Multipoint pacing is associated with improved prognosis and cardiac resynchronization therapy response. MORE-CRT MPP randomized study secondary analyses.

BACKGROUND AND AIMS: Cardiac resynchronization therapy (CRT) via biventricular (BIV) pacing is indicated in patients with heart failure (HF), reduced ejection fraction and prolonged QRS duration. Quadripolar leads and MultiPoint Pacing (MPP) allow multiple left ventricle (LV) sites pacing. We aimed to assess clinical benefit of MPP in patients who do not respond to standard BIV pacing. METHODS: Overall 3724 patients were treated with standard BIV pacing. After 6 months, 1639 patients were considered as CRT non-responders (echo-measured relative reduction in LV end-systolic volume (LVESV) < 15%) and randomized to MPP or BIV. RESULTS: We analysed 593 randomized patients (291 MPP, 302 BIV), who had BIV pacing >97% of time before randomization and complete 12-months clinical and echocardiographic data. The endpoint, composed by freedom from cardiac death and HF hospitalizations, and by LVESV relative reduction ≥15% between randomization and 12 months, occurred more frequently in MPP (96/291 (33.0%)) vs. BIV (71/302 (23.5%), p = 0.0103), also confirmed at multivariate analysis (hazard ratio = 1.55, 95% confidence interval = 1.02-2.34, p = 0.0402 vs. BIV). HF hospitalizations occurred less frequently in MPP (14/291 (4.81%)) vs. BIV (29/302 (9.60%), incidence rate ratio = 50%, p = 0.0245). Selecting patients with large (>30 ms) dispersion of interventricular electrical delay among the 4 LV lead dipoles, reverse remodeling was more frequent in MPP (18/51 (35.3%)) vs. BIV (11/62 (17.7%), p = 0.0335). CONCLUSION: In patients who do not respond to standard CRT, despite high BIV pacing percentage, MPP is associated with lower occurrence of HF hospitalizations and higher probability of reverse LV remodeling, compared with BIV pacing.

Response rate in cardiac resynchronization therapy patients implanted with a left ventricular quadripolar lead and the MultiPoint™ pacing feature early activated. QUARTO III.

BACKGROUND: Although cardiac resynchronization therapy (CRT) is beneficial in most heart failure patients, up to 40% do not respond to CRT. It has been suggested that multipoint left ventricle pacing (MPP) would increase the response rate. AIM: To assess the CRT response rate at 6 months in patients implanted with a CRT device with the MPP feature activated early after the implant. METHODS: This was a multicentre, prospective, open-label and non-randomized study. The primary endpoint was response to biventricular pacing defined as >15% relative reduction in left ventricular end-systolic volume (LVESV) comparing echocardiography measurements performed at baseline and 6 months by a core laboratory. Among secondary endpoints the combined endpoint of mortality or all-cause hospitalizations was evaluated. Primary study endpoint and clinical outcomes were compared to a Quarto II control cohort. RESULTS: Totally, 105 patients were included. The response rate was 64.6% (97.5% lower confidence bound 53%). Mean relative reduction in LVESV was 25.3%, and mean absolute increase in LVEF was 9.4%. The subjects with device programmed using anatomical approach showed a trend towards higher responder rate than those using the electrical approach (72% vs. 61.1%, p = 0.32). Finally, the combined incidence of mortality and or all-cause hospitalizations at 6 month was 12.4%. CONCLUSIONS: Early activation of MPP was not associated to an advantage increasing echocardiography responders to CRT at 6 months of follow-up. Nevertheless, patients programmed using widest pacing cathodes had a numerically higher responder rate. Finally, early activation of MPP was associated to a low incidence of clinical endpoints at 6 months of follow-up.

Electrocardiographic imaging demonstrates electrical synchrony improvement by dynamic atrioventricular delays in patients with left bundle branch block and preserved atrioventricular conduction.

AIMS: Cardiac resynchronization therapy programmed to dynamically fuse pacing with intrinsic conduction using atrioventricular (AV) timing algorithms (e.g. SyncAV) has shown promise; however, mechanistic data are lacking. This study assessed the impact of SyncAV on electrical dyssynchrony across various pacing modalities using non-invasive epicardial electrocardiographic imaging (ECGi). METHODS AND RESULTS: Twenty-five patients with left bundle-branch block (median QRS duration (QRSd) 162.7 ms) and intact AV conduction (PR interval 174.0 ms) were prospectively enrolled. ECGi was performed acutely during biventricular pacing with fixed nominal AV delays (BiV) and using SyncAV (optimized for the narrowest QRSd) during: BiV + SyncAV, LV-only single-site (LVSS + SyncAV), MultiPoint pacing (MPP + SyncAV), and LV-only MPP (LVMPP + SyncAV). Dyssynchrony was quantified via ECGi (LV activation time, LVAT; RV activation time, RVAT; LV electrical dispersion index, LVEDi; ventricular electrical uncoupling index, VEU; and biventricular total activation time, VVtat). Intrinsic conduction LVAT (124 ms) was significantly reduced by BiV pacing (109 ms) (P = 0.001) and further reduced by LVSS + SyncAV (103 ms), BiV + SyncAV (103 ms), LVMPP + SyncAV (95 ms), and MPP + SyncAV (90 ms). Intrinsic RVAT (93 ms), VVtat (130 ms), LVEDi (36 ms), VEU (50 ms), and QRSd (163 ms) were reduced by SyncAV across all pacing modes. More patients exhibited minimal LVAT, VVtat, LVEDi, and QRSd with MPP + SyncAV than any other modality. CONCLUSION: Dynamic AV delay programming targeting fusion with intrinsic conduction significantly reduced dyssynchrony, as quantified by ECGi and QRSd for all evaluated pacing modes. MPP + SyncAV achieved the greatest synchrony overall but not for all patients, highlighting the value of pacing mode individualization during fusion optimization.

Cardiac resynchronization therapy non-responder to responder conversion rate in the MORE-CRT MPP trial.

AIMS: To assess the impact of MultiPoint™ Pacing (MPP) in cardiac resynchronization therapy (CRT) non-responders after 6 months of standard biventricular pacing (BiVP). METHODS AND RESULTS: The trial enrolled 5850 patients who planned to receive a CRT device. The echocardiography core laboratory assessed CRT response before implant and after 6 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 6 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. CONCLUSION: Our trial shows that ∼30% of patients, who do not respond to CRT in the first 6 months, experience significant reverse remodelling in the following 6 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. MultiPoint™ Pacing does not improve CRT response in non-responders to BiVP, even with MPP-AS.

Electrogram analysis to detect cathodal and anodal capture in left ventricular cardiac resynchronization pacing leads.

AIMS: Our study analyzed cardiac electrograms (EGMs) to identify characteristics for detecting cathodal, anodal, or cathodal-anodal (simultaneous) capture in left ventricular (LV) quadripolar pacing leads of cardiac resynchronization therapy (CRT) patients. The relationship between these EGM characteristics and the electrocardiogram (ECG) was also examined. METHODS: We performed a retrospective analysis of 54 bipolar pacing configurations across nine patients with implanted CRT devices and quadripolar leads who had undergone a 12 lead ECG optimization. Three pacing tests (cathode unipolar, anode unipolar, and bipolar) per bipolar pair were performed, examining ECG and EGM morphology changes accompanying each test and any transitions of morphology or amplitude during voltage stepdown. RESULTS: During the cathode and anode unipolar pacing tests, the EGM was biphasic (negative/positive) or monophasic (positive) in 52/53 (98%), and biphasic (positive/negative) or monophasic (negative) in 50/51 (98%), respectively. During bipolar LV capture threshold testing, 30 bipolar pairs displayed a sudden increase in EGM amplitude (median 9.4 mV, interquartile range [7-14 mV]) when transitioning from cathodal-anodal capture to cathodal or anodal capture. Ninety percent of these EGM transitions had a corresponding simultaneous change in ECG, while 10% had no ECG changes. Two patients demonstrated "quad-site" capture on their quadripolar lead with multipoint pacing enabled and cathodal-anodal capture from each stimulus. CONCLUSION: EGM characteristics during LV pacing tests can reliably detect cathodal, anodal, or cathodal-anodal capture, with greater sensitivity than 12 lead ECG changes. Integration of EGM analysis into routine CRT device follow up can be performed easily and may have implications for CRT efficacy.

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Multipoint pacing for cardiac resynchronisation therapy in patients with heart failure: A systematic review and meta-analysis.

INTRODUCTION: Multipoint pacing (MPP) has been proposed as an effective way to improve cardiac resynchronisation therapy (CRT) response. We performed a systematic review and meta-analysis evaluating the efficacy of CRT delivered via MPP compared to conventional CRT. METHODS: A literature search was performed from inception to January 2021 for studies in Medline, Embase and Cochrane databases, comparing MPP to conventional CRT with a minimum of 6 months follow-up. Randomised and nonrandomised studies were assessed for relevant efficacy data including echocardiographic (left ventricular end systolic volume [LVESV] and ejection fraction) or functional changes (New York Heart Association [NYHA] class/Clinical Composite Score). Subgroup analyses were performed by study design and programming type. RESULTS: A total of 7 studies with a total of 1390 patients were included in the final analysis. Overall, MPP demonstrated greater echocardiographic improvement than conventional CRT in nonrandomised studies (odds ratio [OR]: 5.33, 95% confidence interval [CI]: [3.05-9.33], p < .001), however, was not significant in randomised studies (OR: 1.86, 95% CI: [0.91-3.79], p = .086). There was no significant difference in LVESV reduction >15% (OR: 1.96, 95% CI: [0.69-5.55], p = .20) or improvement by ≥1 NYHA class (OR: 2.49, 95% CI: [0.74-8.42], p = .141) when comparing MPP to conventional CRT. In a sub analysis, MPP programmed by widest anatomical separation (MPP-AS) signalled greater efficacy, however, only 120 patients were included in this analysis. CONCLUSION: Overall MPP was more efficacious in nonrandomised studies, and not superior when assessed in randomised studies. There was considerable heterogeneity in study design making overall interpretation of results challenging. Widespread MPP programming in all CRT patients is currently not justified. Further large, randomised studies with patient-specific programming may clarify its effectiveness.

Cardiac resynchronization therapy in heart failure patients: tough road but clear future.

Cardiac resynchronization therapy (CRT) based on biventricular pacing (BVP) is an invaluable intervention currently used in heart failure (HF) patients. The therapy involves electromechanical dyssynchrony, which can not only improve heart function and quality of life but also reduce hospitalization and mortality rates. However, approximately 30% to 40% of patients remain unresponsive to conventional BVP in clinical practice. In the recent years, extensive research has been employed to find a more physiological approach to cardiac resynchronization. The His-Purkinje system pacing (HPSP) including His bundle pacing (HBP) and left bundle branch area pacing (LBBaP) may potentially be the future of CRT. These technologies present various advantages including offering an almost real physiological pacing, less complicated procedures, and economic feasibility. Additionally, other methods, such as isolated left-ventricular pacing and multipoint pacing, may in the future be important but non-mainstream alternatives to CRT because currently, there is no strong evidence to support their effectiveness. This article reviews the current situation and latest progress in CRT, explores the existing technology, and highlights future prospects in the development of CRT.

Clinical impact of MultiPoint pacing in responders to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy demonstrated benefits in heart failure. However, only 60-70% are responders and only 22% are super-responders. MultiPoint pacing (MPP) improves structural remodeling, but data in responder patients is scarce. METHODS: A prospective, randomized study of the efficacy of MPP was conducted in patients who were CRT responders after 6 months of bi-ventricular (BiV) therapy. At 6 months, responder patients (LV end-systolic volume [LVESV] reduction ≥15%) were randomized to either continued BiV therapy or to MPP programmed with wide anatomical separation ≥30 mm, and followed until 12 months. Efficacy was determined by 6-12 month changes in LVESV and LV ejection fraction (LVEF). Evaluations of super-responder rate (LVESV reduction ≥30%) and quality of life (NYHA, EQ-5D, MLHFQ) were also performed. RESULTS: From February 2017 to February 2019, 73 CRTs with Quartet LV leads were implanted (42.9% female, 65.7 ± 10.8 years old, 79.5% dilated cardiomyopathy). At 6 months, 74.2% responded to BiV and were randomized to BiV (n = 25) or MPP (n = 24). MPP versus BiV delivered greater LVESV improvement (8.3% decrease in MPP vs. 10.3% increase in BiV patients, p = .047), greater increase in LVEF (7.7% vs. 1.8%, p = .008), and higher 0-12 month super-responder rate (86.4% vs. 56.0%, p = .027). More MPP vs. BiV patients experienced an improvement in NYHA (84.6% vs. 50.0%, p = .047) and EQ-5D (94.4% vs. 54.0%, p = .006). CONCLUSIONS: MPP with wide anatomical spacing in CRT responder patients resulted in improved LV reverse remodeling with higher rates of super-responders, and better quality of life metrics.

Optimized single-point left ventricular pacing leads to improved resynchronization compared with multipoint pacing.

BACKGROUND: Multipoint pacing (MPP) in cardiac resynchronization therapy (CRT) activates the left ventricle from two locations, thereby shortening the QRS duration and enabling better resynchronization; however, compared with conventional CRT, MPP reduces battery longevity. On the other hand, electrocardiogram-based optimization using the fusion-optimized intervals (FOI) method achieves more significant reverse remodeling than nominal CRT programming. Our study aimed to determine whether MPP could attain better resynchronization than single-point pacing (SPP) optimized by FOI. METHODS: This prospective study included 32 consecutive patients who successfully received CRT devices with MPP capabilities. After implantation, the QRS duration was measured during intrinsic rhythm and with three pacing configurations: MPP, SPP-FOI, and MPP-FOI. In 14 patients, biventricular activation times (by electrocardiographic imaging, ECGI) were obtained during intrinsic rhythm and for each pacing configuration to validate the findings. Device battery longevity was estimated at the 45-day follow-up. RESULTS: The SPP-FOI method achieved greater QRS shortening than MPP (-56 ± 16 vs. -42 ± 17 ms, p < .001). Adding MPP to the best FOI programming did not result in further shortening (MPP-FOI: -58 ± 14 ms, p = .69). Although biventricular activation times did not differ significantly among the three pacing configurations, only the two FOI configurations achieved significant shortening compared with intrinsic rhythm. The estimated battery longevity was longer with SPP than with MPP (8.1 ± 2.3 vs. 6.3 ± 2.0 years, p = .03). CONCLUSIONS: SPP optimized by FOI resulted in better resynchronization and longer battery duration than MPP.

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).

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

INTRODUCTION: The 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). METHODS: Twelve 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. RESULTS: According 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). CONCLUSION: Delay optimization improves hemodynamic response and ventricular contraction synchronicity. The delay of 25 ms-25 ms may be the optimal setting for most MPP patients.

Cardiac resynchronization therapy non-responder to responder conversion rate in the more response to cardiac resynchronization therapy with MultiPoint Pacing (MORE-CRT MPP) study: results from Phase I.

AIMS: To assess the impact of MultiPoint™ Pacing (MPP)-programmed according to the physician's discretion-in non-responders to standard biventricular pacing after 6 months. METHODS AND RESULTS: The study enrolled 1921 patients receiving a quadripolar cardiac resynchronization therapy (CRT) system capable of MPP™ therapy. A core laboratory assessed echocardiography at baseline and 6 months and defined volumetric non-response to biventricular pacing as <15% reduction in left ventricular end-systolic volume (LVESV). Clinical sites randomized patients classified as non-responders in a 1:1 ratio to receive MPP (236 patients) or continued biventricular pacing (231 patients) for an additional 6 months and evaluated rate of conversion to echocardiographic response. Baseline characteristics of both groups were comparable. No difference was observed in non-responder to responder conversion rate between MPP and biventricular pacing (31.8% and 33.8%, P = 0.72). In the MPP arm, 68 (29%) patients received MPP programmed with a wide LV electrode anatomical separation (≥30 mm) and shortest LV1-LV2 and LV2-RV timing delays (MPP-AS); 168 (71%) patients received MPP programmed with other settings (MPP-Other). MPP-AS elicited a significantly higher non-responder conversion rate compared to MPP-Other (45.6% vs. 26.2%, P = 0.006) and a trend in a higher conversion rate compared to biventricular pacing (45.6% vs. 33.8%, P = 0.10). CONCLUSIONS: After 6 months, investigator-discretionary MPP programming did not significantly increase echocardiographic response compared to biventricular pacing in CRT non-responders.

Impact of multipoint pacing on projected battery longevity in cardiac resynchronization therapy. An IRON-MPP study sub-analysis.

BACKGROUND: Multipoint pacing (MPP) may improve clinical outcomes in patients with cardiac resynchronization therapy defibrillators (CRT-D), but its impact on battery longevity in a real-world population has not been investigated in large trials. OBJECTIVE: Compare projected battery longevity in CRT-D patients with and without MPP during long-term follow-up. METHODS: The Italian registry on multipoint left ventricular pacing (IRON-MPP) is a prospective, multicenter registry of patients implanted with MPP-capable CRT-D devices. Projected battery longevity during follow-up was compared for patients with MPP (MPP ON) vs single-site (MPP OFF) left ventricular pacing at CRT-D implantation. A sub-analysis excluded crossover patients with MPP activation or deactivation occurring after implantation. A second sub-analysis excluded patients with a right or left ventricular pacing amplitude >2.5 V. RESULTS: Out of 237 CRT-D patients (71 ± 9 years, 81% male) followed for 1.9 ± 0.8 years, 102 (43%) had MPP ON at implantation. Programmed atrial and ventricular outputs and percentage of pacing were similar between groups. MPP was associated with a 0.44 years reduction in projected battery longevity (P = .03) during long-term follow-up. Results were similar for the first and second sub-analyses, with a 0.57 years (P < .001) and 0.71 years (P < .001) reduction in projected longevity, respectively. CONCLUSION: In this long-term real-world registry, early MPP activation is associated with less than a 1-year reduction in projected battery life compared to single-site biventricular pacing.

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

PURPOSE: To evaluate the acute effect of multipoint pacing (MPP) and search for the better baseline predictors of response to MPP for guiding patient selection. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Leadless multisite pacing: A feasibility study using wireless power transfer based on Langendorff rodent heart models.

INTRODUCTION: Fifteen to thirty percent of patients with impaired cardiac function have ventricular dyssynchrony and warrant cardiac resynchronization therapy (CRT). While leadless pacemakers eliminate lead-related complications, their current form factor is limited to single-chamber pacing. In this study, we demonstrate the feasibility of multisite, simultaneous pacing using miniaturized pacing nodes powered through wireless power transfer (WPT). METHODS: A wireless energy transfer system was developed based on resonant coupling at approximately 200 MHz to power multiple pacing nodes. The pacing node comprises circuitry to efficiently convert the harvested energy to output stimuli. To validate the use of these pacing nodes, ex vivo studies were carried out on Langendorff rodent heart models (n = 4). To mimic biventricular pacing, two beating Langendorff rodent heart models, kept 10 cm apart, were paced using two distinct pacing nodes, each attached on the ventricular epicardial surface of a given heart. RESULTS: All ex vivo Langendorff heart models were successfully paced with a simple coil antenna at 2 to 3 cm from the pacing node. The coil was operated at 198 MHz and 0.3 W. Subsequently, simultaneous pacing of two Langendorff heart models 30 cm apart using an output power of 5 W was reliably demonstrated. CONCLUSION: WPT provides a feasible option for multisite, wireless cardiac pacing. While the current system remains limited in design, it offers support and a conceptual framework for future iterations and eventual clinical utility.

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 improves peripheral hemodynamic response: Noninvasive assessment using radial artery tonometry.

BACKGROUND: Multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], Abbott, Sylmar, CA, USA) improves the response rate to cardiac resynchronization therapy (CRT). We evaluated the feasibility of noninvasive radial artery tonometry (RAT) to characterize arterial pressure morphology changes (pre-ejection period [PEP] and ejection duration [ED]) between conventional CRT and MPP pacing interventions. METHODS: Patients with a MPP-enabled CRT device (Quadra Assura MP™, Abbott) underwent noninvasive RAT assessment (SphygmoCor CVMS, AtCor Medical Inc., Itasca, IL, USA) at 3-6 months after implantation. A pacing protocol was performed in a randomized order including one optimized conventional biventricular CRT (CONV) configuration using the distal electrode and five MPP configurations. The PEP, ED, and PEP/ED ratio were determined for each intervention from the RAT pressure waveform and electrocardiogram. RESULTS: Pressure waveforms were successfully recorded in 19 patients (89% male, QRS 147 ± 16 ms, 63% ischemic). In 17/19 (89%) patients, at least one MPP intervention resulted in improved PEP, ED, and PEP/ED compared to CONV. The MPP intervention with greatest separation of LV cathodes and minimum intra-LV delay significantly improved PEP (mean PEP -15 ± 33% vs -8 ± 32% [CONV], P = 0.04) and ED (mean ED +8 ± 8% [MPP] vs +4 ± 7% [CONV], P = 0.02), and PEP/ED (-0.07 ± 0.14 [MPP] vs -0.04 ± 0.13 [CONV], P = 0.02) compared with CONV. CONCLUSIONS: Noninvasive RAT efficiently characterizes changes in PEP and ED between CONV and MPP interventions. MPP configurations using the widest separation among LV cathodes and minimum intra-LV delay may significantly improve RAT-derived parameters as compared to conventional CRT.

Combination of the best pacing configuration and atrioventricular and interventricular delays optimization in cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy optimization can be pursued by left ventricular pacing vector selection and atrioventricular (AV) and interventricular (VV) delays optimization. The combination of these methods and its comparison with multipoint pacing (MPP) is scarcely studied. METHODS: Using noninvasive cardiac output (CO) measurement, the best of five left ventricular pacing vectors was determined, then AV and VV delays optimization was applied on top of the best vector. Response to the optimization protocol was defined as a >5% CO increase compared to the standard biventricular configuration. RESULTS: Twenty-two patients (18 men, age 71 ± 9 years) were included. Standard biventricular configuration increased CO compared to baseline (4.65 ± 1.55 L/min vs 4.27 ± 1.53 L/min, respectively, P = 0.02). The best quadripolar configuration increased CO to 4.85 ± 1.67 L/min (P = 0.03 compared to the standard biventricular configuration). AV then VV delay optimization both provided additional benefit (final CO 5.56 ± 2.03 L/min, P = 0.001 compared to the best quadripolar configuration). Fifteen (68%) patients responded to the optimization protocol. Anatomical MPP (based on maximal anatomical separation between electrodes) and electrical MPP (based on maximal electrical activation difference between electrodes) were evaluated in 16 patients and yielded a CO similar to that of the optimization procedure. CONCLUSIONS: The combination of choosing the best quadripolar pacing configuration and optimizing atrioventricular and interventricular delays resulted in an improvement of cardiac output compared to standard biventricular stimulation in 68% of patients. The final cardiac output was comparable to multipoint pacing.

Heart failure study of multipoint pacing effects on ventriculoarterial coupling: Rationale and design of the HUMVEE trial.

Cardiac resynchronization therapy (CRT) is an established therapy for symptomatic heart failure (HF). Unfortunately, many recipients remain nonresponders. Studies have revealed the potential role of multipoint pacing (MPP) in improving response and outcomes. The aim of this study is to compare the effects of MPP against those of standard biventricular pacing (BVP) on (i) ventriculoarterial coupling (VAC) and energy efficiency of the failing heart, (ii) diastolic function, (iii) quality of life, and (iv) NT-proBNP levels and glomerular filtration rate (GFR) during a follow-up of 13 months. HUMVEE is a single-center, prospective, observational, crossover cohort study. Seventy-six patients with BVP indication will be implanted with a system able to deliver both pacing modes. BVP will be activated at implantation and optimized 1 month after. At 6 months postoptimization MPP will be activated and optimized. Optimization will be performed based on stroke volume maximization, as assessed by ultrasound. Laboratory measurements (GFR and NT-proBNP) and echocardiographic studies (VAC calculation, strain rate, diastolic function) will be performed at implantation, 6 months post-BVP optimization and at the end of 13 months of follow-up (6 months post-MPP optimization). Potential reduction in arrhythmogenesis by MPP will also be assessed. MPP is a pacing modality with the potential to improve HF patients' outcomes. The HUMVEE trial will attempt to associate any potential added beneficial effects of MPP over standard BVP with alterations in VAC and energy efficiency of the heart, thus uncovering a novel mechanistic link between MPP and improved outcomes in HF.