Cardiac Resynchronization Therapy Optimization Research Articles

Emergent role of dynamic optimization in cardiac resynchronization therapy: Systematic review and network meta-analysis.

Suboptimal device programming is frequent in non-responders to cardiac resynchronization therapy (CRT). However, the role of device optimization and the most appropriate technique are still unknown. The aim of our study was to analyse the effect of different CRT optimization techniques within a network meta-analysis. A systematic search was conducted on MEDLINE, Embase and CENTRAL for studies comparing outcomes with empirical device settings or optimization using echocardiography, static algorithms or dynamic algorithms. Studies investigating the effect of optimization in non-responders were also analysed. A total of 17 studies with 4346 patients were included in the quantitative analysis. Of the treatments and outcomes examined, a significant difference was found only between dynamic algorithms and echocardiography, with the former leading to a higher echocardiographic response rate [odds ratio (OR): 2.02, 95% confidence interval (CI) 1.21-3.35], lower heart failure hospitalization rate (OR: 0.75, 95% CI 0.57-0.99) and greater improvement in 6-minute walk test [mean difference (MD): 45.52m, 95% credible interval (CrI) 3.91-82.44m]. We found no significant difference between empirical settings, static algorithms and dynamic algorithms. Seven studies with 228 patients reported response rates after optimization in non-responders. Altogether, 34.3%-66.7% of initial non-responders showed improvement after optimization, depending on response criteria. At the time of CRT implantation, dynamic algorithms may serve as a resource-friendly alternative to echocardiographic optimization, with similar or better mid-term outcomes. However, their superiority over empirical device settings needs to be investigated in further trials. For non-responders, CRT optimization should be considered, as the majority of patients experience improvement.

Factors that Determined a Positive Response to Resynchronization Therapy in Patients With Chronic Heart Failure and Cardiac Dyssynchrony. One Center Experience.

To evaluate the efficacy of cardiac resynchronization therapy (CRT) in patients with chronic heart failure (CHF) associated with cardiac dyssynchrony and to identify the factors that influence the CRT efficacy. This retrospective study included 155 patients after implantation of CRT devices. The CRT devices with a built-in cardioverter-defibrillator (CRT-D) and without it (CRT-P) were implanted in 139 (89.7%) and 16 (10.3%) patients, respectively. The follow-up period was 52.37±35.94 months. Based on the study results, two groups of patients were formed depending on the presence of a clinical response to CRT, responders and non-responders. The factors that influenced the clinical response to CRT were studied. The effect of the baseline state of patients on the effect of therapy was assessed. The need for CRT optimization and a possibility of using electrocardiographic criteria for that purpose were studied. Modern devices and leads for CRT, their functional capabilities and their influence on the CRT efficacy were characterized. Statistical analysis was performed with an IBM SPSS Statistics 21.0 (Chicago, USA) package. CRT implantation with the left ventricular lead placement according to the traditional technique, through the coronary sinus, was successful in 130 (87.9%) patients. Difficulties with the left ventricular lead placement were noted in 13 (8.3%) patients when other techniques were used. After 6 months, a hemodynamic and clinical response was observed in 112 (72.2%) patients, and no positive response in 43 (27.8%). The increase in left ventricular ejection fraction in the responder group was more than 21.8±3.7%, which was associated with an improvement of the 6-minute walk test results. Th clinical response was significantly influenced by the possibility of stimulation from the basal parts of the heart; the use of more modern devices for CRT and quadripolar left ventricular leads; timely CRT optimization; and persistent dyssynchrony in non-responders. During the follow-up period, 34 (21.9%) patients died. The death rate in the non-responder group was significantly higher than in the responder group, 18 (41.3%) vs. 16 (14.3%), p=0.001. The main cause of death in the group of non-responders was CHF. Heart transplantation was performed in 3 (1.9%) patients. CRT increases the life span and improves the quality of life in patients with CHF and cardiac dyssynchrony. There was a group of patients with no benefit from CRT in this study. Modern devices allow increasing the number of patients who benefit from CRT. Periodic optimization of CRT is necessary. When optimizing CRT, it is possible to use electrocardiographic criteria of effectiveness: duration of the QRS complex and changes in the position of the electrical axis of the heart.

Selection of candidates for cardiac resynchronization therapy and implantation management: an Italian survey promoted by the Italian Association of Arrhythmology and Cardiac Pacing.

Cardiac resynchronization therapy (CRT) represents an effective heart failure treatment, associated with reduction in mortality and heart failure hospitalizations. This Italian survey aimed to address relevant CRT issues. An online survey was administered to AIAC members. One hundred and five electrophysiologists participated, with a median of 40 (23-70) CRT implantations/year (33% in high-volume centres). Forty-five percent of respondents (especially working in high-volume centres) reported an increase in CRT implantations in the last 2 years, in 16% a decrease, and in 38% CRT remained stable. Seventy-five percent of respondents implanted CRT only in patients with European Heart Rhythm Association (EHRA) class I indications. All operators collected ECG and echocardiography before implantation. Eighty-five percent of respondents selected coronary sinus target vein empirically, whereas 10% used mechanical and/or electrical delay techniques. Physicians working in high-volume centres reported a lower failure rate compared with others (16 vs. 34%; P = 0.03). If the coronary sinus lead could not be positioned in the target branch, 80% placed it in another vein, whereas 16% opted for a surgical approach or for conduction system pacing (CSP). Eighty percent accomplished CRT optimization in all patients, 17% only in nonresponders. Regarding anticoagulation, high agreement with EHRA guidelines emerged. CRT represents a valid therapeutic option in heart failure treatment. Nowadays, CRT implantations remain stable and are mainly performed in patients with class I indications. ECG remains the preferred tool for patient selection, whereas imaging is increasingly used to determine the left pacing target area. In most patients, the left ventricular lead can be successfully positioned in the target vein, but in some cases, the result can be unsatisfactory; however, the decision to explore alternative resynchronization approaches is rarely pursued.

Minute ventilation sensor-driven rate response as a part of cardiac resynchronization therapy optimization in older patients.

Chronotropic incompetence (CI) is common among elderly cardiac resynchronization therapy pacemaker (CRT-P) patients on optimal medical therapy. This study aimed to evaluate the impact of optimized rate-adaptive pacing utilizing the minute ventilation (MV) sensor on exercise tolerance. In a prospective, multicenter study, older patients (median age 76years) with a guideline-based indication for CRT were evaluated following CRT-P implantation. If there was no documented CI, requiring clinically rate-responsive pacing, the device was programmed DDD at pre-discharge. At 1month, a 6-min walk test (6MWT) was conducted. If the maximum heart rate was < 100bpm or < 80% of the age-predicted maximum, the response was considered CI. Patients with CI were programmed with DDDR. At 3months post-implant, the 6MWT was repeated in the correct respective programming mode. In addition, heart rate score (HRSc, defined as the percentage of all sensed and paced atrial events in the single tallest 10bpm histogram bin) was assessed at 1 and 3months. CI was identified in 46/61 (75%) of patients without prior indication at enrollment. MV sensor-based DDDR mode increased heart rate in CI patients similarly to non-CI patients with intrinsically driven heart rates during 6MWT. Walking distance increased substantially with DDDR (349 ± 132m vs. 376 ± 128m at 1 and 3months, respectively, p < 0.05). Furthermore, DDDR reduced HRSc by 14% (absolute reduction, p < 0.001) in those with more severe CI, i.e., HRSc ≥ 70%. Exercise tolerance in older CRT-P patients can be further improved by the utilization of an MV sensor.

Impact of myocardial phenotype on atrioventricular delay optimization at rest and during exercise: insights from a virtual patient study

Abstract Background The usefulness of atrioventricular delay (AVD) optimization in cardiac resynchronization therapy (CRT) for heart failure (HF) patients with left bundle branch block (LBBB) and reduced left ventricular ejection fraction (LVEF) is still debated. Yet, studies have not explored the role of non-electrical myocardial disease substrates in determining optimal AVD settings among patients. Purpose We first hypothesized that acute response to AVD optimization might be modulated by various myocardial disease substrates. Furthermore, we hypothesized that cardiac function is more sensitive to changes in AV coupling during exercise and that this sensitivity is also modulated by underlying myocardial disease substrates. Methods We used the CircAdapt model of the human heart and circulation to simulate different types of LV remodeling that can be found in CRT candidates. First, an LBBB-like pattern of mechanical activation was imposed by delaying LV free wall (LVFW) and interventricular septal (IVS) activation relative to right ventricular free wall activation. Then, two types of LV remodeling were simulated by LV dilation with preserved or impaired myocardial contractility, resulting in LVEF &amp;lt;35%. To investigate the effect of diastolic dysfunction, we increased passive myocardial stiffness of the IVS and LVFW on both substrates with LV remodeling until a mean left atrial pressure (mLAP) of 14 mmHg was reached. CRT was simulated by resynchronizing IVS and LVFW. AVD optimization was conducted by gradually reducing the paced AVD from 220 ms to 40 ms in steps of 20 ms. In each simulation, the optimal paced AVD at rest (cardiac output (CO) and heart rate (HR) of 4.2 L/min and 80 bpm, respectively) was assessed using stroke volume (SV) and mLAP which is used as a measure of LV filling pressure. To investigate the relative effect of these myocardial phenotypes during AVD optimization under exercise, CO and HR were increased step-wise. Results The gain in SV by AVD optimization was larger in the simulations with healthy myocardium than in those with hypo-contractile and stiff myocardium (Figure 1: top-row). However, mLAP was comparably decreased by AVD optimization in healthy and diseased myocardium (Figure 1: bottom row). During exercise, the optimum AVD shifted to shorter values (Figure 2: top-row), and mLAP was much more sensitive to AVD, particularly in the presence of hypo-contractile and stiff myocardium (Figure 2: bottom row). Conclusion Virtual patient simulations show that both myocardial hypocontractility and stiffness dampen the effect of AVD optimization on SV. Furthermore, simulations suggest that patients benefit more from AVD optimization during exercise than during resting conditions. These mechanistic insights may help to gain more benefit from AVD optimization for patients undergoing CRT.AVD optimization at restAVD optimization during exercise

Ultra-High-Frequency ECG in Cardiac Pacing and Cardiac Resynchronization Therapy: From Technical Concept to Clinical Application.

Identifying electrical dyssynchrony is crucial for cardiac pacing and cardiac resynchronization therapy (CRT). The ultra-high-frequency electrocardiography (UHF-ECG) technique allows instantaneous dyssynchrony analyses with real-time visualization. This review explores the physiological background of higher frequencies in ventricular conduction and the translational evolution of UHF-ECG in cardiac pacing and CRT. Although high-frequency components were studied half a century ago, their exploration in the dyssynchrony context is rare. UHF-ECG records ECG signals from eight precordial leads over multiple beats in time. After initial conceptual studies, the implementation of an instant visualization of ventricular activation led to clinical implementation with minimal patient burden. UHF-ECG aids patient selection in biventricular CRT and evaluates ventricular activation during various forms of conduction system pacing (CSP). UHF-ECG ventricular electrical dyssynchrony has been associated with clinical outcomes in a large retrospective CRT cohort and has been used to study the electrophysiological differences between CSP methods, including His bundle pacing, left bundle branch (area) pacing, left ventricular septal pacing and conventional biventricular pacing. UHF-ECG can potentially be used to determine a tailored resynchronization approach (CRT through biventricular pacing or CSP) based on the electrical substrate (true LBBB vs. non-specified intraventricular conduction delay with more distal left ventricular conduction disease), for the optimization of CRT and holds promise beyond CRT for the risk stratification of ventricular arrhythmias.

Is CRT Optimization Obsolete? A Referral Center's Experience.

Cardiac resynchronization therapy (CRT) is a well-established therapy for patients with heart failure (HF). However, 30% of HF patients do not show any improvement in clinical status after CRT implantation. In this study, we report our echocardiography-based CRT optimization methodology, in daily practice at our CRT referral center. We included 350 ambulatory patients, who were referred to our center for optimization after CRT implantation. A protocol-driven echocardiographic approach for adjusting mechanical dyssynchrony, whereby adjusting for ventriculoventricular (VV) delays with strain and atrioventricular (AV) delays with Doppler echocardiography was performed. We defined changes in left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) classes as outcome variables in the evaluation of the CRT outcomes. Optimization was obtained in 288 (82%) patients. VV and AV timings were adjusted to 61% and 51%, respectively. In 3%, biventricular pacing was turned off and in 3% left ventricular (LV) only pacing was programmed. The LVEF and NYHA class showed significant improvements in all patients who underwent CRT optimization. CRT optimization remains valuable in improving LVEF and functional status measured using the NYHA class in all patients receiving CRT devices.

Imaging in patients with cardiovascular implantable electronic devices: part 2-imaging after device implantation. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association (EHRA) of the ESC.

Cardiac implantable electronic devices (CIEDs) improve quality of life and prolong survival, but there are additional considerations for cardiovascular imaging after implantation-both for standard indications and for diagnosing and guiding management of device-related complications. This clinical consensus statement (part 2) from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists, cardiac imagers, and pacing specialists regarding the use of imaging in patients after implantation of conventional pacemakers, cardioverter defibrillators, and cardiac resynchronization therapy (CRT) devices. The document summarizes the existing evidence regarding the role and optimal use of various cardiac imaging modalities in patients with suspected CIED-related complications and also discusses CRT optimization, the safety of magnetic resonance imaging in CIED carriers, and describes the role of chest radiography in assessing CIED type, position, and complications. The role of imaging before and during CIED implantation is discussed in a companion document (part 1).

Progress in Cardiac Resynchronisation Therapy and Optimisation.

Cardiac resynchronisation therapy (CRT) has become the cornerstone of heart failure (HF) treatment. Despite the obvious benefit from this therapy, an estimated 30% of CRT patients do not respond ("non-responders"). The cause of "non-response" is multi-factorial and includes suboptimal device settings. To optimise CRT settings, echocardiography has been considered the gold standard but has limitations: it is user dependent and consumes time and resources. CRT proprietary algorithms have been developed to perform device optimisation efficiently and with limited resources. In this review, we discuss CRT optimisation including the various adopted proprietary algorithms and conduction system pacing.

Noninvasive Electrical Mapping Compared with the Paced QRS Complex for Optimizing CRT Programmed Settings and Predicting Multidimensional Response

The aim was to test the hypothesis that left ventricular (LV) and right ventricular (RV) activation from body surface electrical mapping (CardioInsight 252-electrode vest, Medtronic) identifies optimal cardiac resynchronization therapy (CRT) pacing strategies and outcomes in 30 patients. The LV80, RV80, and BIV80 were defined as the times to 80% LV, RV, or biventricular electrical activation. Smaller differences in the LV80 and RV80 (|LV80-RV80|) with synchronized LV pacing predicted better LV function post-CRT (p = 0.0004) than the LV-paced QRS duration (p = 0.32). Likewise, a lower RV80 was associated with a better pre-CRT RV ejection fraction by CMR (r = − 0.40, p = 0.04) and predicted post-CRT improvements in myocardial oxygen uptake (p = 0.01) better than the biventricular-paced QRS (p = 0.38), while a lower LV80 with BIV pacing predicted lower post-CRT B-type natriuretic peptide (BNP) (p = 0.02). RV pacing improved LV function with smaller |LV80-RV80| (p = 0.009). In conclusion, 3-D electrical mapping predicted favorable post-CRT outcomes and informed effective pacing strategies.Graphical

Visualization of the SyncAV® Algorithm for CRT Optimization by Non-invasive Imaging of Cardiac Electrophysiology: NICE-CRT Trial.

(1) Background: Periodic repetitive AV interval optimization using a device-based algorithm in cardiac resynchronization therapy (CRT) devices may improve clinical outcomes. There is an unmet need to successfully transform its application into clinical routine. (2) Methods: Non-invasive imaging of cardiac electrophysiology was performed in different device programming settings of the SyncAV® algorithm in 14 heart failure patients with left bundle branch block and a PR interval ≤ 250 milliseconds to determine the shortest ventricular activation time. (3) Results: the best offset time (to be manually programmed) permitting automatic dynamic adjustment of the paced atrioventricular interval after every 256 heart beats was found to be 30 and 50 milliseconds, decreasing mean native QRS duration from 181.6 ± 23.9 milliseconds to 130.7 ± 10.0 and 130.1 ± 10.5 milliseconds, respectively (p = 0.01); this was followed by an offset of 40 milliseconds (decreasing QRS duration to 130.1 ± 12.2 milliseconds; p = 0.08). (4) Conclusions: The herein presented NICE-CRT study supports the current recommendation to program an offset of 50 milliseconds as default in patients with left bundle branch block and preserved atrioventricular conduction after implantation of a CRT device capable of SyncAV® optimization. Alternatively, offset programming of 30 milliseconds may also be applied as default programming. In patients with no or poor CRT response, additional efforts should be spent to individualize best offset programming with electrocardiographic optimization techniques.

Electrocardiographic Predictors of Complete Heart Block During Right Ventricular Lead Implantation in Patients Who Underwent Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) device procedures have their own complications in addition to the complications associated with standard pacemaker implantations. This study aimed to analyze the predictors of the right bundle branch injury resulting in complete heart block (CHB) during right ventricular (RV) lead implantation in patients who underwent CRT with defibrillator. We conducted an observational study of consecutive 790 patients who underwent CRT with defibrillator device implantation at our institution from 2010 to 2022. Relevant clinical information and complete data regarding the echocardiographic data, implantation procedure, and clinical follow-up were collected into a computerized database. A total of 29 patients (3.7%) had CHB during RV lead implantation. In multivariate analysis, left axis deviation (odds ratio [OR] 2.408, 95% confidence interval [CI] 1.025 to 5.658, p=0.044), QRS width (OR 1.022, 95% CI 1.001 to 1.043, p=0.035) and QRS alternans (OR 4.214, 95% CI 1.788 to 9.930, p=0.001) were found independently related to right bundle branch injury resulting in CHB development during RV lead implantation. In conclusion, left axis deviation, QRS width, and QRS alternans were associated with a higher rate of CHB, and these findings provide insight into optimal and safe CRT device implantation strategies based on preprocedural characteristics.

Machine learning–powered, device-embedded heart sound measurement can optimize AV delay in patients with CRT

Continuous optimization of atrioventricular (AV) delay for cardiac resynchronization therapy (CRT) is mainly performed by electrical means. The purpose of this study was to develop an estimation model of cardiac function that uses a piezoelectric microphone embedded in a pulse generator to guide CRT optimization. Electrocardiogram, left ventricular pressure (LVP), and heart sounds were simultaneously collected during CRT device implantation procedures. A piezoelectric alarm transducer embedded in a modified CRT device facilitated recording of heart sounds in patients undergoing a pacing protocol with different AV delays. Machine learning (ML) was used to produce a decision-tree ensemble model capable of estimating absolute maximal LVP (LVPmax) and maximal rise of LVP (LVdP/dtmax) using 3 heart sound-based features. To gauge the applicability of ML in AV delay optimization, polynomial curves were fitted to measured and estimated values. In the data set of ∼30,000 heartbeats, ML indicated S1 amplitude, S2 amplitude, and S1 integral (S1 energy for LVdP/dtmax) as most prominent features for AV delay optimization. ML resulted in single-beat estimation precision for absolute values of LVPmax and LVdP/dtmax of 67% and 64%, respectively. For 20-30 beat averages, cross-correlation between measured and estimated LVPmax and LVdP/dtmax was 0.999 for both. The estimated optimal AV delays were not significantly different from those measured using invasive LVP (difference -5.6 ± 17.1 ms for LVPmax and +5.1 ± 6.7 ms for LVdP/dtmax). The difference in function at estimated and measured optimal AV delays was not statiscally significant (1± 3 mm Hg for LVPmax and 9 ± 57 mm Hg/s for LVdP/dtmax). Heart sound sensors embedded in a CRT device, powered by a ML algorithm, provide a reliable assessment of optimal AV delays and absolute LVPmax and LVdP/dtmax.

Adaptive CRT algorithm and electrical synchrony

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): United Hospital Medical Education and Research Committee, United Hospital Foundation. Background We have previously shown that optimization of cardiac resynchronization therapy (CRT) nonresponders using a novel electrical dyssynchrony mapping (EDM) system significantly improves electrical dyssynchrony, left ventricle (LV) size and systolic function. Whether this methodology can improve electrical dyssynchrony (and potentially LV function) in nonresponder patients programmed with the adaptive CRT (aCRT) algorithm is not known. Purpose To quantify electrical dyssynchrony in CRT nonresponders programmed using aCRT and determine if it can be improved using EDM. Methods We studied 97 patients programmed with the aCRT algorithm at multiple device settings with an ECG system of 9 anterior and 9 posterior electrodes. We quantified electrical dyssynchrony using a measure of wavefront fusion, cardiac resynchronization index (CRI), calculated as % change in area under the curve between all combinations of anterior and posterior electrodes as compared to native LBBB (CRT off). CRI results were displayed on an electrical dyssynchrony map (EDM) showing atrial-to-right ventricle-paced intervals (A-RVp) on the y-axis and atrial-to-left ventricle-paced intervals (A-LVp) on the x-axis. Results Figure 1 shows an EDM for a typical patient with CRI values marked at different programmed settings. Figure 2 shows CRI for 58 patients programmed LV-only by aCRT at baseline (red bars) and 39 patients programmed biventricular (BiV) by aCRT at baseline (blue bars). CRI at baseline was significantly (p≤0.001) higher in patients programmed LV-only vs. those programmed BiV. In both groups programming to LV-only at the optimal atrial-ventricular delay (AVD) and to sequential BiV pacing at the optimal ventricular-ventricular delay (VVD) produced significantly and markedly better CRI as compared to CRI at aCRT baseline settings. In the patients programmed by aCRT at baseline to LV-only, BiV VV=0 at standard device setting (SAV 120 ms) had significantly worse CRI than baseline. Conclusions Electrical dyssynchrony as measured by CRI is better in patients programmed aCRT LV-only than those programmed aCRT BiV. CRI can be improved by 20% or more by using EDM to program patients to LV-only pacing at the optimal AVD or to BiV pacing at the optimal VVD. EDM technology offers the possibility of substantially improving electrical synchrony in nonresponder patients programmed with aCRT.

Hemodynamic optimization of cardiac resynchronization therapy by heart sound sensor in pulse generator

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU-HORIZON 2020-International Training Network H2020-MSCA-ITN-2017. Background Continuous ambulatory AV-optimization for Cardiac Resynchronization Therapy (CRT) is mainly performed by electrical means. Objective Develop an estimation model of cardiac function that uses feedback from a piezoelectric transducer embedded in an internal pulse generator to guide CRT optimization. Methods During implantation procedures measurements were performed of left ventricular pressure (LVP) and heart sound waveforms, the latter using the piezoelectric alarm transducer of the device in 22 CRT patients at atrioventricular (AV)-delays of 60-330 ms. Post-hoc, machine learning (ML) was employed to produce models that use heart-sound based features to estimate cardiac function in terms of maximum LVP (LVPmax) and the maximum positive derivative of LVP (LVdP/dtmax). Polynomial curve fitting was used to compare estimated and measured AV-delays with highest LVPmax and LVdP/dtmax. Results The figure displays the concept of the study and an example of the measured and estimated optimization curve. With a dataset of ~30,000 beats, ML provided three most suitable features. Using LVPmax, ML-based estimated optimal AV-delays were not significantly different from measured ones (-5.6 ± 17.1ms for LVPmax and +5.1 ± 46.7ms for LVdP/dtmax). The difference in function between the estimated and measured optimal AV-delays was small and not statically significant (1 ± 3mmHg for LVPmax and 9 ± 57mmHg/s for LVdP/dtmax). Conclusion Heart sound sensors in devices in combination with ML provide a reliable assessment of absolute LVPmax and LVdP/dtmax and may be used for continuous optimization of AV-delays in CRT patients.

Interaction between atrial-ventricular and ventricular-ventricular delay in CRT

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): United Hospital Medical Education and Research Committee, United Hospital Foundation. Background Appropriate programming of atrial-ventricular delay (AVD) and ventricular-ventricular delay (VVD) is critical for delivery of optimal cardiac resynchronization therapy (CRT). However, there is debate over how to determine optimal programming for a given patient. This is complicated by the use of 2 distinct methods of defining the activation timing at a given AVD and VVD used by different device manufacturers. Purpose To describe how electrical dyssynchrony is affected by changes in AVD, VVD and the method used to program AVD and VVD. Methods We measured electrical synchrony at multiple combinations of AVD/VVD in 41 patients with underlying left bundle branch block (LBBB) using a novel methodology called electrical dyssynchrony mapping (EDM). Electrical dyssynchrony was quantified by cardiac resynchronization index (CRI), calculated as % change in area under the curve between combinations of 9 anterior and 9 posterior surface electrograms. Results EDM (Figure 1) shows CRI at multiple combinations of atrial-to-RV-paced, (A-RVp, y-axis) and atrial-to-LV-paced (A-LVp, x-axis) intervals. VVD changes to produce LV preactivation are shown at short and long AVDs using the methods of 2 different CRT device manufacturers: Method 1: fixing A-RVp and shortening A-LVp; and Method 2: fixing A-LVp and lengthening A-RVp. During simultaneous BiV pacing, CRI at short AVD (61.7±20.9) was significantly (p&amp;lt;0.001) greater than at long AVD (46.9±14.0). On average, CRI was significantly greater at short AVD than at long AVD during LV preactivation of 20 or 40 ms (Figure 2). At short AVD, Method 2 resulted in slightly but significantly better CRI at VVD 20 and 40 ms. At long AVD, Method 1 resulted in large and significantly better CRI at VVD 20 and 40 ms. Conclusions The interaction between AVD and VVD is complex, and the electrical resynchronization achieved when programming depends on both the AVD at which VVD is programmed, and the programming algorithm used by the device manufacturer. At longer AVDs, Method 1 yields significantly better resynchronization than Method 2 when programming VVD. Studies assessing effects of AVD and VVD programming that involve patients with CRT devices from different manufacturers need to modify programming parameters appropriately in order to accurately interpret results. Methods For programming VVD and EDM

CI-452767-3 MACHINE LEARNING-POWERED, DEVICE-EMBEDDED HEART SOUND MEASUREMENT CAN OPTIMIZE AV DELAY IN CRT PATIENTS

Continuous ambulatory optimization of atrioventricular (AV) delay for cardiac resynchronization therapy (CRT) is mainly performed by electrical means. Development of an estimation model of cardiac function that uses a piezoelectric transducer embedded in an internal pulse generator to guide CRT optimization in patients. Electrocardiogram, left ventricular pressure (LVP) and heart sounds were simultaneously collected during the implantation procedures. A piezoelectric alarm transducer embedded in a modified CRT device facilitated recording heart sound in 22 patients undergoing a pacing protocol with AV delays varying from 60 to 330 ms. Post-hoc, machine learning was employed to produce a decision tree ensemble model capable of estimating maximal LVP (LVPmax) and maximal rate of rise of LVP (LVdP/dtmax) using heart-sound based features. To gauge the applicability of machine learning in AV delay optimization, polynomial curves were fitted to invasively measured and estimated values. The figure illustrates the concept of the study and an example of the invasively measured and heart sound-estimated AV delay optimization curves. In the dataset of ∼30,000 heartbeats, machine learning indicated S1 amplitude, S2 amplitude and S1 integral (or energy) as the most prominent features for AV delay optimization in terms of LVPmax and LVdP/dtmax. Machine learning facilitated categorical beat by beat estimation for absolute values of LVPmax (10 mmHg bin size) and LVdP/dtmax (100 mmHg/s bin size). The right panel illustrates the similar absolute values for LVPmax using 30 second averages. Estimated optimal AV delays using ∼30 second recordings were not significantly different from those measured using invasive LVP (difference: -5.6 ± 17.1 ms for LVPmax and +5.1 ± 46.7 ms for LVdP/dtmax). The difference in function between the estimated and measured optimal AV delays was small and not statically significant (1 ± 3mmHg for LVPmax and 9 ± 57mmHg/s for LVdP/dtmax). Heart sound sensors embedded in a CRT device, powered by a machine learning algorithm provide a reliable assessment of both optimal AV delays and absolute LVPmax and LVdP/dtmax in a clinical environment.

CI-452767-4 NON-INVASIVE 3D ELECTRICAL ACTIVATION MAPPING TO PREDICT CRT RESPONSE: SITE OF LATEST LV ACTIVATION RELATIVE TO PACING SITE

Left ventricular (LV) pacing remote to the latest LV electrically activated site (LEAS) may diminish efficacy of cardiac resynchronization therapy (CRT). However, this has not been evaluated rigorously using global LV mapping. Test whether the distance “dp” between LV pacing site (LVPS) and LEAS influences the rate of CRT response. Consecutive CRT patients in 5 centers underwent noninvasive 3D electrical activation mapping and torso CT 6-24 months post-implant. LVPS, LEAS and dp were assessed. LV end-systolic volume (LVESV) reduction of ≥15% at clinical follow-up defined response. Logistic regression probabilistically modeled Non-Response; variables included demographics, heart failure classification, left bundle branch block (LBBB), ischemic heart disease, atrial fibrillation (AF), baseline QRS duration, baseline ejection fraction (EF), baseline LVESV, comorbidities, use of CRT optimization algorithm, ACE inhibitor/ARB, beta-blocker, diuretics, and dp. Of 111 patients (age 64 ± 11 years, baseline LVEF 28 ± 6%, baseline QRS duration 172 ± 21 ms, baseline LVESV 183 ± 87 mL, implant duration 12 ± 5 months (mean ± SD); 93%/7% had class I/IIa CRT indication, 31%/69% had NYHA Class II/III, 74% were males, 98% had LBBB, 38% had ischemic heart disease and 18% had a history of AF), 67% responded at 10 ±3 months post-implant (55% and 75% for ischemic and non-ischemic patients, respectively). LEAS were outside the mid and basal lateral segments in 35% of the patients. dp was 42 ± 23 mm (range 2-137): 31 ± 14 mm in Responders vs 63 ± 24 mm in Non-Responders. The distance dp, and the use of CRT optimization algorithms, remained the only independent predictors of non-response (area under the curve (AUC) 0.906). dp = 47 mm delineated Responders from Non-Responders (AUC 0.931). The distance between LV pacing site and site of latest electrical activation is a strong independent predictor for CRT response. Non-invasive electrical evaluation to characterize intrinsic activation and guide LV lead deployment may improve CRT efficacy.

Comparison of immediate changes of repolarization parameters after left bundle branch area pacing and traditional biventricular pacing in heart failure patients.

Comparison of immediate changes of repolarization parameters after left bundle branch area pacing and traditional biventricular pacing in heart failure patients.

Additional benefit of echocardiographic optimization of cardiac resynchronization therapy devices according to specific echocardiographic and clinical parameters

Additional benefit of echocardiographic optimization of cardiac resynchronization therapy devices according to specific echocardiographic and clinical parameters