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Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients with left ventricular dysfunction and a left bundle branch block. However, its impact on right ventricular (RV) function remains uncertain. This cardiac magnetic resonance imaging study found that CRT did not improve RV volumes and function, and CRT-off during follow-up had an immediate detrimental effect on the RV, which may suggest potential unfavorable RV remodeling with RV pacing during CRT., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Fusion pacing, which exploits conduction via the intrinsic His-Purkinje system, forms the basis of recent cardiac resynchronization therapy (CRT) optimization algorithms. However, settings need to be constantly adjusted to accommodate for changes in AV conduction, and the algorithms are not always available (eg, depending on the device, in case of AV block or with atrial fibrillation). His-optimized cardiac resynchronization therapy (HOT-CRT), and left-bundle branch optimized cardiac resynchronization therapy (LOT-CRT) which combines conduction system pacing with ventricular fusion pacing, provide constant fusion with ventricular activation (irrespective of intrinsic AV conduction). These modalities provide promising treatment strategies for patients with heart failure, especially in those with chronic atrial fibrillation who require CRT (in whom the atrial port is usually plugged and can be used to connect the conduction system pacing lead)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patients with a class I recommendation for cardiac resynchronization therapy (CRT) are likely to benefit, but the effect of CRT in class II patients is more heterogeneous and additional selection parameters are needed in this group. The recently validated segment length in cine strain analysis of the septum (SLICE-ESS sep ) measurement on cardiac magnetic resonance cine imaging predicts left ventricular functional recovery after CRT but its prognostic value is unknown. This study sought to evaluate the prognostic value of SLICE-ESS sep for clinical outcome after CRT., Methods: Two hundred eighteen patients with a left bundle branch block or intraventricular conduction delay and a class I or class II indication for CRT who underwent preimplantation cardiovascular magnetic resonance examination were enrolled. SLICE-ESS sep was manually measured on standard cardiovascular magnetic resonance cine imaging. The primary combined end point was all-cause mortality, left ventricular assist device, or heart transplantation. Secondary end points were (1) appropriate implantable cardioverter defibrillator therapy and (2) heart failure hospitalization., Results: Two-thirds (65%) of patients had a positive SLICE-ESS sep ≥0.9% (ie, systolic septal stretching). During a median follow-up of 3.8 years, 66 (30%) patients reached the primary end point. Patients with positive SLICE-ESS sep were at lower risk to reach the primary end point (hazard ratio 0.36; P <0.001) and heart failure hospitalization (hazard ratio 0.41; P =0.019), but not for implantable cardioverter defibrillator therapy (hazard ratio, 0.66; P =0.272). Clinical outcome of class II patients with a positive ESS sep was similar to those of class I patients (hazard ratio, 1.38 [95% CI, 0.66-2.88]; P =0.396)., Conclusions: Strain assessment of the septum (SLICE-ESS sep ) provides a prognostic measure for clinical outcome after CRT. Detection of a positive SLICE-ESS sep in patients with a class II indication predicts improved CRT outcome similar to those with a class I indication whereas SLICE-ESS sep negative patients have poor prognosis after CRT implantation.

Objectives: This study sought to evaluate the effectiveness of His-optimized cardiac resynchronization therapy (HOT-CRT) for reducing left ventricular activation time (LVAT) compared to His bundle pacing (HBP) and biventricular (BiV) pacing (including multipoint pacing [MPP]), using electrocardiographic (ECG) imaging., Background: HBP may correct bundle branch block (BBB) and has shown encouraging results for providing CRT. However, HBP does not correct BBB in all patients and may be combined with univentricular or BiV fusion pacing to deliver HOT-CRT to maximize resynchronization., Methods: Nineteen patients with a standard indication for CRT, implanted with HBP without correction of BBB and BiV (n = 14) or right ventricular (n = 5) leads, were prospectively enrolled. Patients underwent ECG imaging while pacing in different configurations using different LV electrodes and at different HBP ventricular pacing (VP) delays. The primary endpoint was reduction in LVAT with HOT-CRT, and the secondary endpoints included various other dys-synchrony measurements including right ventricular activation time (RVAT)., Results: Compared to HBP, HOT-CRT reduced LVAT by 21% (-17 ms [95% confidence interval [CI]: -25 to -9 ms]; p < 0.001) and outperformed BiV by 24% (-22 ms [95% CI: -33 to -10 ms]; p = 0.002) and MPP by 13% (-11 ms [95% CI: -21 to -1 ms]; p = 0.035). Relative to HBP, HOT-CRT also reduced RVAT by 7% (-5 ms [95% CI: -9 to -1 ms; p = 0.035) in patients with right BBB, whereas RVAT was increased by BiV. The other electrical dyssynchrony measurements also improved with HOT-CRT., Conclusions: HOT-CRT acutely improves ventricular electrical synchrony beyond BiV and MPP. The impact of this finding needs to be evaluated further in studies with clinical follow-up. (Electrical Resynchronization and Acute Hemodynamic Effects of Direct His Bundle Pacing Compared to Biventricular Pacing; NCT03452462)., Competing Interests: Funding Support and Author Disclosures This study was supported by Swiss National Science Foundation grant ME11709. Dr. Burri has received speaker fees and research grants from Abbott, Biotronik, Boston Scientific, Medtronic, and Microport. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response., Methods and Results: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRS sep ), systolic stretch index (SSI sep-lat ), and internal stretch factor (ISF sep-lat ) all correlated significantly with LVESV change (R - 0.56; R - 0.53; and R - 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESS sep ) showed strongest correlation with LVESV change (R - 0.63). Multivariable analysis showed ESS sep to be independently related to LVESV change together with age and QRS AREA ., Conclusion: The practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESS sep ) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.

Aims: Patient selection for cardiac resynchronization therapy (CRT) may be enhanced by evaluation of systolic myocardial stretching. We evaluate whether systolic septal rebound stretch (SRSsept) derived from speckle tracking echocardiography is a predictor of reverse remodelling after CRT and whether it holds additive predictive value over the simpler visual dyssynchrony assessment by apical rocking (ApRock)., Methods and Results: The association between SRSsept and change in left ventricular end-systolic volume (ΔLVESV) at 6 months of follow-up was assessed in 200 patients. Subsequently, the additive predictive value of SRSsept over the assessment of ApRock was evaluated in patients with and without left bundle branch block (LBBB) according to strict criteria. SRSsept was independently associated with ΔLVESV (β 0.221, P = 0.002) after correction for sex, age, ischaemic cardiomyopathy, QRS morphology and duration, and ApRock. A high SRSsept (≥optimal cut-off value 2.4) also coincided with more volumetric responders (ΔLVESV ≥ -15%) than low SRSsept in the entire cohort (70.0% and 56.4%), in patients with strict LBBB (83.3% vs. 56.7%, P = 0.024), and non-LBBB (70.7% vs. 46.3%, P = 0.004). Moreover, in non-LBBB patients, SRSsept held additional predictive information over the assessment of ApRock alone since patients that showed ApRock and high SRSsept were more often volumetric responder than those with ApRock but low SRSsept (82.8% vs. 47.4%, P = 0.001)., Conclusion: SRSsept is strongly associated with CRT-induced reduction in left ventricular end-systolic volume and holds additive prognostic information over QRS morphology and ApRock. Our data suggest that CRT patient selection may be improved by assessment of SRSsept, especially in the important subgroup without strict LBBB., Clinical Trial Registration: The MARC study was registered at clinicaltrials.gov: NCT01519908., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study evaluated the acute effect of dP/dt max - versus stroke work (SW)-guided cardiac resynchronization therapy (CRT) optimization and the related acute hemodynamic changes to long-term CRT response., Background: Hemodynamic optimization may increase benefit from CRT. Typically, maximal left ventricular (LV) pressure rise dP/dt max is used as an index of ventricular performance. Alternatively, SW can be derived from pressure-volume (PV) loops., Methods: Forty-one patients underwent CRT implantation followed by invasive PV loop measurements. The stimulation protocol included 16 LV pacing configurations using each individual electrode of the quadripolar lead with 4 atrioventricular (AV) delays. Conventional CRT was defined as pacing from the distal electrode with an AV delay of approximately 120 ms., Results: Compared with conventional CRT, dP/dt max -guided optimization resulted in a one-third additional dP/dt max increase (17 ± 11% vs. 12 ± 9%; p < 0.001). Similarly, SW-guided optimization resulted in a one-third additional SW increase (80 ± 55% vs. 53 ± 48%; p < 0.001). Comparing both optimization strategies, dP/dt max favored contractility (8 ± 12% vs. 5 ± 10%; p = 0.015), whereas SW optimization improved ventricular-arterial (VA) coupling (45% vs. 32%; p < 0.001). After 6 months, mean LV ejection fraction (LVEF) change was 10 ± 9% with 23 (56%) patients becoming super-responders to CRT (≥10% LVEF improvement). Although acute changes in SW were predictive for long-term CRT response (area under the curve: 0.78; p = 0.002), changes in dP/dt max were not (area under the curve: 0.65; p = 0.112)., Conclusions: PV-guided hemodynamic optimization in CRT results in approximately one-third SW improvement on top of conventional CRT, caused by a mechanism of enhanced VA coupling. In contrast, dP/dt max optimization favored LV contractility. Ultimately, acute changes in SW showed larger predictive value for long-term CRT response compared with dP/dt max ., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: 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., Methods and Results: 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)., Conclusion: 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.

Background: In patients with left bundle branch block (LBBB), QRS duration (QRSd) depends on left ventricular (LV) dimension. Previously, we demonstrated that normalizing QRSd to LV dimension, to adjust for variations in LV size, improved prediction of hemodynamic response to cardiac resynchronization therapy (CRT). In addition, sex-specific differences in CRT outcome have been attributed to normalized QRSd. The present study evaluates the effect of normalization of QRSd to LV dimension on prediction of survival after CRT implantation., Methods: In this 2-center study, we studied 250 heart failure patients with LV ejection fraction ≤35% and QRSd ≥120 ms who underwent cardiac magnetic resonance imaging before CRT implantation. LV end-diastolic volumes were used for QRSd normalization (ie, QRSd/LV end-diastolic volumes). The primary end point was a combined end point of death, LV assist device, or heart transplantation., Results: During a median follow-up of 3.9 years, 79 (32%) patients reached the primary end point. Using univariable Cox regression, unadjusted QRSd was unrelated to CRT outcome ( P=0.116). In contrast, normalized QRSd was a strong predictor of survival (hazard ratio, 0.81 per 0.1 ms/mL; P=0.008). Women demonstrated higher normalized QRSd than men (0.62±0.17 versus 0.55±0.17 ms/mL; P=0.003) and showed better survival after CRT (hazard ratio, 0.52; P=0.018). A multivariable prognostic model included normalized QRSd together with age, atrial fibrillation, renal function, and heart failure cause, whereas sex, diabetes mellitus, strict left bundle branch block morphology, and LV end-diastolic volumes were expelled from the model., Conclusions: Normalization of QRSd to LV dimension improves prediction of survival after CRT implantation. In addition, sex-specific differences in CRT outcome might be attributed to the higher QRSd/LV end-diastolic volumes ratio that was found in selected women, indicating more conduction delay.

Aims: Various strain parameters and multiple imaging techniques are presently available including cardiovascular magnetic resonance (CMR) tagging (CMR-TAG), CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). This study aims to compare predictive performance of different strain parameters and evaluate results per imaging technique to predict cardiac resynchronization therapy (CRT) response., Methods and Results: Twenty-seven patients were prospectively enrolled and underwent CMR and echocardiographic examination before CRT implantation. Strain analysis was performed in circumferential (CMR-TAG, CMR-FT, and STE-circ) and longitudinal (STE-long) orientations. Regional strain values, parameters of dyssynchrony, and discoordination were calculated. After 12 months, CRT response was measured by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). Twenty-six patients completed follow-up; mean LVESV change was -29 ± 27% with 17 (65%) patients showing ≥15% LVESV reduction. Measures of dyssynchrony (SD-TTP LV ) and discoordination (ISF LV ) were strongly related to CRT response when using CMR-TAG (R 2 0.61 and R 2 0.57, respectively), but showed poor correlations for CMR-FT and STE (all R 2  ≤ 0.32). In contrast, the end-systolic septal strain (ESS sep ) parameter showed a consistent high correlation with LVESV change for all techniques (CMR-TAG R 2 0.60; CMR-FT R 2 0.50; STE-circ R 2 0.43; and STE-long R 2 0.43). After adjustment for QRS duration and QRS morphology, ESS sep remained an independent predictor of response per technique., Conclusions: End-systolic septal strain was the only parameter with a consistent good relation to reverse remodelling after CRT, irrespective of assessment technique. In clinical practice, this measure can be obtained by any available strain imaging technique and provides predictive value on top of current guideline criteria., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Objectives: This study aimed to compare multipoint pacing (MPP) to optimal biventricular pacing with a quadripolar left ventricular (LV) lead and find factors associated with hemodynamic response to MPP., Background: MPP with a quadripolar LV lead may increase response to cardiac resynchronization therapy., Methods: Heart failure patients with a left bundle branch block underwent cardiac resynchronization therapy implantation. Q to LV sensing interval divided by the intrinsic QRS duration was measured. Invasive pressure-volume loops were assessed during 4 biventricular pacing settings and 3 MPP settings, using 4 atrioventricular delays. Hemodynamic response was defined as change in stroke work (Δ%SW) compared with baseline measurements during intrinsic conduction. Δ%SW of MPP was compared with conventional biventricular pacing using the distal electrode and the electrode with highest Δ%SW (BIV-OPT)., Results: Forty-three patients were analyzed (age 66 ± 10 years, 63% men, 30% ischemic cardiomyopathy, LV ejection fraction 29 ± 8%, and QRS duration 175 ± 13 ms). Q to local LV sensing interval corrected for QRS duration was 84 ± 8%, and variation between LV electrodes was 9 ± 5%. Compared with conventional biventricular pacing using the distal electrode, MPP showed a significant higher increase of SW (Δ%SW +15 ± 35%; p < 0.05) with a large interindividual variation. There was no significant difference in Δ%SW with MPP compared with BIV-OPT (-5 ± 24%; p = 0.19). Male sex and low LV ejection fraction were associated with increase in Δ%SW due to MPP versus BIV-OPT in multivariate analysis, while ischemic cardiomyopathy was only associated in univariate analysis., Conclusions: Optimization of the pacing site of a quadripolar LV lead is more important than to program MPP. However, specific subgroups (i.e., especially men) may benefit substantially from MPP., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Parameters using myocardial strain analysis may predict response to cardiac resynchronization therapy (CRT). As the agreement between currently available strain imaging modalities is unknown, three different modalities were compared. Twenty-seven CRT-candidates, prospectively included in the MARC study, underwent cardiac magnetic resonance (CMR) imaging and echocardiographic examination. Left ventricular (LV) circumferential strain was analysed with CMR tagging (CMR-TAG), CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). Basic strain values and parameters of dyssynchrony and discoordination obtained with CMR-FT and STE were compared to CMR-TAG. Agreement of CMR-FT and CMR-TAG was overall fair, while agreement between STE and CMR-TAG was often poor. For both comparisons, agreement on discoordination parameters was highest, followed by dyssynchrony and basic strain parameters. For discoordination parameters, agreement on systolic stretch index was highest, with fair intra-class correlation coefficients (ICC) (CMR-FT: 0.58, STE: 0.55). ICC of septal systolic rebound stretch (SRS sept ) was poor (CMR-FT: 0.41, STE: 0.30). Internal stretch factor of septal and lateral wall (ISF sep-lat ) showed fair ICC values (CMR-FT: 0.53, STE: 0.46), while the ICC of the total LV (ISF LV ) was fair for CMR-FT (0.55) and poor for STE (ICC: 0.32). The CURE index had a fair ICC for both comparisons (CMR-FT: 0.49, STE 0.41). Although comparison of STE to CMR-TAG was limited by methodological differences, agreement between CMR-FT and CMR-TAG was overall higher compared to STE and CMR-TAG. CMR-FT is a potential clinical alternative for CMR-TAG and STE, especially in the detection of discoordination in CRT-candidates.

Background: Previous studies indicated the importance of the intrinsic left ventricular (LV) electric delay (QLV) for optimal benefit to cardiac resynchronization therapy. We investigated the use of QLV for achieving optimal acute hemodynamic response to cardiac resynchronization therapy with a quadripolar LV lead., Methods and Results: Forty-eight heart failure patients with a left bundle branch block were prospectively enrolled (31 men; age, 66±10 years; LV ejection fraction, 28±8%; QRS duration, 176±14 ms). Immediately after cardiac resynchronization therapy implantation, invasive LV pressure-volume loops were recorded during biventricular pacing with each separate electrode at 4 atrioventricular delays. Acute cardiac resynchronization therapy response, measured as change in stroke work (Δ%SW) compared with intrinsic conduction, was related to intrinsic interval between Q on the ECG and LV sensing delay (QLV), normalized for QRS duration (QLV/QRSd), and electrode position. QLV/QRSd was 84±9% and variation between the 4 electrodes 9±5%. Δ%SW was 89±64% and varied by 39±36% between the electrodes. In univariate analysis, an anterolateral or lateral electrode position and a high QLV/QRSd had a significant association with a large Δ%SW (all P <0.01). In a combined model, only QLV/QRSd remained significantly associated with Δ%SW ( P <0.05). However, a direct relation between QLV/QRSd and Δ%SW was only seen in 24 patients, whereas 24 patients showed an inverse relation., Conclusions: The large variation in acute hemodynamic response indicates that the choice of the stimulated electrode on a quadripolar lead is important. Although QLV/QRSd was associated with acute hemodynamic response at group level, it cannot be used to select the optimal electrode in the individual patient., (© 2018 American Heart Association, Inc.)

Objectives: Although myocardial strain analysis is a potential tool to improve patient selection for cardiac resynchronization therapy (CRT), there is currently no validated clinical approach to derive segmental strains. We evaluated the novel segment length in cine (SLICE) technique to derive segmental strains from standard cardiovascular MR (CMR) cine images in CRT candidates., Methods: Twenty-seven patients with left bundle branch block underwent CMR examination including cine imaging and myocardial tagging (CMR-TAG). SLICE was performed by measuring segment length between anatomical landmarks throughout all phases on short-axis cines. This measure of frame-to-frame segment length change was compared to CMR-TAG circumferential strain measurements. Subsequently, conventional markers of CRT response were calculated., Results: Segmental strains showed good to excellent agreement between SLICE and CMR-TAG (septum strain, intraclass correlation coefficient (ICC) 0.76; lateral wall strain, ICC 0.66). Conventional markers of CRT response also showed close agreement between both methods (ICC 0.61-0.78). Reproducibility of SLICE was excellent for intra-observer testing (all ICC ≥0.76) and good for interobserver testing (all ICC ≥0.61)., Conclusions: The novel SLICE post-processing technique on standard CMR cine images offers both accurate and robust segmental strain measures compared to the 'gold standard' CMR-TAG technique, and has the advantage of being widely available., Key Points: • Myocardial strain analysis could potentially improve patient selection for CRT. • Currently a well validated clinical approach to derive segmental strains is lacking. • The novel SLICE technique derives segmental strains from standard CMR cine images. • SLICE-derived strain markers of CRT response showed close agreement with CMR-TAG. • Future studies will focus on the prognostic value of SLICE in CRT candidates.

Background: Patients with left ventricular (LV) dyssynchrony have a marked misbalance in LV myocardial work distribution, with wasted work in the septum and increased work in the lateral wall. We hypothesized that a low septum-to-lateral wall (SL) myocardial work ratio at baseline predicts acute LV pump function improvement during cardiac resynchronization therapy (CRT)., Methods and Results: Twenty patients (age 65 ± 10 y, 15 men) underwent cardiac magnetic resonance (CMR) tagging for regional LV circumferential strain assessment and invasive pressure-volume loop assessment at baseline and during biventricular pacing. Segmental work at baseline was calculated from regional strain rate and LV pressure. Subsequently, the SL work ratio was calculated and related to acute pump function (stroke work [SW]) improvement during CRT. During biventricular pacing, SW increased by 33% (P <.001). SL work ratio at baseline was found to be significantly related to SW improvement by means of CRT (R = -0.54; P = .015). Moreover, it proved to be the only marker that was significantly related to acute response to CRT, whereas QRS duration and other measures of dyssynchrony or dyscoordination were not., Conclusions: The contribution of the septum to LV work varies widely in CRT candidates with left bundle branch block. The lower the septal contribution to myocardial work at baseline, the higher the acute pump function improvement that can be achieved during CRT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims Patient selection for cardiac resynchronization therapy (CRT) may be enhanced by evaluation of systolic myocardial stretching. We evaluate whether systolic septal rebound stretch (SRSsept) derived from speckle tracking echocardiography is a predictor of reverse remodelling after CRT and whether it holds additive predictive value over the simpler visual dyssynchrony assessment by apical rocking (ApRock). Methods and results The association between SRSsept and change in left ventricular end-systolic volume (ΔLVESV) at 6 months of follow-up was assessed in 200 patients. Subsequently, the additive predictive value of SRSsept over the assessment of ApRock was evaluated in patients with and without left bundle branch block (LBBB) according to strict criteria. SRSsept was independently associated with ΔLVESV (β 0.221, P  =   0.002) after correction for sex, age, ischaemic cardiomyopathy, QRS morphology and duration, and ApRock. A high SRSsept (≥optimal cut-off value 2.4) also coincided with more volumetric responders (ΔLVESV ≥ −15%) than low SRSsept in the entire cohort (70.0% and 56.4%), in patients with strict LBBB (83.3% vs. 56.7%, P  =   0.024), and non-LBBB (70.7% vs. 46.3%, P  =   0.004). Moreover, in non-LBBB patients, SRSsept held additional predictive information over the assessment of ApRock alone since patients that showed ApRock and high SRSsept were more often volumetric responder than those with ApRock but low SRSsept (82.8% vs. 47.4%, P  =   0.001). Conclusion SRSsept is strongly associated with CRT-induced reduction in left ventricular end-systolic volume and holds additive prognostic information over QRS morphology and ApRock. Our data suggest that CRT patient selection may be improved by assessment of SRSsept, especially in the important subgroup without strict LBBB. Clinical trial registration The MARC study was registered at clinicaltrials.gov: NCT01519908. [ABSTRACT FROM AUTHOR]

Aims: 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.Methods and Results: 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).Conclusion: 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. [ABSTRACT FROM AUTHOR]