Benefit Of Cardiac Resynchronization Therapy Research Articles

Meta-Analysis on Drug and Device Therapy of New York Heart Association Functional Class IV Heart Failure With Reduced Ejection Fraction

Heart failure with reduced ejection fraction (HFrEF) is associated with significant morbidity and mortality, particularly in patients with New York Heart Association (NYHA) functional class IV symptoms. Decades of discovery have heralded significant advancements in the pharmacologic management of HFrEF. However, patients with NYHA IV symptoms remain an under-represented population in almost every clinical trial to date, leaving clinicians with limited evidence with which to guide drug treatment decisions in this patient group with severe heart failure. Randomized controlled trials of adult patients with NYHA IV symptoms of HFrEF randomized to current guideline-recommended medical therapy were included in this systematic review and meta-analysis. The outcomes of interest included the rate of all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A total of 39 randomized controlled trials were included. A total of 6 studies examined angiotensin converting enzyme inhibitors, with meta-analyses of 2 demonstrating a reduced risk of all-cause mortality (relative risk (RR) 0.76, 95% confidence interval 0.59 to 0.97, p=0.03). A total of 11 studies examined β blockers, with meta-analysis of 6 demonstrating a reduced risk of all-cause mortality (risk ratio 0.74, 95% confidence interval 0.60 to 0.92, p=0.008). A study examined the mineralocorticoid antagonist spironolactone, reporting a reduced risk of all-cause mortality in the NYHA IV subgroup. A total of 6 studies examined device therapy, demonstrating the benefit of cardiac resynchronization therapy with or without an implantable cardiac defibrillator in reducing hospitalization in the NYHA IV subgroup. Although trial evidence exists for angiotensin converting enzyme inhibitors, β-blockers, and mineralocorticoid antagonist therapy in the NYHA IV population, the role of angiotensin receptor blockers is unclear. Ivabradine, angiotensin receptor neprilysin inhibitors, and sodium-glucose transport protein 2 inhibitors remain underinvestigated and have not been proved to provide any benefit above standard heart failure therapy in patients with HFrEF and NYHA IV symptoms.

CTR-D without the left lead vs single/dual chamber ICD implantation: a cost saving strategy to avoid future upgrading of the latter?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction/Background: Implantation of cardioverter defibrillators (ICD) to prevent sudden death is common in patients with left ventricular dysfunction (LVD) (1).However, these devices are expensive and there is increasing controversy about their cost benefit ratio. More agreement is present about the benefits of cardiac resynchronization therapy (CRT) in patients with LVD and concurrent heart failure (HF) and left bundle branch block (LBB) (2). Nevertheless, LVD often presents without one these two conditions which may only develop at follow up. This makes unclear the benefits of CRT at the time of ICD implantation (CRT-D) in these patients. Some have advocated implanting a CRT-D without the left ventricle lead instead of a conventional single/dual chamber ICD which would give the possibility to add CRT pacing without replacing the device generator at follow-up. However, this practice has been never evaluated and it is unclear its potential impact on cost. Methods This study included all CRT devices implanted in our institution since 2005. Patients with LVD but just heart failure (HF) or left bundle branch block (LBB) were considered for CRT-D implantation without the left lead. The number of patients who needed implantation of a LV lead at follow-up was analyzed. Only patients who needed device replacement due to battery depletion were included in the final analysis Results A total of 913 CRT devices were implanted of which 115 (12.59%) were implanted without a left ventricular lead. The left ventricular lead was not implanted due to technical reasons in 46 cases (5%) and electively in the remaining. CRT device replacement (due to Elective Replacement Indicator (ERI) activation) was necessary in 38 patients of the latter and a LV lead had been never implanted in 32 (84.21%) of them during follow-up (7 +/- 2 years). In patients who needed a LV lead added, device replacement (because of battery depletion) was necessary during left ventricular lead implant procedure in 2 (6.25%). Using the average cost of these devices in our institution (22,000 euros), around 384,000 euros could have been saved if the CRT-D had not been implanted until left ventricular lead was. Conclusions Implantation of a CRT-D without the left ventricle lead instead of a conventional single/dual chamber ICD in patient with border line indication for CRT is not cost effective and does not result is significant savings in ICD generators.

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<0.001), a higher baseline serum creatinine (1.3 mg/dl versus 1.2 mg/dl, p<0.001), and a lower left ventricular ejection fraction (25% versus 26%, p<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.

PO-688-07 IMPACT OF BASELINE PR INTERVAL ON RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY: AN INDIVIDUAL PATIENT DATA META-ANALYSIS OF FIVE RANDOMIZED TRIALS

Longer QRS duration predicts greater benefit from cardiac resynchronization therapy (CRT). Many patients receiving CRT also have a prolonged PR interval, but it is unclear whether PR interval is also an important determinant of the effects of CRT. To investigate whether PR interval is an important determinant of the benefits of CRT. Individual patient data from five randomized trials (MIRACLE, MIRACLE-ICD, CARE-HF, RAFT and REVERSE) comparing CRT and control were pooled. The composite primary endpoint was heart failure hospitalization (HFH) and all-cause mortality. Multivariable analyses were performed including PR interval as well as variables associated with heart failure outcomes including age, gender, QRS duration and morphology, heart failure etiology, systolic blood pressure, beta-blocker use, left ventricular ejection fraction (LVEF) and New York Heart Failure Association class. Of 3872 patients, 1849 were assigned to control and 2023 to CRT. Follow-up ranged from six to 40 months. There are a number of independent predictors of clinical outcomes (Table 1). However, CRT benefit on HFH or death was only significantly influenced by baseline QRS duration (p<0.0001) and PR interval (p=0.0214) and not QRS morphology (p=0.1107). For patients with QRS duration at or above the median value (160ms), the effect of CRT was substantial and similar regardless of PR interval. For patients with QRS duration below the median, CRT was effective only for those with the shortest quartile of PR interval, with progressively less evidence of benefit as PR interval became more prolonged (Table 2). PR interval as well as QRS duration are important determinants of the response to CRT. Patients with marked QRS prolongation benefit from CRT regardless of PR interval. When QRS is not as prolonged, patients with longer PR intervals may obtain little or no benefit.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Acute hemodynamic impact of atrioventricular delay and left ventricular pacing vector programming in MultiPoint Pacing.

The benefits of cardiac resynchronization therapy (CRT) in heart failure patients have been shown to depend on device programming, particularly atrioventricular delay (AVD) and left ventricular (LV) pacing site selection. This study compared the hemodynamic AVD optimization for commonly used biventricular (BiV) and MultiPoint Pacing(MPP, Abbott) LV vector selection strategies. After de novo CRT-D (Abbott Quadra Assura MP) and quadripolar LV lead (Abbott Quartet) implant, acute LV pressure was measured across a range of AVDs (60-225 ms) in four pacing modes: BiV with most proximal cathode, BiV with most distal cathode, MPP using two cathodes with earliest and latest right ventricle (RV)-LV activation times, and MPP using two cathodes with maximal anatomical separation. Hemodynamic improvement was evaluated by changes in maximum LV pressure first-derivative versus RV pacing (ΔdP/dt). Twenty patients (64 years old, 68% male) completed the acute pacing protocol at six centers in China. Hemodynamic improvement versus RV pacing for BiV (proximal), BiV (Distal), MPP (electrical), and MPP (anatomical) was 22.1% ± 13.6%, 23.7% ± 13.4%, 24.5% ± 13.4%, and 25.1% ± 13.9%, respectively. The best MPP setting was marginally superior to the best BiV across all patients (25.8% ± 13.4% vs. 24.5% ± 13.1%, p = .040) and in the majority of patients (75.0% vs. 25.0%, p = .004). AVD programmed as little as 20 ms from optimum significantly reduced the ΔdP/dt benefit for all modes. The maximal hemodynamic improvement across AV delays in this population was greater with MPP than BiV. Furthermore, patient-specific AVD programming was critical in achieving the full hemodynamic response for all BiV and MPP modes.

Tricuspid regurgitation after cardiac resynchronization therapy: evolution and prognostic significance.

AimsTricuspid regurgitation (TR) is common in patients with heart failure (HF) and is associated with worse outcome. This study investigated the effect of cardiac resynchronization therapy (CRT) on TR severity and long-term outcome.Methods and resultsTricuspid regurgitation severity was assessed at baseline and 6 months after CRT implantation, using a multiparametric approach. Patients were divided into four groups: (i) no or mild TR without progression; (ii) no or mild TR with progression to significant (moderate–severe) TR; (iii) significant TR with improvement to no or mild TR; and (iv) significant TR without improvement. The primary endpoint was all-cause mortality. A total of 852 patients (mean age 65 ± 11 years, 77% male) were included. At baseline, 184 (22%) patients had significant TR, with 75 (41%) showing significant improvement at 6-month follow-up. After a median follow-up of 92 (50–137) months, 494 (58%) patients died. Patients with significant TR showing improvement at follow-up had better outcomes than those showing no improvement (P = 0.016). On multivariable analysis, no or mild TR progressing to significant TR [hazard ratio (HR) 1.745; 95% confidence interval (CI): 1.287–2.366; P < 0.001] and significant TR without improvement (HR 1.572; 95% CI: 1.198–2.063; P = 0.001) were independently associated with all-cause mortality, whereas significant TR with improvement at follow-up was not (HR: 1.153; 95% CI: 0.814–1.633; P = 0.424).ConclusionImprovement of significant TR after CRT is observed in a substantial proportion of patients, highlighting the potential benefit of CRT for patients with HF having significant TR. Significant TR at 6 months after CRT is independently associated with increased long-term mortality.

Vectorcardiographic QRS area as a predictor of response to cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a good treatment for heart failure accompanied by ventricular conduction abnormalities. Current ECG criteria in international guidelines seem to be suboptimal to select heart failure patients for CRT. The criteria QRS duration and left bundle branch block (LBBB) QRS morphology insufficiently detect left ventricular activation delay, which is required for benefit from CRT. Additionally, there are various definitions for LBBB, in which each one has a different association with CRT benefit and is prone to subjective interpretation. Recent studies have shown that the objectively measured vectorcardiographic QRS area identifies left ventricular activation delay with higher accuracy than any of the current ECG criteria. Indeed, various studies have consistently shown that a high QRS area prior to CRT predicts both echocardiographic and clinical improvement after CRT. The beneficial relation of QRS area with CRT-outcome was largely independent from QRS morphology, QRS duration, and patient characteristics known to affect CRT-outcome including ischemic etiology and sex. On top of QRS area prior to CRT, the reduction in QRS area after CRT further improves benefit. QRS area is easily obtainable from a standard 12-lead ECG though it currently requires off-line analysis. Clinical applicability will be significantly improved when QRS area is automatically determined by ECG equipment.

Left bundle branch pacing in heart failure patients with left bundle branch block: A systematic review and meta-analysis.

The clinical benefit of cardiac resynchronization therapy (CRT) in heart failure patients with left bundle branch block (LBBB) has been demonstrated. However, a nonresponse rate of CRT nearly 1/3. Recent studies have reported left bundle branch pacing (LBBP) has achieved remarkable effect in CRT. This study aim to explore the efficacy and safety of LBBP in heart failure patients with LBBB. We searched PubMed, Cochrane Library, Web of science, and CNKI databases for studies about LBBP in heart failure patients with LBBB. QRS duration (QRSd), New York Heart Association (NYHA) classification, B-type natriuretic peptide (BNP) concentration, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), pacing threshold and other related data were extracted and summarized. A total of 6 studies were included, and the success rate of LBBP was 93.2%. Compared with baseline, LBBP could shorten QRSd (MD=61.23, 95% CI: 58.21-64.25, p<.01). Echocardiographic parameters including LVEF and LVEDD significantly improved (both with p<.01). Clinical outcomes including NYHA classification and BNP dramatically reduced (both with p<.01). Compared with biventricular pacing (BVP), LBBP could further improve QRSd, LVEF, LVEDD, and NYHA classification (all with p<.01). However, the pacing threshold at follow-up was 0.06 V higher than that at baseline (p<.01), and the incidence of complications was 2.4%. LBBP is effective and safe in heart failure patients with LBBB, whether it is better than BVP needs to be verified by randomized controlled trials.

Complications and Mortality Following CRT-D Versus ICD Implants in Older Medicare Beneficiaries With Heart Failure

ObjectivesThis study sought to assess the comparative effectiveness of cardiac resynchronization therapy with defibrillator (CRT-D) over implantable cardioverter-defibrillator (ICD) alone in older Medicare patients with heart failure with reduced ejection fraction (HFrEF). BackgroundDespite growing numbers of older patients with HFrEF, the benefits of cardiac resynchronization therapy (CRT) in this group are largely unknown. MethodsA cohort of fee-for-service Medicare beneficiaries ≥65 years of age with HFrEF and enrolled in Medicare Part D who underwent CRT-D or ICD implantation from January 2008 to August 2015 was identified. Beneficiaries were divided by age (65-74, 75-84, and 85+ years), and outcomes were compared between the CRT-D and ICD groups after inverse probability weighting. ResultsCompared with the ICD group, the CRT-D group was older and more likely to be White, be female, and have left bundle branch block. After weighting, overall complications were high across age and device groups (14%-20%). The 1-year mortality was high across all groups. In the 2 oldest age strata, the hazard of death was lower in the CRT-D group (HR: 0.90; 95% CI: 0.86-0.95 and HR: 0.81; 95% CI: 0.72-0.90, respectively; P < 0.001); the hazard of heart failure hospitalization was lower for CRT-D vs ICD in the 85+ years age group (HR: 0.82; 95% CI: 0.74-0.92; P < 0.001). ConclusionsIn older Medicare beneficiaries undergoing ICD with or without CRT, complications and 1-year mortality were high. Compared with ICD alone, CRT-D was associated with a lower hazard of mortality in patients ≥74 years of age and lower hazard of HF hospitalization in those ≥85 years of age. These findings support the use of CRT in eligible older patients undergoing ICD implantation.

Cardiac Contractility Modulation for Advanced Heart Failure

Heart failure with reduced ejection fraction (HFrEF) is a major health burden affecting over 13 million people worldwide. Despite emergence of novel pharmacotherapies, it remains a condition with high mortality and morbidity. Currently, guidelines recommend cardiac resynchronization therapy (CRT) for the treatment of medically refractory HFrEF associated with widened QRS on ECG. However, clinical benefits of CRT do not extend to the majority of HFrEF patients who have no significant intraventricular conduction delay. In addition, even in those who fulfilled the stringent criteria for CRT implantation, two-thirds do not respond to therapy. Cardiac contractility modulation (CCM) is a device-based therapy that involves administration of non-excitatory electrical impulses to the right ventricular septum during the absolute refractory period. Studies have shown that these electrical impulses increase cytosolic calcium and regulates local gene expression, resulting in an improved functional capacity and reduces hospitalization in those with symptomatic HFrEF. In this presentation, we summarize the pathophysiological mechanisms, clinical data, potentials and limitations of CCM. Heart failure with reduced ejection fraction (HFrEF) is a major health burden affecting over 13 million people worldwide. Despite emergence of novel pharmacotherapies, it remains a condition with high mortality and morbidity. Currently, guidelines recommend cardiac resynchronization therapy (CRT) for the treatment of medically refractory HFrEF associated with widened QRS on ECG. However, clinical benefits of CRT do not extend to the majority of HFrEF patients who have no significant intraventricular conduction delay. In addition, even in those who fulfilled the stringent criteria for CRT implantation, two-thirds do not respond to therapy. Cardiac contractility modulation (CCM) is a device-based therapy that involves administration of non-excitatory electrical impulses to the right ventricular septum during the absolute refractory period. Studies have shown that these electrical impulses increase cytosolic calcium and regulates local gene expression, resulting in an improved functional capacity and reduces hospitalization in those with symptomatic HFrEF. In this presentation, we summarize the pathophysiological mechanisms, clinical data, potentials and limitations of CCM.

Left bundle branch block causes left atrial dyssynchrony: a result of atrio-ventricular mechanical interaction

Abstract Introduction Left bundle brach block (LBBB) leads to left ventricular (LV) mechanical dyssynchrony with septal flash and delayed lateral wall contractions. Since atrium and ventricle are anatomically connected, dyssynchronous LV contractions may be transmitted to the left atrium, thereby disturbing left (LA) function. Purpose To test the hypothesis that patients with LBBB have LA dyssynchrony induced by tethering to the dyssynchronous left ventricle. Methods Myocardial strain was measured by speckle-tracking echocardiography in 20 non-ischaemic heart failure patients with LBBB, before and 6 months after cardiac resynchronization therapy (CRT), and in 20 healthy controls. For the LA, dyssynchrony was measured as time delay between onset of the interatrial septum and the lateral wall, and for the LV, between onset septal flash and onset lateral wall contraction. White arrows in Figure indicate onset LA stretch. Results As shown in the Figure, patients with LBBB and HF had marked LA reservoir phase dyssynchrony. Before CRT time delay from onset LA septal stretch to onset lateral wall stretch was 125±71 ms (mean±SD), and decreased to 23±70 (p&amp;lt;0.0001) with CRT. In controls there was a small delay of 34±56 ms. The LA dyssynchrony correlated with LV dyssynchrony (r=0.50, p=0.033), supporting the hypothesis that LA dyssynchrony in LBBB represents mechanical interaction due to tethering between the respective walls. Conclusions Patients with LBBB had marked LA reservoir phase dyssynchrony, which was abolished with CRT. The LA dyssynchrony was attributed to direct LV-LA mechanical interaction. The observed LA resynchronization by CRT represent an additional benefit of CRT in patients with heart failure. Funding Acknowledgement Type of funding sources: None. Left atrial and ventricular dyssynchrony

Cardiac resynchronization therapy defibrillators in patients with permanent atrial fibrillation.

AimsThere are conflicting data on the benefit of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with permanent atrial fibrillation (AF). We aimed to compare patient outcomes according to the presence or absence of permanent AF at device implantation.Methods and resultsWe retrospectively analysed remote monitoring data from 1141 CRT defibrillators. Propensity score with inverse‐probability weighting method was used to balance AF and sinus rhythm (SR) groups. Analysis endpoints included total mortality, appropriate defibrillation shocks, and CRT percentage. There were 229 patients (20.1%) in the AF group and 912 patients (79.9%) in the SR group. Compared with SR patients, AF patients were older (median age, 77 vs. 72 years, P < 0.001), more frequently male (82.5% vs. 75.5%, P = 0.02), and had higher heart rate (75.7 vs. 71.0 b.p.m., P < 0.001). Of the 229 AF patients, 162 (70.7%) received suboptimal CRT (<98%) and 67 (29.3%) had adequate CRT (≥98%). During a median follow‐up of 24 months, total mortality did not differ between AF and SR groups (propensity‐score‐weighted hazard ratio, HR 1.32 [95% confidence interval, 0.82–2.15], P = 0.25). The risk of appropriate shocks was significantly higher in the AF group with <98% CRT than in the SR group (weighted‐HR, 1.99 [1.21–3.26], P = 0.006) and was similar in the AF group with ≥98% CRT versus the SR group (1.29 [0.66–2.53], P = 0.45). During follow‐up, sinus rhythm was recovered in 23 patients in the AF group (10%) after a median time of 106 (42–256) days. The rate of sinus rhythm recovery in the AF group was 4.5 (95% CI, 2.8–6.7) per 100 patient‐years; the rate of permanent AF occurrence in the SR group was 2.5 (95% CI, 1.9–3.3) per 100 patient‐years.ConclusionsAlthough mortality was similar across patient groups, patients with permanent AF and suboptimal CRT had twofold higher risk of appropriate shocks than SR patients or AF patients with CRT ≥ 98%.

B-PO04-181 AN EVALUATION OF LEFT VENTRICULAR REVERSE REMODELING IN PATIENTS WITH LEFT BUNDLE BRANCH BLOCK AND QRS DURATION LESS THAN 150MS

The benefit of cardiac resynchronization therapy (CRT) for patients with left bundle branch block (LBBB) and QRS duration (QRSd) between 120 and 150 milliseconds (ms) remains contested. Left ventricular (LV) reverse remodeling may help identify the benefit of CRT in these patients. We hypothesized that patients with LBBB QRSd between 120 and 150ms would have significant LV reverse remodeling on echocardiography after initiation of CRT comparable to patients with LBBB QRSd > 150ms. We aimed to study the effects of CRT on LV reverse remodeling in patients with LBBB QRSd < 150ms compared to patients with QRSd > 150ms. From a cohort of 258 patients who initiated CRT between 2016 and 2019, we performed a retrospective case-control study comparing the reduction in LV end-systolic volume (LVESV) of 19 patients with New York Heart Association Class II-III symptoms on goal-directed medical therapy (GDMT) with LBBB and QRSd < 150ms who received CRT and 19 controls with QRSd > 150ms. LVESV was measured on echocardiography within 6 months prior to CRT implantation and at least 1 year after implantation. There was a significant reduction in LVESV (mL) in patients with QRSd < 150ms from 121.25 to 84.91 (p = 0.0399) and in patients with QRSd > 150ms from 162.2 to 140.1 (p = 0.019). There was no significant difference in the absolute or relative magnitude of the reduction in LVESV between the two groups (absolute: 25.74 vs 44.98 mL, p = 0.48, relative: 27.67% and 28.91%, p = 0.91). Spacing of the echocardiograms before and after CRT introduction did not significantly differ between cases and controls (432.4 vs 460.9 days, p = 0.579). LV reverse remodeling occurred significantly and comparably in both patients with LBBB and QRSd < 150ms and patients with LBBB and QRSd > 150ms. As reduction in LVESV is an important predictor of survival with biventricular pacing, CRT may provide benefit to patients with systolic dysfunction on GDMT with LBBB and QRSd < 150ms.

Long-term mortality benefit of adding an ICD to CRT in non-ischemic patients

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the ÚNKP-20-3-I New National Excellence Program if the Ministry for Innovation and Technology in Hungary, the National Research, Development, and Innovation Office of Hungary (NKFIA; NVKP_16-1-2016-0017 National Heart Program), and the Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development thematic program of the Semmelweis University. This work was also supported by the Artificial Intelligence Research Filed Excellence Program of the National Research, Development and Innovation Office of the Ministry of Innovation and Technology in Hungary (TKP/ITM/NKFIH). The research was also financed by the Thematic Excellence Program (Tématerületi Kiválósági Program, 2020-4.1.1-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Bioimaging thematic program of the Semmelweis University." OnBehalf Heart failure study group Background Data is incomprehensive about the long-term mortality benefit of Cardiac Resynchronization Therapy with (CRT-D) or without (CRT-P) a defibrillator. Purpose To assess the long-term all-cause mortality benefit of CRT-D compared to CRT-P by ischemic aetiology. Methods Between 2000 and 2018, patients after a successful CRT implantation were registered. From 2524 patients, 1099 (44%) had CRT-P and 1366 (54%) CRT-D implantation. Those 59 (2%) patients, who had an ICD upgrade with a CRT-P device during the follow-up, were excluded from the current analysis. The primary composite endpoint was all-cause mortality, LVAD implantation or heart transplantation. Kaplan-Meier and multivariate Cox regression analyses were used to evaluate all-cause mortality in the total cohort and by ischemic aetiology. Results During the median follow-up time of 3,6 years, 1389 patients died from any cause, 697 patients (50%) with a CRT-P, 692 patients (50%) with a CRT-D device. Patients in the CRT-D cohort were younger (67 years vs. 70 years; p &amp;lt; 0.001), had a less advanced functional class (NYHA III/IV., 52.2% vs. 61.4%; p &amp;lt; 0.001), wider QRS [160ms (140/180) vs. 160ms (140/170); p = 0.03] and less females (18.9% vs. 33.3%; p &amp;lt; 0.001) with an ischemic aetiology (57.7% vs. 40.2%; p &amp;lt; 0.0001). CRT-D patients had a better renal function [eGFR, 60.5 (ml/min/1.73m2) vs. 57 (ml/min/1.73m2); p = 0.02], decreased ejection fraction (28% vs. 30%; p = 0.002), had more frequently ventricular arrhythmia (36% vs. 9.8%; p &amp;lt; 0.001) and less frequently diabetes (77% vs. 87,2%; p &amp;lt; 0.001). CRT-D patients took more amount of beta-blockers (90.2% vs. 87.3%; p = 0.03), MRA (72.2% vs. 61.6%; p &amp;lt; 0.001) and amiodaron (32.2% vs. 20%; p &amp;lt; 0.001). By multivariate analysis, aetiology, gender, functional class, renal function, and the presence of ICD were independent predictors of all-cause mortality in the total cohort. By multivariate analysis, patients with a CRT-D device showed a 25% decreased risk of long-term mortality compared to CRT-P alone (aHR 0.75; 95%CI 0.58-0.97; p = 0.03). When patients were dichotomized by their etiology, those with non-ischemic cardiomyopathy showed a long-term benefit from ICD even after adjusting for relevant clinical variables (aHR 0.45; 95%CI 0.28-0.72; p &amp;lt; 0.01). In ischemic patients despite of having a clear mortality benefit of ICD during the mid-term follow-up, it is decreasing after 5 years and less pronounced after adjusting for clinical variables (aHR 0.92; 95%CI 0.67-1.27; p = 0.60). Conclusions However, during mid-term follow up, CRT-D had a clear mortality benefit in ischemic patients compared to CRT-P alone, after 5 years it became less pronounced. While in patients with non-ischemic cardiomyopathy, the benefit of adding an ICD to CRT lasts over 10 years.

Long-term cardiac reverse remodeling after cardiac resynchronization therapy.

IntroductionThe benefit of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) have been observed in the first year. However, there are few data on long‐term follow‐up and the effect of changes of LVEF on mortality. This study aimed to assess the LV remodeling after CRT implantation and the probable effect of changes in LVEF with repeated measures on mortality over time in a real‐world registry.MethodsAmong our cohort of 328 consecutive CRT patients, mixed model effect analysis have been made to describe the temporal evolution of LVEF and LVESV changes over time up with several explanatory variables. Besides, the effect of LVEF along time on the probability of mortality was evaluated using joint modeling for longitudinal and survival data.ResultsThe study population included 328 patients (253 men; 70.2 ± 9.5 years) in 4.2 (2.9) years follow‐up. There was an increase in LVEF of 11% and a reduction in LVESV of 42 mL during the first year. These changes are more important during the first year, but slight changes remain during the follow‐up. The largest reduction in LVESV occurred in patients with left bundle branch block (LBBB) and the smallest reduction in patients with NYHA IV. The smallest increase in LVEF was an ischemic etiology, longer QRS, and LV electrode in a nonlateral vein. Besides, the results showed that the LVEF profiles taken during follow‐up after CRT were associated with changes in the risk of death.ConclusionReverse remodeling of the left ventricle is observed especially during the first year, but it seems to be maintained later after CRT implantation in a contemporary cohort of patients. Longitudinal measurements could give us additional information at predicting the individual mortality risk after adjusting by age and sex compared to a single LVEF measurement after CRT.

The role of contractile reserve by stress test echocardiography for predicting cardiac resynchronization therapy responder: systematic review and meta-analysis

Introduction: Up to one-third of patients who received resynchronization devices do not experience full benefit of cardiac resynchronization therapy (CRT). Echocardiography plays an important role in heart failure patients treated with CRT. Contractile reserved is a strong prognostic factor to predict positive response to CRT (CRT responder).&#x0D; Objective: We perform a systematic review and meta-analysis of published data to assess the relationship between contractile reserve (CR) and response to CRT.&#x0D; Methods: We conduct a systematic search from major medical databases on all clinical trials published up to June 2020, written in English, full-text availability, and human subject. We used Newcastle-Ottawa Scale to measure the quality of evidence. We employed the Mantel–Haenszel random-effects meta-analysis of using RevMan 5.4.&#x0D; Results: We identified 17 studies involving 1399 patients. The type of stress was either dobutamine (n=15) or exercise (n=2). The presence of CR was associated with a higher chance of CRT responder (OR 7.68, 95%CI 4.27–13.82, p&lt;0.001) using a random-effects model. The ORs slightly differed when studies were analyzed separately based on the stress test type and definition of CR. Contractile reserve, assessed with dobutamine stress echocardiography (DSE), defined as an increase in LVEF (OR 5.10, 95% CI 2.29–11.32, P &lt;0.00001) was numerically lower than defined as increased LV contractility (OR 6.86, 95% CI 3.36–12.88, P &lt;0.00001). The presence of CR assessed with exercise stress test are associated with higher chance of CRT responder (OR 49.11, 95% CI 15.04–160.36, P &lt;0.00001). From our meta-analysis, we found non-ischemic has better respond to CRT compare to patient with ischemic etiology (OR 0.41; 95% CI 0.31-0.55, P &lt;0.01).&#x0D; Conclusion: The presence of CR during stress test echocardiography with either dobutamine or exercise stress test is associated with a higher chance of CRT responder.

Segment length in cine (SLICE) strain analysis: a practical approach to estimate potential benefit from cardiac resynchronization therapy

BackgroundSegment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response.Methods and resultsFifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRSsep), systolic stretch index (SSIsep-lat), and internal stretch factor (ISFsep-lat) all correlated significantly with LVESV change (R − 0.56; R − 0.53; and R − 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESSsep) showed strongest correlation with LVESV change (R − 0.63). Multivariable analysis showed ESSsep to be independently related to LVESV change together with age and QRSAREA.ConclusionThe practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESSsep) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.

Cardiac resynchronization therapy left ventricular lead through middle cardiac vein

Purpose: The benefits of cardiac resynchronization therapy (CRT) depend on multiple factors including patient selection and left ventricular (LV) lead position in the coronary sinus. The ideal position for stimulation is the posterolateral region of the left ventricle, since this is the site where maximum contractile delay is seen. But this ideal site of LV lead placement is not possible in many patients due to anatomical limitations. Our study evaluated the feasibility of the middle cardiac vein (MCV) as an alternative target for LV lead placement with short-term outcomes result in a small cohort of patients. Methods: This is a single-center experience over a span of 2 years where in patients with anatomical limitations, we positioned our LV leads through MCV. In this period, we had implanted a total of 76 CRTs in our institution, out of which 6 cases we used MCV. We utilized collateral circulation to reach as close possible to the lateral surface of the left ventricle. Right ventricular (RV) leads were positioned to either outflow tract or upper septum to enhance the electrical gap in between two ventricular leads. Results: We achieved satisfactory periprocedural end results in all the cases as evident by appropriate threshold/impedances of all the leads, lack of diaphragmatic stimulation, etc. There were no procedural complications. Optimum short- and midterm improvement of symptomatic class and LV ejection fraction was observed. None of the patients had any lead dislodgement, abnormal change in lead threshold parameters, or need for hospitalizations for heart failure in follow-ups. Conclusion: We conclude that when usual posterolateral or lateral target veins cannot be accessed for LV lead placement, as an alternative approach utilizing MCV collateral circulation to reach as close possible to the lateral surface may be considered in CRT. RV leads to be positioned at the outflow tract or upper septum in those cases.

Cardiac resynchronisation therapy in patients with cardiac amyloidosis: A multicentre retrospective study

Cardiac resynchronisation therapy (CRT) is highly effective in dilated cardiomyopathy patients with impaired LVEF and LBBB. In cardiac amyloidosis (CA) patients, left ventricular dysfunction and conduction disorders are common but the potential benefit of CRT in this particular setting is unknown. We aimed to investigate outcomes of CA patients who were implanted of CRT devices with respect to left ventricular ejection fraction (LVEF) evolution and major cardiovascular events (MACE). Our retrospective observational study included CA patients implanted with a CRT pacemaker (CRT-P) or defibrillator (CRT-D) from 2012 to 2019, in 8 French university hospitals. MACE were defined as either hospitalisation for heart failure or death at follow-up after CRT implantation. We included 46 patients, [77 (± 5) years old, 42 (91%) male sex]. Cardiac amyloidosis form was AL in 8 patients (17%) and senile/TTR in 38 (83%) patients. CRT indication was LBBB + LVEF < 35% in 27 (59%) patients, upgrading for a LVEF drop after right ventricle pacing in 10 (22%) patients, RBBB + LVEF < 35% in 6 (13%) patients and complete AV block (“Block HF” indication) in the remaining 3 (7%) patients. The implanted device was CRT-D in 19 patients (41%) and CRT-P in 27 patients (59%). At the time of CRT implantation, the mean LVEF was 31 (± 8%). During a mean follow-up after CRT implantation of 620 days, 31 (67%) MACE occurred. After Cox multivariate analysis, the only predictor of MACE was NYHA > 2 at the time of CRT implantation [OR: 2.18 (1.03–4.60); P = 0.059]. We tested the clinical impact of CRT response with various definitions (10/20/25%) validated in the literature but none was significantly associated with MACE. In cardiac amyloidosis patients implanted with a CRT device, the one-year echocardiographic response is not significantly associated with a reduction of MACE at long-term follow up. Thus, the benefit of CRT in CA patients appears uncertain.

Sex-Specific Ventricular Arrhythmias and Mortality in Cardiac Resynchronization Therapy Recipients.

The study goal was to examine whether there are sex-related differences in the incidence of ventricular arrhythmias and mortality in CRT-defibrillator (CRT-D) recipients. Few studies have evaluated sex-related benefits of cardiac resynchronization therapy (CRT). Moreover, data on sex-related differences in the occurrence of ventricular tachyarrhythmias in this population are limited. A multicenter retrospective study was conducted in 460 patients (355 male subjects and 105 female subjects) from the UMBRELLA (Incidence of Arrhythmia in Spanish Population With a Medtronic Implantable Cardiac Defibrillator Implant) national registry. Patients were followed up through remote monitoring after the first implantation of a CRT-D during a median follow-up of 2.2 ± 1.0 years. Sex differences were analyzed in terms of ventricular arrhythmia-treated incidence and death during the follow-up period, with a particular focus on primary prevention patients. Baseline New York Heart Association functional class was worse in women compared with that in men (67.0% of women in New York Heart Association functional class III vs. 49.7% of men; p=0.003), whereas women had less ischemic cardiac disease (20.8% vs. 41.7%; p<0.001). Female sex was an independent predictor of ventricular arrhythmias (hazard ratio: 0.40; 95% confidence interval: 0.19 to 0.86; p=0.020), as well as left ventricular ejection fraction and nonischemic cardiomyopathy. Mortality in women was one-half that of men, although events were scarce and without significant differences (2.9% vs. 5.6%; p=0.25). Women with left bundle branch block and implanted CRT have a lower rate of ventricular tachyarrhythmias than men. All-cause mortality in patients is, at least, similar between female and male subjects.