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Abstract Aims We tested the hypothesis that shortening of time‐to‐peak left ventricular pressure rise (Td) reflect resynchronization in an animal model and that Td measured in patients will be helpful to identify long‐term volumetric responders [end‐systolic volume (ESV) decrease >15%] in cardiac resynchronization therapy (CRT). Methods Td was analysed in an animal study (n = 12) of left bundle‐branch block (LBBB) with extensive instrumentation to detect left ventricular myocardial deformation, electrical activation, and pressures during pacing. The sum of electrical delays from the onset of pacing to four intracardiac electrodes formed a synchronicity index (SI). Pacing was performed at baseline, with LBBB, right and left ventricular pacing and finally with biventricular pacing (BIVP). We then studied Td at baseline and with BIVP in a clinical observational study in 45 patients during the implantation of CRT and followed up for up to 88 months. Results We found a strong relationship between Td and SI in the animals (R = 0.84, P

BackgroundCardiac resynchronization therapy (CRT) is helpful in selected patients; however, responder rates rarely exceed 70%. Optimization of CRT may therefore benefit a large number of patients. Time-to-peak dP/dt (Td) is a novel marker of myocardial synergy that reflects the degree of myocardial dyssynchrony with the potential to guide and optimize treatment with CRT. Optimal electrical activation is a prerequisite for CRT to be effective. Electrical activation can be altered by changing the electrical wave-front fusion resulting from pacing to optimize resynchronization. We designed this study to understand the acute effects of different electrical wave-front fusion strategies and LV pre-/postexcitation on Td and QRS duration (QRSd). A better understanding of measuring and optimizing resynchronization can help improve the benefits of CRT.MethodsTd and QRSd were measured in 19 patients undergoing a CRT implantation. Two biventricular pacing groups were compared: pacing the left ventricle (LV) with fusion with intrinsic right ventricular activation (FUSION group) and pacing the LV and right ventricle (RV) at short atrioventricular delay (STANDARD group) to avoid fusion with intrinsic RV activation. A quadripolar LV lead enabled pacing from widely separated electrodes; distal (DIST), proximal (PROX) and both electrodes combined (multipoint pacing, MPP). The LV was stimulated relative in time to RV activation (either RV pace-onset or QRS-onset), with the LV stimulated prior to (PRE), simultaneous with (SIM) or after (POST) RV activation. In addition, we analyzed the interactions of the two groups (FUSION/STANDARD) with three different electrode configurations (DIST, PROX, MPP), each paced with three different degrees of LV pre-/postexcitation (PRE, SIM, POST) in a statistical model.ResultsWe found that FUSION provided shorter Td and QRSd than STANDARD, MPP provided shorter Td and QRSd than DIST and PROX, and SIM provided both the shortest QRSd and Td compared to PRE and POST. The interaction analysis revealed that pacing MPP with fusion with intrinsic RV activation simultaneous with the onset of the QRS complex (MPP*FUSION*SIM) shortened QRSd and Td the most compared to all other modes and configurations. The difference in QRSd and Td from their respective references were significantly correlated (β = 1, R = 0.9, p < 0.01).ConclusionPacing modes and electrode configurations designed to optimize electrical wave-front fusion (intrinsic RV activation, LV multipoint pacing and simultaneous RV and LV activation) shorten QRSd and Td the most. As demonstrated in this study, electrical and mechanical measures of resynchronization are highly correlated. Therefore, Td can potentially serve as a marker for CRT optimization.

The aim of the SYNSEQ (Left Ventricular Synchronous vs. Sequential MultiSpot Pacing for CRT) study was to evaluate the acute hemodynamic response (AHR) of simultaneous (3P-MPP syn) or sequential (3P-MPP seq) multi-3-point-left-ventricular (LV) pacing vs. single point pacing (SPP) in a group of patients at risk of a suboptimal response to cardiac resynchronization therapy (CRT). Twenty five patients with myocardial scar or QRS ≤ 150 or the absence of LBBB (age: 66 ± 12 years, QRS: 159 ± 12 ms, NYHA class II/III, LVEF ≤ 35%) underwent acute hemodynamic assessment by LV + dP/dtmax with a variety of LV pacing configurations at an optimized AV delay. The change in LV + dP/dt max (%ΔLV + dP/dt max) with 3P-MPP syn (15.6%, 95% CI: 8.8%-22.5%) was neither statistically significantly different to 3P-MPP seq (11.8%, 95% CI: 7.6-16.0%) nor to SPP basal (11.5%, 95% CI:7.1-15.9%) or SPP mid (12.2%, 95% CI:7.9-16.5%), but higher than SPP apical (10.6%, 95% CI:5.3-15.9%, p = 0.03). AHR (defined as a %ΔLV + dP/dt max ≥ 10%) varied between pacing configurations: 36% (9/25) for SPP apical, 44% (11/25) for SPP basal, 54% (13/24) for SPP mid, 56% (14/25) for 3P-MPP syn and 48% (11/23) for 3P-MPP seq.Fifteen patients (15/25, 60%) had an AHR in at least one pacing configuration. AHR was observed in 10/13 (77%) patients with a LBBB but only in 5/12 (42%) patients with a non-LBBB (p = 0.11). To conclude, simultaneous or sequential multipoint pacing compared to single point pacing did not improve the acute hemodynamic effect in a suboptimal CRT response population.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT02914457.

Background We designed this study to assess the acute effects of different fusion strategies and left ventricular (LV) pre-excitation/post-excitation on LV dP/dtmax and QRS duration (QRSd).Methods We measured LV dP/dtmax and QRSd in 19 patients having cardiac resynchronisation therapy (CRT). Two groups of biventricular pacing were compared: pacing the left ventricle (LV) with FUSION with intrinsic right ventricle (RV) activation (FUSION), and pacing the LV and RV with NO FUSION with intrinsic RV activation. In the NO FUSION group, the RV was paced before the expected QRS onset. A quadripolar LV lead enabled distal, proximal and multipoint pacing (MPP). The LV was stimulated relative in time to either RV pace or QRS-onset in four pre-excitation/post-excitation classes (PCs). We analysed the interactions of two groups (FUSION/NO FUSION) with three different electrode configurations, each paced with four different degrees of LV pre-excitation (PC1–4) in a statistical model.Results LV dP/dtmax was higher with NO FUSION than with FUSION (769±46 mm Hg/s vs 746±46 mm Hg/s, p

Background: We sought to determine whether presence, amount and distribution of scar impacts the degree of acute hemodynamic response (AHR) with multisite pacing.Multi-vein pacing (MVP) or multipolar pacing (MPP) with a multi-electrode left ventricular (LV) lead may offer benefits over conventional biventricular pacing in patients with myocardial scar. Methods: In this multi-center study left bundle branch block patients underwent an hemodynamic pacing study measuring LV dP/dtmax. Patients had cardiac magnetic resonance scar imaging to assess the effect of scar presence, amount and distribution on AHR. Results: 24 patients (QRS 171 ± 20 ms) completed the study (83% male). An ischemic etiology was present in 58% and the mean scar volume was 6.0 ± 7.0%. Overall discounting scar, MPP and MVP showed no significant AHR increase compared to an optimized “best BiV” (BestBiV) site. In a minority of patients (6/24) receiver-operator characteristic analysis of scar volume (cut off 8.48%) predicted a small AHR improvement with MPP (sensitivity 83%, specificity 94%) but not MVP. Patients with scar volume > 8.48% had a MPP-BestBiV of 3 ± 6.3% vs. −6.4 ± 7.7% for those below the cutoff. There was a significant correlation between the difference in AHR and scar volume for MPP-BestBiV (R = 0.49, p = 0.02) but not MVP-BestBiV(R = 0.111, p = 0.62). The multielectrode lead positioned in scar predicted MPP AHR improvement (p = 0.04). Conclusions: Multisite pacing with MPP and MVP shows no AHR benefit in all-comers compared to optimized BestBiV pacing. There was a minority of patients with significant scar volume in relation to the LV site that exhibited a small AHR improvement with MPP.(Study identifier NCT01883141) Keywords: Cardiac resynchronization therapy, Multisite pacing, Acute hemodynamic response, Left ventricular scar

Recent efforts to increase CRT response by multiSPOT pacing (MSP) from multiple bipols on the same left ventricular lead are still inconclusive.The Left Ventricular (LV) MultiSPOTpacing for CRT (iSPOT) study compared the acute hemodynamic response of MSP pacing by using 3 electrodes on a quadripolar lead compared with conventional biventricular pacing (BiV).Patients with left bundle branch block (LBBB) underwent an acute hemodynamic study to determine the %change in LV+dP/dtmax from baseline atrial pacing compared to the following configurations: BiV pacing with the LV lead in a one of lateral veins, while pacing from the distal, mid, or proximal electrode and all 3 electrodes together (i.e. MSP). All measurements were repeated 4 times at 5 different atrioventricular delays. We also measured QRS-width and individual Q-LV durations.Protocol was completed in 24 patients, all with LBBB (QRS width 171±20 ms) and 58% ischemic aetiology. The percentage change in LV+dP/dtmax for MSP pacing was 31.0±3.3% (Mean±SE), which was not significantly superior to any BiV pacing configuration: 28.9±3.2% (LV-distal), 28.3±2.7% (LV-mid), and 29.5±3.0% (LV-prox), respectively. Correlation between LV+dP/dtmax and either QRS-width or Q-LV ratio was poor.In patients with LBBB MultiSPOT LV pacing demonstrated comparable improvement in contractility to best conventional BiV pacing. Optimization of atrioventricular delay is important for the best performance for both BiV and MultiSPOT pacing configurations.ClinicalTrials.gov NTC01883141.