MPP in comparison with BIP. We systematically searched the databases of EMBASE, Ovid medline, and Cochrane Library through May 2018 for studies comparing the clinical outcome of MPP with BIP in the patients who accepted CRT. Hospitalization for reason of heart failure, left ventricular eject fraction (LVEF), CRT response, all-cause morbidity, and cardiovascular death rate was collected for meta-analysis. A total of 11 studies with 29,606 participants were included in this meta-analysis. Compared with BIP group, MPP decreased heart failure hospitalization (OR, 0.41; 95% CI, 0.33 to 0.50; P< 0.00001), improved LVEF (mean difference, 4.97; 95% CI, 3.11 to 6.83; P< 0.00001), increased CRT response (OR, 3.64; 95% CI, 1.68 to 7.87; P = 0.001), and decreased all-cause morbidity (OR, 0.41; 95% CI, 0.26-0.66; P = 0.0002) and cardiovascular death rate (OR, 0.21; 95% CI, 0.11-0.40; P< 0.00001). The published literature demonstrates that MPP was more effective than BIP in the heart failure patients who accepted cardiac resynchronization therapy.

Multipoint Pacing Reduces Predicted Health Care Costs in the Majority of Cardiac Resynchronization Therapy Patients

Introduction The Abbott MultiPoint Pacing (MPP) IDE trial showed safety and efficacy of MPP in cardiac resynchronization therapy patients. Patients programmed to pace from anatomically distant poles (MPP-AS) responded at significantly higher rates than those programmed to other MPP settings. Hypothesis MPP-AS is associated with reduced heart failure-related (HFR) healthcare utilization compared to quadripolar biventricular pacing (QUAD-BiV). Methods All QUAD-BiV and MPP-AS patients from the MPP IDE trial were included. Costs were modeled using a Markov cohort model (1-month cycle length, 10-year time horizon). Rates of HFR hospitalization, emergency room visits, outpatient visits, office visits and death were calculated from the MPP IDE trial. Devices programmed to QUAD-BiV were assumed to have a 7-year battery life, and MPP-AS was assumed to shorten battery life by 9 months. Costs were estimated for each visit type using the Marketscan Database (2012-2016, updated to 2017 using Medical CPI). The simulation was repeated 10,000 times. Results In the MPP IDE trial, 52 patients had MPP-AS programmed and 232 had QUAD-BiV. The MPP-AS group had 2 HFR non-emergency inpatient stays. The QUAD-BiV group had 10 HFR non-emergency inpatient stays, 4 HFR inpatient stays admitted via the ER, 2 HFR outpatient ER visits, 3 HFR outpatient hospitalizations and 3 HFR office visits. Mortality was assumed to be 7% for both groups. The MPP-AS group cost an average of $72,139 (95% CI: $33,070, $117,299) per patient and the QUAD-BiV group cost an average of $92,933 (95% CI: $33,070, $167,211) per patient. MPP-AS resulted in average cost savings of $20,794 (95% CI: -$37,957, $97,124) and in simulation was less expensive than QUAD-BiV 66.6% of the time. MPP-AS had lower expected cost for patients surviving less than 6.25 years or more than 7 years. Conclusions Over a 10-year horizon, MPP-AS was associated with fewer HFR health care events, and in simulation, was less expensive than QUAD-BiV most of the time.

Atrioventricular optimization in cardiac resynchronization therapy with quadripolar leads: should we optimize every pacing configuration including multi-point pacing?

This study aims to define an atrioventricular (AV) delay optimization method for cardiac resynchronization therapy (CRT) with a quadripolar left ventricular (LV) lead based on intrinsic conduction intervals. Heart failure patients with a left bundle branch block underwent CRT implantation with a quadripolar LV lead. Invasive LV pressure-volume loops were recorded during four biventricular and three multi-point pacing (MPP) settings, using four patient-specific paced AV delays. Haemodynamic response was defined as change in stroke work (Δ%SW) compared to intrinsic rhythm and was related to the following conduction intervals: right atrial pacing to right ventricular sensing interval (RAp-RVs), Q to LV sensing interval normalized to QRS duration (QLV/QRSd), PR-interval, and P-wave duration. In 44 patients, the largest Δ%SW (104 ± 76%) occurred at a paced AV delay of 128 ± 32 ms, at 47 ± 9% of RAp-RVs. Optimal AV delay of biventricular pacing (126 ± 26 ms) did not differ from MPP (126 ± 21 ms, P = 0.29). Intra-class correlation coefficient between optimal AV delays of different pacing configurations was 0.64 (0.45-0.78, P < 0.001). Although not statistically significant, Δ%SW at 50% of RAp-RVs (98 ± 74%) was closer to the maximal achievable Δ%SW increase than a fixed interval of 120 ms (96 ± 73%, P = 0.60). RAp-RVs, QLV/QRSd, PR interval, and P-wave duration were associated with the optimal AV delay in univariate analysis, but only RAp-RVs remained significantly associated in multivariate analysis (R = 0.69). The AV delay that provides highest haemodynamic response is similar for various LV pacing configurations and for MPP. An AV delay ∼50% of RAp-RVs creates an acute haemodynamic response close to the maximal patient-specific response.

Improved acute haemodynamic response to cardiac resynchronization therapy using multipoint pacing cannot solely be explained by better resynchronization

BackgroundThe recently developed quadripolar left ventricular (LV) leads have been developed to increase the benefit of cardiac resynchronization therapy (CRT). These leads offer the option to stimulate the LV on multiple sites (multipoint pacing, MPP). Invasive haemodynamic measurements have shown that MPP increases haemodynamic response. PurposeTo investigate whether the beneficial effect of MPP can be explained by better electrical resynchronization. MethodsDifferent LV lead locations were tested during biventricular (BiV) pacing and MPP in 29 CRT candidates. The 12-lead electrocardiogram (ECG) and the invasive LV pressure curves were measured simultaneously. The Kors matrix was used to convert the ECG into a vectorcardiogram (VCG). The acute haemodynamic benefit of MPP was compared with the reduction in QRS duration and VCG-derived QRS area. ResultsOut of the 29 patients, three patients were excluded due to missing LV pressures or ECG measurements. In the remaining 26 patients MPP resulted in a significant haemodynamic improvement compared to BiV pacing without a significant change in QRS duration and QRS area. In only 5 out of the 26 patients the QRS area decreased during MPP compared to BiV pacing. In 17 patients MPP did not change QRS duration and significantly increased QRS area but moved the direction of the maximal QRS vector (azimuth) more opposite from baseline compared to BiV pacing. In 4 patients the QRS area was small during baseline, indicating limited electrical dyssynchrony. ConclusionThe acute haemodynamic benefit of MPP over BiV pacing is achieved by either electrical resynchronization (reduction in QRS area) or by a rotation of the maximal QRS vector, indicating a more LV dominated activation sequence. The latter property was found in two-thirds of the cohort studied.

Long-term reverse remodeling by cardiac resynchronization therapy with MultiPoint Pacing: A feasibility study of noninvasive hemodynamics–guided device programming

Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint Pacing [MPP]) improves acute hemodynamics and chronic outcomes in comparison to conventional biventricular pacing (BiV), though MPP programming questions persist. In this multicenter feasibility study, we evaluated the feasibility of using noninvasive systolic blood pressure (SBP) to guide MPP programming and assessed the chronic 6-month echocardiographic CRT response. Patients implanted with MPP-enabled CRT-defibrillator devices underwent noninvasive hemodynamic assessment (finger arterial pressure) during a pacing protocol that included atrial-only pacing and various BiV and MPP configurations. Each configuration was repeated 4 times, alternating with a reference pacing configuration, to calculate the SBP difference relative to reference (ΔSBP). CRT configurations with the greatest ΔSBP were programmed. An independent core laboratory analyzed baseline and 6-month echocardiograms, with CRT response defined as a 6-month reduction in LV end-systolic volume ≥ 15%. Forty-two patients (71% male; LV ejection fraction 30.3% ± 7.5%; QRS duration 161 ± 19 ms; 26% had ischemic cardiomyopathy) were enrolled in 4 European centers. Relative to atrial-only pacing, the best BiV and best MPP configurations produced significant SBP elevations of 3.1 ± 4.2 (P < .01) and 4.1 ± 4.1 mm Hg (P < .01), respectively (BiV vs MPP; P < .01). Greater SBP elevations were associated with the best MPP compared with the best BiV configurations in 29 of 37 patients completing the pacing protocol (78%). Of MPP-programmed patients completing the 6-month follow-up visit, 23 of 27 (85%) were classified as CRT responders (6-month reduction in LV end-systolic volume 37.0% ± 13.6%). Acute noninvasive hemodynamics after CRT device implantation predominantly favored MPP over BiV programming. MPP programming guided by noninvasive hemodynamics resulted in positive LV structural remodeling.