Cardiac Resynchronization Therapy Device Research Articles

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.

ANATOMICAL FEATURES OF THE CARDIAC VENOUS SYSTEM, SIGNIFICANT FOR THE LEFT VENTRICULAR LEAD PLACEMENT: LITERATURE REVIEW AND EXPERIENCE

HighlightsThe article is a comprehensive literature review on anatomical variations and anomalies of cardiac veins. A classification of coronary venous anatomy and anomalies detailing clinical, anatomical and radiological features is proposed. Developing such classification is important for the field of left ventricular lead placement, as it would cover a variety of clinically significant anomalies of cardiac veins. AbstractWith the advancements in the cardiac resynchronization therapy, the role of cardiac vein anatomy has become vital due to the complications associated with poor left ventricle lead placement. The cardiac vein anatomy varies much more than the anatomy of the coronary arteries, thus making cardiac veins much harder to study. In this article we have analyzed different approaches to description and naming of cardiac veins, and have summarized venous anomalies and features described in literature or encountered in real clinical practice. All anatomical features described in the article have a clinical significance in the left ventricle lead placement. Moreover, we have analyzed the wide variety of suggestions to overcoming anatomical obstacles. As a result of the analysis, we have proposed a clinical classification of the coronary venous anomalies and features that can be used during the implantation of cardiac resynchronization therapy devices.

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.

Localization of the ventricular pacing site from BSPM and standard 12-lead ECG: a comparison study

Inverse ECG imaging methods typically require 32–250 leads to create body surface potential maps (BSPM), limiting their routine clinical use. This study evaluated the accuracy of PaceView inverse ECG method to localize the left or right ventricular (LV and RV, respectively) pacing leads using either a 99-lead BSPM or the 12-lead ECG. A 99-lead BSPM was recorded in patients with cardiac resynchronization therapy (CRT) during sinus rhythm and sequential LV/RV pacing. The non-contrast CT was performed to localize precisely both ECG electrodes and CRT leads. From a BSPM, nine signals were selected to obtain the 12-lead ECG. Both BSPM and 12-lead ECG were used to localize the RV and LV lead, and the localization error was calculated. Consecutive patients with dilated cardiomyopathy, previously implanted with a CRT device, were enrolled (n = 19). The localization error for the RV/LV lead was 9.0 [IQR 4.8–13.6] / 7.7 [IQR 0.0–10.3] mm using the 12-lead ECG and 9.1 [IQR 5.4–15.7] / 9.8 [IQR 8.6–13.1] mm for the BSPM. Thus, the noninvasive lead localization using the 12-lead ECG was accurate enough and comparable to 99-lead BSPM, potentially increasing the capability of 12-lead ECG for the optimization of the LV/RV pacing sites during CRT implant or for the most favorable programming.

Significance of effective cardiac resynchronization therapy pacing for clinical responses: An analysis based on the effective cardiac resynchronization therapy algorithm

High percent ventricular pacing maximizes cardiac resynchronization therapy (CRT) response. An effective CRT algorithm classifies each left ventricular (LV) pace as effective or ineffective on the basis of the detection of QS or QS-r morphology on the electrogram; however, the relationship between percent effective CRT pacing (%e-CRT) and responses is unclear. We aimed to clarify the association between %e-CRT and clinical outcomes. Of the 136 consecutive CRT patients, 49 using the adaptive and effective CRT algorithm with percent ventricular pacing > 90% were evaluated. The primary and secondary outcomes were heart failure (HF) hospitalization and prevalence of CRT responders, defined as patients with an improvement in LV ejection fraction of ≥10% or a reduction in LV end-systolic volume of ≥15% after CRT device implantation, respectively. We divided the patients into the effective group (n = 25) and the less effective group (n = 24) by the median value of %e-CRT (97.4%). During the median follow-up period of 507 days (interquartile range 335-730 days), the effective group had a significantly lower risk of HF hospitalization than did the less effective group as revealed by Kaplan-Meier analysis (log-rank, P = .016). Univariate analysis revealed %e-CRT ≥ 97.4% (hazard ratio 0.12; 95% confidence interval 0.01-0.95; P = .045) as a predictor of HF hospitalization. The effective group had a higher prevalence of CRT responders than did the less effective group (23 [92%] vs 9 [38%]; P < .001). Univariate analysis revealed that %e-CRT ≥ 97.4% (odds ratio 19.20; 95% confidence interval 3.63-101.00; P < .001) was a predictor of CRT response. High %e-CRT is associated with high CRT responder prevalence and low HF hospitalization risk.

Potential feasibility of a novel over-the-wire microelectrode catheter for recording coronary sinus electrograms in patients with cardiac resynchronization therapy devices.

The placement of an electrode catheter into the coronary sinus (CS) is important for differentiating multiple atrial tachycardias (ATs). Based on its high selective performance in placement into small veins, inserting a novel over-the-wire 2.7Fr microcatheter (EPstar Fix AIV; Japan Lifeline) into the CS may be feasible even in patients implanted with a cardiac resynchronization therapy device.

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.

Cardiac implantable electronic devices and outcomes in heart failure patients with syncope

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Mayo Clinic Background/Introduction Syncope is a common presentation in heart failure (HF) patients. However, the associations between syncope and prognosis in HF patients with the cardiac implantable electronic device (CIED) have not been demonstrated. It is unclear whether syncope increases all-cause mortality in HF patients with CIED. Purpose We aimed to examine the association between syncope and all-cause mortality in the largest cohort of HF with reduced ejection fraction (HFrEF), mid-ranged ejection fraction (HFmEF), and preserved ejection fraction (HFpEF) patients with and without CIED. Methods A retrospective cohort of patients with HF and syncope at our hospital between 2010 and 2015 were identified, and 1:1 propensity was matched with a control group of HF patients without syncope. A chart review was conducted. The multivariate Cox regression model was applied to estimate the association between syncope and the all-cause mortality endpoint. Results 3,449 HF patients were diagnosed with syncope (mean age, 72.8±14.5 years; 41.5% women), and the propensity-matched control HF patients without syncope (n=3,449) aged 72.8±14.3 years, and 42.5% women were selected. Cardiac implantable electronic devices were implanted more in HF patients with syncope (32.5% versus 13.7%, p&amp;lt;0.001). Implantable cardioverter defibrillators were implanted more in HF patients with syncope (15.6% versus 8.3%, p&amp;lt;0.001) as well as pacemakers (16.9% versus 7.5%, p&amp;lt;0.001) and cardiac resynchronization therapy devices (6.9% versus 4.8%, p=0.015). Among HF patients with CIED, syncope significantly increased the risk of all-cause mortality in HFrEF patients (hazard ratio [HR]=1.479, 95% confidence interval [CI]: 1.197-1.828, p&amp;lt;0.001) but not in HFpEF (HR=0.980, 95%CI: 0.793-1.210, p=0.849)(Figure 1). Syncope also tended to increase the risk of all-cause mortality in HFmEF patients with CIED but was not significant (HR=1.193, 95%CI: 0.762-1.865, p=0.762)(Figure 1). Among HF patients without CIED, syncope did not increase the risk of all-cause mortality in HFrEF (HR=0.923, 95%CI: 0.806-1.057, p=0.247), HFmEF (HR=1.074, 95%CI: 0.848-1.360, p=0.554), or HFpEF (HR=0.964, 95%CI: 0.883-1.052, p=0.406). Conclusions Syncope significantly increased the risk of all-cause mortality in HFrEF patients but not in HFmEF or HFpEF patients with CIED. The association of syncope and increased mortality in HFrEF patients with CIED suggests that syncope may be a marker and a factor of mortality and warrants further investigation.

Blood stream infection in patients with implantable-cardioverter defibrillator admitted to non-cardiology units: incidence, diagnostic work-up and outcome

Abstract Funding Acknowledgements Type of funding sources: None. Background There is limited knowledge on the incidence of blood stream infections (BSI) in patients with implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy devices (CRTs), as well as about the diagnostic work-up and outcome when these patients are admitted to non-cardiology units. Purpose We assessed the incidence of BSI in patients with an ICD or CRT, evaluated the diagnostic work-up performed, and investigated the outcome. Methods This is a single-center, retrospective cohort analysis of all 515 patients implanted with a de-novo ICD or CRT between 2012 and 2021 at our centre, and subsequently admitted to a non-cardiology unit of any public hospital in Canton Ticino with a BSI (≥ 2 positive blood cultures). Device infection was defined according to the 2019 International Cardiac Implantable Electronic Device (CIED) Infection Criteria. Results A total of 43 patients were diagnosed with BSI during a median follow-up of 48 months (IQR 24-78 months). Incidence rate for BSI was 19 (95%-CI 14 – 26) and 23 (95%-CI 14 – 35) per 1000 patient-years for ICDs and CRTs, respectively. The most common source for BSI was urinary tract infection (21%), which was mostly caused by gram positive pathogens (68%) with coagulase-negative staphylococci being the most frequent one (39%). Definite CIED infection rate in patients presenting with BSI was 11.6% (see table). The majority of patients (56%) had no cardiac imaging including transthoracic or transesophageal echocardiography; a PET-CT was performed in only 4 patients (9%). Nearly all patients (86%) were treated with short-term antibiotics; in contrast, system extraction (2.3%) and chronic antibiotic therapy (4.7%) were rarely performed. Throughout the entire follow-up period, patients with BSI had a 8-fold higher probability (HR 7.8, 95% CI 4.8-12.7; p&amp;lt;0.001) of all-cause mortality compared to those without BSI. Conclusions Awareness in non-cardiology units about possible device infection in patients with BSI is rather low leading to limited diagnostic work-up and ultimately to a high mortality rate of these 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

Long-term mortality in cardiac resynchronization therapy upgrade procedures compared with de novo implantations - a nationwide cohort study

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Cardiovascular Academy Background Patients with an implanted pacemaker (PM) or implantable cardioverter-defibrillator (ICD) who develop heart failure (HF) and have frequent right ventricular (RV) pacing, may be upgraded to a Cardiac Resynchronization Therapy (CRT) device. Such upgrades constitute approximately one fourth of CRT implantations. Limited research has been devoted to long-term outcomes after upgrade implantations and diverging results have been reported. Purpose We aimed to investigate long-term mortality in patients undergoing upgrade to CRT after previous PM or ICD implantation and patients undergoing CRT de novo implantation. Methods This was a nationwide register-based cohort study. The patient cohort was identified via the Danish Pacemaker and ICD Registry and consisted of consecutive Danish patients undergoing a CRT de novo implantation or an upgrade to CRT, from 01.01.2000 to 31.08.2018. Upgrade from a CRT pacemaker to a CRT defibrillator, and simple device replacement procedures were not included. Data were cross-linked with the Danish Patient Registry via the unique central person registration number. The endpoint was total mortality. Unadjusted- and adjusted Cox proportional hazard regression was used to assess the association between the procedure type (upgrade or de novo), baseline characteristics and total mortality. Results We identified 8,880 patients of whom 6,685 (75.3%) underwent de novo CRT implantation and 2,195 (24.7%) underwent upgrade to CRT from a previous PM or ICD. The median (IQR) follow-up time was 3.9 years (5.3) and 4.6 years (4.3) for upgrade and de novo implantations respectively. At baseline, patients who underwent upgrade to CRT were older (median 71.9 vs. 69.3 years) and more likely to have ischemic heart disease (66.8% vs. 57.1%), atrial fibrillation or atrial flutter (57.5% vs. 33.4%) and chronic kidney disease (10.3% vs. 7.2%) compared to patients who had de novo implantation. The proportion of males was larger among patients who underwent upgrade to CRT compared to de novo implantation (84.1% vs. 74.9%). Upgrade implantations were associated with higher minimally adjusted (age and sex) total mortality (HR 1.13, [95% CI 1.05;1.21], p&amp;lt;0.001) compared to de novo implantations. There was no difference in total mortality between upgrade and de novo implantations after adjusting for age, sex, diabetes, hypertension, chronic ischemic heart disease, atrial fibrillation or atrial flutter, chronic obstructive pulmonary disease, and chronic kidney disease (HR 1.03, [95% CI 0.96;1.10], p=0.46). Conclusion There are major differences in co-morbidities among patients undergoing upgrade to CRT and patients undergoing CRT de novo implantation. When adjusting for these differences, there was no difference in total mortality between the two populations. This suggests that CRT is equally beneficial in both de novo and upgrade implantations.

Prognostic value of nutritional status in post-implant CRT outcomes in patients with chronic heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Introduction There’s a close relationship between chronic heart failure (CHF) and malnutrition, and their main pathophysiological modifications are well known. Cardiac resynchronization therapy (CRT) has proven to be a promising therapy in symptomatic heart failure (HF) patients with broad QRS complexes and impaired systolic function with optimized medical therapy. However, there is still a considerable amount of non-responder patients. The role of nutritional status in CRT therapy response has yet still not been well assessed. Purpose Assess the prognostic value of nutritional status in post-op outcomes in patients with Chronic Heart Failure and (CRT) Methods Single-center retrospective study of patients submitted to CRT implantation between January 2007 and march 2021. Inclusion criteria were patients meeting criteria for CRT implantation, QRS duration ≥ 120ms, FEVE ≤ 35%, NYHA class II–IV and no adverse events during the follow up. Primary outcomes measured were all-cause mortality, cardiovascular mortality, and hospitalizations due to HF in a 1-year follow-up. To evaluate patient's nutritional status the CONUT score was used with patients being categorized in 2 groups: Low CONUT (Score 0-4: normal/low malnutrition) and Hight CONUT (Score 5-12: moderate/severe malnutrition). Results 198 patients (83%) exhibited Low CONUT status, and 41 patients (17%) exhibited High CONUT status. Patients with Hight CONUT were older (72.9 yrs vs 65.9 yrs, p&amp;lt;0.001), and exhibited higher percentage of chronic obstructive pulmonary disease (43.9% vs 27.3%, p=0.004), atrial fibrillation (72.9%, vs 25.3%, p&amp;lt;0.001), hypertension (78.1% vs 60.6%, p=0.038), chronic kidney disease (39.1% vs 21.2%, p=0.016) and NYHA IV (19.5% vs 5.1%, p&amp;lt;0.001). Cardiovascular mortality was 3.7% in the low CONUT group vs 29.3% in the Hight CONUT group (p&amp;lt;0.001; HR, 0.12; 95% CI, 0.05-0.29) and total HF hospitalizations were 16 and43, respectively (p=0.013; HR, 0.482, 95% CI, 0.27 to 0.86). The nutritional status prior to CRT assessed by the CONUT score showed to be an independent predictor of cardiovascular mortality (p=0.007; HR, 0.16 95% CI, 0.04-0,60). Conclusion Malnutrition was a common condition in our CRT patients showing that deficient nutrition status remains highly underdiagnosed. Patients with worse nutritional status before CRT device implantation presented higher morbidity and were more prone to worst outcomes such as cardiovascular mortality and mortality by all causes as well as higher incidence of hospitalizations secondary to HF decompensation. Assessment of nutritional status using screening tools may provide additional prognostic information in patients with HF and help early identification of those who may benefit from further assessment and nutritional intervention.

The impact of intravenous ferric carboxymaltose on reverse electrical remodeling following cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background The effect of intravenous ferric carboxymaltose (FCM) on reverse electrical remodeling (RER) in patients with heart failure with reduced ejection fraction (HFrEF) following cardiac resynchronization therapy (CRT) implantation is unknown. Purpose The current study aims to examine the effect of iron replacement with intravenous FCM on RER in CRT-implanted patients with HFrEF and iron deficiency. Methods The present study retrospectively analyzed 65 patients with successful CRT-D device implantation between March 2017 and January 2020 with iron deficiency (defined as ferritin &amp;lt;100 μg/L) at implantation. Follow-up data were obtained from the 6-month routine follow-up visits of patients following CRT implantation. Demographic characteristics, laboratory results, medical history, medication details, functional status, information on whether intravenous FCM therapy was administered during CRT device implantation, echocardiographic left ventricular (LV) measurements, baseline electrocardiogram (ECG) recorded before CRT device implantation, and follow-up ECG were collected for analysis for each study patient. From baseline to 6-month follow-up, the change in intrinsic QRS duration (without biventricular pacing) was calculated as a primary endpoint, and the change in LV ejection fraction (LVEF) was assessed as a secondary endpoint of the study. Results Thirty-five of 65 patients were in the FCM group, while the remaining 30 study participants were in the non-FCM. The two study groups were similar regarding baseline characteristics, except for ferritin levels, which were minimally significantly lower in the FCM group (10.7±5.0μg/L vs 13.5 ±3.9μg/L, p= 0.012). At the 6-month follow-up, both mean ferritin levels increased significantly in the FCM group compared to baseline (from 10.7±5.0 to 86.5±7.6μg/L, p &amp;lt; 0.0001), while these levels were not significantly increased in the non-FCM group (from 13.5±3.9 to 14.1±4.2μg/L, p = 0.962). There was a significant reduction in intrinsic QRS durations compared to baseline at 6-month follow-up after CRT implantation in both FCM and non-FCM group (from 148.4±5.3 to 138.0±5.1ms, p &amp;lt; 0.0001; from 149.8±5.0 to 146.8±4.6ms, p &amp;lt; 0.0001, respectively). The change in intrinsic QRS duration from baseline to 6-month follow-up was significantly greater in the FCM group than in the non-FCM group (-10.4±2.2ms vs -3±2.9ms, p &amp;lt; 0.0001). At the 6-month follow-up, the change in LVEF from baseline was significantly higher in the FCM group than in the non-FCM group (+3.6±1.6% vs -0.1±1.7%, p &amp;lt; 0.0001). The change in ferritin level was negatively correlated with the change in intrinsic QRS duration (r = -0.725, p &amp;lt; 0.0001), whereas there was a positive correlation between the change in ferritin level and the change in LVEF (r = 0.712, p &amp;lt; 0.0001). Conclusions Treatment with FCM was induced RER and improvement in LVEF in HFrEF patients with iron deficiency following CRT implantation.

C28 LEFT VENTRICULAR OUTFLOW TRACT VELOCITY–TIME INTEGRAL (LVOT–VTI) IMPROVES RISK STRATIFICATION IN HEART FAILURE PATIENTS WITH SECONDARY MITRAL REGURGITATION

Abstract Background Reduced left ventricular ejection fraction (LVEF) has been used as a key criterion for the management of mitral regurgitation (MR) in patients with heart failure (HF), including the decision about mitral valve repair. However, LVEF, not taking into account mitral regurgitant volume, may be an imprecise predictor of outcome in HF patients with MR. Conversely, the estimation of the forward volume through the LV outflow tract (LVOT) may be a better metric in this setting. In this regard, LVOT velocity time integral (LVOT–VTI), not relying on geometrical assumptions, has been shown to be more reproducible than the calculated stroke volume (i.e., LVOT–VTI * LVOT cross sectional area). Objective To assess the prognostic significance of LVOT–VTI in a contemporary cohort of patients with chronic HF and significant MR. Methods Consecutive patients with chronic HF with reduced (≤40%) or mildly reduced (41–49%) LVEF and moderate–to–severe or severe MR, according to the latest European Society of Cardiology criteria, were selected and followed–up for the endpoint of cardiac death. Results 287 patients were enrolled in the study (74±11 years, 70% men, 46% ischemic etiology, HFrEF 89%, LVEF 30±9%, mean LVOT–VTI 20±5 cm). Most patients showed a NYHA class II (40%) or III (31%) and received beta–blockers (93%), ACE–inhibitors/ARBs or ARNI (77%), and mineralocorticoid receptor antagonists (76%). One hundred and ten patients (39%) had permanent atrial fibrillation and 82 (29%) a cardiac resynchronization therapy device. Over a median follow–up of 33 (16–47) months, 114 patients died, 71 of whom for cardiac cause, and 28 underwent mitral valve repair/replacement. The risk of cardiac death increased proportionally to the decrease of LVOT–VTI (Figure 1, panel A), with an optimal prognostic cut–off of 17 cm (Figure 1, panel B). Reduced LVOT–VTI was associated with higher NYHA class, NT–proBNP concentration, and worse right ventricle systolic function (all p&amp;lt;0.005). At multivariable competing risks regression analysis, a unit decrease of LVOT–VTI (HR 0.87 [95%CI 0.80–0.93], p&amp;lt;0.001), but not of LVEF (p=0.254), was independently associated with a higher risk of cardiac death (Figure 1, panel C). Conclusion Left ventricular forward volume, noninvasively estimated through LVOT–VTI, but not LVEF, predicts the risk of cardiac death in patients with chronic HF and significant MR.

P247 QRS INDEX TO PREDICT CARDIAC RESYNCHRONIZATION THERAPY RESPONSE: A TRICENTRIC STUDY

Abstract Background Several studies have evaluated the role of QRS duration (QRSd) or QRS narrowing as predictor of response to cardiac resynchronization therapy (CRT) in order to reduce non–responders. However, their results have been conflicting. In our study we analyzed retrospectively a cohort of patients from three centers to better correlate the association between the relative change in QRS narrowing index (QI) and clinical outcome and prognosis in patients who underwent CRT implantation. Methods We included 398 patients in whom a CRT device was implanted in accordance with current guidelines in our three centres. Baseline clinical variables, echocardiographic parameters and pharmacological therapies were included. QRS duration before and after CRT implantation and QI [(pre implant QRS duration – QRS duration during CRT)/pre implant QRS duration × 100] were measured. Results Respect to echocardiographic follow up at 6 months, a significant improvement in all parameters (EF, LVEDV, LVESV) was observed. In 68% of patients, LVESV decreased by 10% or more. QI was significantly related to reverse remodelling (r = + 0.22; 95% CI: 0.11 to 0.32, p = 0.001). The cut–off value of QI that predicted best LV reverse remodelling after 6 months of CRT was 12.25% (sensitivity 65,49%, specificity 75%, area under the curve 0.7, p = 0.001). Regarding clinical outcomes at 12 mounths, a statistically significant difference was found between patients with a QI &amp;lt; 12.25%, and those with a QI &amp;gt; 12.25%, in terms of NYHA class worsening (p 0,04). Another statistically significant difference was found analyzing the relation between QI and the causes of deaths, the mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes. (p 0,0179). Conclusions Therefore decrease in QRSd after CRT initiation was related to greater echocardiographic reverse remodelling and better outcome from death or cardiovascular hospitalization. Even if larger studies are needed, QI seems to be an easy–to– measure variable that could be used or evaluated to predict CRT response.

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.

PO-02-016 PHYSIOLOGIC SIGNALS FROM CRT DEVICES ARE INDICATIVE OF CRT RESPONSE IN SMART-MSP STUDY

Cardiac resynchronization therapy (CRT) is a well-established treatment for some heart failure patients with reduced ejection fraction, but a subset of these patients does not respond to CRT. Multi-site pacing (MSP) is proposed to improve clinical response to CRT, but it is unclear which CRT subset would benefit from MSP. Physiologic sensor data from CRT devices may provide insights into this question. To determine whether device based physiologic parameters are indicative of CRT response/non-response and thus identify potential candidates for MSP. SMART-MSP study evaluated 6-month CRT response, defined by improved Clinical Composite Score, in patients with CRT defibrillators (CRT-D). Device parameters considered for this analysis included third (S3) and first (S1) heart sounds, thoracic impedance (ITTI), respiration rate, rapid shallow breathing index (RSBI), activity, and the multi-sensor HeartLogic index. From a randomly selected 60% development set of patients (183 CRT responders and 40 non-responders) with at least 150 days of data, the following statistical measures were calculated for each parameter based on the first 60- and 150-day epoch after CRT-D implant: mean (μ), standard deviation (σ) and change from first 30-day mean to last 30-day mean (Δ). To evaluate the effect of each measure on CRT response, odds ratios were calculated and tested for significance via univariable and multivariable logistic regression. The 60-day analysis (Fig 1A) shows that increases in σ60 for S3, S3/S1, RSBI, respiration rate, and HeartLogic index as well as μ60 for RSBI were significantly associated with reduced odds of CRT response in the univariable model. The only signal to survive multivariate elimination was respiration rate σ60. The 150-day analysis (Fig 1B) shows the same indications and that increases in μ150 for RSBI and HeartLogic index were associated with reduced odds while increases in μ150 and Δ150 for activity were associated with increased odds of CRT response. Both respiration rate σ150 and activity Δ150 survived multivariate elimination. Multiple device-based physiologic parameters significantly differed between CRT responders versus non-responders in the SMART-MSP study. 60-day results indicate that there is potential for device-based parameters to identify patients who may benefit from switching to MSP sooner. However, while useful parameters are apparent early on (60-day window), more parameters become significant over a longer follow-up (150 days).

Spontaneous QRS complex narrowing predicts left ventricle reverse remodeling in CRT patients

Mechanical cardiac dyssynchrony is an important component of cardiac remodeling during heart failure with reduced ejection fraction. Furthermore, echocardiographic assessment of left ventricle reverse remodelingrepresents the major tool to evaluate cardiac resynchronization therapy (CRT) response. In contrast, according to major randomized trialsmechanical dyssynchrony assessment failed and electrocardiographic proof of dyssynchrony is needed to indicate CRT, therefore; electrical reverse remodeling was suggested by few clinical studies conducted with a small number of patients. Additional information is required on the relationship between electrical (ERR) and structural reverse remodeling (SRR) in patients treated with cardiac resynchronization therapy. We investigated whether ERR defined as narrowing of the native electrocardiographic QRS duration after CRT might predict improvement in echocardiographic outcome. We collected 75 patients who underwent successful CRT device implantation in our department. Clinical, electrocardiographic and echocardiographic parameters were collected before implantation and after a variable duration of follow up in the outpatient clinic. SRR was defined as an improvement of LVEF > 5% and/or a reduction in LVESV > 15%. ERR was defined as a decrease in native QRS duration > 10 milliseconds (was recorded after switching off biventricular pacing). After a mean follow up duration of 69 months from the time of implantation, 51 patients had an echocardiographic response (SRR) and among 45 patients who had demonstrated an electrocardiographic response (ERR), 75% developed SRR (vs. 55% for those without ERR P = 0.07) and only 7.5% of them were ischemic cardiomyopathy. Mean QRS reduction was at 16 milliseconds in patients with SRR versus 8 milliseconds in patients without SRR (P = 0.02). Reversal electric remodeling as assessed by native QRS narrowing was associated with greater improvements in mean LVEF (16% vs. 10%, P = 0.1), mean LVEDV (85 mL vs. 35 mL, P = 0.04) and mean LVESV (77 mL vs. 37 mL, P = 0.1). Native QRS narrowing after initiation of CRT in patients with HFrEF was positively correlated tostructural reverse remodeling parameters assessed by echocardiography and consequently to the echocardiographic outcome.

PO-05-055 A META-ANALYTIC COMPARISON OF OUTCOMES OF LEFT BUNDLE BRANCH AREA PACING (LBBP) VERSUS BI-VENTRICULAR PACING FOR CARDIAC RESYNCHRONIZATION THERAPY

Left bundle branch area pacing (LBBP), has emerged as a novel method to deliver cardiac resynchronization therapy (CRT), as an alternative to biventricular pacing (BVP). We aimed to evaluate the outcomes of LBBP as an alternative to BVP as a method of CRT. We aimed to evaluate the outcomes of LBBP as an alternative to BVP as a method of CRT. A systematic literature-based search was performed on various electronic databases, i.e., PubMed, Embase, Scopus, and Cochrane libraries, for studies that compared LBBP with BVP. The primary outcomes that were studied were changes in left ventricular end-diastolic diameter (LVEDD), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF) and paced QRS duration post CRT device implantation. Six articles (1 randomized trial and five observational studies) with a total of 399 patients (42% with LBBP as CRT) were included in the final analysis. A pooled random-effects analysis of the primary outcomes revealed that patients who underwent LBBP had a significantly greater reduction in left ventricular end-diastolic diameter [Mean Difference (MD) 0.40 (95% Confidence Interval (CI), 0.17-0.63); p < 0.001] and paced QRS duration [MD 1.03 (95% CI, 0.63-1.43); p < 0.001] as compared to the BVP group. There was also a significantly greater improvement in NYHA class [MD 0.64 (95% CI, 0.33-0.96); p < 0.001] and the LVEF [MD 0.83 (95% CI, 0.33-1.33); p < 0.001] in the LBBP group. (Figure 1 with the forest plots) LBBP has the potential to improve clinical outcomes over conventional BVP in patients undergoing CRT. This finding should be further confirmed by randomized trials with a larger sample size and well-defined outcome measures and feasibility indicators. Although limited by the observational nature of the included studies, our meta-analysis sets the stage towards the consideration of LBBP in patients who meet the indications for CRT.

PO-03-080 OPTIMIZING POST-IMPLANT CRT MANAGEMENT

Implementing a post-implant cardiac resynchronization therapy (CRT) clinic using a combined electrophysiology (EP) & heart failure (HF) advanced practice provider (APP) model may improve subspecialty collaboration & prevent delays in device & medical optimization. Some previously described models evaluate patients 6 months post-procedure. Early follow-up post-implant may further improve response. To determine if a 1 month post-implant device interrogation provides actionable data to improve CRT response at 6 months using a dual-APP multidisciplinary model. We designed a multidisciplinary clinic to formally evaluate patients after CRT device implant. The team involves an advanced HF APP, an EP APP & a HF nurse. Standard device clinic follow up is maintained with the addition of a device interrogation at 1 month to evaluate device function & CRT pacing. Interventions are made at 1 month as necessary. Patients are then seen in the multidisciplinary clinic 6 months following implant & undergo device interrogation, ECG, echocardiogram, & 6-minute walk test. Patients are simultaneously seen by the APPs & a unified plan of care is developed. The electronic medical records were reviewed prospectively for clinical characteristics pre-implant & at 1 & 6 months post-implant, which were summarized with descriptive statistics, including correlation between 1 month data & 6 month CRT response. CRT responders at 6 months were defined as having an LVEF improvement of ≥5% & a reduction in LVESVi ≥10%. Ninety-six patients seen in the clinic from September 2020 to April 2022 were evaluated. The mean age was 70 years; 66 (69%) were male; 40 (42%) had ischemic cardiomyopathy; 53 (56%) had no documented arrhythmia history prior to device implant; 13 (13.5%) were considered to have permanent atrial fibrillation (AF). Of these patients, 52 (54%) were considered CRT responders at 6 months. One month CRT pacing >95% correlated with 6 month CRT response (coefficient of 0.11, std error 0.04, p= 0.01). PVC burden >5% negatively correlated with CRT response (coefficient of 0.15, std error 0.15, p=.02). AF burden did not correlate with CRT response (coefficient of 0.01, std error 0.01, p=0.14). Multivariate analysis did not show these variables to be independently predictive of CRT response. An APP-led, early post-implant evaluation of CRT patients may provide an opportunity to improve six-month CRT response.