Indication For Cardiac Resynchronization Therapy Research Articles

Implant failure predictors of left bundle branch pacing used as cardiac resynchronization therapy: importance of left ventricular diameter and QRS morphology

Abstract Background Left bundle branch pacing (LBBP) is considered an alternative to cardiac resynchronization therapy (CRT). However, LBBP is not suitable for all heart failure patients. Purpose The aim of our study was to identify predictors of unsuccessful LBBP implantation in CRT candidates. Methods A cohort of consecutive patients with indications for CRT were included. Clinical, echocardiography and electrocardiographic variables were prospectively recorded. Results A total of 157 patients were included in the analysis. The LBBP implant was successful in 129/157 (82.2%) patients, and the implant failed in 28/157 patients (17.8%). The causes of failed implantation were as follows: unsatisfactory paced QRS (21/28; 75%); impossibility of screwing the helix (4/28; 14.3%); lead instability (2/28; 7.1%); and high pacing thresholds (1/28; 3.6%). Left ventricular end diastolic diameter (LVEDD), nonspecific intraventricular conduction delay morphology (IVCD), and QRS width were predictors of failed implants according to the univariate analysis. In a multivariable regression analysis, LVEDD [OR 1.44 per 5 mm increase (95% CI 1.13, 1.82) p=0.003] and IVCD [OR 2.96 (95% CI 0.74, 11.84) p=0.09] were independent predictors of unsuccessful LBBP implantation. An LVEDD of 60 mm has 75% sensitivity and 67% specificity to predict LBBP implant failure. Conclusions When LBBP was used as CRT, LVEDD and IVCD predicted unsuccessful implantation. IVCD triples the possibility of failed implantation independently of LVEDD. Caution should be exercised when considering these parameters to plan the best pacing strategy in patients.

Absence of late gadolinium enhancement and outcomes of cardiac resynchronization therapy in non-ischemic dilated cardiomyopathy

Abstract Background Among patients with non-ischemic dilated cardiomyopathy (DCM) with indication for cardiac resynchronization therapy (CRT), there are no clear recommendations about who should receive a CRT-defibrillator (CRT-D) and who should have CRT-pacemaker (CRT-P). Absence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has a high negative predictive value for ventricular arrhythmias (VA) and sudden death (SD) in DCM and is a predictor of reverse remodelling in several scenarios. Purpose To evaluate the association between absence of LGE and VA/SD or echocardiographic response to CRT in DCM patients treated with CRT. Methods Multicenter retrospective observational cohort study including consecutive DCM patients with de-novo CRT implant and with available CMR. The primary endpoints were: 1) a combined arrhythmic endpoint including appropriate defibrillator therapies, sustained VA and sudden death. 2) echocardiographic response to CRT, intended as an increase ≥10% in left ventricular ejection fraction (LVEF). Results We included 167 patients, 55% males, with median QRS duration of 160ms and median LVEF of 25%. LGE was present in 46% of cases (LGE+). A CRT-D was implanted in 73% of patients. Median follow-up was 63 months. Of note, among patients without LGE (LGE-) we did not record any event of the combined arrhythmic endpoint. The cumulative incidence of the arrhythmic endpoint was significantly higher in LGE+ than in LGE- patients (25% vs 0%, p<0.001) and LGE was an independent predictor of this endpoint (adjusted HR 42, p<0.001). The proportion of responders to CRT was significantly higher in LGE- than in LGE+ cases (81% vs 53%, p<0.001); absence of LGE was the strongest predictor of echocardiographic response to CRT at multivariate analysis (adjusted OR 4.1, p=0.001). Super-responders (i.e. those with LVEF≥50% at follow-up) were also more frequent among LGE- than LGE+ patients (46% vs 21%, p=0.001) and absence of LGE was an independent predictor of LVEF normalization (HR 2.6, p=0.03). Conclusions Among DCM patients who receive CRT, those without LGE have an extremely low (or null in this case) arrhythmic risk and, at the same time, they have a high probability of echocardiographic response to CRT. Thus, LGE- patients could be ideal candidates for CRT-P instead of CRT-D.

ECG imaging as a real time tool to guide left bundle branch pacing implant in patients with left bundle branch block and resynchronization therapy indication

Abstract Background Left bundle branch pacing (LBBP) has emerged as a promising alternative technique for cardiac resynchronization therapy (CRT). ECG imaging (ECGI) may provide an accurate assessment of electrical resynchronization using real-time maps during LBBP implant. Purpose To evaluate the usefulness of ECGI to guide LBBP implant, by analyzing the ventricular activation times and the degree of resynchronization at each screwing step during the lead implant. Methods Four patients with CRT indication and left bundle branch block (LBBB) referred for LBBP were prospectively enrolled. ECGI was performed during the implant procedure. Cardiac signals were recorded using ECGI and projected into an artificial intelligence-derived geometric model. Thus, generating imageless and non-invasive activation maps at defined stages during lead screwing: basal rhythm (LBBB), right ventricular (RV) septum, mid-septal, deep-septal, and finally pacing from the left bundle branch (according with guidelines ECG criteria). The following parameters were measured: a) total activation time (TAT); b) left ventricular activation time (LVAT); c) left ventricular dyssynchrony index (LVDI) (as a quantifier of intraventricular dyssynchrony); d) ventricular electrical uncoupling (VEU); and e) histogram overlap between LV and RV distribution (the last 2 markers of interventricular dyssynchrony). Results The study cohort comprised men with a median age of 68 [Q1 59- Q3 79], with a median basal LBBB QRS duration of 175 ms [160-188] and a median LVEF of 32% [28-39]. A shortening of the activation times and a decrease in intra and interventricular dyssynchrony was achieved when the final lead position was reached. See the results in Figure 2. Conclusion Real-time and imageless ECGI system may offer a novel approach for guiding LBBP and it is useful to ensure left ventricular resynchronization.ECGI to guide LBBP implantActivation and dyssynchrony measurements

Left-ventricular-only cardiac resynchronization therapy with electrocardiographic optimization: 100-day follow-up

Abstract Background LV-only (LVo) cardiac resynchronization therapy (CRT) was recognized in 2013 as a non-inferior alternative to bi-ventricular (biV) CRT [1]. In a triple-chamber device it can extend service life, reduce atrial fibrillation risk. A number of LVo systems have been proposed but have not been shown to be superior to biV [2] due to a lack of individualized optimization of the LV atrio-ventricular delay. Purpose An LVo algorithm with an electrocardiographic optimization for each patient along general principles was developed and successfully implanted in a dozen patients with triple-chamber devices. The algorithm has been reported earlier. Since the RV lead is redundant, a dual chamber CRT (dcCRT) version was developed, with just the RA and LV leads. A preliminary series of 8 dcCRT implants were performed with good results. Methods A 2-week training class on LV lead implantation was held in July 2023. Fourteen dcCRT’s were implanted. Inclusion criteria: CRT indications, Left-bundle-branch block, good A-RV conduction, mostly sinus rhythm. 100-day follow-ups were performed on 15 patients (including 2 earlier patients) and reported here. Results In Fig.1 Implant LVEFs (Simpson): 16% to 38%. At the 100-day follow-ups, the LVEFs range from 24% to 62%. 6 (40%) remained below LVEF 35%, 9 (60%) exceeded the 35% threshold, 3 (20%) exceeded 45%, including 2 (13%) with 56% and 62%. Only 3 patients with small 2-3% LVEF improvements. All others were >5%, up to 29%. Since the devices can measure thoracic impedance, Z, 1024 times/hour, with the hourly average combined for a daily average, the 100-day daily Z trends were analyzed. The implant and 100-day Z’s are plotted in Fig.2. Except for the 2 patients whose Z measurements were left off, the universal upward Z trend is an indication of improved LV blood flow in all patients, helping reduced excessive lung fluid. Z changes range from 14 to 34 Ohms. Of the 2 patients in Fig.1 with only 2% LVEF improvements, their Z improvements were meaningful 23 Ohms increases! The Z and LVEF trends indicate that the therapy had a 100% success. Conclusions The 100-day follow-ups of the ECG optimized LVo CRT of 15 patients with dcCRTs show results superior to what have been reported in previous biV studies, thanks to the ECG optimization. This indicates that this may be a superior alternative to biV CRT. While the study was done with dcCRT, it should be applicable to all triple chamber CRT (-P/-D) devices which can support LVo pacing. Unlike other CRT algorithms, if the device supports LVo, it can be applied. It is safe since the programming can be reverted to biV at any time! This opens the possibility for improving the health of current CRT patients and extending the service lives of their devices, in addition to improved de novo results. The dcCRT is no longer viable since bipolar LV leads have been discontinued in favor of quadripolar leads, but the results apply to all CRT systems.Fig 1. LVEF @ implant & 100 dayFig 2. Thoracic Z @implant & 100 day

Comparison of long-term risk of device-related complications between left bundle branch area pacing and biventricular pacing in candidates for resynchronization therapy

Abstract Introduction Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS. Left bundle branch area pacing (LBBAP) has recently been shown to be a feasible and effective alternative to BVP. Comparative data on the risk of complications between LBBAP and BVP among CRT candidates are lacking. Purpose The aim of this study was to compare the long-term risk of device-related complications between LBBAP and BVP in a cohort of patients undergoing CRT. Methods Prospective, multicenter, observational study enrolling 668 consecutive patients (71.2±10.0 years, 52.2% male, 59.4% NYHA class >II), with LVEF ≤35% (mean 33.4±4.3%) who underwent BVP (n=560) or LBBAP (n=108) for the first time for Class I or II indications for CRT from January 2020 to June 2023 at 6 Italian centers. Propensity matching for baseline characteristics yielded 90 matched pairs. Rate and nature of device-related complications occurring during follow-up were prospectively collected and compared between the two groups. Results During a mean follow-up of 18 months, device-related complications were observed in 14 patients: 11 in BVP (12.2%), and in 3 in LBBAP (3.3%) (p=0.026). Compared to BVP patients, LBBAP patients showed a higher cumulative survival free from first device–related complication (Figure). Complications related to coronary sinus lead were most frequently observed in BVP patients (36.4% of all complications). The rate of overall lead-related complications was 6.7 and 2.2% in BVP and LBBAP patients, respectively (p=0.149). Conclusion LBBAP was associated with a lower long-term risk of device-related complications compared with BVP in patients with CRT indications.

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT.

Left bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. This study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. We analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER,≥5% absolute LVEF increase) were assessed at 6months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. There were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0 to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P=0.037), with more than 3-fold increased odds of ER (odds ratio: 4.35; P=0.033). In high sepal scar subgroups (≥5.7%, range: 5.7% to 65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P=0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P=0.002) and LVEF improvement (P=0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8 to 42.1) months, the composite clinical outcome occurred in 34.7% (n=51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. Remodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

Baroreflex activation therapy in patients with heart failure and a reduced ejection fraction: Long-term outcomes.

Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement. BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance. The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL.

Atrioventricular optimization improves cardiac resynchronization response in patients with long interventricular electrical delays: A pooled analysis of the SMART-AV and SMART-CRT trials

BackgroundThe utility of atrioventricular (AV) optimization (AVO) algorithms remains in question. A substudy of the SMART-AV trial found that patients with prolonged interventricular delays ≥70 ms were more likely to benefit from cardiac resynchronization therapy (CRT) with AVO. The SMART-CRT trial evaluated AVO on the basis of these results, but the study was underpowered. ObjectiveTo increase statistical power, data from SMART-AV patients meeting the inclusion criterion of interventricular delay ≥70 ms were pooled with data from SMART-CRT to reassess AVO. MethodsSMART-CRT and SMART-AV were prospective, randomized, multicenter clinical trials. Patients in both studies were randomized to be programmed with an AVO algorithm (SmartDelay) or fixed AV delay (120 ms). Paired echocardiograms obtained at baseline and 6 months were compared, with CRT response defined as ≥15% reduction in left ventricular end-systolic volume. ResultsA total of 451 complete patient data sets were pooled and analyzed. The baseline demographics between studies did not differ statistically in terms of age, sex, left ventricular ejection fraction, or left ventricular end-systolic volume. The AVO group had a greater proportion of CRT responders (SmartDelay, 73.9%; fixed, 63.1%; P = .014) and greater changes in measures of reverse remodeling. SmartDelay patients with a recommended sensed AV delay outside the nominal range (100–120 ms) had 2.3 greater odds of CRT response than fixed AV delay patients. ConclusionGreater CRT response and measures of reverse remodeling were observed in patients with SmartDelay enabled vs a fixed AV delay. This study supports the use of SmartDelay in patients with a CRT indication and interventricular delay ≥70 ms. ClinicalTrials.gov registrationNCT00677014 and NCT03089281

Landmark Evolutions in Time and Indication for Cardiac Resynchronization Therapy: Results from a Multicenter Retrospective Registry.

Background: Cardiac resynchronization therapy (CRT) has evolved into an established therapy for patients with chronic heart failure and a wide QRS complex. Data on long-term outcomes over time are scarce and the criteria for implantation remain a subject of investigation. Methods: An international, multicenter, retrospective registry includes 2275 patients who received CRT between 30 November 2000 and 31 December 2019, with a mean follow-up of 3.6 ± 2.7 years. Four time periods were defined, based on landmark trials and guidelines. The combined endpoint was a composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results: The composite endpoint occurred in 656 patients (29.2%). The mean annual implantation rate tripled from 31.5 ± 17.4/year in the first period to 107.4 ± 62.4/year in the last period. In the adjusted Cox regression analysis, the hazard ratio for the composite endpoint was not statistically different between time periods. When compared to sinus rhythm with left bundle branch block (LBBB), a non-LBBB conduction pattern (sinus rhythm: HR 1.51, 95% CI 1.12-2.03; atrial fibrillation: HR 2.08, 95% CI 1.30-3.33) and a QRS duration below 130 ms (HR 1.64, 95% CI 1.29-2.09) were associated with a higher hazard ratio. Conclusions: Despite innovations, an adjusted regression analysis revealed stable overall survival over time, which can at least partially be explained by a shift in patient characteristics.

Cardiac contractility modulation in patients with heart failure - A review of the literature.

Experimental in vivo and in vitro studies showed that electric currents applied during the absolute refractory period can modulate cardiac contractility. In preclinical studies, cardiac contractility modulation (CCM) was found to improve calcium handling, reverse the foetal myocyte gene programming associated with heart failure (HF), and facilitate reverse remodeling. Randomized control trials and observational studies have provided evidence about the safety and efficacy of CCM in patients with HF. Clinically, CCM therapy is indicated to improve the 6-min hall walk, quality of life, and functional status of HF patients who remain symptomatic despite guideline-directed medical treatment without an indication for cardiac resynchronization therapy (CRT) and have a left ventricular ejection fraction (LVEF) ranging from 25 to 45%. Although there are promising results about the role of CCM in HF patients with preserved LVEF (HFpEF), further studies are needed to elucidate the role of CCM therapy in this population. Late gadolinium enhancement (LGE) assessment before CCM implantation has been proposed for guiding the lead placement. Furthermore, the optimal duration of CCM application needs further investigation. This review aims to present the existing evidence regarding the role of CCM therapy in HF patients and identify gaps and challenges that require further studies.

Real-time three-dimensional transthoracic echocardiography in quantification of left ventricular dyssynchrony

Aim. To compare endocardial and epicardial left ventricular (LV) pacing using real-time electrocardiography (ECG)-synchronized three-dimensional echocardiography (3DE).Methods. Experimental intraoperative study included 88 points obtained from 12 patients with compensated heart failure of II-IV functional class NYHA (LV ejection fraction &lt; 35%) and cardiac resynchronization therapy indications - ECG pattern of complete left bundle branch block (LBBB) and QRS complex duration &gt; 150 ms. During isolated LV pacing as part of cardiac resynchronization therapy implantation procedure endocardial and epicardial stimulation points matched under fluoroscopic control using quadripolar coronary sinus leads and endocardial electrodes for temporary pacing were obtained. The overall number of corresponding pacing sites included 44 endocardial and 44 epicardial stimulation positions. The mean age of patients was 68.5 [63; 73.5] years, 83% males (n=10). Before study enrollment, 12-channel ECG, echocardiography, and a six-minute walk test were performed for all participants along with cardiac magnetic resonance imaging and control coronary angiography if indicated. The prevalence of coronary heart disease was 50% (n=6) while dilated cardiomyopathy was the most common etiology of chronic heart failure in other cases. Intraoperative ECG with estimation of paced QRS complex morphology at each point was registered via LabSystem Pro Electrophysiological Recording System (Bard Electrophysiology, USA). 3DE was performed using TomTec and Philips Qlab 3DQ Advanced software (Philips Medical Systems, USA).Results. Three-dimensional parametric imaging of LV regional segmental excursion and myocardial contractility using 3DE revealed statistically significant difference in semi-quantative parameters such as ExcAvg (p&lt;0.001), ExcMax (p=0.001), ExcMin (p&lt;0.001) and LV ejection fraction based on 3D modelling (p=0.003) while endocardial pacing was more beneficial. During the course of endocardial stimulation, the 3DE dyssynchrony index estimated at the 2nd stimulation site was also significantly lower (p=0.03). Identical dyssynchrony parameters valid for the 16 and 12-segment 3D models (SDI-16, Tmsv-12SD) (at p=0.06) demonstrated only a tendency for significant difference. The duration of QRS complex at the time of endocardial pacing was significantly shorter (&lt;190 [179;215] ms) (p=0.0008). Semi-quantitative and quantitative 3DE parameters showed the benefit of endocardial pacing resulting in cardiac contractility improvement with less dyssynchrony and LV volume reducing during intraoperative period.Conclusion. Endocardial pacing has potential benefit over the epicardial pacing represented by intraoperative dynamics of LV global and local contractility, intraventricular dyssynchrony estimated by 3DE and also ECG criteria. 3DE is helpful in more precise and reproducibile determing of late activation zone for target LV lead placement that is more manoeuvrable in case of endocardial stimulation.

Visualization of Left Ventricular Endocardium Activation Time during Cardiac Conduction System Pacing

Introduction. Right ventricular myocardial pacing leads to asynchronous contraction of the left ventricle (LV) and can impair its contractility over time. Stimulation of the conduction system of the heart ensures physiological activation of the ventricles.&#x0D; The aim. To visualize the pattern of propagation of the electrical front on the activation map of the LV endocardium during conduction system pacing and during right ventricular myocardial pacing.&#x0D; Materials and methods. In two patients with the conduction system pacing, who were operated at the National Amosov Institute of Cardiovascular Surgery, invasive LV activation mapping was performed on various options of cardiac pacing using the EnSite Precision TM navigation system. One patient with complete atrioventricular block had nonselective His bundle pacing. The second patient had dilated cardiomyopathy and indications for cardiac resynchronization therapy and ablation of the atrioventricular junction due to chronic tachyform of atrial fibrillation. After an unsuccessful attempt to place LV lead in coronary sinus, a lead for left bundle branch pacing was implanted. Different activation maps of the LV endocardium were built in two patients with two types of cardiac pacing: right ventricular myocardial pacing and cardiac conduction system pacing.&#x0D; Results. The total LV endocardial activation time was significantly different in the two studied patients with different pacing options. In a patient with non-selective stimulation of His bundle, the total LV endocardial activation time was 43 ms (QRS width 126 ms, the interval from the stimulus to the peak of the R wave in lead V6 78 ms). After switching to right ventricular myocardial pacing with a decrease in the pacing amplitude, the total LV endocardial activation time prolonged to 90 ms (QRS width 165 ms, the interval from the stimulus to the peak of the R wave in lead V6 117 ms). In a patient with left bundle branch pacing, total LV endocardial activation time was 51 ms (QRS width 160 ms, the interval from the stimulus to the peak of the R wave in lead V6 66 ms). With switching exclusively to right ventricular pacing the total LV endocardial activation time prolonged to 93 ms (stimulated QRS width 180 ms). At the same time, the activation pattern of the LV endocardium was significantly different, since the right ventricular lead was located closer to the apex.&#x0D; Conclusions. Conduction system pacing provides rapid physiological LV activation and potentially avoids the negative consequences of asynchronous slow ventricular activation during right ventricular pacing.

Indications for Cardiac Resynchronization Therapy in Patients with Congenital Heart Disease.

Heart failure in patients with congenital heart disease (CHD) stems from unique causes compared with the elderly. Patients with CHD face structural abnormalities and malformations present from birth, leading to altered cardiac function and potential complications. In contrast, elderly individuals primarily experience heart failure due to age-related changes and underlying cardiovascular conditions. Cardiac resynchronization therapy (CRT) can benefit patients with CHD, although it presents numerous challenges. The complexities of CHD anatomy and limited access to appropriate venous sites for lead placement make CRT implantation demanding.

Techniques for Cardiac Resynchronization Therapy in Patients with Congenital Heart Disease.

Cardiac resynchronization therapy (CRT) for congenital heart disease has shown promising suucess as an adjunct to medical therapy for heart failure. While cardiac conduction defects and need for ventricular pacing are common in congential heart disease, CRT indications, techniques and long term outcomes have not been well establaished. This is a review of the techniques nad short term outcomes of CRT for the following complex congenital heart disease conditions: single ventricle physiology, systemic right ventricle, and the subpulmonic right ventricle.

Associations of 2013 and 2021 ESC definitions of left bundle-branch block with mechanical dyssynchrony and CRT-induced reverse remodeling

Abstract Background In 2021, a new and stricter ECG-based definition of LBBB was proposed and implemented in the European Society of Cardiology (ESC) guidelines on cardiac pacing and cardiac resynchronization therapy (CRT). Aim To investigate the association between the 2021 and the 2013 LBBB definitions with CRT-induced left ventricular (LV) reverse remodeling, as well as mechanical dyssynchrony. Methods CRT patients (n=191) were retrospectively investigated. Pre-CRT digitally stored ECGs were analyzed and categorized according to the LBBB definition of 2013 (LBBB-2013) and the 2021 (LBBB-2021). Mechanical dyssynchrony (Dyss) was assessed pre-CRT using 2D-echocardiography and was defined as the presence of apical rocking and/or septal flash. CRT-induced LV reverse remodeling was measured as the relative change of left ventricular end systolic volume (LVESV) at 12 ± 6 months after CRT compared to baseline. Results Patients’ characteristics were as follows; age 70 ± 10 years, 69% males and NYHA class 2.7 ± 0.5. QRS width was 156 ± 18 ms and LVEF 33 ± 11%, and 52% had ischemic etiology. Dyss was present in 59% of the population. The percentage of the cohort that was considered to have LBBB was considerably lower according to the LBBB-2021 than according to the LBBB-2013 (18 vs. 57% respectively). Similarly, percentages of patients with LBBB+Dyss were 16 and 46% according to LBBB-2021 and LBBB-2013 respectively, with a respective Kappa coefficient of 0.16 and 0.47 (Figure A). At CRT follow up, LBBB-2013 patients showed significantly more LV reverse remodeling compared to non-LBBB patients (P &amp;lt; 0.001), while there was no significant difference between patients with LBBB-2021 and non-LBBB (P = 0.09, Figure B). Conclusion The LBBB definition proposed in the 2021 ESC guidelines excludes many patients from a class I indication for CRT. It is less associated with mechanical dyssynchrony and with CRT-induced LV reverse remodeling than the 2013 LBBB definition. Therefore, the new LBBB definition appears to be counterproductive with regards to selection of CRT patients.

Prognostic influence of left atrial strain in heart failure patients with intermediate ECG criteria for cardiac resynchronization therapy

Abstract Background Heart failure (HF) patients with left bundle branch block (LBBB) with QRS width ≥150ms is class I indication for cardiac resynchronization therapy (CRT), whereas it is still controversy to CRT response in HF with QRS width 120-149ms or non-LBBB as intermediate ECG criteria in routine echocardiography. Left atrial (LA) adverse remodeling is a prognostic marker in patients with heart failure. Nevertheless, the prognostic significance of LA strain (LAS) imaging in HF patients with intermediate ECG criteria is not well understood. Purpose The objective of this study was to determine the prognostic value of LA deformation analysis in patients undergoing CRT implantation who met the intermediate ECG criteria. Methods We studied 94 patients who were defined routine CRT indication by the clinical guidelines. LAS was calculated as the average strain using apical two- and four-chamber views. The predefined endpoint was death, hospitalization due to worsening HF for 5 years after CRT implantation. Results Of the 94 patients, LAS is feasible in 76 patients (81%) with aged 69 ± 11 years, 30±8% of LV ejection fraction. 46 patients (61%) fulfilled intermediate ECG criteria. The predefined endpoint occurred in 43 patients (57%). The median LAS was 15%. LAS below 15% were associated with a high probability of unfavorable outcomes over 5 years (Log-rank, p = 0.002). After adjusting for left ventricular ejection fraction, LAS remained significantly associated with poor outcomes (hazard ratio 0.92, 95% confidence interval 0.87-0.97, p&amp;lt;0.001). There is no difference in the probability of poor outcomes between LBBB with QRS width ≥150ms and intermediate ECG criteria. Patients with intermediate ECG criteria and LAS &amp;lt;15% had worse outcome than in those with LBBB with QRS width ≥150ms and in those with intermediate ECG criteria patients with LAS ≥15% (Log-rank: p = 0.046, p = 0.029, respectively). Conclusion Baseline LA functional deterioration by deformation analysis was significantly associated with poor outcome after CRT implantation regardless of the ECG criteria for CRT indication and has promise for clinical utility.

Abstract 16921: The Capture of the Left Conduction System Appears to Be Essential for Left Bundle Branch Area Pacing to Provide a Greater Acute Hemodynamic Response Than Biventricular Pacing

Introduction: Left bundle branch area pacing (LBBAP), which includes left bundle branch pacing (LBBP) and left septal myocardial capture (LVSP), is a novel alternative of cardiac resynchronization therapy (CRT). However, it is unknown whether the left conduction system capture is required or whether LV septal capture only is sufficient in patients with a CRT indication. Hypothesis: To study the effect of biventricular (Biv) CRT, LBBAP, and, more specifically, LBBP and LVSP on the effectivity of LV performance using a dedicated protocol of blood pressure measurements. Methods: Patients with QRSd ≥ 130 ms of nonRBBB morphologies and an indication for CRT were included. During implantation, the leads were placed in the RV apico-septum, lateral/posterolateral branch of the coronary sinus, and the left septal area to obtain LBBAP. LBBAP was further classified as LBBP or LVSP during decremental output pacing. The acute hemodynamic response was calculated from the changes in the systolic blood pressure measured invasively from the peripheral artery using a high-precision protocol with multiple transitions between the tested pacing configurations. Results: CRT was attempted in 25 consecutive patients with an average age of 68 years. Biv CRT and LBBAP were successful in 23 and 24 patients, respectively. LBBP was achieved 17 and LVSP 13 times (in 6 patients, both capture types were observed). Eight patients had ischemic cardiomyopathy, mean LVEF was 30 ± 6 %, and QRSd during spontaneous rhythm was 174 ± 18 ms. Both Biv CRT and LBBAP significantly reduced QRSd (51 ± 24 ms and 47 ± 22 ms) and resulted in an increase of systolic blood pressure (8 ± 0 mmHg for Biv CRT, and 11 ± 0 mmHg, for LBBAP; p &lt; 0.001 for both) compared to right ventricular pacing. LBBAP increased systolic blood pressure more than Biv CRT (3 ± 0 mmHg; p &lt; 0.001). This was mainly due to a significant increase in blood pressure during LBBP compared to Biv CRT (5 ± 1 mmHg; p &lt; 0.001), while no difference was observed between LVSP and Biv CRT (1 ± 0 mmHg; p = 0.174). Conclusions: In consecutive patients with CRT indication, LBBAP improved acute hemodynamic response more than Biv CRT. Capturing the left conduction system appears to be essential for LBBAP to outperform Biv CRT.

Abstract 19063: An Updated Meta-Analysis Comparing Left Bundle Branch Area Pacing and Biventricular Pacing for Cardiac Resynchronization Therapy

Introduction: Left bundle branch area pacing (LBBAP) is a type of conduction system pacing that has been considered as an alternative to biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy (CRT). Hypothesis: We performed a meta-analysis comparing the clinical and echocardiographic outcomes between LBBAP and BVP in patients requiring CRT. Methods: We performed a systematic literature review in Embase, PubMed, and SCOPUS for all the related articles until November 2022. The literature search yielded 44 publications, of which 6 studies fulfilled the inclusion criteria. The Inverse Variance random effects model was used for continuous variables to calculate Mean Difference (MD) and 95% confidence intervals (CI) and Mantel- Haenszel random effects model was used for dichotomous variables to calculate odds ratio (OR) and 95% confidence intervals (CI). Outcomes analyzed were changed in left ventricle ejection fraction (LVEF), left ventricle end-diastolic dimension (LVEDD), NYHA class, and QRS duration and patients with the echocardiographic response (as defined as LVEF improvement &gt;5%) and heart failure hospitalizations. Results: Over a mean follow up of 8+/-2 months, LBBAP when compared to BVP resulted in significant difference in LVEF improvement (MD = 5.78 % (95% CI [4.75%, 6.80%], P&lt;0.00001), QRS duration reduction (MD = -24.77 ms) (95% CI [-32.78, -16.77], P&lt;0.00001), NYHA class reduction (MD = -0.43, 95% CI [-0.78, -0.08], P=0.02) and number of patients with echocardiographic response (OR = 2.94, 95% CI [1.40-6.14], P=0.004) at follow up. There was no significant difference in LVEDD reduction (MD = -0.5 mm, 95% CI [-3.36, 2.37], P=0.73) and HF hospitalization rates (OR = 0.42, 95% CI [0.11-1.61], P=0.21) between the 2 groups. Conclusions: LBBAP is an effective alternative to BVP in patients with an indication for CRT.

Abstract 12377: Differing Response to Left Bundle Branch Area Pacing versus Biventricular Pacing for Cardiac Resynchronization According to Septal Scar Burden Among Nonischemic Cardiomyopathy Patients

Introduction: Whether left bundle branch area pacing (LBBAP) have similar benefit compared with biventricular pacing (BVP) for cardiac resynchronization therapy (CRT) in nonischemic cardiomyopathy (NICM) with different septal scar burden is still unknown. Hypothesis: We hypothesize that a higher septal scar burden might attenuate the relative benefits of LBBAP versus BVP. Aims: This study aims to assess the effect of the septal scar on the response to LBBAP and BVP for CRT. Methods: We retrospectively included nonischemic cardiomyopathy (NICM) patients with wide QRS complex and CRT indications who underwent pre-procedure cardiac magnetic resonance (CMR) examination and received either BVP or LBBAP. Late gadolinium enhancement (LGE) was analyzed for scar quantification. CRT response was defined as an absolute increase of≥ 5% in left ventricular ejection fraction (LVEF) at 6 months follow-up. Results: A total of 147 patients were included. Fifty-one patients (34.7%) had LBBAP, and 96 (65.3%) had BVP. As septal LGE extent increased, LVEF improvement at 6-month follow-up gradually decreased in the BVP group whereas dropped sharply in the LBBAP group. The nonlinear inverse relationship between the relative benefit of LBBAP versus BVP for response and septal LGE extent, as well as cut-off points (4.4%, 13.3%) of septal LGE extent, were determined using a restricted cubic spline model. Among patients with low septal scar extent (&lt;4.4%), LBBAP was associated with higher response odds than BVP [Odds Ratio (OR) 3.87,95% confidence interval (CI): 0.99-15.17,p=0.052]. In the medium septal scar extent (4.4%-13.3%) group, response odds did not differ between LBBAP and BVP (OR 2.00,95%CI: 0.41-9.74, p=0.391). Among patients with high septal scar extent (&gt;13.3%), BVP was associated with higher response odds (OR 0.12, 95%CI: 0.03-0.54, p=0.006). Conclusions: Response to LBBAP and BVP among NICM patients might be impacted by septal scar burden.

Cardiac magnetic resonance-derived myocardial scar is associated with echocardiographic response and clinical prognosis of left bundle branch area pacing for cardiac resynchronization therapy.

Left bundle branch area pacing (LBBAP) is a novel approach for cardiac resynchronization therapy (CRT), but the impact of myocardial substrate on its effect is poorly understood. This study aims to assess the association of cardiac magnetic resonance (CMR)-derived scar burden and the response of CRT via LBBAP. Consecutive patients with CRT indications who underwent CMR examination and successful LBBAP-CRT were retrospectively analysed. Cardiac magnetic resonance late gadolinium enhancement was used for scar assessment. Echocardiographic reverse remodelling and composite outcomes (defined as all-cause death or heart failure hospitalization) were evaluated. The echocardiographic response was defined as a ≥15% reduction of left ventricular end-systolic volume. Among the 54 patients included, LBBAP-CRT resulted in a 74.1% response rate. The non-responders had higher global, septal, and lateral scar burden (all P < 0.001). Global, septal, and lateral scar percentage all predicted echocardiographic response [area under the curve (AUC): 0.857, 0.864, and 0.822; positive likelihood ratio (+LR): 9.859, 5.594, and 3.059; and negative likelihood ratio (-LR): 0.323, 0.233, and 0.175 respectively], which was superior to QRS morphology criteria (Strauss left bundle branch abnormality: AUC: 0.696, +LR 2.101, and -LR 0.389). After a median follow-up time of 20.3 (11.5-38.7) months, higher global, lateral and septal scar burdens were all predictive of the composite outcome (hazard ratios: 4.996, 7.019, and 4.741, respectively; P's < 0.05). Lower scar burden was associated with higher response rate of LBBAP-CRT. The pre-procedure CMR scar evaluation provides further useful information to identify potential responders and clinical outcomes.