Short-Time Estimation of Fractionation in Atrial Fibrillation with Coarse-Grained Correlation Dimension for Mapping the Atrial Substrate

[EN] Atrial ¿brillation (AF) is currently the most common cardiac arrhythmia, with catheter ablation (CA) of the pulmonary veins (PV) being its ¿rst line therapy. Ablation of complex fractionated atrial electrograms (CFAEs) outside the PVs has demonstrated improved long-term results, but their identi¿cation requires a reliable electrogram (EGM) fractionation estimator. This study proposes a technique aimed to assist CA procedures under real-time settings. The method has been tested on three groups of recordings: Group 1 consisted of 24 highly representative EGMs, eight of each belonging to a different AF Type. Group 2 contained the entire dataset of 119 EGMs, whereas Group 3 contained 20 pseudo-real EGMs of the special Type IV AF. Coarse-grained correlation dimension (CGCD) was computed at epochs of 1 s duration, obtaining a classi¿cation accuracy of 100% in Group 1 and 84.0¿85.7% in Group 2, using 10-fold cross-validation. The receiver operating characteristics (ROC) analysis for highly fractionated EGMs, showed 100% speci¿city and sensitivity in Group 1 and 87.5% speci¿city and 93.6% sensitivity in Group 2. In addition, 100% of the pseudo-real EGMs were correctly identi¿ed as Type IV AF. This method can consistently express the fractionation level of AF EGMs and provides better performance than previous works. Its ability to compute fractionation in short-time can agilely detect sudden changes of AF Types and could be used for mapping the atrial substrate, thus assisting CA procedures under real-time settings for atrial substrate modi¿cation.This research has been supported by grants DPI2017-83952-C3 from MINECO/AEI/FEDER EU, SBPLY/17/180501/000411 from JCCM and AICO/2019/036 from GVA.Vraka, A.; Hornero, F.; Bertomeu-Gonzalez, V.; Osca, J.; Alcaraz, R.; Rieta, JJ. (2020). Short-Time Estimation of Fractionation in Atrial Fibrillation with Coarse-Grained Correlation Dimension for Mapping the Atrial Substrate. Entropy. 22(2):1-20. https://doi.org/10.3390/e22020232S120222Go, A. S., Hylek, E. M., Phillips, K. A., Chang, Y., Henault, L. E., Selby, J. V., & Singer, D. E. (2001). Prevalence of Diagnosed Atrial Fibrillation in Adults. JAMA, 285(18), 2370. doi:10.1001/jama.285.18.2370Goette, A., Honeycutt, C., & Langberg, J. J. (1996). Electrical Remodeling in Atrial Fibrillation. Circulation, 94(11), 2968-2974. doi:10.1161/01.cir.94.11.2968Chugh, S. S., Roth, G. A., Gillum, R. F., & Mensah, G. A. (2014). Global Burden of Atrial Fibrillation in Developed and Developing Nations. Global Heart, 9(1), 113. doi:10.1016/j.gheart.2014.01.004Cappato, R., Calkins, H., Chen, S.-A., Davies, W., Iesaka, Y., Kalman, J., … Biganzoli, E. (2010). Updated Worldwide Survey on the Methods, Efficacy, and Safety of Catheter Ablation for Human Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology, 3(1), 32-38. doi:10.1161/circep.109.859116Cox, J. L., Canavan, T. E., Schuessler, R. B., Cain, M. E., Lindsay, B. D., Stone, C., … Boineau, J. P. (1991). The surgical treatment of atrial fibrillation. The Journal of Thoracic and Cardiovascular Surgery, 101(3), 406-426. doi:10.1016/s0022-5223(19)36723-6Haïssaguerre, M., Jaïs, P., Shah, D. C., Takahashi, A., Hocini, M., Quiniou, G., … Clémenty, J. (1998). Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins. New England Journal of Medicine, 339(10), 659-666. doi:10.1056/nejm199809033391003Kornej, J., Schumacher, K., Zeynalova, S., Sommer, P., Arya, A., Weiß, M., … Hindricks, G. (2019). Time-dependent prediction of arrhythmia recurrences during long-term follow-up in patients undergoing catheter ablation of atrial fibrillation: The Leipzig Heart Center AF Ablation Registry. Scientific Reports, 9(1). doi:10.1038/s41598-019-43644-2YOSHIDA, K., ULFARSSON, M., TADA, H., CHUGH, A., GOOD, E., KUHNE, M., … ORAL, H. (2008). Complex Electrograms Within the Coronary Sinus: Time- and Frequency-Domain Characteristics, Effects of Antral Pulmonary Vein Isolation, and Relationship to Clinical Outcome in Patients with Paroxysmal and Persistent Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 19(10), 1017-1023. doi:10.1111/j.1540-8167.2008.01175.xKonings, K. T., Kirchhof, C. J., Smeets, J. R., Wellens, H. J., Penn, O. C., & Allessie, M. A. (1994). High-density mapping of electrically induced atrial fibrillation in humans. Circulation, 89(4), 1665-1680. doi:10.1161/01.cir.89.4.1665Rolf, S., Kircher, S., Arya, A., Eitel, C., Sommer, P., Richter, S., … Piorkowski, C. (2014). Tailored Atrial Substrate Modification Based on Low-Voltage Areas in Catheter Ablation of Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology, 7(5), 825-833. doi:10.1161/circep.113.001251Takahashi, Y., O’Neill, M. D., Hocini, M., Dubois, R., Matsuo, S., Knecht, S., … Haïssaguerre, M. (2008). Characterization of Electrograms Associated With Termination of Chronic Atrial Fibrillation by Catheter Ablation. Journal of the American College of Cardiology, 51(10), 1003-1010. doi:10.1016/j.jacc.2007.10.056Atienza, F., Almendral, J., Jalife, J., Zlochiver, S., Ploutz-Snyder, R., Torrecilla, E. G., … Berenfeld, O. (2009). Real-time dominant frequency mapping and ablation of dominant frequency sites in atrial fibrillation with left-to-right frequency gradients predicts long-term maintenance of sinus rhythm. Heart Rhythm, 6(1), 33-40. doi:10.1016/j.hrthm.2008.10.024Nademanee, K., McKenzie, J., Kosar, E., Schwab, M., Sunsaneewitayakul, B., Vasavakul, T., … Ngarmukos, T. (2004). A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. Journal of the American College of Cardiology, 43(11), 2044-2053. doi:10.1016/j.jacc.2003.12.054Ciaccio, E. J., Biviano, A. B., Whang, W., Coromilas, J., & Garan, H. (2011). A new transform for the analysis of complex fractionated atrial electrograms. BioMedical Engineering OnLine, 10(1), 35. doi:10.1186/1475-925x-10-35Ciaccio, E. J., Biviano, A. B., & Garan, H. (2013). Computational method for high resolution spectral analysis of fractionated atrial electrograms. Computers in Biology and Medicine, 43(10), 1573-1582. doi:10.1016/j.compbiomed.2013.07.033TSAI, W.-C., LIN, Y.-J., TSAO, H.-M., CHANG, S.-L., LO, L.-W., HU, Y.-F., … CHEN, S.-A. (2010). The Optimal Automatic Algorithm for the Mapping of Complex Fractionated Atrial Electrograms in Patients With Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 21(1), 21-26. doi:10.1111/j.1540-8167.2009.01567.xTeh, A. W., Kistler, P. M., Lee, G., Medi, C., Heck, P. M., Spence, S. J., … Kalman, J. M. (2011). The relationship between complex fractionated electrograms and atrial low-voltage zones during atrial fibrillation and paced rhythm. Europace, 13(12), 1709-1716. doi:10.1093/europace/eur197Lin, Y.-J., Lo, M.-T., Chang, S.-L., Lo, L.-W., Hu, Y.-F., Chao, T.-F., … Chen, S.-A. (2016). Benefits of Atrial Substrate Modification Guided by Electrogram Similarity and Phase Mapping Techniques to Eliminate Rotors and Focal Sources Versus Conventional Defragmentation in Persistent Atrial Fibrillation. JACC: Clinical Electrophysiology, 2(6), 667-678. doi:10.1016/j.jacep.2016.08.005Verma, A., Jiang, C., Betts, T. R., Chen, J., Deisenhofer, I., Mantovan, R., … Sanders, P. (2015). Approaches to Catheter Ablation for Persistent Atrial Fibrillation. New England Journal of Medicine, 372(19), 1812-1822. doi:10.1056/nejmoa1408288Ammar-Busch, S., Reents, T., Knecht, S., Rostock, T., Arentz, T., Duytschaever, M., … Deisenhofer, I. (2018). Correlation between atrial fibrillation driver locations and complex fractionated atrial electrograms in patients with persistent atrial fibrillation. Pacing and Clinical Electrophysiology, 41(10), 1279-1285. doi:10.1111/pace.13483Almeida, T. P., Chu, G. S., Salinet, J. L., Vanheusden, F. J., Li, X., Tuan, J. H., … Schlindwein, F. S. (2016). Minimizing discordances in automated classification of fractionated electrograms in human persistent atrial fibrillation. Medical & Biological Engineering & Computing, 54(11), 1695-1706. doi:10.1007/s11517-016-1456-2De Bakker, J. M. T., & Wittkampf, F. H. M. (2010). The Pathophysiologic Basis of Fractionated and Complex Electrograms and the Impact of Recording Techniques on Their Detection and Interpretation. Circulation: Arrhythmia and Electrophysiology, 3(2), 204-213. doi:10.1161/circep.109.904763Luca, A., Buttu, A., Pruvot, E., Pascale, P., Bisch, L., & Vesin, J.-M. (2016). Nonlinear analysis of right atrial electrograms predicts termination of persistent atrial fibrillation within the left atrium by catheter ablation. Physiological Measurement, 37(3), 347-359. doi:10.1088/0967-3334/37/3/347Corana, A., Casaleggio, A., Rolando, C., & Ridella, S. (1991). Efficient computation of the correlation dimension from a time series on a LIW computer. Parallel Computing, 17(6-7), 809-820. doi:10.1016/s0167-8191(05)80068-7Fraser, A. M., & Swinney, H. L. (1986). Independent coordinates for strange attractors from mutual information. Physical Review A, 33(2), 1134-1140. doi:10.1103/physreva.33.1134Martínez-Iniesta, M., Ródenas, J., Alcaraz, R., & Rieta, J. J. (2017). Waveform Integrity in Atrial Fibrillation: The Forgotten Issue of Cardiac Electrophysiology. Annals of Biomedical Engineering, 45(8), 1890-1907. doi:10.1007/s10439-017-1832-6Theiler, J., Eubank, S., Longtin, A., Galdrikian, B., & Doyne Farmer, J. (1992). Testing for nonlinearity in time series: the method of surrogate data. Physica D: Nonlinear Phenomena, 58(1-4), 77-94. doi:10.1016/0167-2789(92)90102-sNakamura, T., Small, M., & Hirata, Y. (2006). Testing for nonlinearity in irregular fluctuations with long-term trends. Physical Review E, 74(2). doi:10.1103/physreve.74.026205SHAPIRO, S. S., & WILK, M. B. (1965). An analysis of variance test for normality (complete samples). Biometrika, 52(3-4), 591-611. doi:10.1093/biomet/52.3-4.591Mandelbrot, B. (1961). Contributions to Probability and Statistics: Essays in Honor of Harold Hotelling (Ingram Olkin, Sudhist G. Ghurye, Wassily Hoeffding, William G. Madow, and Henry B. Mann, eds.). SIAM Review, 3(1), 80-80. doi:10.1137/1003016Mann, H. B., & Whitney, D. R. (1947). On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other. The Annals of Mathematical Statistics, 18(1), 50-60. doi:10.1214/aoms/1177730491Křemen, V., Lhotská, L., Macaš, M., Čihák, R., Vančura, V., Kautzner, J., & Wichterle, D. (2008). A new approach to automated assessment of fractionation of endocardial electrograms during atrial fibrillation. Physiological Measurement, 29(12), 1371-1381. doi:10.1088/0967-3334/29/12/002Haley, C. L., Gula, L. J., Miranda, R., Michael, K. A., Baranchuk, A. M., Simpson, C. S., … Redfearn, D. P. (2012). Validation of a novel algorithm for quantification of the percentage of signal fractionation in atrial fibrillation. EP Europace, 15(3), 447-452. doi:10.1093/europace/eus361Nollo, G., Marconcini, M., Faes, L., Bovolo, F., Ravelli, F., & Bruzzone, L. (2008). An Automatic System for the Analysis and Classification of Human Atrial Fibrillation Patterns from Intracardiac Electrograms. IEEE Transactions on Biomedical Engineering, 55(9), 2275-2285. doi:10.1109/tbme.2008.923155Kirchner, M., Faes, L., Olivetti, E., Riccardi, R., Scaglione, M., Gaita, F., & Antolini, R. (s. f.). Local electrical characterisation of human atrial fibrillation. Computers in Cardiology 2000. Vol.27 (Cat. 00CH37163). doi:10.1109/cic.2000.898567Cirugeda–Roldán, E., Novak, D., Kremen, V., Cuesta–Frau, D., Keller, M., Luik, A., & Srutova, M. (2015). Characterization of Complex Fractionated Atrial Electrograms by Sample Entropy: An International Multi-Center Study. Entropy, 17(12), 7493-7509. doi:10.3390/e17117493Corino, V. D. A., Rivolta, M. W., Sassi, R., Lombardi, F., & Mainardi, L. T. (2013). Ventricular activity cancellation in electrograms during atrial fibrillation with constraints on residuals’ power. Medical Engineering & Physics, 35(12), 1770-1777. doi:10.1016/j.medengphy.2013.07.010Rieta, J. J., Hornero, F., Alcaraz, R., & Moratal, D. (2007). Ventricular Artifacts Cancellation from Atrial Epicardial Recordings in Atrial Tachyarrhythmias. 2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. doi:10.1109/iembs.2007.4353849Williams, G. (1997). Chaos Theory Tamed. doi:10.1201/9781482295412Havstad, J. W., & Ehlers, C. L. (1989). Attractor dimension of nonstationary dynamical systems from small data sets. Physical Review A, 39(2), 845-853. doi:10.1103/physreva.39.84

Nonsurgical transthoracic epicardial radiofrequency ablation An alternative in incessant ventricular tachycardia

AbstractObjectivesThe purpose of this study was to analyze the feasibility, efficacy, and safety of epicardial radiofrequency (RF) ablation in patients with incessant ventricular tachycardia (VT).BackgroundManagement of patients with incessant VT is a difficult clinical problem. Drugs and RF catheter ablation are not always effective. A nonsurgical transthoracic epicardial RF ablation can be an alternative in patients refractory to conventional therapy.MethodsEpicardial RF ablation was performed in 10 patients who presented with incessant VT despite the use of two or more intravenous antiarrhythmic drugs.ResultsIn eight patients, endocardial ablation (EdA) failed to control the tachycardia. In the remaining two patients, epicardial ablation (EpA) was first attempted because of left ventricular thrombus and severe artery disease, respectively. Eight patients had a diagnosis of coronary artery disease with healed myocardial infarction. One patient had dilated cardiomyopathy, and one patient had idiopathic, incessant VT. In patients with structural heart disease, the mean ejection fraction was 0.28 ± 0.10%. Four patients previously received an implantable defibrillator. The EpA effectively terminated the incessant tachycardia in eight patients, which represents a success rate of 80%. In them, after a follow-up of 18 ± 18 months, a single episode of a different VT was documented in one patient. No significant complications occurred related to the procedure.ConclusionsIn patients with incessant VT despite the use of drugs or standard EdA, the epicardial approach was very effective and should be considered as an alternative in this life-threatening situation

Acute Hemodynamic Effects of Simultaneous and Sequential Multi-Point Pacing in Heart Failure Patients With an Expected Higher Rate of Sub-response to Cardiac Resynchronization Therapy: Results of Multicenter SYNSEQ Study

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 Registration: ClinicalTrials.gov, identifier: NCT02914457

Personalized assessment of the cumulative complication risk of the atrial fibrillation ablation track: The AF-TRACK calculator

Atrial fibrillation (AF) ablation strategy is associated with a non-negligible risk of complications and often requires repeat procedures (AF ablation track), implying repetitive exposure to procedural risk.The purpose of this study was to develop and validate a model to estimate individualized cumulative risk of complications in patients undergoing the AF ablation track (Atrial Fibrillation TRAck Complication risK [AF-TRACK] calculator).The model was derived from a multicenter cohort including 3762 AF ablation procedures in 2943 patients. A first regression model was fitted to predict the propensity for repeat ablation. The AF-TRACK calculator computed the risk of AF ablation track complications, considering the propensity for repeat ablation. Internal (cross-validation) and external (independent cohort) validation were assessed for discrimination capacity (area under the curve [AUC]) and goodness of fit (Hosmer-Lemeshow [HL] test).Complications (N = 111) occurred in 3.7% of patients (2.9% of procedures). Predictors included female sex, heart failure, sleep apnea syndrome, and repeat procedures. The model showed fair discrimination capacity to predict complications (AUC 0.61 [0.55-0.67]) and likelihood of repeat procedure (AUC 0.62 [0.60-0.64]), with good calibration (HL χ2 12.5; P = .13). The model maintained adequate discrimination capacity (AUC 0.67 [0.57-0.77]) and calibration (HL χ2 5.6; P = .23) in the external validation cohort. The validated model was used to create the Web-based AF-TRACK calculator.The proposed risk model provides individualized estimates of the cumulative risk of complications of undergoing the AF ablation track. The AF-TRACK calculator is a validated, easy-to-use, Web-based clinical tool to calibrate the risk-to-benefit ratio of this treatment strategy.© 2022 Heart Rhythm Society. Published by Elsevier Inc

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Cardiac Resynchronization Therapy with a Quadripolar Electrode Lead Decreases Complications at 6 Months Results of the MORE-CRT Randomized Trial

Objectives The aim of this study was to test the hypothesis that a quadripolar left ventricular (LV) lead results in fewer LV lead-related events than a bipolar cardiac resynchronization therapy (CRT) system in a prospective randomized trial. Background Bipolar LV leads cannot be implanted at the optimal site in up to 10% of patients who need CRT, because of anatomic or technical challenges (pacing threshold, phrenic stimulation, or mechanical instability). Methods The MORE-CRT (More Options Available With a Quadripolar LV Lead Provide In-Clinic Solutions to CRT Challenges) trial enrolled 1,078 patients. Patients with indications for CRT defibrillator therapy were randomized into 2 groups in a 1:2 ratio: a group with a bipolar CRT lead system (the BiP group; any manufacturer) and a group with a quadripolar CRT system (the Quad group; Quartet LV lead). The primary endpoint was freedom from a composite endpoint of intraoperative and post-operative LV lead-related events at 6 months. Results A total of 1,074 of 1,078 patients (99%) were randomized and contributed to the primary endpoint. Freedom from the composite endpoint was significantly greater in the Quad than the BiP group (83.0% vs. 74.4%, p = 0.0002). The intraoperative component of the endpoint was met less frequently by Quad group patients (6.26% Quad vs. 12.1% BiP), whereas there was no difference for the post-operative component (7.1% Quad vs. 7.6% BiP). Conclusions The Quartet LV system significantly reduced total LV lead-related events at 6 months after implantation compared with a bipolar CRT system. The reduction in events demonstrates the superiority of this quadripolar technology to effectively manage CRT patients. (More Options Available With a Quadripolar LV Lead Provide In-Clinic Solutions to CRT Challenges [MORE-CRT]; NCT01510652)

Acute Hemodynamic Effects of Simultaneous and Sequential Multi-Point Pacing in Heart Failure Patients With an Expected Higher Rate of Sub-response to Cardiac Resynchronization Therapy : Results of Multicenter SYNSEQ Study

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 Registration: ClinicalTrials.gov, identifier: NCT02914457