Efficacy Of Cardiac Resynchronization Therapy Research Articles

Predictors of responders to cardiac resynchronization therapy in patients with non-left bundle branch block with mid-wide QRS duration

Abstract Background Cardiac resynchronization therapy (CRT) is useful for patients with severe heart failure with dyssynchrony of left ventricular contraction, significantly reducing total mortality or heart failure rehospitalization. In patient with left bundle branch block (LBBB) or QRS duration (QRSd) ≥ 150 ms, CRT is a well-established therapy at guidelines in Japan and other countries. However, CRT may be more useful and effective in Asian patients with middle range wide QRSd, because of smaller body size than in the West. Few reports have shown the usefulness and efficacy of CRT in patients with non-LBBB and middle range wide QRS duration (mid-wide QRSd). Purpose To evaluate the predictors of CRT responders in heart failure patients with non LBBB and mid wide QRSd. Methods We retrospectively studied 174 consecutive patients who underwent a denovo CRT device implantation at two institutions between September 2013 and March 2023. Follow up echocardiography examination could be performed after 150 days postoperatively. CRT responders were defined as a decrease in left ventricular end systolic volume ≥15% on echocardiography. We plotted thereceiver operating characteristic (ROC) curve for predicting CRT responders. The area under the curve (AUC) was calculated to determine the best cut off value. Results A total of 34 patients with non LBBB and 120≤ QRSd <150 ms were enrolled in this study. Sixteen of 34 (47%) patients were the responders for CRT. There was no significant difference in gender between the responder and non responder groups (p=0.274). Non ischemic cardiomyopathy was more prevalent in the responder group (p=0.046). The ROC curve analysis confirmed that 0.809 was the better optimal cut off value of QRSd/left ventricular end diastolic volume (LVEDV) for predicting CRT responders (AUC = 0.688). The multivariate analysis demonstrated that QRSd/LVEDV was significantly associated with CRT responders [odds ratio (OR) 9.88, 95% confidence interval 1.51 64.90, p = 0.017]. Conclusion The corrected QRSd for heart size using LVEDV could be the independent predictor of CRT responders in Japanese patients with non LBBB and mid wide QRSd.

Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study.

A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot. Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation. A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%-44%] at baseline to 42% [32%-50%] at early follow-up (P<0.001) and remained improved from baseline thereafter (P≤0.002). The QRS duration decreased from 180 [160-205] ms at baseline to 152 [133-182] ms at early follow-up (P<0.001) and remained decreased at intermediate and late follow-up (P≤0.001). Patients with upgraded CRT had consistent improvement in left ventricular ejection fraction and QRS duration at each time point (P≤0.004). Patients had a significantly improved New York Heart Association functional class after CRT implantation at each time point compared with baseline (P≤0.002). The transplant-free survival rates at 3, 5, and 8 years after CRT implantation were 85%, 79%, and 73%. In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population.

Clinical utility of QRS duration normalized to left ventricular volume for predicting cardiac resynchronization therapy efficacy in patients with “mid-range” QRS duration

BackgroundCardiac resynchronization therapy (CRT) is effective for patients with heart failure with QRS duration (QRSd) ≥150 ms. However, its beneficial effect seems to be limited for those with “mid-range” QRSd (120–149 ms). Recent studies have demonstrated that modifying QRSd to left ventricular end-diastolic volume (LVEDV)—modified QRSd—improves the prediction of clinical outcomes of CRT. ObjectiveThe purpose of this study was to investigate the clinical impact of the modified QRSd on the efficacy of CRT in patients with “mid-range” QRSd. MethodsWe conducted a retrospective, multicenter, observational study, with heart failure hospitalization (HFH) after CRT as the primary endpoint. Modified QRSd is defined as QRSd divided by LVEDV, determined through the Teichholtz method of echocardiography. ResultsAmong the 506 consecutive patients considered, 119 (mean age 61 ± 15 years; 80% male, QRSd 135 ± 9 ms) with a “mid-range” QRSd who underwent de novo CRT device implantation were included for analysis. During median follow-up of 878 days [interquartile range 381–1663 days], HFH occurred in 45 patients (37%). Fine-Gray analysis revealed modified QRSd was an independent predictor of HFH (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.96–0.99; P <.01). Receiver operating characteristic curve analysis revealed a cutoff value of 0.65 ms/mL for the modified QRSd in predicting HFH. Patients above the threshold exhibited a significantly lower incidence of HFH than patients below the threshold (HR 0.46; 95% CI 0.25–0.86; P = .01). ConclusionModified QRSd can effectively predict the efficacy of CRT in patients with a “mid-range” QRSd.

Multicenter Study of Survival Benefit of Cardiac Resynchronization Therapy in Pediatric and Congenital Heart Disease

BackgroundEvidence for the efficacy of cardiac resynchronization therapy (CRT) in pediatric and congenital heart disease (CHD) has been limited to surrogate outcomes. ObjectivesThis study aimed to assess the impact of CRT upon the risk of transplantation or death in a retrospective, high-risk, controlled cohort at 5 quaternary referral centers. MethodsBoth CRT patients and control patients were <21 years of age or had CHD; had systemic ventricular ejection fraction <45%; symptomatic heart failure; and significant electrical dyssynchrony (QRS duration z score >3 or single-site ventricular pacing >40%) at enrollment. Patients with CRT were matched with control patients via 1:1 propensity score matching. CRT patients were enrolled at CRT implantation; control patients were enrolled at the outpatient clinical encounter where inclusion criteria were first met. The primary endpoint was transplantation or death. ResultsIn total, 324 control patients and 167 CRT recipients were identified. Mean follow-up was 4.2 ± 3.7 years. Upon propensity score matching, 139 closely matched pairs were identified (20 baseline indices). Of the 139 matched pairs, 52 (37.0%) control patients and 31 (22.0%) CRT recipients reached the primary endpoint. On both unadjusted and multivariable Cox regression analysis, the risk reduction associated with CRT for the primary endpoint was significant (HR: 0.40; 95% CI: 0.25-0.64; P < 0.001; and HR: 0.44; 95% CI: 0.28-0.71; P = 0.001, respectively). On longitudinal assessment, the CRT group had significantly improved systemic ventricular ejection fraction (P < 0.001) and shorter QRS duration (P = 0.015), sustained to 5 years. ConclusionsIn pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplantation-free survival.

Activation time at left ventricular pacing site (QLV) in relation to actual site of latest activation; effect on response to cardiac resynchronization therapy

Abstract Background Among techniques to improve CRT efficacy, longer QLV (activation time at the left ventricular (LV) pacing site (LVPS)) has been proposed to correlate to response to cardiac resynchronization therapy (CRT), supporting that pacing close to the latest LV electrically activated site (LEAS) improves CRT efficacy. A QLV cut-off of &amp;gt; 95 ms has been proposed, however, predictive value was modest. This may be because LEAS was not identified, and empirically delivered leads may have missed it (described by a longer interval QLEAS (activation time at LEAS) to QLV. Purpose We compared QLEAS to QLV, and assessed effect of the interval QLEAS-QLV, on response to CRT. Methods We studied patients who had received CRT for Class I or Class IIa indications, regardless of CRT response, at 5 European sites. LV lead placement, device programming and follow up (FU) followed physician preference and site protocol. All patients had clinical FU 6-12 months post-implant, including echocardiographic study. CRT non-response was defined as LV end-systolic volume (LVESV) reduction of &amp;lt;15%. Patients underwent noninvasive 3D electrical activation mapping and torso CT 6-24 months post-implant. QLV and QLEAS were assessed from the noninvasive activation map in a blinded core lab. Logistic regression modelling was conducted for QLV and the interval QLEAS-QLV against CRT response, and the optimal cut-off points were calculated. Results Of 111 patients (age 64±11 years (mean±SD), 74% male, 98% LBBB, QRS duration 172±21 ms, baseline LVEF 28±6%, LVESV 183±87 mL, implant duration 12±5 months, 31%/69% NYHA Class II/III, 38% ischemic heart disease), 67% responded at 10±3 months post-implant. QLV overall was 97±23 ms (range 42-148 ms), 103±21 ms for responders and 83±22 for non- responders (p&amp;lt;0.001), QLEAS was 109±19 ms (range 66-150 ms), 109±20 ms for responders and 110±19 ms for non- responders (p=0.74). QLEAS-QLV overall was 13±18 ms (range 0-120 ms), 6±10 ms for responders and 27±22 ms for non-responders (p&amp;lt;0.001) (Figure 1). Optimal cut-off point for QLV was 85 ms with sensitivity 0.89, specificity 0.57 and an AUC of 0.742 (95% CI: 0.637- 0.846). Optimal cut-off point for QLEAS-QLV was 6 ms (sensitivity 0.77, specificity 0.95, AUC 0.901 (95% CI: 0.844-0.957) (Figure 1). The AUC of QLV cut-off and QLEAS-QLV cut-off differed significantly (p&amp;lt;0.001). 18/111 patients (16%) were non-responders despite a QLV≥85 ms, whereas 2 patients (2%) were non-responders despite a QLEAS-QLV≤6 ms. Conclusion QLEAS has greater discriminatory power than a QLV cut-off of 85 ms to separate CRT responders from non-responders in patients with LBBB and long QRS duration. QLV guided LV lead placement without prior knowledge of the latest LV activation in individual patients will miss the ideal LV pacing site in 16% of cases. Using noninvasive 3D global mapping to identify LEAS pre-CRT implant and directing LV lead placement to within 6 ms of this may improve CRT efficacy.Figure 1

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.

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.

Cardiac resynchronization therapy for patients with heart failure and nonspecific intraventricular conduction delay.

The efficacy of cardiac resynchronization therapy (CRT) in heart failure patients with left bundle branch block (LBBB) is well established with Class I or IIa recommendation according to 2021 ESC Guidelines on cardiac pacing and CRT, whereas non-LBBB morphology is less recommended. There is insufficient evidence that proves patients with NICD could benefit from CRT. As patients with NICD are characterized by heterogeneity, the effect of CRT on these patients is still controversial. Although the proportion of NICD in the population is lower than that of LBBB patients, it is still worth investigating the effects of CRT on patients with NICD in an era of His-Purkinje conduction system pacing (HPCSP).

Long-term cardiovascular outcomes among immigrants and non-immigrants in cardiac resynchronization therapy: a nationwide study.

To date, potential differences in outcomes for immigrants and non-immigrants with a cardiac resynchronization therapy (CRT), in a European setting, remain underutilized and unknown. Hence, we examined the efficacy of CRT measured by heart failure (HF)-related hospitalizations and all-cause mortality among immigrants and non-immigrants. All immigrants and non-immigrants who underwent first-time CRT implantation in Denmark (2000-2017) were identified from nationwide registries and followed for up to 5 years. Differences in HF related hospitalizations and all-cause mortality were evaluated by Cox regression analyses. From 2000 to 2017, 369 of 10 741 (3.4%) immigrants compared with 7855 of 223 509 (3.5%) non-immigrants with a HF diagnosis underwent CRT implantation. The origins of the immigrants were Europe (61.2%), Middle East (20.1%), Asia-Pacific (11.9%), Africa (3.5%), and America (3.3%). We found similar high uptake of HF guideline-directed pharmacotherapy before and after CRT and a consistent reduction in HF-related hospitalizations the year before vs. the year after CRT (61% vs. 39% for immigrants and 57% vs. 35% for non-immigrants). No overall difference in 5-year mortality among immigrants and non-immigrants was seen after CRT [24.1% and 25.8%, respectively, P-value = 0.50, hazard ratio (HR) = 1.2, 95% confidence interval (CI): 0.8-1.7]. However, immigrants of Middle Eastern origin had a higher mortality rate (HR = 2.2, 95% CI: 1.2-4.1) compared with non-immigrants. Cardiovascular causes were responsible for the majority of deaths irrespective of immigration status (56.7% and 63.9%, respectively). No overall differences in efficacy of CRT in improving outcomes between immigrants and non-immigrants were identified. Although numbers were low, a higher mortality rate among immigrants of Middle Eastern origin was identified compared with non-immigrants.

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

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

Non-invasive three-dimensional electrical activation mapping to predict cardiac resynchronization therapy response: site of latest left ventricular activation relative to pacing site.

Pacing remote from the latest electrically activated site (LEAS) in the left ventricle (LV) may diminish response to cardiac resynchronization therapy (CRT). We tested whether proximity of LV pacing site (LVPS) to LEAS, determined by non-invasive three-dimensional electrical activation mapping [electrocardiographic Imaging (ECGI)], increased likelihood of CRT response. Consecutive CRT patients underwent ECGI and chest/heart computed tomography 6-24 months of post-implant. Latest electrically activated site and the distance to LVPS (dp) were assessed. Left ventricular end-systolic volume (LVESV) reduction of ≥15% at clinical follow-up defined response. Logistic regression probabilistically modelled non-response; variables included demographics, heart failure classification, left bundle branch block (LBBB), ischaemic heart disease (IHD), atrial fibrillation, QRS duration, baseline ejection fraction (EF) and LVESV, comorbidities, use of CRT optimization algorithm, angiotensin-converting enzyme inhibitor(ACE)/angiotensin-receptor blocker (ARB), beta-blocker, diuretics, and dp. Of 111 studied patients [64 ± 11 years, EF 28 ± 6%, implant duration 12 ± 5 months (mean ± SD), 98% had LBBB, 38% IHD], 67% responded at 10 ± 3 months post CRT-implant. Latest electrically activated sites were outside the mid-to-basal lateral segments in 35% of the patients. dp was 42 ± 23 mm [31 ± 14 mm for responders vs. 63 ± 24 mm non-responders (P < 0.001)]. Longer dp and the lack of use of CRT optimization algorithm were the only independent predictors of non-response [area under the curve (AUC) 0.906]. dp of 47 mm delineated responders and non-responders (AUC 0.931). The distance between LV pacing site and latest electrical activation is a strong independent predictor for CRT response. Non-invasive electrical evaluation to characterize intrinsic activation and guide LV lead deployment may improve CRT efficacy.

Association of left ventricular remodeling with cardiac resynchronization therapy outcomes

Cardiac resynchronization therapy (CRT) response stratified by left ventricular (LV) remodeling revealed differing mortality profiles for distinct patient cohorts. Measuring functional end points, as well as mortality, may better assess CRT efficacy and inform patient management. However, the association between LV remodeling and functional outcomes after CRT is not well understood. The purpose of this study was to evaluate long-term CRT outcomes by extent of LV remodeling. REsynchronization reVErses Remodeling in Systolic Left vEntricular dysfunction (Clinical Trials.gov identifier NCT00271154) was a prospective, double-blind, randomized trial of CRT. Patients were classified on the basis of LV end-systolic volume (LVESV) change from baseline to 6 months post-CRT: worsened (increase), stabilized (0%-≤15% reduction), responder (>15%-<30% reduction), and super-responder (≥30% reduction). Subjects were evaluated annually for 5 years. The analyses included 353 patients randomized to CRT-ON arm. All-cause mortality was higher in the worsened group than in the other 3 response groups (29.8% vs 8.0%; P < .0001), with no difference in survival among those groups (P = .87). A significant interaction between the LVESV group and time was observed for health status and quality of life (P = .02 for both). The interaction was not significant for 6-minute hall walk (P=.79); however, super-responders had increased walk distance compared with the other 3 response groups (P = .03). Preventing further increase in LVESV with CRT was associated with reduced mortality, whereas functional measure improvement was associated with LV remodeling magnitude. These results support the consideration of functional and mortality end points to assess CRT efficacy and provide further evidence that the dichotomous "responder and nonresponder" classification should be modified.

Long-term outcome and mortality predictors in patients with extremely enlarged left ventricle end-diastolic diameter undergoing cardiac resynchronization therapy

Abstract Background Data on efficacy of cardiac resynchronization therapy (CRT) and prognosis of CRT recipients with extremely enlarged left ventricular prior to device implantation are scarce. Aim To determine outcome and mortality predictors in patients with heart failure (HF) and extremely increased left ventricle end-diastolic diameter (LVEDD) treated with cardiac resynchronization therapy. Methods Study population consisted of 1059 consecutive patients with CRT implanted between 2002 and 2019 in a tertiary care university hospital, in a densely inhabited, urban region of Poland (949 subjects [89.6%] with CRT-D; 110 patients with CRT-P [10.4%]). Results The median LVEDD before CRT implantation was 68 mm (56–80). We divided all CRT patients into quartiles as per LVEDD: I &amp;lt;61 mm, II 61–67 mm, III 68–73 mm and IV ≥74 mm. During the median follow-up of 1661 days (10th and 90th percentile: 323–3995) mortality rates for quartiles I–IV were 41.2, 49.6, 55.9 and 68.1%, respectively (P&amp;lt;0.001). The LVEDD ≥74 mm (quartile IV) appeared to be an independent risk factor for death (HR 1.29, 95% CI 1.05–1.6, P=0.02). On multivariable analysis, severe mitral regurgitation (MR; HR 1.54, 95% CI 1.1–2.16, P=0.01) and advanced age (HR 1.02, 95% CI 1.01–1.03, P=0.02) were independent risk factors for death in quartile IV. During observation, mortality rate for quartile IV patients aged &amp;gt;65 years and with severe MR was 90%. Exclusion of subjects with severe MR and aged &amp;gt;65 from quartile IV resulted in similar mortality rate (53.1%) as for patients in lower quartiles. Conclusions Mortality rates in CRT recipients with extremely enlarged LVEDD is significantly higher compared to those with LVEDD &amp;lt;74 mm. CRT offer to HF patients with LVEDD ≥74 mm (and in particular those with accompanying severe MR and aged &amp;gt;65 years) should be very carefully assessed and other HF therapies (i.e. left ventricular assist devices) should be considered, as more than 90% of those die within 4 years since CRT implantation. Funding Acknowledgement Type of funding sources: None.

Sex-related differences in the prognosis of patients with cardiac sarcoidosis treated with cardiac resynchronization therapy.

Past studies have shown the sex-related difference in the efficacy of cardiac resynchronization therapy (CRT). However, the data for cardiac sarcoidosis (CS) are limited. The purpose of this study was to assess the sex-related prognostic differences in CS patients with CRT. This multicenter CS survey included 430 patients (295 females) who met the diagnostic criteria for CS. Patients were divided into those treated with primary CRT or upgraded CRT from the pacemaker (CRT group; n = 73) and others (control group; n = 357). Sex differences in the incidence of all-cause death, heart failure (HF) death including heart transplantation, ventricular arrhythmia events (VAEs) (sudden death, appropriate device therapy), cardiac adverse events (CAEs) (HF death, VAEs), changes in serum brain natriuretic peptide (BNP) levels, and left ventricular ejection fraction (LVEF) over the follow-up period were analyzed. During median follow-up of 5.2 years, males, but not females, in the CRT group had significantly worse all-cause mortality than patients in the control group (P <.001). In the CRT group, there was no significant sex-related difference in the incidence of HF death; however, females had significantly better VAE- and CAE-free survival than males (P = .033 and P = .008, respectively). Multivariate analysis of the CRT group showed that female sex (hazard ratio 0.37; 95% confidence interval 0.15-0.89; P = .02 and P = .6) independently predicted freedom from CAEs. During follow-up, BNP levels were significantly improved in all groups. LVEF was maintained in females with CRT. In CS patients with CRT, HF death-free survival was similar between sexes. However, females exhibited better VAE- and CAE-free survival than males.

Cardiac resynchronization therapy in patients with a history of atrial fibrillation: insights from five major clinical trials

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Heart, Lung, and Blood Institute Background Many patients with heart failure who are considered for cardiac resynchronization therapy (CRT) have a history of (h/o) atrial fibrillation (AF) but there are doubts about the efficacy of CRT in patients with AF. Purpose To investigate the association of CRT on morbidity and mortality among patients with and without a h/o AF. Methods Original, patient-level data from five clinical trials of CRT that permitted enrolment of patients with a h/o AF were included: COMPANION, MADIT-CRT, BLOCK HF, REVERSE, and MIRACLE trial. Patients with permanent or persistent AF were excluded from these trials, and therefore from this analysis. The outcomes of interest were the composite endpoint of time to heart failure hospitalization (HFH) or all-cause mortality or all-cause mortality alone. The association of CRT (versus no CRT) with outcomes for patients with and without a h/o AF was assessed using a Bayesian-Weibull survival regression model with random terms for the trial-specific treatment effects and the trial-specific baseline hazard functions including an interaction between history of paroxysmal AF and CRT. All results are presented as hazard ratios (HRs) with 95% posterior credible intervals (CIs) and posterior probabilities of no association, adjusting for baseline characteristics. Results A total of 4062 patients were included, 661 (16.3%) of whom had a h/o AF. Patients with a h/o AF were older (mean [SD] age 68 [10] years versus 64 [11] years) and had a higher proportion of ischemic cardiomyopathy (67% versus 53%, p&amp;lt;0.001), a higher baseline serum creatinine (1.3 mg/dl versus 1.2 mg/dl, p&amp;lt;0.001), and a lower left ventricular ejection fraction (25% versus 26%, p&amp;lt;0.001). The HRs for all outcomes and the interaction term are shown in Table 1. For the overall population, CRT delayed the time to HFH or all-cause mortality (HR: 0.74, 95% CI: 0.62 – 0.87, p=0.005); for patients with a h/o AF, it did not (HR: 0.87, 95% CI: 0.64 to 1.19, p=0.37). In this patient-level meta-analysis, CRT was not associated with a reduction in mortality, overall or by h/o AF. Howevber, the interaction (estimate shown as a ratio of HRs) between those with or without a h/o AF and the effects of CRT was not significant for either outcome (Table 1). Conclusion In the largest post hoc analysis to date, we confirm the benefits of CRT in patients without a h/o AF in reducing HFH or mortality. There was no statistically significant interaction between CRT and h/o AF for any analysed outcome.

Dubious effect of the high biventricular paced beats percentage itself on the cardiac resynchronization efficacy in patients with atrial fibrillation. The randomized Pilot-CRAfT Study results

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Cardiology statutory grant Background The presence of atrial fibrillation (AF) in cardiac resynchronization therapy (CRT) recipients is common and AF is a marker of poorer CRT response. The negative influence of AF on CRT efficacy is belived to be mediated mainly by the drop of effectively captured biventricular paced beats percentage (BiVp%). According to observational trials, the minimal BiVp associated with better outcomes is 95-98%, however there is lack of randomized trials to confirm this findings. Purpose The purpose of the study was to assess the influence of BiVp% itself on the clinical outcomes in the population CRT patients with atrial fibrillation in a prospective, randomized cohort. Methods The study included the prospective Pilot-CRAfT study participants that is patients with CRT and permanent or persistent AF lasting for ≥6 months that were randomly assigned to rhythm or rate control strategy. We divided the whole study population according to their BiVp at the 12 month follow-up with two borderline BiVp values (BiVp &amp;gt;98% vs &amp;lt;98% and &amp;gt;95% vs &amp;lt;95%) and analysed the echocardiographic indices, exercise tolerance and quality of life between the prespecified groups. Results The study included 43 CRT patients (97,7% males) aged 68,4 (SD: ±8,3) years with mean BiVp% 82,4% ±9,7% at baseline. The mean baseline left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD) and maximal oxygen uptake (VO2max) were: 30 ±8%, 65 ±8 mm, 14 ±5 mL/(kg*min), respectively. In both of the study arms the BiVp% raised significantly reaching 98,1 ±2,3% and 96,3 ±3,9% in the rhythm control and the rate control arms respectively (P=0,093). As a result the were overall 21 patients with BiVp &amp;gt;98% and 29 patients with BiVp &amp;gt;95% at the end of the study. The BiVp groups &amp;gt;98% vs &amp;lt;98% and &amp;gt;95% vs &amp;lt;95% did not differ as to baseline characteristics and we have not observed any differences in the mean LVEF, mean LVEDD, mean VO2max, and quality of life in the prespecified BiVp% groups at the end of the follow up. Moreover no linear correlations between the BiVp% and LVEF, LVEDD, VO2max values were observed. However, in the rate control group patients with AVNA performed had lower LVEDD at the end of the study (57,7 ±3,0 vs 65,4 ±7,0 p=0,007) and significant decrease in the LVEDD after AVNA was observed (-8,6 95%CI [-14,9; -2,3]). Conclusions The BiVp &amp;gt;98% or &amp;gt;95% alone does not seem to warrant good response to cardiac resynchronization in patients with persistent atrial fibrillation as assessed in the prospective randomized cohort. However, performing AVNA in this group of patients may be beneficial in terms of LVEDD decrease.

PO-663-07 IMPACT OF INTRINSIC AND PACED PARAMETERS ON BEST ELECTRICAL RESYNCHRONIZATION IN CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH HEART FAILURE AND LBBB

Electrical factors that may influence efficacy of cardiac resynchronization therapy (CRT) are transseptal conduction time during intrinsic conduction (the source of QRS prolongation in LBBB), success of left ventricular (LV) preexcitation during LV pacing, and programmed AV interval. These have been tested separately, and whether they are co-dependent is unknown.

Electrogram analysis to detect cathodal and anodal capture in left ventricular cardiac resynchronization pacing leads.

Our study analyzed cardiac electrograms (EGMs) to identify characteristics for detecting cathodal, anodal, or cathodal-anodal (simultaneous) capture in left ventricular (LV) quadripolar pacing leads of cardiac resynchronization therapy (CRT) patients. The relationship between these EGM characteristics and the electrocardiogram (ECG) was also examined. We performed a retrospective analysis of 54 bipolar pacing configurations across nine patients with implanted CRT devices and quadripolarleads who had undergone a12 lead ECG optimization. Three pacing tests (cathode unipolar, anode unipolar, and bipolar) per bipolar pair were performed, examining ECG and EGM morphology changes accompanying each test and any transitions of morphology or amplitude during voltage stepdown. During the cathode and anode unipolar pacing tests, the EGM was biphasic (negative/positive) or monophasic (positive) in 52/53 (98%), and biphasic (positive/negative) or monophasic (negative) in 50/51 (98%), respectively. During bipolar LV capture threshold testing, 30 bipolar pairs displayed a sudden increase in EGM amplitude (median 9.4mV, interquartile range [7-14mV]) when transitioning from cathodal-anodal capture to cathodal or anodal capture. Ninety percent of these EGM transitions had a corresponding simultaneous change in ECG, while 10% had no ECG changes.Two patients demonstrated "quad-site" capture on their quadripolar lead with multipoint pacing enabled and cathodal-anodal capture from each stimulus. EGM characteristics during LV pacing tests can reliably detect cathodal, anodal, or cathodal-anodal capture, with greater sensitivity than 12 lead ECG changes. Integration of EGM analysis into routine CRT device follow up can be performed easily and may have implications for CRT efficacy.

Abstract 11215: Cardiac Resynchronization Therapy via Left Bundle Branch Pacing Vvrsus Optimized Biventricular Pacing with Adaptive Algorithm in Heart Failure with Left Bundle Branch Block: A Prospective, Multi-Center, Observational Study

Objectives: The purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized bi-ventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction≤35% (HFrEF) and left bundle branch block (LBBB). Methods: One hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into 2 groups (LBBP-CRT, n=49; BVP-aCRT, n=51) in 4 centers. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up. Results: The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07 %. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (102.61±9.66ms vs 126.54±11.67ms, P&lt;0.001). Higher absolute LVEF and ΔLVEF was also achieved in LBBP-CRT than BVP-aCRT at 6-month (P=0.008,P=0.020) and 1-year follow-up (P=0.021,P=0.015). There was no significant difference in response rate between two groups while higher super-response rate was observed in LBBP-CRT as compared to BVP-aCRT at 6-month(53.06% vs 36.59%, p=0.016) and 12-month(61.22% vs 39.22%, p=0.028) during follow-up. The pacing threshold was lower in LBBP-CRT at implant and during 1-year follow-up(both p&lt;0.001). Procedure-related complications and adverse clinical outcomes including heart failure hospitalization and mortality were not significantly different in 2 groups. Conclusions: The feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.

Cardiac resynchronization therapy via left bundle branch pacing vs. optimized biventricular pacing with adaptive algorithm in heart failure with left bundle branch block: a prospective, multi-centre, observational study.

AimsThe purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized biventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction ≤35% (HFrEF) and left bundle branch block (LBBB).Methods and resultsOne hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into two groups (LBBP-CRT, n = 49; BVP-aCRT, n = 51) in four centres. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up. The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07%. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (126.54 ± 11.67 vs. 102.61 ± 9.66 ms, P < 0.001). Higher absolute left ventricular ejection fraction (LVEF) and △LVEF was also achieved in LBBP-CRT than BVP-aCRT at 6-month (47.58 ± 12.02% vs. 41.24 ± 10.56%, P = 0.008; 18.52 ± 13.19% vs. 12.89 ± 9.73%, P = 0.020) and 1-year follow-up (49.10 ± 10.43% vs. 43.62 ± 11.33%, P = 0.021; 20.90 ± 11.80% vs. 15.20 ± 9.98%, P = 0.015, P = 0.015). There was no significant difference in response rate between two groups while higher super-response rate was observed in LBBP-CRT as compared to BVP-aCRT at 6 months (53.06% vs. 36.59%, P = 0.016) and 12 months (61.22% vs. 39.22%, P = 0.028) during follow-up. The pacing threshold was lower in LBBP-CRT at implant and during 1-year follow-up (both P < 0.001). Procedure-related complications and adverse clinical outcomes including heart failure hospitalization and mortality were not significantly different in two groups.ConclusionsThe feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.