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 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.

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.

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.

Ventricular scar channel entrances identified by new wideband cardiac magnetic resonance sequence to guide ventricular tachycardia ablation in patients with cardiac defibrillators.

AIMS: Ventricular tachycardia (VT) substrate-based ablation has become a standard procedure. Electroanatomical mapping (EAM) detects scar tissue heterogeneity and define conduction channels (CCs) that are the ablation target. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is able to depict CCs and increase ablation success. Most patients undergoing VT ablation have an implantable cardioverter-defibrillator (ICD) that can cause image artefacts in LGE-CMR. Recently wideband (WB) LGE-CMR sequence has demonstrated to decrease these artefacts. The aim of this study is to analyse accuracy of WB-LGE-CMR in identifying the CC entrances. METHODS AND RESULTS: Thirteen consecutive ICD-patients who underwent VT ablation after WB-LGE-CMR were included. Number and location of CC entrances in three-dimensional EAM and in WB-LGE-CMR reconstruction were compared. Concordance was compared with a historical cohort matched by cardiomyopathy, scar location, and age (26 patients) with LGE-CMR prior to ICD and VT ablation. In WB-CMR group, 101 and 93 CC entrances were identified in EAM and WB-LGE-CMR, respectively. In historical cohort, 179 CC entrances were identified in both EAM and LGE-CMR. The EAM/CMR concordance was 85.1% and 92.2% in the WB and historical group, respectively (P = 0.66). There were no differences in false-positive rate (CC entrances detected in CMR and absent in EAM: 7.5% vs 7.8% in WB vs. conventional CMR, P = 0.92) nor in false-negative rate (CC entrances present in EAM not detected in CMR: 14.9% vs.7.8% in WB vs. conventional CMR, P = 0.23). Epicardial CCs was predictor of poor CMR/EAM concordance (OR 2.15, P = 0.031). CONCLUSION: Use of WB-LGE-CMR sequence in ICD-patients allows adequate VT substrate characterization to guide VT ablation with similar accuracy than conventional LGE-CMR in patients without an ICD.

Mortality and morbidity reduction after frequent premature ventricular complexes ablation in patients with left ventricular systolic dysfunction.

AIMS: Ablation of frequent premature ventricular complexes (PVCs) improves left ventricular ejection fraction in patients with left ventricular (LV) systolic dysfunction. This study aims to evaluate the long-term hard outcomes and potential prognostic variables in this population. METHODS AND RESULTS: Prospective multicentre study including 101 consecutive patients [56 ± 12 years old, 62 (61%) men] with LV systolic dysfunction and frequent PVCs who underwent PVC ablation before November 2015. The last evaluation performed was considered the long-term follow-up (LTFUP) evaluation. Mean follow-up was 34 ± 16 months (range 24-84 months). Ablation was successful in 95 (94%) patients. There was a significant reduction in the PVC burden from 21 ± 12% at baseline to 3.8 ± 6% at LTFUP, P < 0.001. Left ventricular ejection fraction improved from 32 ± 8% at baseline to 39 ± 12% at LTFUP (P < 0.001) and New York Heart Association class from 2.2 ± 0.6% to 1.3 ± 0.6% (P < 0.001). Brain natriuretic peptide levels decreased from 136 (78-321) to 68 (32-144) pg/mL (P = 0.007). Most of this improvement occurs during the first 6 months after ablation. Persistent abolition of at least 18 points of the baseline PVC burden was independently and inversely associated with the composite endpoint of cardiac mortality, cardiac transplantation, or hospitalization for heart failure during follow-up [hazard ratio 0.18 (0.05-0.66), P = 0.01]. CONCLUSION: In patients with LV systolic dysfunction, ablation of frequent PVCs induces a significant improvement in functional, structural, and neurohormonal status, which persists at LTFUP. A sustained reduction in the baseline PVC burden is associated with a lower risk of cardiac mortality, cardiac transplantation, or hospitalization for heart failure during follow-up.

Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial.

AIMS: Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms. METHODS AND RESULTS: Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo). Pre-operative LVEF was 27 ± 6% in CD133 patients and 26 ± 6% in placebo patients. Outcome was assessed after 6 months, and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI) at rest. The incidence of adverse events was similar in both groups. There was no difference in 6-min walking distance, Minnesota Living with Heart Failure score, or Canadian Cardiovascular Society (CCS) class between groups at follow-up, and New York Heart Association class improved more in the placebo group (P = 0.004). By cardiac MRI, LVEF at 6 months was 33 ± 8% in the placebo group and 31 ± 7% in verum patients (P = 0.3), with an average inter-group difference of -2.1% (95% CI -6.3 to 2.1). Systolic or diastolic LV dimensions at 6 months were not different, either. In the CD133 group, myocardial perfusion at rest recovered in more LV segments than in the placebo group (9 vs. 2%, P < 0.001). Scar mass decreased by 2.2 ± 5 g in CD133(+) patients (P = 0.05), but was unchanged in the placebo group (0.3 ± 4 g, P = 0.7; inter-group difference in change = 2 g (95% CI -1.1 to 5)). By speckle-tracking echocardiography, cell-treated patients showed a better recovery of regional wall motion when the target area was posterior. CONCLUSION: Although there may be some improvements in scar size and regional perfusion, intra-myocardial injection of CD133(+) BMC has no effect on global LV function and clinical symptoms. Improvements in regional myocardial function are only detectable in patients with posterior infarction, probably because the interventricular septum after anterior infarction is not accessible by trans-epicardial injection. CLINICAL TRIAL REGISTRATION: This trial was registered at http://www.clinicaltrials.gov under NCT00462774.

Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial.

AIMS: Sympathetic stimulation induces left ventricular hypertrophy and is associated with increased cardiovascular risk. Catheter-based renal denervation (RDN) has been shown to reduce sympathetic outflow and blood pressure (BP). The present multi-centre study aimed to investigate the effect of RDN on anatomic and functional myocardial parameters, assessed by cardiac magnetic resonance (CMR), in patients with resistant hypertension. METHODS AND RESULTS: Cardiac magnetic resonance was performed in 72 patients (mean age 66 ± 10 years) with resistant hypertension (55 patients underwent RDN, 17 served as controls) at baseline and after 6 months. Clinical data and CMR results were analysed blindly. Renal denervation significantly reduced systolic and diastolic BP by 22/8 mm Hg and left ventricular mass index (LVMI) by 7.1% (46.3 ± 13.6 g/m(1.7) vs. 43.0 ± 12.6 g/m(1.7), P < 0.001) without changes in the control group (41.9 ± 10.8 g/m(1.7) vs. 42.0 ± 9.7 g/m(1.7), P = 0.653). Ejection fraction (LVEF) in patients with impaired LVEF at baseline (<50%) significantly increased after RDN (43% vs. 50%, P < 0.001). Left ventricular circumferential strain as a surrogate of diastolic function in the subgroup of patients with reduced strain at baseline increased by 21% only in the RDN group (-14.8 vs. -17.9; P = 0.001) and not in control patients (-15.5 vs. -16.4, P = 0.508). CONCLUSIONS: Catheter-based RDN significantly reduced BP and LVMI and improved EF and circumferential strain in patients with resistant hypertension, occurring partly BP independently.

Fusion-optimized intervals (FOI): a new method to achieve the narrowest QRS for optimization of the AV and VV intervals in patients undergoing cardiac resynchronization therapy.

BACKGROUND: Optimization of atrioventricular (AV) and interventricular (VV) intervals may improve cardiac resynchronization therapy (CRT) response but is a complex task. Fusion with intrinsic conduction may increase the benefit of CRT. The aim was to describe fusion-optimized intervals (FOI), a new method of optimizing CRT based on QRS duration. METHODS AND RESULTS: Seventy-six consecutive patients with preserved AV conduction who received CRT were prospectively included. The AV interval was optimized by searching the narrowest QRS obtained within the fusion band during left ventricular (LV) pacing. The VV interval was then adjusted, comparing QRS duration in simultaneous biventricular, LV preexcitation (-30 milliseconds), right ventricular (RV) preexcitation (-30 milliseconds) and LV-only pacing. A substudy in 31 patients evaluated the invasive LV +dP/dtmax . The best fusion-optimized AV interval was 136 ± 30 milliseconds during atrial sensing and 192 ± 35 milliseconds during atrial pacing. The best QRS was obtained with simultaneous biventricular pacing in 28 patients (37%), LV preexcitation in 22 (29%), LV-only in 20 (26%), and RV preexcitation in 6 (8%). Baseline QRS was shortened more by FOI (59 ± 19 milliseconds) than by nominal settings (40 ± 21 milliseconds; P < 0.001). Sixty-five patients (86%) showed >10% shortening of the baseline QRS with FOI; none prolonged the QRS duration by FOI compared to nominal settings. All echocardiographic asynchrony parameters were corrected by FOI. Baseline +dP/dtmax improvement was greater in FOI (127 ± 95 mmHg/seconds) than in nominal settings (102 ± 71 mmHg/seconds; P = 0.05). CONCLUSION: The FOI method is feasible, further reduces QRS duration, and improves acute hemodynamic response compared to nominal programming of CRT.

Effect of cardiac resynchronization therapy on left ventricular diastolic function: implications for clinical outcome.

Background: The definition of response to cardiac resynchronization therapy (CRT) remains controversial,with variable rates of response depending on the criteria used. Our aim was to analyze the impact of CRT on diastolic function in different degrees of response, particularly in patients with positive clinical but no echocardiographic response.Methods and Results: In 250 CRT patients clinical evaluation and echocardiography were performed before and after CRT. Absolute response to CRT was defined as a reduction in left ventricular (LV)end-systolic volume of ≥ 15% at 1-year follow-up. Additionally, patients were classified into 4 subgroups according to their amount of response: extensive reverse remodeling (RR), slight RR, clinical response without RR, and neither clinical response nor RR. An improvement in estimates of LV filling pressure and a decrease in left atrial dimensions were observed only in responders to CRT. Patients with clinical but no echocardiographic response had significant improvement in E-wave and deceleration time and nonsignificant improvement in other parameters.Conclusions: LV diastolic function improves with CRT. Clinical responders without echocardiographic response show improvement in parameters of diastolic function. That suggests that clinical-only response to CRT is secondary to a real effect of the therapy, rather than a placebo effect.

Predictors of failed left bundle branch pacing implant in heart failure with reduced ejection fraction: importance of left ventricular diameter and QRS morphology.

BACKGROUND: Left bundle branch pacing (LBBP) is considered an alternative to cardiac resynchronization therapy (CRT). However, LBBP is not suitable for all heart failure patients. OBJECTIVE: The aim of our study was to identify predictors of unsuccessful LBBP implantation in CRT candidates. METHODS: A cohort of consecutive patients with indications for CRT were included. Clinical, echocardiography and electrocardiography variables were prospectively recorded. RESULTS: A total of 187 patients were included in the analysis. LBBP implantation was successful in 152/187 (81.2%) patients and failed in 35/187 (18.7%) patients. The causes of unsuccessful implantation were unsatisfactory paced QRS (28/35; 80%), inability to screw the helix (4/35; 11.4%), lead instability (2/35; 5.7%), and high pacing thresholds (1/35; 2.8%). The left ventricular end diastolic diameter (LVEDD), non-LBBB (left bundle branch block) QRS morphology, and QRS width were predictors of failed implantation according to the univariate analysis. According to the multivariable regression analysis, LVEDD [OR 1.31 per 5 mm increase (95% CI 1.05, 1.63) p=0.02] and non-LBBB [OR 3.07 (95% CI 1.08, 8.72) p=0.03] were found to be independent predictors of unsuccessful LBBP implantation. An LVEDD of 60 mm has 60% sensitivity and 71% specificity for predicting LBBP implant failure. CONCLUSIONS: When LBBP was used as CRT, LVEDD and non-LBBB QRS morphology predicted unsuccessful implantation. Non-LBBB triples the likelihood of failed implantation independent of LVEDD. Caution should be taken when considering these parameters to plan the best pacing strategy for patients.

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.

Longitudinal comparison of dyssynchrony correction and strain improvement by conduction system pacing: LEVEL-AT trial secondary findings.

Longitudinal dyssynchrony correction and strain improvement by comparable cardiac resynchronization therapy techniques is unreported. AIMS: Our purpose was to compare echocardiographic dyssynchrony correction and strain improvement by conduction system pacing (CSP) vs. biventricular pacing (BiVP) as a marker of contractility improvement during one-year follow-up. METHODS AND RESULTS: A treatment-received analysis was performed in patients included in the LEVEL-AT trial (NCT04054895), randomized to CSP or BiVP, and evaluated at baseline (ON and OFF programming) and at 6 and 12 months (n = 69, 32% women). Analysis included intraventricular (septal flash), interventricular (difference between left and right ventricular outflow times), and atrioventricular (diastolic filling time) dyssynchrony and strain parameters (septal bounce, global longitudinal strain [GLS], left bundle branch block pattern and mechanical dispersion).Baseline left ventricular ejection fraction (LVEF) was 27.5 ± 7% and left ventricular end-systolic volume (LVESV) was 138 ± 77 ml, without differences between groups. Longitudinal analysis showed LVEF and LVESV improvement (p < 0.001), without between-group differences. At 12-month follow-up, adjusted mean LVEF was 46% with CSP (95%CI 42.2%, 49.3%) vs. 43% with BiVP (95%CI 39.6%, 45.8%) (p = 0.31) and LVESV was 80 ml (95%CI 55.3 ml, 104.5 ml) vs. 100 ml (95%CI 78.7 ml, 121.6 ml), respectively (p = 0.66).Longitudinal analysis showed a significative improvement of all dyssynchrony parameters and GLS over time (p < 0.001), without differences between groups. Baseline GLS significantly correlated with LVEF and LVESV at 12-month follow-up. CONCLUSION: CSP and BiVP provided similar dyssynchrony and strain correction over time. Baseline global longitudinal strain correction predicted ventricular remodeling at 12-month follow-up.

Effect of cardiac resynchronization therapy on left ventricular diastolic function: implications for clinical outcome.

BACKGROUND: The definition of response to cardiac resynchronization therapy (CRT) remains controversial, with variable rates of response depending on the criteria used. Our aim was to analyze the impact of CRT on diastolic function in different degrees of response, particularly in patients with positive clinical but no echocardiographic response. METHODS AND RESULTS: In 250 CRT patients clinical evaluation and echocardiography were performed before and after CRT. Absolute response to CRT was defined as a reduction in left ventricular (LV) end-systolic volume of ≥15% at 1-year follow-up. Additionally, patients were classified into 4 subgroups according to their amount of response: extensive reverse remodeling (RR), slight RR, clinical response without RR, and neither clinical response nor RR. An improvement in estimates of LV filling pressure and a decrease in left atrial dimensions were observed only in responders to CRT. Patients with clinical but no echocardiographic response had significant improvement in E-wave and deceleration time and nonsignificant improvement in other parameters. CONCLUSIONS: LV diastolic function improves with CRT. Clinical responders without echocardiographic response show improvement in parameters of diastolic function. That suggests that clinical-only response to CRT is secondary to a real effect of the therapy, rather than a placebo effect.

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.

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).

Comparison of hemodynamic versus dyssynchrony assessment for interventricular delay optimization with echocardiography in cardiac resynchronization therapy.

BACKGROUND: Best practice for cardiac resynchronization therapy (CRT) device optimization is not established. This study compared Tissue Doppler Imaging (TDI) to study left ventricular (LV) synchrony and left ventricular outflow tract velocity-time integral (LVOT VTI) to assess hemodynamic performance. METHODS: LVOT VTI and LV synchrony were tested in 50 patients at three interventricular (VV) delays (LV preactivation at -30 ms, simultaneous biventricular pacing, and right ventricular preactivation at +30 ms), selecting the highest VTI and the greatest degree of superposition of the displacement curves, respectively, as the optimum VV delay. RESULTS: In 39 patients (81%), both techniques agreed (Kappa = 0.65, p < 0.0001) on the optimum VV delay. LV preactivation (VV - 30) was the interval most frequently chosen. CONCLUSIONS: Both TDI and LVOT VTI are useful CRT programming methods for VV optimization. The best hemodynamic response correlates with the best synchrony. In most patients, the optimum VV interval is LV preactivation.

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.