Practical approach for atrial cardiomyopathy characterization in patients with atrial fibrillation.

Atrial fibrillation (AF) causes progressive structural and electrical changes in the atria that can be summarized within the general concept of atrial remodeling. In parallel, other clinical characteristics and comorbidities may also affect atrial tissue properties and make the atria susceptible to AF initiation and its long-term persistence. Overall, pathological atrial changes lead to atrial cardiomyopathy with important implications for rhythm control. Although there is general agreement on the role of the atrial substrate for successful rhythm control in AF, the current classification oversimplifies clinical management. The classification uses temporal criteria and does not establish a well-defined strategy to characterize the individual-specific degree of atrial cardiomyopathy. Better characterization of atrial cardiomyopathy may improve the decision-making process on the most appropriate therapeutic option. We review current scientific evidence and propose a practical characterization of the atrial substrate based on 3 evaluation steps starting with a clinical evaluation (step 1), then assess outpatient complementary data (step 2), and finally include information from advanced diagnostic tools (step 3). The information from each of the steps or a combination thereof can be used to classify AF patients in 4 stages of atrial cardiomyopathy, which we also use to estimate the success on effective rhythm control.

Magnetic resonance detection of advanced atrial cardiomyopathy increases the risk for atypical atrial flutter occurrence following atrial fibrillation ablation.

AIMS: Recurrence of arrhythmia after catheter ablation of atrial fibrillation (AF) in the form of atypical atrial flutter (AFL) is common among a significant number of patients and often requires redo ablation with limited success rates. Identifying patients at high risk of AFL after AF ablation could aid in patient selection and personalized ablation approach. The study aims to assess the relationship between pre-existing atrial cardiomyopathy and the occurrence of AFL following AF ablation. METHODS AND RESULTS: We analysed a cohort of 1007 consecutive AF patients who underwent catheter ablation and were included in a prospective registry. Patients who did not have baseline cardiac magnetic resonance imaging and late gadolinium enhancement (LGE-CMR) or did not experience any recurrences were excluded. A total of 166 patients were included gathering 56 patients who underwent re-ablation due to AFL recurrences and 110 patients who underwent re-ablation due to AF recurrences (P = 0.11). A multiparametric assessment of atrial cardiomyopathy was based on basal LGE-CMR, including left atrial (LA) volume, LA sphericity, and global and segmental LA fibrosis using semiautomated post-processing software. Out of the initial cohort of 1007 patients, AFL and AF occurred in 56 and 110 patients, respectively. An age higher than 65 [odds ratio (OR) = 5.6, 95% confidence interval (CI): 2.2-14.4], the number of previous ablations (OR = 3.0, 95% CI: 1.2-7.8), and the management of ablation lines in the index procedure (OR = 2.5, 95% CI: 1.0-6.3) were independently associated with AFL occurrence. Furthermore, several characteristics assessed by LGE-CMR were identified as independent predictors of AFL recurrence after the index ablation for AF, such as enhanced LA sphericity (OR = 1.3, 95% CI: 1.1-1.6), LA global fibrosis (OR = 1.03, 95% CI: 1.01-1.07), and increased fibrosis in the lateral wall (OR = 1.03, 95% CI: 1.01-1.04). CONCLUSION: Advanced atrial cardiomyopathy assessed by LGE-CMR, such as increased LA sphericity, global LA fibrosis, and fibrosis in the lateral wall, is independently associated with arrhythmia recurrence in the form of AFL following AF ablation.

Stepwise application of ECG and electrogram-based criteria to ensure electrical resynchronization with left bundle branch pacing.

AIMS: To define a stepwise application of left bundle branch pacing (LBBP) criteria that will simplify implantation and guarantee electrical resynchronization. Left bundle branch pacing has emerged as an alternative to biventricular pacing. However, a systematic stepwise criterion to ensure electrical resynchronization is lacking. METHODS AND RESULTS: A cohort of 24 patients from the LEVEL-AT trial (NCT04054895) who received LBBP and had electrocardiographic imaging (ECGI) at 45 days post-implant were included. The usefulness of ECG- and electrogram-based criteria to predict accurate electrical resynchronization with LBBP were analyzed. A two-step approach was developed. The gold standard used to confirm resynchronization was the change in ventricular activation pattern and shortening in left ventricular activation time, assessed by ECGI. Twenty-two (91.6%) patients showed electrical resynchronization on ECGI. All patients fulfilled pre-screwing requisites: lead in septal position in left-oblique projection and W paced morphology in V1. In the first step, presence of either right bundle branch conduction delay pattern (qR or rSR in V1) or left bundle branch capture Plus (QRS ≤120 ms) resulted in 95% sensitivity and 100% specificity to predict LBBP resynchronization, with an accuracy of 95.8%. In the second step, the presence of selective capture (100% specificity, only 41% sensitivity) or a spike-R <80 ms in non-selective capture (100% specificity, sensitivity 46%) ensured 100% accuracy to predict resynchronization with LBBP. CONCLUSION: Stepwise application of ECG and electrogram criteria may provide an accurate assessment of electrical resynchronization with LBBP (Graphical abstract).

Conduction System Pacing vs Biventricular Pacing in Heart Failure and Wide QRS Patients: LEVEL-AT Trial.

BACKGROUND: Conduction system pacing (CSP) has emerged as an alternative to biventricular pacing (BiVP). Randomized studies comparing both therapies are scarce and do not include left bundle branch pacing. OBJECTIVES: This study aims to compare ventricular resynchronization achieved by CSP vs BiVP in patients with cardiac resynchronization therapy indication. METHODS: LEVEL-AT (Left Ventricular Activation Time Shortening with Conduction System Pacing vs Biventricular Resynchronization Therapy) was a randomized, parallel, controlled, noninferiority trial. Seventy patients with cardiac resynchronization therapy indication were randomized 1:1 to BiVP or CSP, and followed up for 6 months. Crossover was allowed when primary allocation procedure failed. Primary endpoint was the change in left ventricular activation time, measured using electrocardiographic imaging. Secondary endpoints were left ventricular reverse remodeling and the combined endpoint of heart failure hospitalization or death at 6-month follow-up. RESULTS: Thirty-five patients were allocated to each group. Eight (23%) patients crossed over from CSP to BiVP; 2 patients (6%) crossed over from BiVP to CSP. Electrocardiographic imaging could not be performed in 2 patients in each group. A similar decrease in left ventricular activation time was achieved by CSP and BiVP (-28 ± 26 ms vs -21 ± 20 ms, respectively; mean difference -6.8 ms; 95% CI: -18.3 ms to 4.6 ms; P < 0.001 for noninferiority). Both groups showed a similar change in left ventricular end-systolic volume (-37 ± 59 mL CSP vs -30 ± 41 mL BiVP; mean difference: -8 mL; 95% CI: -33 mL to 17 mL; P = 0.04 for noninferiority) and similar rates of mortality or heart failure hospitalizations (2.9% vs 11.4%, respectively) (P = 0.002 for noninferiority). CONCLUSIONS: Similar degrees of cardiac resynchronization, ventricular reverse remodeling, and clinical outcomes were attained by CSP as compared to BiVP. CSP could be a feasible alternative to BiVP. (LEVEL-AT [Left Ventricular Activation Time Shortening With Conduction System Pacing vs Biventricular Resynchronization Therapy]; NCT04054895).

Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunction and AV block.

BACKGROUND: It is unknown whether His-Purkinje conduction system pacing (HPCSP), as either His bundle or left bundle branch pacing, could be an alternative to cardiac resynchronization therapy (BiVCRT) for patients with left ventricular dysfunction needing ventricular pacing due to atrioventricular block. The aim of the study is to compare the echocardiographic response and clinical improvement between HPCSP and BiVCRT. METHODS: Consecutive patients who successfully received HPCSP were compared with a historical cohort of BiVCRT patients. Patients were 1:1 matched by age, LVEF, atrial fibrillation, renal function and cardiomyopathy type. Responders were defined as patients who survived, did not require heart transplantation and increased LVEF ≥5 points at 6-month follow-up. RESULTS: HPCSP was successfully achieved in 92.5% (25/27) of patients. During follow-up, 8% (2/25) of HPCSP patients died and 4% (1/25) received a heart transplant, whereas 4% (1/25) of those in the BiVCRT cohort died. LVEF improvement was 10% ± 8% HPCSP versus 7% ± 5% BiVCRT (p = .24), and the percentage of responders was 76% (19/25) HPCSP versus 64% (16/25) BiVCRT (p = .33). Among survivors, the percentage of patients who improved from baseline II-IV mitral regurgitation (MR) to 0-I MR was 9/11 (82%) versus 2/8 (25%) (p = .02). Compared to those with BiVCRT, patients with HPCSP achieved better NYHA improvement: 1 point versus 0.5 (OR 0.34; p = .02). CONCLUSION: HPCSP in patients with LVEF ≤45% and atrioventricular block improved the LVEF and induced a response similar to that of BiVCRT. HPCSP significantly improved MR and NYHA functional class. HPCSP may be an alternative to BiVCRT in these patients. (Figure 1. Central Illustration). [Figure: see text].

Septal flash correction with His-Purkinje pacing predicts echocardiographic response in resynchronization therapy.

BACKGROUND: His-Purkinje conduction system pacing (HPCSP) has been proposed as an alternative to Cardiac Resynchronization Therapy (CRT); however, predictors of echocardiographic response have not been described in this population. Septal flash (SF), a fast contraction and relaxation of the septum, is a marker of intraventricular dyssynchrony. METHODS: The study aimed to analyze whether HPCSP corrects SF in patients with CRT indication, and if correction of SF predicts echocardiographic response. This retrospective analysis of prospectively collected data included 30 patients. Left ventricular ejection fraction (LVEF) was measured with echocardiography at baseline and at 6-month follow-up. Echocardiographic response was defined as increase in five points in LVEF. RESULTS: HPCSP shortened QRS duration by 48 ± 21 ms and SF was significantly decreased (baseline 3.6 ± 2.2 mm vs. HPCSP 1.5 ± 1.5 mm p < .0001). At 6-month follow-up, mean LVEF improvement was 8.6% ± 8.7% and 64% of patients were responders. There was a significant correlation between SF correction and increased LVEF (r = .61, p = .004). A correction of ≥1.5 mm (baseline SF - paced SF) had a sensitivity of 81% and 80% specificity to predict echocardiographic response (area under the curve 0.856, p = .019). CONCLUSION: HPCSP improves intraventricular dyssynchrony and results in 64% echocardiographic responders at 6-month follow-up. Dyssynchrony improvement with SF correction may predict echocardiographic response at 6-month follow-up.

Long-term prognostic value of vasodilator stress cardiac magnetic resonance in patients with atrial fibrillation.

AIMS: Although the prevalence of coronary artery disease (CAD) is high among patients with atrial fibrillation (AF), studies on stress perfusion cardiac magnetic resonance (CMR) imaging frequently exclude patients with AF, and its prognostic and diagnostic value in high-risk patients with suspected or known CAD remains unclear. METHODS AND RESULTS: In this longitudinal cohort study, we included 164 consecutive patients with AF during vasodilator perfusion CMR. Diagnostic value was evaluated regarding invasive coronary angiography in a subset of patients. We targeted a follow-up of >5 years and used CMR results as stratification, and the primary outcome was major adverse cardiac events [MACE, cardiovascular (CV) death and myocardial infarction (MI)]. Secondary outcomes included late coronary revascularization or stroke and the components of the primary outcome. Of the whole cohort (73.8% male, mean age 72.2 years ± 7.8 SD), 99.4% were successfully scanned (163/164 patients). Median CHA2DS2-VASc score was 4 [interquartile range (IQR) 3-5], and median 10-year risk for CV events based on SMART risk score was high (24%, IQR 16-32%). Thirty-two patients (19.6%) presented with ischaemia and 52 patients (31.9%) with late gadolinium enhancement (LGE). A combination of LGE and inducible ischaemia was present in 20 patients (12.3%). Diagnostic accuracy was 86.2% [confidence interval (CI) 68.3-96.1%]. The median follow-up was 6.6 years (IQR 3.6-7.8). Ischaemia in vasodilator perfusion CMR was significantly associated with the occurrence of MACE [P < 0.01; hazard ratio (HR) 2.65, CI 1.39-5.08], as well as LGE (P = 0.03; 1.74, CI 1.07-3.64) and the combination of both (P < 0.01; HR 2.67, CI 1.59-5.62). After adjustment by age, left ventricular ejection fraction, and the presence of diabetes, ischaemia in vasodilator perfusion CMR remained significantly associated with the occurrence of MACE (2.10, CI 1.08-4.10; P = 0.03). In secondary endpoint analysis, there was a significant association of ischaemia in CMR with CV death (P < 0.05; HR 1.93, CI 0.95-3.9) and MI (P < 0.01; HR 13, CI 1.35-125.4), while no significant association was found regarding the occurrence of revascularization (P = 0.45; HR 1.43, CI 0.57-3.58) or stroke (P = 0.99; HR 0.99, CI 0.21-2.59). CONCLUSIONS: Vasodilator stress perfusion CMR demonstrated an excellent diagnostic and significant prognostic value at long-term follow-up in high-risk patients with persistent AF and suspected or known CAD.

Improving the robustness of MOLLI T1 maps with a dedicated motion correction algorithm.

Myocardial tissue T1 constitutes a reliable indicator of several heart diseases related to extracellular changes (e.g. edema, fibrosis) as well as fat, iron and amyloid content. Magnetic resonance (MR) T1-mapping is typically achieved by pixel-wise exponential fitting of a series of inversion or saturation recovery measurements. Good anatomical alignment between these measurements is essential for accurate T1 estimation. Motion correction is recommended to improve alignment. However, in the case of inversion recovery sequences, this correction is compromised by the intrinsic contrast variation between frames. A model-based, non-rigid motion correction method for MOLLI series was implemented and validated on a large database of cardiac clinical cases (n = 186). The method relies on a dedicated similarity metric that accounts for the intensity changes caused by T1 magnetization relaxation. The results were compared to uncorrected series and to the standard motion correction included in the scanner. To automate the quantitative analysis of results, a custom data alignment metric was defined. Qualitative evaluation was performed on a subset of cases to confirm the validity of the new metric. Motion correction caused noticeable (i.e. > 5%) performance degradation in 12% of cases with the standard method, compared to 0.3% with the new dedicated method. The average alignment quality was 85% ± 9% with the default correction and 90% ± 7% with the new method. The results of the qualitative evaluation were found to correlate with the quantitative metric. In conclusion, a dedicated motion correction method for T1 mapping MOLLI series has been evaluated on a large database of clinical cardiac MR cases, confirming its increased robustness with respect to the standard method implemented in the scanner.

Automated Pattern Recognition in Whole-Cardiac Cycle Echocardiographic Data: Capturing Functional Phenotypes with Machine Learning.

BACKGROUND: Echocardiography provides complex data on cardiac function that can be integrated into patterns of dysfunction related to the severity of cardiac disease. The aim of this study was to demonstrate the feasibility of applying machine learning (ML) to automate the integration of echocardiographic data from the whole cardiac cycle and to automatically recognize patterns in velocity profiles and deformation curves, allowing the identification of functional phenotypes. METHODS: Echocardiography was performed in 189 clinically managed patients with hypertension and 97 healthy individuals without hypertension. Speckle-tracking analysis of the left ventricle and atrium was performed, and deformation curves were extracted. Aortic and mitral blood pool pulsed-wave Doppler and mitral annular tissue pulsed-wave Doppler velocity profiles were obtained. These whole-cardiac cycle deformation and velocity curves were used as ML input. Unsupervised ML was used to create a representation of patients with hypertension in a virtual space in which patients are positioned on the basis of the similarity of their integrated whole-cardiac cycle echocardiography data. Regression methods were used to explore patterns of echocardiographic traces within this virtual ML-derived space, while clustering was used to define phenogroups. RESULTS: The algorithm captured different patterns in tissue and blood-pool velocity and deformation profiles and integrated the findings, yielding phenotypes related to normal cardiac function and others to advanced remodeling associated with pressure overload in hypertension. The addition of individuals without hypertension into the ML-derived space confirmed the interpretation of normal and remodeled phenotypes. CONCLUSIONS: ML-based pattern recognition is feasible from echocardiographic data obtained during the whole cardiac cycle. Automated algorithms can consistently capture patterns in velocity and deformation data and, on the basis of these patterns, group patients into interpretable, clinically comprehensive phenogroups that describe structural and functional remodeling. Automated pattern recognition may potentially aid interpretation of imaging data and diagnostic accuracy.

Etiology-Discriminative Multimodal Imaging of Left Ventricular Hypertrophy and Synchrotron-Based Assessment of Microstructural Tissue Remodeling.

Background: Distinguishing the etiology of left ventricular hypertrophy (LVH) is clinically relevant due to patient outcomes and management. Easily obtained, echocardiography-based myocardial deformation patterns may improve standard non-invasive phenotyping, however, the relationship between deformation phenotypes and etiology-related, microstructural cardiac remodeling has not been reported. Synchrotron radiation-based X-ray phase-contrast imaging (X-PCI) can provide high resolution, three-dimensional (3D) information on myocardial microstructure. The aim of this pilot study is to apply a multiscale, multimodality protocol in LVH patients undergoing septal myectomy to visualize in vivo and ex vivo myocardial tissue and relate non-invasive LVH imaging phenotypes to the underlying synchrotron-assessed microstructure. Methods and findings: Three patients (P1-3) undergoing septal myectomy were comprehensively studied. Medical history was collected, and patients were imaged with echocardiography/cardiac magnetic resonance prior to the procedure. Myocardial tissue samples obtained during the myectomy were imaged with X-PCI generating high spatial resolution images (0.65 µm) to assess myocyte organization, 3D connective tissue distribution and vasculature remodeling. Etiology-centered non-invasive imaging phenotypes, based on findings of hypertrophy and late gadolinium enhancement (LGE) distribution, and enriched by speckle-tracking and tissue Doppler echocardiography deformation patterns, identified a clear phenotype of hypertensive heart disease (HTN) in P1, and hypertrophic cardiomyopathy (HCM) in P2/P3. X-PCI showed extensive interstitial fibrosis with normal 3D myocyte and collagen organization in P1. In comparison, in P2/P3, X-PCI showed 3D myocyte and collagen disarray, as well as arterial wall hypertrophy with increased perivascular collagen, compatible with sarcomere-mutation HCM in both patients. The results of this pilot study suggest the association of non-invasive deformation phenotypes with etiology-related myocyte and connective tissue matrix disorganization. A larger patient cohort could enable statistical analysis of group characteristics and the assessment of deformation pattern reproducibility. Conclusion: High-resolution, 3D X-PCI provides novel ways to visualize myocardial remodeling in LVH, and illustrates the correspondence of macrostructural and functional non-invasive phenotypes with invasive microstructural phenotypes, suggesting the potential clinical utility of non-invasive myocardial deformation patterns in phenotyping LVH in everyday clinical practice.

Optimized single-point left ventricular pacing leads to improved resynchronization compared with multipoint pacing.

BACKGROUND: Multipoint pacing (MPP) in cardiac resynchronization therapy (CRT) activates the left ventricle from two locations, thereby shortening the QRS duration and enabling better resynchronization; however, compared with conventional CRT, MPP reduces battery longevity. On the other hand, electrocardiogram-based optimization using the fusion-optimized intervals (FOI) method achieves more significant reverse remodeling than nominal CRT programming. Our study aimed to determine whether MPP could attain better resynchronization than single-point pacing (SPP) optimized by FOI. METHODS: This prospective study included 32 consecutive patients who successfully received CRT devices with MPP capabilities. After implantation, the QRS duration was measured during intrinsic rhythm and with three pacing configurations: MPP, SPP-FOI, and MPP-FOI. In 14 patients, biventricular activation times (by electrocardiographic imaging, ECGI) were obtained during intrinsic rhythm and for each pacing configuration to validate the findings. Device battery longevity was estimated at the 45-day follow-up. RESULTS: The SPP-FOI method achieved greater QRS shortening than MPP (-56 ± 16 vs. -42 ± 17 ms, p < .001). Adding MPP to the best FOI programming did not result in further shortening (MPP-FOI: -58 ± 14 ms, p = .69). Although biventricular activation times did not differ significantly among the three pacing configurations, only the two FOI configurations achieved significant shortening compared with intrinsic rhythm. The estimated battery longevity was longer with SPP than with MPP (8.1 ± 2.3 vs. 6.3 ± 2.0 years, p = .03). CONCLUSIONS: SPP optimized by FOI resulted in better resynchronization and longer battery duration than MPP.

Distribution of myocardial work in arterial hypertension: insights from non-invasive left ventricular pressure-strain relations.

A index of non-invasive myocardial work (MWI) can account for pressure during the assessment of cardiac function, potentially separating the influence of loading conditions from the influence of the underlying tissue remodelling. The aim is to assess LV function accounted for loading and explore hypertensive MWI distribution by comparing healthy individuals to hypertensive patients without and with localized basal septal hypertrophy (BSH). An echocardiogram was performed in 170 hypertensive patients and 20 healthy individuals. BSH was defined by a basal-to-mid septal wall thickness ratio ≥ 1.4. LV speckle-tracking was performed, and the MWI calculated globally and regionally for the apical, mid and basal regions. An apex-to-base gradient, seen in regional strain values, was preserved in the distribution of myocardial work, with the apical region compensating for the impairment of the basal segments. This functional redistribution was further pronounced in patients with localized BSH. In these patients, segmental MWI analysis revealed underlying impairment of regional work unrelated to acute loading conditions. Non-invasive MWI analysis offers the possibility to compare LV function regardless of blood pressure at the time of observation. Changes in MWI distribution can be seen in hypertension unrelated to the load-dependency of strain. Accentuated functional changes affirm the role of BSH as an echocardiographic marker in hypertension.

Cardiac Myxomas Show Elevated Native T1, T2 Relaxation Time and ECV on Parametric CMR.

Introduction: While cardiac tumors are rare, their identification and differentiation has wide clinical implications. Recent cardiac magnetic resonance (CMR) parametric mapping techniques allow for quantitative tissue characterization. Our aim was to examine the range of values encountered in cardiac myxomas in correlation to histological measurements. Methods and Results: Nine patients with histologically proven cardiac myxomas were included. CMR (1.5 Tesla, Philips) including parametric mapping was performed in all patients pre-operatively. All data are reported as mean ± standard deviation. Compared to myocardium, cardiac myxomas demonstrated higher native T1 relaxation times (1,554 ± 192 ms vs. 1,017 ± 58 ms, p < 0.001), ECV (46.9 ± 13.0% vs. 27.1 ± 2.6%, p = 0.001), and T2 relaxation times (209 ± 120 ms vs. 52 ± 3 ms, p = 0.008). Areas with LGE showed higher ECV than areas without (54.3 ± 17.8% vs. 32.7 ± 18.6%, p = 0.042), with differences in native T1 relaxation times (1,644 ± 217 ms vs. 1,482 ± 351 ms, p = 0.291) and T2 relaxation times (356 ± 236 ms vs. 129 ± 68 ms, p = 0.155) not reaching statistical significance. Conclusions: Parametric CMR showed elevated native T1 and T2 relaxation times and ECV values in cardiac myxomas compared to normal myocardium, reflecting an increased interstitial space and fluid content. This might help in the differentiation of cardiac myxomas from other tumor entities.

Ventricular arrhythmia risk is associated with myocardial scar but not with response to cardiac resynchronization therapy.

AIMS: Sudden cardiac death (SCD) risk estimation in patients referred for cardiac resynchronization therapy (CRT) remains a challenge. By CRT-mediated improvement of left ventricular ejection fraction (LVEF), many patients loose indication for primary prevention implantable cardioverter-defibrillator (ICD). Increasing evidence shows the importance of myocardial scar for risk prediction. The aim of this study was to investigate the prognostic impact of myocardial scar depending on the echocardiographic response in patients undergoing CRT. METHODS AND RESULTS: Patients with indication for CRT were prospectively enrolled. Decision about ICD or pacemaker implantation was based on clinical criteria. All patients underwent delayed-enhancement cardiac magnetic resonance imaging. Median follow-up duration was 45 (24-75) months. Primary outcome was a composite of sustained ventricular arrhythmia, appropriate ICD therapy, or SCD. A total of 218 patients with LVEF 25.5 ± 6.6% were analysed [158 (73%) male, 64.9 ± 10.7 years]. Myocardial scar was observed in 73 patients with ischaemic cardiomyopathy (ICM) (95% of ICM patients); in 62 with non-ischaemic cardiomyopathy (45% of these patients); and in all but 1 of 36 (17%) patients who reached the primary outcome. Myocardial scar was the only significant predictor of primary outcome [odds ratio 27.7 (3.8-202.7)], independent of echocardiographic CRT response. A total of 55 (25%) patients died from any cause or received heart transplant. For overall survival, only a combination of the absence of myocardial scar with CRT response was associated with favourable outcome. CONCLUSION: Malignant arrhythmic events and SCD depend on the presence of myocardial scar but not on CRT response. All-cause mortality improved only with the combined absence of myocardial scar and CRT response.