Conventional Biventricular Pacing Research Articles

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.

Conventional biventricular pacing is still preferred to conduction system pacing for atrioventricular block in patients with reduced ejection fraction and narrow QRS.

It is well established that right ventricular pacing is detrimental in patients with reduced cardiac function who require ventricular pacing (VP), and alternatives nowadays are comprised of biventricular pacing (BiVP) and conduction system pacing (CSP). The latter modality is of particular interest in patients with a narrow baseline QRS as it completely avoids, or minimizes, ventricular desynchronization associated with VP. In this article, experts debate whether BiVP or CSP should be used to treat these patients.

Beyond biventricular pacing: Exploring the advantages of his-bundle pacing and left bundle branch pacing in heart failure-A systematic review and meta-analysis.

This meta-analysis compares His-Purkinje system pacing (HPSP), a novel cardiac resynchronization therapy (CRT) technique that targets the intrinsic conduction system of the heart, with conventional biventricular pacing (BiVP) in heart failure (HF) patients with left ventricular (LV) dysfunction and dyssynchrony. We searched multiple databases up to May 2023 and identified 18 studies (five randomized controlled trials and 13 observational studies) involving 1291 patients. The outcome measures were QRS duration, left ventricular ejection fraction (LVEF) improvement, left ventricular end-diastolic diameter (LVEDD) change, HF hospitalization, and New York Heart Association (NYHA) functional class improvement. We used a random-effects model to calculate odds ratios (OR), and mean differences (MD) with 95% confidence intervals (CI). We also assessed the methodological quality of the studies. The mean LVEF was 30.7% and the mean follow-up duration was 8.1 months. Among LBBP, HBP, and BiVP, HBP provided the shortest QRS duration [MD: -18.84ms, 95% CI: -28.74 to -8.94; p=0.0002], while LBBP showed the greatest improvement in LVEF [MD: 5.74, 95% CI: 2.74 to 7.46; p<0.0001], LVEDD [MD: -5.55mm, 95% CI: -7.51 to -3.59; p<0.00001], and NYHA functional class [MD: -0.58, 95% CI: -0.80 to --0.35; p<0.00001]. However, there was no significant difference in HF hospitalization between HPSP and BiVP. LBBP as modality of HPSP demonstrated superior outcomes in achieving electrical ventricular synchrony and systolic function, as well as alleviating HF symptoms, compared to other pacing techniques.

Emerging Technologies in Cardiac Pacing.

Cardiac pacing to treat bradyarrhythmias has evolved in recent decades. Recognition that a substantial proportion of pacemaker-dependent patients can develop heart failure due to electrical and mechanical dyssynchrony from traditional right ventricular apical pacing has led to development of more physiologic pacing methods that better mimic normal cardiac conduction and provide synchronized ventricular contraction. Conventional biventricular pacing has been shown to benefit patients with heart failure and conduction system disease but can be limited by scarring and fibrosis. His bundle pacing and left bundle branch area pacing are novel techniques that can provide more physiologic ventricular activation as an alternative to conventional or biventricular pacing. Leadless pacing has emerged as another alternative pacing technique to overcome limitations in conventional transvenous pacemaker systems. Our objective is to review the evolution of cardiac pacing and explore these new advances in pacing strategies.

Abstract 16969: Assessment of the Electromechanical Window in Patients With Conventional Biventricular Pacing as Compared to Patients With Conduction System Pacing

Introduction: The Electromechanical Window (EMW) is a validated measurement reflecting electromechanical coupling of the ventricles, and is defined as the difference between electrical and mechanical ventricular activation times. A larger (more negative) EMW is associated with worse clinical outcomes, especially greater arrhythmic risk, in various clinical conditions such as long QT syndrome, risk of drug-inducd torsade, hypertrophic cardiomyopathy, etc. Cardiac resynchronization therapy (CRT) can be achieved by conventional bi-ventricular pacing (BiVP) or conduction system pacing (CSP). We assessed the EMW in patients undergoing CRT via these 2 modalities. Methods: Total mechanical activation time was measured from the 5 chamber echocardiographic view as the interval (ms) from the onset of the Q wave to aortic valve closure (mean of 3 measurements). Total electrical activation time (QTcBazett interval, ms) was measured from 12 lead ECGs recorded within 24 hours of the echocardiogram. The EMW was calculated as the difference between the QTc and the mechanical ventricular activation time. Results: A total of 60 pts (BiVP=31, CSP=29) were analyzed. There was no significant difference between the heart rates during the ECG and the echocardiogram recorded within 24 hours of each other (74.6 ± 16.5 vs 71.5 ± 12.0 bpm, P=NS). The EMW was significantly more negative in patients with BiVP as compared to CSP (-99.5 ± 70.9 vs -55.2 ± 52.7 ms, P=0.03). When restricting the analysis to patients where the ECG and echocardiographic HRs were within 10 bpm of each other, the difference remained significant (P=0.03). Conclusions: Patients in whom CRT is achieved by CSP have less negative EMWs as compared to patients with BiVP. Based on the known association of more negative EMW with increased arrhythmic risk, these data, if confirmed in larger populations with correlation to clinical outcomes, add to the growing evidence to support CSP as the preferred modality for achieving CRT.

Abstract 13067: Conduction System Pacing to Achieve Cardiac Resynchronization Therapy: Is There a Sex Difference in Response Rates?

Background: It is well established that in patients with dyssynchronous heart failure related to left bundle branch block (LBBB) and reduced left ventricular ejection fraction (LVEF), females show higher response rates than males when cardiac resynchronization (CRT) is achieved by conventional biventricular (BiV) pacing. Whether this sex difference is also true when CRT is achieved via conduction system pacing is unknown. Hypothesis: There is no difference between women and men in response rates when CRT is achieved by conduction system pacing (CSP), either by His bundle pacing (HBP) or by left bundle area pacing (LBAP). Methods: Patients who underwent CSP with a baseline LVEF ≤40% and a QRS duration ≥140 milliseconds (ms) were retrospectively selected from a CSP database maintained at our institution. 52 patients were included: 17 females and 35 males. Baseline clinical, electrocardiographic, echocardiographic, and follow up data were gathered and analyzed. Electrocardiograms and echocardiograms closest to the dates of implant and at last known follow up were used. Super-response was defined as absolute EF improvement ≥15%. Results: At baseline, there were no statistically significant differences in clinical, electrocardiographic, and echocardiographic characteristics between females and males except for higher prevalence of coronary disease in men, and higher percentage use of guideline directed medical therapy in men (Table 1). At median follow up of 113 days, there were no differences in electrocardiographic or echocardiographic response, number of super-responders, and mortality between females and males (Table 1). Conclusions: Unlike conventional CRT where females show superior response rates, CRT with CSP seems to provide comparable benefits in females and males. If confirmed in larger data sets, this may represent an important advantage of CSP over conventional CRT.

Acute Hemodynamic Effect of a NovelDual-Vein, Multisite Biventricular Pacing Configuration.

Biventricular pacing (BVP) from multiple left ventricular (LV) sites could enhance the efficacy of cardiac resynchronization therapy (CRT) by engaging a greater myocardial mass. The goal of this study was to evaluate the acute hemodynamic effect of various multisite pacing (MSP) configurations against conventional BVP. Twenty patients with nonischemic dilated cardiomyopathy and left bundle branch block (mean age: 59 ± 14 years; LV ejection fraction: 27% ± 6%; native QRS: 171 ± 16 milliseconds) were investigated during a routine CRT implant procedure. In addition to conventional right atrial and right ventricular leads, 2 quadripolar leads were placed in the distant coronary venous branches. LV hemodynamics was evaluated by using a micromanometer-tipped catheter during atrioventricular BVP with 4 LV lead configurations: single-lead conventional BVP; single-lead multipoint pacing; triventricular pacing from distal dipoles of 2 LV leads; and maximum MSP (MSP-Max) from 4 dipoles of 2 LV leads. Compared with right atrial pacing, any BVP configuration produced a significant increase in the maximal LV diastolic pressure rise (LVdP/dTMax) (amedian relative increase of 28% [IQR: 8%-45%], 25% [IQR: 18%-46%], 36% [IQR: 18%-54%], and 38% [IQR: 28%-58%], respectively; all, P< 0.001). MSP-Max but no other multisite BVP generated a significant increase of the maximal LVdP/dTMax than conventional BVP (P=0.041). Increased LVdP/dTMax during MSP-Max was associated with greater LV diameter and lower LV ejection fraction, independently of the QRS width. The study shows the hemodynamic advantage of a novel dual-vein MSP-Max configuration that could be useful for CRT in patients with advanced LV remodeling.

Conduction System Pacing versus Conventional Biventricular Pacing for Cardiac Resynchronization Therapy: Where Are We Heading?

Over the last few years, pacing of the conduction system (CSP) has emerged as the new standard pacing modality for bradycardia indications, allowing a more physiological ventricular activation compared to conventional right ventricular pacing. CSP has also emerged as an alternative modality to conventional biventricular pacing for the delivery of cardiac resynchronization therapy (CRT) in heart failure patients. However, if the initial clinical data seem to support this new physiological-based approach to CRT, the lack of large randomized studies confirming these preliminary results prevents CSP from being used routinely in clinical practice. Furthermore, concerns are still present regarding the long-term performance of pacing leads when employed for CSP, as well as their extractability. In this review article, we provide the state-of-the-art of CSP as an alternative to biventricular pacing for CRT delivery in heart failure patients. In particular, we describe the physiological concepts supporting this approach and we discuss the future perspectives of CSP in this context according to the implant techniques (His bundle pacing and left bundle branch area pacing) and the clinical data published so far.

The evolving state of cardiac resynchronization therapy and conduction system pacing: 25 years of research at EP Europace journal.

Cardiac resynchronization therapy (CRT) was proposed in the 1990s as a new therapy for patients with heart failure and wide QRS with depressed left ventricular ejection fraction despite optimal medical treatment. This review is aimed first to describe the rationale and the physiologic effects of CRT. The journey of the landmark randomized trials leading to the adoption of CRT in the guidelines since 2005 is also reported showing the high level of evidence for CRT. Different alternative pacing modalities of CRT to conventional left ventricular pacing through the coronary sinus have been proposed to increase the response rate to CRT such as multisite pacing and endocardial pacing. A new emerging alternative technique to conventional biventricular pacing, conduction system pacing (CSP), is a promising therapy. The different modalities of CSP are described (Hirs pacing and left bundle branch area pacing). This new technique has to be evaluated in clinical randomized trials before implementation in the guidelines with a high level of evidence.

Left bundle branch area pacing for heart failure patients requiring cardiac resynchronization therapy: A meta-analysis.

Left bundle branch area pacing (LBBP) is a novel conduction system pacing method to achieve effective physiological pacing and an alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) for patients with heart failure with reduced ejection fraction (HFrEF). We conduted this meta-analysis and systemic review to review current data comparing BVP and LBBP in patients with HFrEF and indications for CRT. We searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications for CRT were included. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated risk ratios (RRs) with the Mantel-Haenszel method and mean difference (MD) with inverse variance using random effect models. We assessed heterogeneity using the I2 index, with I2  > 50% indicating significant heterogeneity. Ten studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time (MD: 9.68, 95% confidence interval [CI]: 4.49-14.87, I2  = 95%, p < .01, minutes) as well as a shorter procedural time (MD 33.68, 95% CI: 17.80-49.55, I2  = 73%, p < .01, minutes) during the implantation of LBBP CRT compared to conventional BVP CRT. LBBP was shown to have a greater reduction in QRS duration (MD 25.13, 95% CI: 20.06-30.20, I2  = 51%, p < .01, milliseconds), a greater left ventricular ejection fraction improvement (MD: 5.80, 95% CI: 4.81-6.78, I2  = 0%, p < .01, percentage), and a greater left ventricular end-diastolic diameter reduction (MD: 2.11, 95% CI: 0.12-4.10, I2  = 18%, p = .04, millimeter). There was a greater improvement in New York Heart Association function class with LBBP (MD: 0.37, 95% CI: 0.05-0.68, I2  = 61%, p = .02). LBBP was also associated with a lower risk of a composite of heart failure hospitalizations (HFH) and all-cause mortality (RR: 0.48, 95% CI: 0.25-0.90, I2  = 0%, p = .02) driven by reduced HFH (RR: 0.39, 95% CI: 0.19-0.82, I2  = 0%, p = .01). However, all-cause mortality rates were low in both groups (1.52% vs. 1.13%) and similar (RR: 0.98, 95% CI: 0.21-4.68, I2  = 0%, p = .87). This meta-analysis of primarily nonrandomized studies suggests that LBBP is associated with a greater improvement in left ventricular systolic function and a lower rate of HFH compared to BVP. There was uniformity of these findings in all of the included studies. However, it would be premature to conclude based solely on the current meta-analysis alone, given the limitations stated. Dedicated, well-designed, randomized controlled trials and observational studies are needed to elucidate better the comparative long-term efficacy and safety of LBBP CRT versus BIV CRT.

Left bundle branch area pacing reduces epicardial dispersion of repolarization compared with biventricular cardiac resynchronization therapy

Biventricular endocardial pacing (BiV-endo) and left bundle branch area pacing (LBBAP) are novel methods of delivering cardiac resynchronization therapy. These techniques are associated with improved activation times and acute hemodynamic response compared with conventional biventricular epicardial pacing (BiV-epi); however, the effects on repolarization and arrhythmic risk are unknown. The purpose of this study was to compare the effects of temporary BiV-epi, BiV-endo, and LBBAP on epicardial left ventricular (LV) repolarization using electrocardiographic imaging (ECGi). Eleven patients indicated for cardiac resynchronization therapy underwent a temporary pacing protocol with ECGi. BiV-endo was delivered via endocardial stimulation of the LV lateral wall. LBBAP was delivered by pacing the LV septum. Epicardial LV repolarization time (LVRT-95; time taken for 95% of the LV to repolarize), LV RT dispersion, mean LV activation recovery interval (ARI), LV ARI dispersion, and RT gradients were calculated. The protocol was completed in 10 patients. During LBBAP, there were significant reductions in LVRT-95 (94.9 ± 17.4 ms vs 125.0 ± 29.4 ms; P=.03) and LV RT dispersion (29.4 ± 6.3 ms vs 40.8 ± 11.4 ms; P = .015) compared with BiV-epi. In contrast, there were no significant differences between baseline, BiV-epi, or BiV-endo. There was a nonsignificant reduction in mean RT gradients between LBBAP and baseline rhythm (0.74 ± 0.22 ms/mm vs 1.01 ± 0.31 ms/mm; P = .07). There were no significant differences in mean LV ARI or LV ARI dispersion between groups. Temporary LBBAP reduces epicardial dispersion of repolarization compared with conventional BiV-epi. Further study is required to determine whether these repolarization changes on ECGi translate into a reduced risk of ventricular arrhythmia in clinical practice.

Clinical outcomes of conduction system pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis.

Conduction system pacing (CSP) is observed to produce greater improvements in echocardiographic and hemodynamic parameters as compared to conventional biventricular pacing (BiVP). However, whether these surrogate endpoints directly translate to improvements in hard clinical outcomes such as death and heart failure hospitalization (HFH) with CSP remains uncertain as studies reporting these outcomes are scarce. The aim of this meta-analysis was to analyze the existing data to compare the clinical outcomes of CSP versus BiVP. A systematic search of the Embase and PubMed database was performed for studies comparing CSP and BiVP for patients indicated to receive a CRT device. The coprimary endpoints were all-cause mortality and HFH. Other secondary outcomes included change in left ventricular ejection fraction (LVEF), change in NYHA class, and increase in NYHA class ≥1. A random-effects model was chosen a priori to analyze the composite effects given the anticipated heterogeneity of included trials. Twenty-one studies (4 randomized and 17 observational) were identified reporting either primary outcome and were included in the meta-analysis. In total 1960 patients were assigned to CSP and 2367 to BiVP. Median follow-up time was 10.1 months (ranging 2-33 months). CSP was associated with a significant reduction in all-cause mortality (odds ratio [OR] 0.68, 95% confidence interval [CI]: 0.56-0.83) and HFH (OR 0.52, 95% CI: 0.44-0.63). Mean improvement in LVEF was also greater with CSP (mean difference 4.26, 95% CI: 3.19-5.33). Reduction in NYHA class was significantly greater with CSP (mean difference -0.36, 95% CI: -0.49 to -0.22) and the number of patients with an increase in NYHA class ≥1 was significantly greater with CSP (OR 2.02, 95% CI: 1.70-2.40). CSP was associated with a significant reduction in all-cause mortality and HFH when compared to conventional BiVP for CRT. Further large-scale randomized trials are needed to verify these observations.

Repolarization changes following left bundle branch area pacing versus conventional biventricular pacing in patients with dyssynchronous heart failure

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation. Background Biventricular pacing (BiVP) is the standard treatment for patients with dyssynchronous heart failure. Despite the effectiveness of BiVP, 6% of patients develop ventricular tachyarrhythmia’s (VTAs) within one year following implantation. The relationship between BiVP and the development of VTAs is still under debate. The left-sided epicardium-to-endocardium activation during BiVP creates a nonphysiological activation and repolarization and might provoke VTAs. A relatively new treatment option is left bundle branch area pacing (LBBAP), in which the physiological activation of the left ventricle is restored. We hypothesize that LBBAP leads to a more homogenous repolarization compared to conventional BiVP. Purpose To compare time-dependent repolarization changes in patients with dyssynchronous heart failure receiving LBBAP versus BiVP. Methods Patients with dyssynchronous heart failure eligible for cardiac resynchronization therapy who underwent LBBAP (n=13) or BiVP (n=28) were retrospectively included. Standard 12-lead electrocardiograms (ECG) obtained prior to implantation [baseline], shortly following implantation (0-2 days,[acute]) and during follow-up (31-180 days, [FU]) were analyzed. The QT interval and Tpeak to Tend interval (Tpeak-Tend) were calculated using a semi-automatic approach in MATLAB. Repolarization differences between LBBAP and BiVP patients were determined using the Mann-Whitney U-test. Time-dependent changes within groups were determined using the Wilcoxon signed rank tests. Significance was defined as a p-value ≤0.05. Results The QT interval did not significantly change over time in BiVP patients, but it decreased immediately following implantation and during FU in LBBAP patients. At FU, QT interval was significantly lower in LBBAP than in BiVP patients (Figure 1, left panel). A slight increase in Tpeak-Tend interval over time in BiVP patients, while it tends to decrease over time in LBBAP patients can be seen in the right panel. Acutely and long term after implantation, Tpeak-Tend was significantly lower in LBBAP than in BiVP patients. Conclusion LBBAP is associated with lower QT and Tpeak-Tend intervals compared to BiVP during FU, suggesting that LBBAP leads to less heterogeneity of repolarization over time. These findings suggest a more physiological repolarization pattern in LBBAP compared to BiVP, which may decrease the risk of developing VTAs.

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-02-017 CHARACTERIZATION OF PATIENTS WHO STABILIZE AFTER CARDIAC RESYNCHRONIZATION THERAPY

Cardiac resynchronization therapy (CRT) is an effective treatment in appropriately selected patients with heart failure. While a subset responds well, a large proportion either stabilizes or deteriorates. We examined the predictors and outcomes of patients who do not demonstrate a reduction in left ventricular end-systolic volume (LVESV) >15% at 6 months; however, who do stabilize between 6 and 12 months (reduction in LVESV 0-15%). The MORE-CRT MPP study is a prospective, randomized, multicenter study. All patients (n = 5803) initially received conventional biventricular (BiV) CRT for 6 months. At this stage, echocardiographic non-responders (i.e., are reduction in LVESV < 15%) were randomized to either continued conventional BiV pacing, or MultiPoint pacing. This post-hoc analysis evaluated the BiV pacing group only. This group was split into i) the stabilization group (reduction in LVESV between 0-15% at 6- and 12-months follow-ups); ii) deterioration group (increase in LVESV >0% at 6 and 12 months). Of the 464 patients in the analysis, 51.2% (n=238) stabilized, and 48.8% (n=226) deteriorated following CRT implant. On multivariable analysis, increased left ventricular ejection fraction (LVEF) and increased QRS duration/left ventricular end-diastolic volume (LVEDV) ratio at baseline were statistically significant for predicting deterioration (see table). Freedom from heart failure hospitalization was similar in both groups until 6 months, and there was a significant separation of the Kaplan-Meier curves after 6 months (p<0.001) (see figure). Patients with an increased LVEF and higher QRSd/LVEDV ratio (i.e., higher degree of dyssynchrony relative to heart size) were more likely to deteriorate than to stabilize following conventional BiV CRT. The risk of heart failure hospitalization in both groups remained similar at 6 months, however, significantly worsened if there was an echo deterioration following CRT. This suggests the need for longer follow up when evaluating clinical endpoints following CRT.Tabled 1Univariate and multivariate Cox regression model to predict likelihood of deterioration to cardiac resynchronization therapy (CRT).ParametersUnivariable Analysis (n=464)Multivariable Analysis (n=383)OR [95% CI]p-valueOR [95% CI]p-valueAge0.979 [0.961, 0.997]0.01960.98 [0.96, 1.00]0.1296COPD (Yes vs No)0.699 [0.393, 1.244]0.2234Diabetes (Yes vs No)0.750 [0.512, 1.098]0.139Female vs Male1.011 [0.649, 1.577]0.96031.13 [0.67, 1.93]0.644Hypertension (Yes vs No)0.811 [0.556, 1.180]0.2735Ischaemic vs Non-Ischaemic0.732 [0.508, 1.055]0.0939LBBB vs Non-LBBB1.617 [1.077, 2.429]0.02061.52 [0.98, 2.36]0.0626LVEF0.938 [0.913, 0.963]<.00010.95 [0.92, 0.98]0.0007NYHA I/II vs NYHA III/IV1.180 [0.819, 1.699]0.3745QRS duration/LVEDV ratio1.007 [0.999, 1.014]0.08890.43 [0.19, 0.98]0.0439Renal disease (Yes vs No)0.724 [0.451, 1.161]0.1799 Open table in a new tab

PO-02-020 CHARACTERIZING PREDICTORS AND OUTCOMES OF LATE RESPONDERS TO CARDIAC RESYNCHRONIZATION THERAPY

Typically, response to cardiac resynchronization therapy (CRT) is evaluated at 6 months. There is a subset of patients who do not fully respond to CRT at this point, however, do demonstrate improvement at 12 months. Characterizing these patients and their outcomes has not been widely explored. We examined in the MORE-CRT MPP study, the predictors of patients who do not demonstrate a reduction in left ventricular end-systolic volume (LVESV) >15% at 6 months, who however do reach that endpoint at 12 months. The MORE-CRT MPP study is a prospective, randomized, multicenter study. All patients (n = 5803) initially received conventional biventricular (BiV) CRT for 6 months. At this stage, echocardiographic non-responders were randomised to either continued conventional BiV pacing, or MultiPoint pacing. This post-hoc analysis evaluated the BiV pacing group only. This group was split into: i) non-responders (<15% reduction in LVESV at 6 and 12 months), ii) early responders (>15% reduction in LVESV at 6 months), and iii) delayed responders (<15% reduction in LVESV at 6 months, but >15% improvement at 12 months). Logistic regression models were used to assess the baseline characteristics of delayed responders. Heart failure hospitalization was the clinical endpoint. Of the 2,920 patients in the analysis 16.7% (n=486) were non-responders, 78% were early responders (n=2263), and 5.8% (n=171) were delayed responders. On multivariable analysis, only patients with ischaemic aetiology and a reduced QRS duration/left ventricular end-diastolic volume (LVEDV) ratio at baseline were statistically significant for predicting delayed response (see table). Freedom from heart failure hospitalization was similar in the early and late CRT responders, and significantly worse in the non-responder group. Patients with increased scar burden and those with a lower QRS/LVEDV ratio (i.e., reduced relative degree of dyssynchrony) were likely to be delayed responders to conventional BiV CRT. Early and delayed CRT responders have a similar risk of heart failure hospitalization despite the slower echo remodelling.Tabled 1Univariate and multivariate Cox regression model to predict likelihood of delayed response to cardiac resynchronization therapy (CRT).ParameterUnivariate AnalysisMultivariate AnalysisOR [95% CI]p-valueSample SizeOR [95% CI]p-valueAge1.004 [0.990, 1.019]0.5724351.01 [0.99, 1.02]0.46COPD (Yes vs No)0.804 [0.466, 1.388]0.432436Diabetes (Yes vs No)1.106 [0.795, 1.539]0.552436Hypercholesterolaemia (Yes vs No)1.099 [0.800, 1.509]0.562436Hypertension (Yes vs No)0.857 [0.624, 1.176]0.342436Ischaemic vs Non-Ischaemic1.638 [1.198, 2.240]0.00224361.64 [1.13, 2.37]0.009LBBB vs Non-LBBB0.650 [0.448, 0.944]0.02418640.75 [0.51, 1.10]0.14LVEF0.983 [0.961, 1.006]0.152436NYHA I/II vs NYA III/IV1.066 [0.779, 1.459]0.692427QRS duration/LVEDV ratio1.000 [0.993, 1.006]0.9320670.47 [0.22, 0.99]0.047Renal disease (Yes vs No)1.244 [0.799, 1.937]0.332436Female vs Male0.786 [0.555, 1.112]0.1724360.96 [0.63, 1.46]0.84 Open table in a new tab

A New Electromechanical Wave Imaging Dispersion Metric for the Characterization of Ventricular Activation in Different Cardiac Resynchronization Therapy Pacing Schemes.

Conventional biventricular (BiV) pacing cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients. Recently, multiple novel CRT delivering technologies such as His-Bundle pacing have been investigated as alternative pacing strategies for optimal treatment benefit. Electromechanical Wave Imaging (EWI), a high frame-rate echocardiography-based modality, is capable of visualizing the change from dyssynchronous activation to resynchronized BiV-paced ventricles in 3D. This proof-of-concept study introduces a new EWI-based dispersion metric to further characterize ventricular activation. Patients with His-Bundle device implantation (n = 4), left-bundle branch block (n = 10), right-ventricular (RV) pacing (n = 10), or BiV pacing (n = 15) were imaged, as well as four volunteers in normal sinus rhythm (NSR). EWI successfully mapped the ventricular activation resulting from His-Bundle pacing. Additionally, very similar activation patterns were obtained in the NSR subjects, confirming recovery of physiological activation with His pacing. The dispersion metric was the most sensitive EWI-based metric that identified His pacing as the most efficient treatment (lowest activation time spread), followed by BiV and RV pacing. More specifically, the dispersion metric significantly (p < 0.005) distinguished His pacing from the other two pacing schemes as well as LBBB. The initial findings presented herein indicate that EWI and its new dispersion metric may provide a useful resynchronization evaluation clinical tool in CRT patients under both novel His-Bundle pacing and more conventional BiV pacing strategies.

Conduction system pacing for cardiac resynchronization therapy: State of the art, current controversies, and future perspectives.

Biventricular pacing (BVP) is the established treatment to perform cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and left bundle branch block (LBBB). However, BVP is an unnatural pacing modality still conditioned by the high percentage of non-responders and coronary sinus anatomy. Conduction system pacing (CSP)-His bundle pacing (HBP) and Left bundle branch area pacing (LBBAP)- upcomes as the physiological alternative to BVP in the quest for the optimal CRT. CSP showed promising results in terms of better electro-mechanical ventricular synchronization compared to BVP. However, only a few randomized control trials are currently available, and technical challenges, along with the lack of information on long-term clinical outcomes, limit the establishment of a primary role for CSP over conventional BVP in CRT candidates. This review provides a comprehensive literature revision of potential applications of CSP for CRT in diverse clinical scenarios, underlining the current controversies and prospects of this technique.

Dyssynchronous Heart Failure: A Clinical Review.

Dyssynchrony occurs when portions of the cardiac chambers contract in an uncoordinated fashion. Ventricular dyssynchrony primarily impacts the left ventricle and may result in heart failure. This entity is recognized as a major contributor to the development and progression of heart failure. A hallmark of dyssynchronous heart failure (HFd) is left ventricular recovery after dyssynchrony is corrected. This review discusses the current understanding of pathophysiology of HFd and provides clinical examples and current techniques for treatment. Data show that HFd responds poorly to medical therapy. Cardiac resynchronization therapy (CRT) in the form of conventional biventricular pacing (BVP) is of proven benefit in HFd, but is limited by a significant non-responder rate. Recently, conduction system pacing (His bundle or left bundle branch area pacing) has also shown promise in correcting HFd. HFd should be recognized as a distinct etiology of heart failure; HFd responds best to CRT.

Biventricular endocardial pacing and left bundle branch area pacing for cardiac resynchronization: Mechanistic insights from electrocardiographic imaging, acute hemodynamic response, and magnetic resonance imaging

Biventricular endocardial pacing (BiV-endo) has demonstrated superior cardiac resynchronization compared to conventional biventricular epicardial pacing (BiV-epi). Left bundle branch area pacing (LBBAP) may also achieve effective cardiac resynchronization therapy (CRT). The purpose of this study was to compare the acute electrical and hemodynamic effects of BiV-epi, BiV-endo, and LBBAP delivered from the LV endocardium and to assess how myocardial scar affects response. Eleven patients with heart failure and indications for CRT underwent a temporary pacing study with electrocardiographic imaging (ECGi) and hemodynamic assessment. BiV-endo was delivered by stimulation of the left ventricular (LV) lateral wall, and LBBAP was delivered by stimulation of the LV septum, at the site of a Purkinje potential. LV activation time (LVAT-95), LV dyssynchrony index (LVDI), biventricular activation time (BIVAT-90), and biventricular dyssynchrony index (BIVDI) were calculated. Myocardial scar was assessed using magnetic resonance imaging (MRI). The protocol was completed in 10 patients. Compared to BiV-epi (LVAT-95: 79.2 ± 13.1 ms; LVDI: 26.6 ± 3.4 ms) LV resynchronization was superior during BiV-endo (LVAT-95: 48.5 ± 14.9 ms; P = .001; LVDI: 16.6 ± 6.4 ms; P = .002) and LBBAP (LVAT-95: 48.9 ± 12.5 ms; P = .001; LVDI: 15.3 ± 3.4 ms; P = .001). Biventricular resynchronization was similarly superior during BiV-endo and LBBAP vs BiV-epi (BIVAT-90 and BIVDI; P <.05). The rate of acute hemodynamic responders was higher during BiV-endo (90%) and LBBAP (70%) vs BiV-epi (50%). The benefits of LBBAP (but not BiV-endo) on LV resynchronization were attenuated when septal scar was present in a subset of 8 patients who underwent MRI. Our findings suggest superior electrical resynchronization and a higher proportion of acute hemodynamic responders during BiV-endo and LBBAP compared to BiV-epi. Electrical resynchronization was similar between BiV-endo and LBBAP; however, septal scar seemed to attenuate response to LBBAP.