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Multipoint LV Pacing Improves Mid-Term CRT Response Introduction Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing in a single coronary sinus branch improves acute LV function. We hypothesized that multipoint pacing (MPP) can improve midterm echocardiographic and clinical response compared with conventional CRT. Methods and Results Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical, Sylmar, CA, USA) were randomized to receive biventricular (BiV) pacing with either conventional LV pacing (CONV group) or MPP (MPP group). For each patient, an optimal pacing configuration for the assigned pacing mode was programmed based on intraoperative pressure-volume (PV) loop measurements. A clinical evaluation and transthoracic echocardiogram were performed before implant (BASELINE) and at 3 months postimplant and analyzed by a blinded observer. A reduction in end-systolic volume (ESV) of ≥15% relative to BASELINE was prospectively defined as response to CRT. Forty-four patients (NYHA Class III, EF 29 ± 6%, QRS duration 152 ± 17 milliseconds) were enrolled and randomized. One patient in the MPP group was lost to follow-up and excluded from further analysis. After 3 months, 11 of 22 (50%) CONV patients and 16 of 21 (76%) MPP patients were classified as responders. ESV reduction, EF increase, and NYHA class reduction relative to BASELINE were significantly greater in the MPP group than in the CONV group (ESV: -21.0 ± 13.9 vs. -12.6 ± 11.1%, P = 0.03; EF: +9.8 ± 5.1 vs. +2.0 ± 7.8 percentage points, P < 0.001; ΔNYHA: -1.05 ± 0.22 vs. -0.72 ± 0.46 functional classes, P = 0.006). Conclusion PV loop optimized BiV pacing with MPP resulted in an improved rate of response to CRT.

Background: Cardiac resynchronization therapy (CRT) involves stimulation of both right ventricle (RV) and left ventricle (LV). LV pacing from the sites of delayed electrical activation improves CRT response. The RV-LV conduction is typically measured in intrinsic rhythm. The differences in RV-LV conduction patterns and timing between intrinsic rhythm and during paced RV activation, these differences are not fully understood. Methods: Enrolled patients were implanted with a de novo CRT device and quadripolar LV lead, with lead implant locations at the implanting physician's discretion. QRS duration and conduction delay between the RV lead and each of the four LV electrodes (D1, M2, M3, and P4) were measured during intrinsic conduction and RV pacing. Results: Conduction measurements were collected from 275 patients across 14 international centers (68 ± 13 years of age, 73% male, 45% ischemic, 158 ± 22ms QRS duration). Mean RV-LV conduction time was shorter during intrinsic conduction versus RV pacing by 59.6ms (106.5 ± 36.5versus 166.1 ± 32.1ms, p&nbsp

Background: Optimal timing of the atrioventricular delay in cardiac resynchronization therapy (CRT) can improve synchrony in patients suffering from heart failure. The purpose of this study was to evaluate the impact of SyncAV™ on electrical synchrony as measured by vectorcardiography (VCG) derived QRS metrics during bi-ventricular (BiV) pacing. Methods: Patients implanted with a cardiac resynchronization therapy (CRT) device and quadripolar left ventricular (LV) lead underwent 12‑lead ECG recordings. VCG metrics, including QRS duration (QRSd) and area, were derived from the ECG by a blinded observer during: intrinsic conduction, BiV with nominal atrioventricular delays (BiV Nominal), and BiV with SyncAV programmed to the optimal offset achieving maximal synchronization (BiV + SyncAV Opt). Results: One hundred patients (71% male, 40% ischemic, 65% LBBB, 32 ± 9% ejection fraction) completed VCG assessment. QRSd during intrinsic conduction (166 ± 25 ms) was narrowed successively by BiV Nominal (137 ± 23 ms, p

Purpose: Multipoint pacing (MPP) improves left ventricular (LV) electrical synchrony in cardiac resynchronization therapy (CRT). SyncAV automatically adjusts atrioventricular delay (AVD) according to intrinsic AV intervals and may further improve synchrony. Their combination has not been assessed. The objective was to evaluate the improvement in electrical synchrony achieved by SyncAV combined with MPP in an international, multicenter study. Methods: Patients with LBBB undergoing CRT implant with a quadripolar lead (Abbott Quartet™) were prospectively enrolled. QRS duration (QRSd) was measured by blinded observers from 12-lead ECG during: intrinsic conduction, BiV pacing (conventional biventricular pacing, nominal static AVD), MPP (2 LV cathodes maximally spaced, nominal static AVD), BiV + SyncAV, and MPP + SyncAV. All SyncAV offsets were individualized for each patient to yield the narrowest QRSd during BiV pacing. QRSd changes were compared by ANOVA and post hoc Tukey-Kramer tests. Results: One hundred and three patients were enrolled (65.7 ± 12.1years, 67% male, 37% ischemic, EF 26.4 ± 6.5%, PR 190.3 ± 39.1ms). Relative to intrinsic conduction (QRSd of 165 ± 16ms), BiV reduced QRSd by 11.9% to 145 ± 18ms (P < 0.001 vs intrinsic), and MPP reduced QRSd by 13.3% to 142 ± 19ms (P < 0.001 vs intrinsic). However, enabling SyncAV with a patient-optimized offset nearly doubled this QRSd reduction. BiV + SyncAV reduced QRSd by 22.0% to 128 ± 13ms (P < 0.001 vs BiV), while MPP + SyncAV reduced QRSd further by 25.6% to 122 ± 14ms (P < 0.05 vs BiV + SyncAV). Conclusion: SyncAV can significantly improve acute electrical synchrony beyond conventional CRT, with further improvement achieved by superimposing MPP.

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 ± 16ms, 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.

Aims Clinical outcomes after radiofrequency catheter ablation (RFCA) remain suboptimal in the treatment of non-paroxysmal atrial fibrillation (AF). Electrophysiological mapping may improve understanding of the underlying mechanisms. To describe the arrhythmia substrate in patients with persistent (Pers) and long-standing persistent (LSPers) AF, undergoing RFCA, using an integrated mechanism mapping technique. Methods and results Patients underwent high-density electroanatomical mapping before and after catheter ablation. Integrated maps characterized electrogram (EGM) cycle length (CL) in regions with repetitive–regular (RR) activations, stable wavefront propagation, fragmentation, and peak-to-peak bipolar voltage. Among 83 patients (72% male, 60 ± 11 years old), RR activations were identified in 376 regions (mean CL 180 ± 31 ms). PersAF patients (n = 43) showed more RR sites per patient (5.3 ± 2.4 vs. 3.7 ± 2.1, P = 0.002) with faster CL (166 ± 29 vs. 190 ± 29 ms; P 75% of RR sites (Q4 82.6%, Q3 63.1%, Q2 35.1%, and Q1 0%; P Conclusion The integrated mapping technique allowed characterization of multiple arrhythmic substrates in non-paroxysmal AF patients. This technique might serve as tool for a substrate-targeted ablation approach.

Purpose: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP]) improves long-term LV reverse remodeling, though questions persist about how to program LV pacing vectors and delays. We evaluated if an empirical method of programming MPP vectors and delays between pacing pulses improved CRT response similar to pressure-volume loop (PVL) optimized MPP programming. Methods: Patients undergoing CRT implant (Quadra Assura MP™ CRT-D and Quartet™ LV lead) received MPP with programmed settings optimized either by PVL measurements at implant (PVL-OPT group) or empirically determined by maximizing the spatial separation between the two cathodes and minimal delays between the three ventricular pacing pulses (MAX-SEP group). CRT response was prospectively defined as a reduction in end-systolic volume (ESV) of ≥ 15% relative to baseline at 6months as determined by a blinded observer. Results: Patient characteristics at baseline (NYHA II–III, ejection fraction [EF] 27 ± 6%, QRS 151 ± 17ms) were not significantly different between the PVL-OPT (n = 27) and MAX-SEP (n = 26) groups. During the follow-up period, there were no differences in the number of patients requiring reprogramming due to phrenic nerve stimulation or a high threshold for PVL-OPT vs. MAX-SEP (5/27 [19%] vs. 7/26 [27%], p= 0.53). After 6months, ESV reduction, EF increase, and CRT response rate (RR) were similar for PVL-OPT vs. MAX-SEP (ESV − 20 ± 11 vs. − 22 ± 11%, p = 0.59; EF + 10 ± 4 vs. + 9 ± 7%, p = 0.53; RR 20/27 [74%] vs. 21/26 [81%], p = 0.74), while fewer patients in the PVL-OPT group experienced NYHA class reduction ≥ 2 (4/27 [15%] vs.15/26 [58%], p = 0.002). Conclusions: Both evaluated methods of MPP programming resulted in similar CRT outcomes. Empirical MPP programming by maximum spatial separation of LV cathodes may be an effective, simple, and non-invasive alternative to pressure-volume optimization.

Background Patient-specific programming of cardiac resynchronization therapy (CRT) is often neglected, despite significant nonresponse rates. The device-based SyncAV CRT algorithm dynamically adjusts atrioventricular delays to the intrinsic AV interval, reduced by a programmable offset, to accommodate each patient's changing needs. Objective The purpose of this study was to evaluate the acute effect of biventricular (BiV) pacing enhanced by SyncAV on electrical synchrony in a broad patient population. Methods Patients with existing CRT implants were prospectively evaluated at 5 international centers. Blinded 12-lead electrocardiographic QRS duration (QRSd) measurements were used to compare intrinsic conduction with nominal BiV pacing, BiV + SyncAV (default 50 ms offset), and BiV + SyncAV (optimized, patient-specific offset). BiV configurations were tested twice using the latest activating and earliest activating left ventricular (LV) electrodes as cathodes. Results Ninety patients (mean age 67.1 ± 9.5 years; 67 (74%) men; 55 (63%) with left bundle branch block; 37 (43%) with ischemic cardiomyopathy; LV ejection fraction 32% ± 9%) with intact atrioventricular conduction (PR interval 195 ± 45 ms) were enrolled. With BiV pacing from the latest activating LV electrode, the intrinsic QRSd of 155 ± 29 ms was reduced by 9% ± 20% to 138 ± 27 ms using traditional BiV pacing and by 13% ± 14% to 133 ± 25 ms using BiV + SyncAV (50 ms offset). The maximal QRSd reduction by 20% ± 10% to 123 ± 22 ms was achieved by BiV + SyncAV with an optimized offset. Similar QRSd reductions were observed with BiV pacing from the earliest activating LV electrode across all settings. Of all baseline characteristics, intrinsic QRSd was the only significant predictor of QRSd reduction magnitude. Conclusion SyncAV improved acute electrical synchrony beyond conventional CRT, particularly with patient-specific optimization. The degree of synchrony restored was contingent on intrinsic QRSd, but not limited by other baseline characteristics or by the LV pacing electrode used.

Background Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], St. Jude Medical) improves acute LV function and LV reverse remodeling at 3 months. Objective The purpose of this study was to test the hypothesis that MPP can also improve LV function at 12 months. Methods Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were randomized to receive pressure–volume (PV) loop optimized biventricular pacing with either conventional cardiac resynchronization therapy (CONV) or MPP. CRT response was defined by a reduction in end-systolic volume (ESV) ≥15% relative to BASELINE as determined by a blinded observer and alive status. Results Forty-four patients (New York Heart Association class III, ejection fraction [EF] 29% ± 6%, QRS 152 ± 17 ms) were enrolled and randomized to either CONV (N = 22) or MPP (N = 22). During the observation period, 2 patients died of noncardiac causes and 2 patients were lost to follow-up. After 12 months, 12 of 21 patients (57%) in the CONV group and 16 of 21 patients (76%) in the MPP group were classified as CRT responders ( P = .33). ESV reduction and EF increase relative to BASELINE were significantly greater with MPP than with CONV (ESV: median –25%, interquartile range [IQR] [–39% to –20%] vs median –18%, IQR [–25% to –2%], P = .03; EF: median +15%, IQR [8% to 20%] vs median +5%, IQR [–1% to 8%], P Conclusion Sustaining the trend observed 3 months postimplant, PV loop-guided multipoint LV pacing resulted in greater LV reverse remodeling and increased LV function at 12 months compared to PV loop-guided conventional CRT.

Background: Clinical outcomes after ablation of persistent atrial fibrillation remain suboptimal. Identification of AF drivers using a novel integrated mapping technique may be crucial to ameliorate the clinical outcome. Methods and Results: Persistent AF patients were prospectively enrolled to undergo high-density electrophysiological mapping to identify repetitive-regular activities (RRas) before modified circumferential pulmonary vein (PV) ablation. They have been randomly assigned (1:1 ratio) to ablation of RRa followed by modified circumferential PV ablation (mapping group; n=41) or modified circumferential PV ablation alone (control group; n=40). The primary end point was freedom from arrhythmic recurrences at 1 year. In total, 81 persistent AF patients (74% male; mean age, 61.7±10.6 years) underwent mapping/ablation procedure. The regions exhibiting RRa were 479 in 81 patients (5.9±2.4 RRa per patient): 232 regions in the mapping group (n=41) and 247 in the control group (n=40). Overall, 185 of 479 (39%) RRas were identified within the PVs, whereas 294 of 479 (61%) in non-PV regions. Mapping-guided ablation resulted in higher arrhythmia termination rate when compared with conventional strategy (25/41, 61% versus 12/40, 30%; P P =0.38), mapping ( P =0.46), and fluoroscopy times ( P =0.69) were not significantly different between the groups. No major procedure-related adverse events occurred. After 1 year, 73.2% of mapping group patients were free from recurrences versus 50% of control group ( P =0.03). Conclusions: Targeted ablation of regions showing RRa provided an adjunctive benefit in terms of arrhythmia freedom at 1-year follow-up in the treatment of persistent AF. These findings might support a patient-tailored strategy in subjects with nonparoxysmal AF and should be confirmed by additional larger, randomized, multicenter studies. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier NCT02571218.

International audience; AIMS: The aim of this study was to evaluate any benefits to the number of viable pacing vectors and maximal spatial coverage with quadripolar left ventricular (LV) leads when compared with tripolar and bipolar equivalents in patients receiving cardiac resynchronization therapy (CRT). METHODS AND RESULTS: A meta-analysis of five previously published clinical trials involving the Quartet™ LV lead (St Jude Medical, St Paul, MN, USA) was performed to evaluate the number of viable pacing vectors defined as capture thresholds ≤2.5 V and no phrenic nerve stimulation and maximal spatial coverage of viable vectors in CRT patients at pre-discharge (n = 370) and first follow-up (n = 355). Bipolar and tripolar lead configurations were modelled by systematic elimination of two and one electrode(s), respectively, from the Quartet lead. The Quartet lead with its four pacing electrodes exhibited the greatest number of pacing vectors per patient when compared with the best bipolar and the best tripolar modelled equivalents. Similarly, the Quartet lead provided the highest spatial coverage in terms of the distance between two furthest viable pacing cathodes when compared with the best bipolar and the best tripolar configurations (P \textless 0.05). Among the three modelled bipolar configurations, the lead configuration with the two most distal electrodes resulted in the highest number of viable pacing vectors. Among the four modelled tripolar configurations, elimination of the second proximal electrode (M3) resulted in the highest number of viable pacing options per patient. There were no significant differences observed between pre-discharge and first follow-up analyses. CONCLUSION: The Quartet lead with its four electrodes and the capability to pace from four anatomical locations provided the highest number of viable pacing vectors at pre-discharge and first follow-up visits, providing more flexibility in device programming and enabling continuation of CRT in more patients when compared with bipolar and tripolar equivalents

Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing [MultiPoint™ Pacing (MPP), St. Jude Medical, Sylmar, CA, USA] improves LV function and clinical response relative to conventional CRT in patients receiving a de novo device implant. We hypothesized that patients with a previously implanted conventional CRT device would receive additional benefit by switching to MPP. Patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were programmed to conventional CRT (i.e. biventricular pacing with right ventricular and single LV sites) optimized by intraoperative haemodynamic measurements. After 12 months of conventional therapy, patients were reprogrammed to MPP and re-evaluated at 16 months post-implant. Response to CRT was prospectively defined as reduction in end-systolic volume (ESV) of ≥15% relative to baseline as determined by a blinded observer. Eight patients with an implanted CRT device [New York Heart Association III, ejection fraction (EF) 30 ± 5%, QRS 149 ± 18 ms] received 12 months of conventional CRT and were switched to MPP. After 12 months of conventional CRT, ESV reduction and EF increase relative to baseline were −18 ± 12 and +5 ± 4%, respectively, and six of eight (75%) patients were considered CRT responders. After 4 months of MPP, two of two (100%) patients classified as non-responders to conventional CRT became responders with additional reduction in ESV of −33 and −20% and improvement in EF of +15 and +4%. The remaining six patients classified as responders experienced additional reduction in ESV of −13 ± 21% and improvement in EF of +7 ± 7% after switching to MPP. Multipoint LV pacing may provide additional improvement to LV function in patients receiving conventional CRT.

Backgound Conventional cardiac resynchronization therapy (CRT) improves acute cardiac hemodynamics. Objective To investigate if CRT with multipoint left ventricular (LV) pacing in a single coronary sinus branch (MultiPoint Pacing [MPP], St Jude Medical, Sylmar, CA) can offer further hemodynamic benefits to patients. Methods Forty-four consecutive patients (80% men, New York Heart Association III, end-systolic volume 180 ± 77 mL, ejection fraction 27% ± 6%, and QRS duration 152 ± 17 ms) receiving a CRT device implant (Unify Quadra MP or Quadra Assura MP and Quartet LV lead, St Jude Medical) underwent intraoperative assessment of LV hemodynamics by using a pressure-volume loop system (Inca, CD Leycom). A pacing protocol was performed, including 9 biventricular pacing interventions with conventional CRT (CONV) using distal and proximal LV electrodes and various MPP configurations. Each pacing intervention was performed twice in randomized order with right ventricular pacing (BASELINE) repeated after every intervention. Results Evaluable recordings were obtained in 42 patients. Relative to BASELINE, the best MPP intervention significantly increased the rate of pressure change (dP/dtmax; 15.9% ± 10.0% vs 13.5% ± 8.8%; P