Reduction In End-systolic Volume Research Articles

Intra-operative ultra high-frequency ECG in relation to left ventricular reverse remodelling after cardiac resynchronization therapy

Abstract Aims Ultra-high-frequency electrocardiography (UHF-ECG) has evolved as a potential tool for the assessment of ventricular dyssynchrony. We sought to determine whether changes in ventricular dyssynchrony at the time of cardiac resynchronization therapy (CRT) device implantation, measured using UHF-ECG, relate to post-implantation left ventricular reverse remodelling (LVRR). Methods and Results Patients undergoing CRT (n = 46; aged 70.3 ± 11.2 years; 37/46 male) underwent intra-operative UHF-ECG assessment of ventricular dyssynchrony before and after CRT. Multiple frequency bands (n=16) within the 150 to 1000Hz range were used to create ventricular depolarization maps (Figure). Ventricular dyssynchrony (e-DYS) was assessed using the maximum time difference in ms between the QRS complex centres of mass of leads V1 to V6. Left ventricular reverse remodelling was defined in terms of a reduction in left ventricular end-systolic volume (LVESV) at 3 months post-implantation. During implantation, CRT led to a 103% reduction in e-DYS from 36.6 ms during AAI pacing to 1.4 ms during CRT (P<0.001). CRT also led to a reduction in QRS duration (from 156.3 ms during AAI pacing to 119.9 ms during CRT [P<0.001]) and QRS area (from 100.5 ms*mV (or µVs) during AAI pacing to 65.6 ms during CRT [P<0.001]). In regression analyses, intra-operative Δ e-DYS (ms) was associated with ΔLVESV at 3 months (Figure). In contrast, no associations were observed between intra-operative ΔQRS duration or ΔQRS area and ΔLVESV. Conclusion Intra-operative Δ e-DYS derived from UHF-ECG, relates to LVRR after CRT. In contrast, no such relationship emerged for ΔQRS or ΔQRS area.

Mitral regurgitation assessment by cardiovascular magnetic resonance imaging during continuous in-scanner exercise: a feasibility study.

Exercise imaging using current modalities can be challenging. This was patient focused study to establish the feasibility and reproducibility of exercise-cardiovascular magnetic resonance imaging (EX-CMR) acquired during continuous in-scanner exercise in asymptomatic patients with primary mitral regurgitation (MR). This was a prospective, feasibility study. Biventricular volumes/function, aortic flow volume, MR volume (MR-Rvol) and regurgitant fraction (MR-RF) were assessed at rest and during low- (Low-EX) and moderate-intensity exercise (Mod-EX) in asymptomatic patients with primary MR. Twenty-five patients completed EX-CMR without complications. Whilst there were no significant changes in the left ventricular (LV) volumes, there was a significant increase in the LVEF (rest 63 ± 5% vs. Mod-EX 68 ± 6%;p = 0.01). There was a significant reduction in the right ventricular (RV) end-systolic volume (rest 68ml(60-75) vs. Mod-EX 46ml(39-59);p < 0.001) and a significant increase in the RV ejection fraction (rest 55 ± 5% vs. Mod-EX 65 ± 8%;p < 0.001). Whilst overall, there were no significant group changes in the MR-Rvol and MR-RF, individual responses were variable, with MR-Rvol increasing by ≥ 15ml in 4(16%) patients and decreasing by ≥ 15ml in 9(36%) of patients. The intra- and inter-observer reproducibility of LV volumes and aortic flow measurements were excellent, including at Mod-EX. EX-CMR is feasible and reproducible in patients with primary MR. During exercise, there is an increase in the LV and RV ejection fraction, reduction in the RV end-systolic volume and a variable response of MR-Rvol and MR-RF. Understanding the individual variability in MR-Rvol and MR-RF during physiological exercise may be clinically important.

A novel method combining gated SPECT and vectorcardiography to guide left ventricular lead placement to improve response to cardiac resynchronization therapy: A proof of concept study

BackgroundThe segment of the latest mechanical contraction (LMC) does not always overlap with the site of the latest electrical activation (LEA). By integrating both mechanical and electrical dyssynchrony, this proof-of-concept study aimed to propose a new method for recommending left ventricular (LV) lead placements, with the goal of enhancing response to cardiac resynchronization therapy (CRT). MethodsThe LMC segment was determined by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) phase analysis. The LEA site was detected by vectorcardiogram. The recommended segments for LV lead placement were as follows: (1) the LMC viable segments that overlapped with the LEA site; (2) the LMC viable segments adjacent to the LEA site; (3) If no segment met either of the above, the LV lateral wall was recommended. The response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) 6-months after CRT. Patients with LV lead located in the recommended site were assigned to the recommended group, and those located in the non-recommended site were assigned to the non-recommended group. ResultsThe cohort comprised of 76 patients, including 54 (71.1%) in the recommended group and 22 (28.9%) in the non-recommended group. Among the recommended group, 74.1% of the patients responded to CRT, while 36.4% in the non-recommended group were responders (P = .002). Compared to pacing at the non-recommended segments, pacing at the recommended segments showed an independent association with an increased response by univariate and multivariable analysis (odds ratio 5.00, 95% confidence interval 1.73-14.44, P = .003; odds ratio 7.33, 95% confidence interval 1.53-35.14, P = .013). Kaplan–Meier curves showed that pacing at the recommended LV lead position demonstrated a better long-term prognosis. ConclusionOur findings indicate that pacing at the recommended segments, by integrating of mechanical and electrical dyssynchrony, is significantly associated with an improved CRT response and better long-term prognosis.

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

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

Acute Effect in Mechanical Efficiency by Pressure-Volume Loop Analysis after Transcatheter Aortic Valve Implantation.

This study aimed to evaluate the immediate effect of transcatheter aortic valve implantation (TAVI) on mechanical efficiency. A total of 46 patients (25 females) with an average age of 83 ± 6.4 years underwent TAVI using the CoreValve system. During the same hospitalization, we conducted a comprehensive comparison of the patients before and after TAVI without inotropic support using echocardiography. The parameters encompassed left ventricular (LV) geometry, valvular load, global LV afterload and ventricular hemodynamics. The analysis using pressure-volume loops enabled the determination of load-independent contractility (Ees) and afterload, in addition to assessing potential energy, stroke work, and mechanical efficiency. The immediate effect was an augmented aortic valve area accompanied by a reduction in the transvalvular pressure gradient. We observed reductions in left ventricular end-systolic volume and end-diastolic volume, and also reductions in global afterload and end-systolic meridional wall stress. The Ea index decreased, while the Ees index remained relatively stable. We noted increases in stroke volume and systemic arterial compliance, indicating more efficient blood transfer from the ventricle to aorta. These changes contributed to the normalization of ventricular-arterial coupling. In terms of mechanical work of the chamber, we observed significant decreases in potential energy, stroke work, and pressure-volume area. There was an increase in the mechanical efficiency of the chamber. The TAVI procedure immediately reduced global afterload and improved diastolic compliance of the chamber, resulting in enhanced ventricular function and mechanical efficiency.

Efficacy of left bundle branch area pacing versus biventricular pacing in patients treated with cardiac resynchronization therapy: Select site – cohort study

BackgroundCardiac resynchronization therapy (CRT) is typically attempted with biventricular (BiV) pacing. One-third of patients are nonresponders. Left bundle branch area pacing (LBBAP) has been evaluated as an alternative means. ObjectiveThe purpose of this study was to assess the feasibility and clinical response of permanent LBBAP as an alternative to BiV pacing. MethodsOf 479 consecutive patients referred with heart failure, 50 with BiV-CRT and 51 with LBBAP-CRT were included in this analysis after study exclusions. Quality-of-Life (QoL) assessments, echocardiographic measurements, and New York Heart Association (NYHA) class were obtained at baseline and at 6-monthly intervals. ResultsThere were no differences in baseline characteristics between groups (all P > .05). Clinical outcomes such as left ventricular ejection fraction, left ventricular end-systolic volume, QoL, and NYHA class were significantly improved for both pacing groups compared to baseline. The LBBAP-CRT group showed greater improvement in left ventricular ejection fraction at 6 months (P = .001) and 12 months (P = .021), accompanied by greater reduction in left ventricular end-systolic volume (P = .007). QRS duration < 120 ms (baseline 160.82 ± 21.35 ms vs 161.08 ± 24.48 ms) was achieved in 30% in the BiV-CRT group vs 71% in the LBBAP-CRT group (P ≤ .001). Improvement in NYHA class (P = .031) and QoL index was greater (P = .014). Reduced heart failure admissions (P = .003) and health care utilization (P < .05) and improved lead performance (P < .001) were observed in the LBBAP-CRT group. ConclusionLBBAP-CRT is feasible and effective CRT. It results into a meaningful improvement in QoL and reduction in health care utilization. This can be offered as an alternative to BiV-CRT or potentially as first-line therapy.

The Prognostic Role of Global Longitudinal Strain and NT-proBNP in Heart Failure Patients Receiving Cardiac Resynchronization Therapy.

We aimed to evaluate whether baseline GLS (global longitudinal strain), NT-proBNP, and changes in these after cardiac resynchronization therapy (CRT) can predict long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). We enrolled 143 patients with stable ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiography were obtained before and 6 months after. The patients were followed up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint). A total of 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered CRT responders and 39 non-responders. At baseline, event-free patients had higher absolute GLS values (p < 0.001) and lower NT-proBNP serum levels (p < 0001) than those achieving the primary endpoint. A similar pattern was observed in favor of CRT responders vs. non-responders. On Cox regression analysis, baseline absolute GLS value (HR = 0.77; 95% CI, 0.51-1.91; p = 0.002) was beneficially associated with lower primary endpoint incidence, while baseline NT-proBNP levels (HR = 1.55; 95% CI, 1.43-2.01; p = 0.002) and diabetes presence (HR = 1.27; 95% CI, 1.12-1.98; p = 0.003) were related to higher primary endpoint incidence. In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

Personalized cardiac resynchronization therapy guided by real-time electrocardiographic imaging for patients with non–left bundle branch block

BackgroundPatients with heart failure and a non–left bundle branch block (non-LBBB) QRS pattern have a limited response to biventricular pacing (BVP). ObjectiveA personalized cardiac resynchronization therapy (CRT) implantation approach guided by real-time electrocardiographic imaging (ECGi) was studied. MethodsTwenty patients with left ventricular ejection fraction (LVEF) ≤ 35%, QRS duration ≥ 120 ms, and non-LBBB [13 (65%) with right bundle branch block and 7 (35%) with intraventricular conduction delay] were recruited. During CRT implantation, right atrial, right ventricular, coronary sinus, His-bundle, and/or left bundle leads were inserted. The total activation time (TAT) with different pacing combinations were measured in real time during implantation by ECGi. The configuration producing the shortest TAT was chosen. Clinical response was defined as ≥1 New York Heart Association class improvement. Echocardiographic response was defined as left ventricular end-systolic volume reduction ≥ 15% and/or LVEF improvement ≥ 10% at 6 months. ResultsAfter ECGi-guided CRT implantation, LVEF improved from 26% ± 6% to 34% ± 11% (P < .01) and New York Heart Association class improved from 3.0 ± 0.5 to 2.0 ± 0.6 (P < .01). Both clinical and echocardiographic response rates were 70%. The ECGi approach resulted in better acute electrical resynchronization over BVP as measured by TAT reduction (40% vs 14%; P < .01). The percentage of TAT reduction was found to be a strong predictor for echocardiographic response (area under the curve for the receiver operating characteristic curve 0.91; 95% confidence interval 0.78–1.00). A strong positive correlation between percentage TAT reduction and percentage LVEF improvement (Pearson R = 0.70; P = .001) was found. ConclusionECGi-guided CRT implantation in patients with non-LBBB generates superior acute electrical resynchronization compared with BVP and is associated with favorable clinical and echocardiographic outcomes.

In-Hospital Levels of Circulating MicroRNAs as Potential Predictors of Left Ventricular Remodeling Post-Myocardial Infarction.

Background and Objectives: Biochemical and molecular regulation of both adaptive and pathological responses of heart tissue to ischemic injury is widely investigated. However, it is still not fully understood. Several biomarkers are tested as predictors of left ventricle (LV) remodeling after myocardial infarction (MI). The aim of this study was to assess the relationship between selected microRNAs (miRNAs) and LV function and morphology in patients after MI. Materials and Methods: Selected miRNAs related to heart failure were assessed in the acute phase of MI: miR-150-3p, miR-21-5p, miR-19b-3p, miR-155-5p, miR-22-5p. Echocardiography with 3D imaging was performed at baseline and after 6 months. Remodeling was defined as >20% increase in LV end-diastolic volume, whereas reverse remodeling was defined as >10% reduction in LV end-systolic volume. Results: Eighty patients entered the registry. Remodeling occurred in 26% and reverse remodeling was reported in 51% of patients. In the presented study, none of the analyzed miRNAs were found to be a significant LV remodeling predictor. The observed correlations between miRNAs and other circulating biomarkers of myocardial remodeling were relatively weak. Conclusions: Our analysis does not demonstrate an association between the analyzed miRNAs and LV remodeling in patients with MI.

Echocardiographic predictors of positive left ventricular remodeling in patients with a history of active myocarditis.

Myocarditis may be difficult to diagnose because of the variety of its clinical manifestations, and the clinical course of the disease can be unpredictable. Nevertheless, some patients may exhibit partial or full contractile recovery following myocarditis. Standard and speckle-tracking echocardiography may serve as tools to follow this recovery. We aimed to evaluate predictors of positive left ventricular (LV) remodeling after active myocarditis (AM). A database of a high‑volume, tertiary cardiology center was searched for patients with AM hospitalized between 2016 and 2019. They were included in the analysis based on clinical manifestations and presence of at least 1 of the following diagnostic criteria: positive findings on electrocardiography / Holter monitoring, echocardiography, elevated troponin T/I levels, functional or structural abnormalities on cardiac imaging, or tissue characterization by cardiac magnetic resonance. LV global longitudinal strain and mechanical dispersion (MD; defined as SD of the time to peak longitudinal strain derived from all LV segments in 3 apical views) were determined. Echocardiographic response (positive LV remodeling measured by transthoracic echocardiography) was defined as end‑systolic volume (ESV) reduction by 15% or greater or end-diastolic volume (EDV) reduction by 15% or greater from the baseline values. A total of 61 consecutive patients were recruited. The median follow‑up was 1.4 years (range, 0.3-4). The mortality rate was 1.6%. Echocardiographic response was noted in 24 patients (39.4%). A multivariable Cox regression model including significant baseline differences as covariates showed that QRS duration (hazard ratio [HR], 1.31; 95% CI, 1.17-1.57; P = 0.049), MD (HR, 1.03; 95% CI, 1.01-1.07; P = 0.04), and mineralocorticoid receptor antagonist [MRA] use (HR, 8.60; 95% CI, 1.50-46.49; P = 0.01) were independently associated with positive LV remodeling with ESV reduction. MD (HR, 1.04; 95% CI, 1.02-1.06; P = 0.04) was also independently associated with positive LV remodeling with EDV reduction. Mechanical dispersion, QRS duration, and MRA use are independent predictors of positive LV remodeling in individuals with a history of AM.

Effect of left bundle branch pacing on right ventricular function: A 3-dimensional echocardiography study

BackgroundThe effect of left bundle branch pacing (LBBP) on right ventricular (RV) function is not well known, and there is conflicting evidence regarding whether cardiac resynchronization therapy improves RV function. ObjectivesThe study aimed to investigate the effect of LBBP on RV function and to evaluate the response of RV dysfunction (RVD) to LBBP. MethodsSixty-five LBBP candidates were prospectively included in the study and underwent echocardiography at baseline and 6-month follow-up. LBBP response was left ventricular (LV) reverse remodeling, defined as a reduction in LV end-systolic volume of ≥15% at follow-up. ResultsPatients were assigned to 2 subgroups on the basis of 3-dimensional echocardiography–derived RV ejection fraction (EF) before LBBP implantation: 30 patients (46%) in the no RVD group and 35 patients (54%) in the RVD group. The RVD group was characterized by higher N-terminal pro–brain natriuretic peptide levels, New York Heart Association functional class, and larger LV/RV size. LBBP induced a significant reduction in QRS duration, LV size, and improvement in LVEF and mechanical dyssynchrony in both the no RVD and RVD groups, and a significant improvement in RV volumes and RVEF in the RVD group (all P<.01). LBBP resulted in a similar percentage reduction in QRS duration, LV dimensions, LV volumes, and percentage improvement in LVEF in RVD and no RVD groups (all P＞.05). LV reverse remodeling (29 of 35 patients vs 27 of 30 patients; P = .323) in the RVD group was similar to that in the no RVD group after LBBP. ConclusionLBBP induces excellent electrical and mechanical resynchronization, with a significant improvement in RV volumes and function. RVD did not diminish the beneficial effects on LV reverse remodeling after LBBP.

Cardiac Magnetic Resonance Identifies Responders to Cardiac Resynchronization Therapy with an Assessment of Septal Scar and Left Ventricular Dyssynchrony.

Background: The response to cardiac resynchronization therapy (CRT) depends on septal viability and correction of abnormal septal motion. This study investigates if cardiac magnetic resonance (CMR) as a single modality can identify CRT responders with combined imaging of pathological septal motion (septal flash) and septal scar. Methods: In a prospective, multicenter, observational study of 136 CRT recipients, septal scar was assessed using late gadolinium enhancement (LGE) (n = 127) and septal flash visually from cine CMR sequences. The primary endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume with echocardiography after 6 months. The secondary endpoint was heart transplantation or death of any cause assessed after 39 ± 13 months. Results: Septal scar and septal flash were independent predictors of CRT response in multivariable analysis (both p < 0.001), while QRS duration and morphology were not. The combined approach of septal scar and septal flash predicted CRT response with an area under the curve of 0.86 (95% confidence interval (CI): 0.78-0.94) and was a strong predictor of long-term survival without heart transplantation (hazard ratio 0.27, 95% CI: 0.10-0.79). The accuracy of the approach was similar in the subgroup with intermediate (130-150 ms) QRS duration. The combined approach was superior to septal scar and septal flash alone (p < 0.01). Conclusions: The combined assessment of septal scar and septal flash using CMR as a single-image modality identifies CRT responders with high accuracy and predicts long-term survival.

Prognostic implications of invasive hemodynamics during cardiac resynchronization therapy: Stroke work outperforms dP/dtmax

Invasive measurements of left ventricular (LV) hemodynamic performance can evaluate acute response to cardiac resynchronization therapy (CRT). The study sought to determine which metric, maximum rate of LV pressure rise (LV dP/dtmax) or LV stroke work (LVSW), is more strongly associated with long-term prognosis. CRT patients were prospectively included from 3 academic centers. Invasive pressure-volume loop measurements during implantation were performed, and LV dP/dtmax and LVSW were determined at baseline and during biventricular pacing (BVP) as well as their relative increase (%Δ). Hazard ratios (HRs) for the primary outcome of 8-year all-cause mortality were derived using Cox proportional hazards. The secondary endpoint was echocardiographic response, defined as 6-month LV end-systolic volume reduction ≥15%. Paired data from 82 patients were analyzed (67% male; age 66 ± 9 years; QRS duration 158 ± 22 ms, median survival time 72 months). Survival was better when LVSW during BVP was ≥4400 mL∙mm Hg (HR 0.21, 95% CI 0.08-0.58, P < .003) or when ΔLVSW% was ≥10% (HR 0.22, 95% CI 0.08-0.65, P=.006). In multivariate analysis, following direct comparison of continuous measures of acute ΔLV dP/dtmax% and ΔLVSW%, only ΔLVSW% remained associated with the primary endpoint (HR 0.982 per percentage point, P = .028). In contrast to LV dP/dtmax (all P > .05), significant associations with echocardiographic response were found for stroke work during BVP (area under the receiver-operating characteristic curve 0.745, P = .001) and ΔLVSW% (area under the receiver-operating characteristic curve 0.803, P < .001). Stroke work, but not LV dP/dtmax, is consistently associated with long-term prognosis and response after CRT. Our results therefore favor the use of stroke work as the hemodynamic parameter to predict long-term outcome after CRT.

The predictive role of left ventricular cathode topography relative to CMR-determined latest mechanical activation and scar segments on response to cardiac resynchronisation therapy

Abstract Background Cardiac resynchronisation therapy (CRT) is still burdened by considerable rates of non-response. Herein left ventricular cathode (LVC) positioning has the greatest room for optimisation. Nonetheless, a purely CMR-based approach exploring LVC topography relative to both mechanical delay and tissue viability is yet to be investigated. Purpose To retrospectively analyse the effect on reverse remodelling of CMR-determined LVC topography relative to latest mechanical activation (LMA) and scar segments in a CRT population. Methods This is a retrospective single-centre analysis of 104 CRT-D/P consecutive patients with CMR performed within 6 months before implantation. Electrical delay (Q-LV time) was mapped on all suitable veins with LV lead positioning and cathode programming set in the region of latest electrical activation. Through CART-Tech® software analysis of CMR images, 36-segment 3D anatomical models of radial strain and scar were superimposed on their corresponding fluoroscopy images (Figure 1). Patients were then stratified based on LVC concordance (within), semi-concordance (adjacent) or non-concordance (at least one segment away) with LMA and scar segments (defined as segments with &amp;gt;50% scar transmurality). Follow-up echocardiography was performed at least 6 months after implantation and the degree of reverse remodelling expressed as percentage reduction in end-systolic volume (ESV). Results Of the 104 patients, 36 were excluded due to suboptimal CMR quality (8), switch to conduction system pacing (5), loss to follow-up (18) or death within 6 months of implantation (5), leaving a total of 68 (63 CRT-D and 5 CRT-P). LVC concordance with LMA was associated with a statistically significant improvement in reverse remodelling (Figure 2, A), while the contrary occurred with regards to scar (Figure 2, B). A greater impact of distance from scar compared to LMA proximity was observed, thus a combined analysis of LVC topography relative to both was developed accordingly. Patients were stratified into 4 categories of LVC optimality: optimal (LVC-LMA concordance + LVC-scar non-concordance), semi-optimal (LVC-LMA semi-concordance + LVC-scar non-concordance), suboptimal (LVC-LMA non-concordance + LVC-scar non-concordance), and unfavourable (LVC-scar semi-concordance or concordance regardless of LVC-LMA). The unfavourable group had higher rates of atrial fibrillation, non-LBBB QRS morphology and higher scar burden, while no significant differences were observed in the other 3 groups. This classification appears to predict the degree of reverse remodelling, ESV reduction being more pronounced the more optimal the group (Figure 2, C). Conclusions CMR-determined LVC topography relative to LMA and scar segments predicts left ventricular reverse remodelling in Q-LV-guided CRT implants. Optimisation of CRT response may thus benefit from a CMR-based approach assessing mechanical delay and tissue viability to guide LVC positioning.Figure 1Figure 2

Hemodynamic forces from 4D flow magnetic resonance imaging for optimised prediction of cardiac resynchronisation therapy outcome

Abstract Background Patients with heart failure and left bundle branch block (LBBB) may receive cardiac resynchronisation therapy (CRT), but many patients have limited treatment response (1). The use of imaging to optimise patient selection has been repeatedly attempted with some success (2), and scar detected on late gadolinium enhancement (LGE) imaging has been associated with reduced response rates (3). Intraventricular hemodynamic force (HDF) analysis has been suggested as a novel marker for assessment of patients eligible for CRT (4). The aim of this study was therefore to investigate if septal scar from LGE or left ventricular HDF computed from cardiac magnetic resonance (CMR) imaging can improve prediction of CRT outcome. Methods Patients with heart failure, EF&amp;lt;35% and LBBB (n=22) underwent CMR with 4D flow at 1.5T or 3T (Achieva, Philips Healthcare) prior to CRT (Figure 1). Scar was assessed by LGE. Left ventricular HDF were computed based on the Navier-Stokes equations, using a validated module in the software Segment v3.3 R10057 (Medviso, Lund, Sweden) (5). Forces (N) were analysed in three orthogonal directions as root mean square (RMS) and peak values, reported in median [interquartile range]. Transversal/longitudinal HDF ratio was calculated for systole and diastole. Echocardiography was performed before and six months after CRT, and patients with end-systolic volume reduction ≥15% at follow-up were defined as responders. The Mann-Whitney U test was used for group comparisons, Fisher’s exact test for binary categorical data, Wilcoxon test for paired comparisons, and receiver operating characteristic analysis for prediction of CRT response. Results There was no difference between responders and non-responders in LGE (Table 1). Non-responders had smaller HDF than responders in the inferior-anterior direction in systole (RMS: 0.055 [0.027] vs 0.070 [0.032], p=0.04; peak: 0.11 [0.069] vs 0.15 [0.083], p=0.03), and in the apex-base direction in diastole (RMS: 0.087 [0.018] vs 0.11 [0.046], p=0.047). Non-responders had larger diastolic HDF ratio than responders (RMS: 0.89 [0.45] vs 0.67 [0.20], p=0.004; peak: 1.1 [0.51] vs 0.57 [0.40], p=0.01) (Figure 1). Receiver operating characteristic analysis of diastolic HDF ratio found an area under the curve of 0.88 (p=0.005). Identification of non-responders using diastolic HDF ratio with a specificity of 100%, resulted in a ratio of &amp;gt;0.87 for non-responders, with a sensitivity of 57%. Intragroup comparison found higher HDF ratio in systole than diastole for responders but not for non-responders (Figure 1). Conclusions Prediction of left ventricular remodelling following CRT may be optimized by hemodynamic force analysis from 4D flow CMR, while septal scar from LGE was not found indicative of CRT outcome in this pilot study. Larger-scale studies are required before clinical implementation of HDF analysis.Table 1Figure 1

Effect of Sacubitril/Valsartan and enalapril on left ventricular function in patients with hematologic malignancies after bone marrow transplantation

Abstract Background and Aims Optimizing treatment for heart failure early after initiation of chemotherapy may prevent myocardial dysfunction. We hypothesized that early initiation of treatment with sacubitril/valsartan (sac/val) or enalapril (ena) may prevent cardiotoxicity. Patients and methods 90 patients (mean age 45.7 ± 14,1 years old, 52 male) with normal LV ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive sacubitril/valsartan 24/26 mg bid daily or enalapril 5 mg bid daily or placebo. We measured at baseline, before transplantation and after six months: i) Global Longitudinal Strain (GLS) of left ventricle (LV) by speckle tracking imaging, ii) myocardial global work index (GWI), global constructive work (GCW), global wasted work (GWW) and myocardial global work efficiency (GWE), by longitudinal strain-peripheral blood pressure loops, and iii) Left Ventricular Ejection Fraction (LVEF). Results The 3 treatment groups had similar age, sex, risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with sacubitril/valsartan or enalapril for six months did not show a deterioration of LV GLS (-19.8±2.8 vs -19.3±4.1%, p=0.403 for sac/val, -20.3±2.8 vs -20.0±3.6%, p=0.634 for ena). Conversely, patients treated with placebo for six months, presented a significant impairment of LV GLS (-20.9±2.1% vs -18.5±2.2, p=0,001). No significant changes were found in LVEF after treatment with sacubitril/valsartan or enalapril for six months (57.5±4.9 vs 57.9±6.8%, p=0.826 for sac/val, 58.8±5.4 vs 60.7±7.1%, p=0.419, for ena), while a borderline deterioration was noticed after treatment with placebo (60.6±5.4 vs 57.7±6.7%, p=0.045). Moreover, in the sacubitril/valsartan group, we noticed a significant reduction of left ventricular end diastolic and end-systolic volume [(102.3±26.9 vs 93.9±21.5 ml, p=0.042 and 44.5±15.4 vs 38.6±9.6ml, p=0.012), respectively]. At 6 months, we did not observe any alteration in GWi, GCW, GWW, GWE in patients treated with enalapril (p&amp;gt;0.05). Conversely, in patients treated with sacubitril/valsartan GWE was improved (94.2±3.1 vs 95.8±1.8 %, p=0.030) and GWW was reduced (111.5±75.7 vs 86.4±43.1 mmHg%, p=0.045), while GWI and GCW did not show any significant alteration. Conversely, in the placebo group, GWI was reduced (1909.9±336.4 vs 1727.9±340.9 mmHg%, p=0.027), GWW was increased (80.7±60.6 vs 110.6±65.1 mmHg%, p=0.045), GWE was also reduced (94.2±3.1 vs 95.8±1.8 %, p=0.030) and GCW did not change at 6 months. Conclusions Treatment with sacubitril/valsartan or enalapril prevented deterioration of myocardial function six months after bone marrow transplantation in patients with hematologic malignancies and preserved LV ejection fraction. Moreover, sacubitril/valsartan showed a more favorable effect on myocardial work.

The effectiveness of eplerenone vs spironolactone on left ventricular systolic function, hospitalization and cardiovascular death in patients with chronic heart failure - HFrEF

Abstract Background Heart failure remains one of the most prevalent clinical syndromes associated with significant morbidity and mortality. According to current guidelines MRA are recommended to reduce the risk of HF hospitalization and death in all patients with symptomatic heart failure. Purpose The aim of our study was to determine the efficacy of eplerenone vs. spironolactone on left ventricular systolic function (LVEF) in patients with chronic heart failure, especially their effect on preventing hospitalization, reducing mortality, and improving clinical status among patients with chronic HF. Methods From June 2021 to June 2022, the study was a randomized, prospective clinical trial single blind study. A total of 142 patients of chronic heart failure with reduced ejection fraction were selected by random sampling. Each patient was randomly allocated into either of the two groups and was continued receiving treatment with either spironolactone (Spiron-HF group) or eplerenone (Epler-HF group). Patients in Epler-HF group were compared with an arm of the same size. Each patient was evaluated clinically and echocardiographically at the beginning of treatment, after 6 months and at the end of 12th month. Results After 12 months of treatment, significant improvement of left ventricular ejection fraction was observed in eplerenone treated arm (37.9 ± 3.8 ± 4.6 in Spiron-HF group versus 40.1 ± 5.7 in Epler-HF group; P &amp;lt; 0.05). A significant reduction in left ventricular end-systolic volume (6.3 ± 2.5ml in Spiron-HF versus 17.8± 4.4ml in Epler-HF group; P &amp;lt; 0.05) and left ventricular systolic diameter volume (2.7 ± 0.5ml in Spiron-HF versus 6.7 ± 0.2ml in Epler-HF group; P &amp;lt; 0.05), occurred after 12 months of treatment. The effects of both MRA agents' spironolactone and eplerenone on the primary composite outcome, each of the individual mortality and hospital admission outcomes are shown in Figure 1 and 2. Patients of the Epler-HF group showed statistically significant lower cardiovascular mortality (HR 0.53; 95% CI 0.34–0.82; p= 0.007) and all-cause mortality (HR 0.64; 95% CI 0.44–0.93; p= 0.022) than patients of the Spiron-HF group. The statistical analysis did not show a statistically significant difference between Epler -HF and Spiron-HF study groups regarding the risk of the primary composite outcome; cardiovascular death or hospitalization due to HF (Hazard Ratio (HR) eplerenone vs. spironolactone = 0.95; 95% Confidence Interval (CI) 0.73– 1.27; p= 0.675). Conclusion Our study has demonstrated favorable effects of eplerenone on cardiac remodeling parameters and reduction of cardiovascular mortality and all-cause mortality compared with spironolactone in the treatment of HFrEF. The ability of eplerenone to effectively block the mineralocorticoid receptor while minimizing side effects and a significant reduction in the risk of hospitalization and cardiovascular death confirms its key role in the treatment of patients with chronic HFrEFCumulative estimates of cardiovascular mCumulative incidence of the primary end-

Association of echocardiography-derived hemodynamic force parameters with left ventricular reverse remodeling after cardiac resynchronization in non-ischemic cardiomyopathy

Abstract Background Cardiac resynchronization therapy (CRT) improves outcome in selected heart failure patients and can induce left ventricular (LV) reverse remodeling. Echocardiography-derived hemodynamic forces (HDF) are a new clinical tool which provides insight in fluid dynamics. Purpose To evaluate whether baseline HDF parameters are associated with LV reverse remodeling at six months after CRT implantation in patients with non-ischemic cardiomyopathy. Methods From a CRT database, patients with LV ejection fraction &amp;lt;35%, QRS duration &amp;gt;130ms and left bundle branch block were included. At baseline, the following HDF parameters were measured for the complete heart cycle (Figure 1): 1) apical-basal strength, representing the magnitude of the longitudinal HDF, 2) lateral-septal strength, representing the magnitude of the transversal HDF and 3) the angle, representing the HDF orientation. In the systolic thrust (i.e. the positive part of systole in the apical-basal curve), the apical-basal impulse (AB impulse) and the systolic angle were measured. LV reverse remodeling was defined as a reduction of LV end-systolic volume ≥15% at six months. Results In total, 196 patients were included (age 64±11 years, 62% male). LV reverse remodeling was observed in 136 (69%) patients (i.e. responders). Baseline characteristics are presented in Table 1. Responders had a higher angle in the complete heart cycle (67.1 vs 64.1; p = 0.002) as compared to non-responders, indicating less deviation of HDF orientation in responders. Responders also had a higher AB impulse (5.0% vs. 3.4%, p = 0.012) and higher systolic angle (74.0 vs. 71.0), p&amp;lt;0.001), indicating larger magnitude of HDF and less deviation of HDF orientation in the systolic thrust. Univariable logistic regression showed a significant association of loop diuretic use, LV global longitudinal strain (LV GLS), left atrial volume index (LAVI), the angle, AB impulse and the systolic angle with LV reverse remodeling. To minimize collinearity, two multivariable models were built. Loop diuretic use, LV GLS, LAVI and AB impulse were inserted in both models, while the angle was inserted in the first model and the systolic angle in the second model. In the first model, the angle (HR 1.082 (95%CI 1.018, 1.150), p = 0.011) was independently associated with LV reverse remodeling while the systolic angle (HR 1.073 (95%CI 1.011, 1.140), p = 0.021) was independently associated with LV reverse remodeling in the second model. Conclusion At baseline, responders have better orientation of HDF in the complete heart cycle and larger magnitude and better orientation of HDF in the systolic thrust as compared to non-responders. The orientation of HDF in the complete heart cycle and systolic thrust is independently associated with LV reverse remodeling. As such, the angle and systolic angle of HDF have the potential to identify patients that are likely to experience LV reverse remodeling after CRT.Figure 1.HDF in non-ischemic CMPTable 1.Baseline characteristics

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

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

Personalized cardiac resynchronization therapy guided by real-time electrocardiographic imaging for non-left bundle branch block patients

Abstract Background Heart failure patients with non-left bundle branch block (non-LBBB) QRS pattern have limited response rate to biventricular pacing (BVP). Objective A personalized cardiac resynchronization therapy (CRT) implantation approach guided by real-time electrocardiographic imaging (ECGi) was studied. Methods Twenty patients with left ventricular ejection fraction (LVEF) ≤35%, QRS duration ≥120ms and non-LBBB (13 right bundle branch block and 7 intraventricular conduction delay) were recruited. During CRT implantation, right atrial, right ventricular, coronary sinus, His-bundle and/or Left-bundle leads were inserted. The total activation time (TAT) with different pacing combinations were measured real-time during implantation by ECGi. The configuration producing shortest TAT would be chosen. Clinical response was defined as ≥1 New York Heart Association (NYHA) class improvement. Echocardiographic response was defined as LV end systolic volume reduction ≥15% and/or LVEF improvement ≥10% at 6-months. Results After ECGi guided CRT implantation, LVEF improved from 26±6% to 34±11% (both p&amp;lt;0.01) and NYHA class improved from 3.0±0.5 to 2.0±0.6 (p&amp;lt;0.01). Both clinical and echocardiographic response rates were 70%. ECGi approach resulted in better acute electrical resynchronization over BVP as measured by TAT reduction (40% vs 14%, p&amp;lt;0.01). Percentage of TAT reduction was found to be a strong predicator for echocardiographic response (AUC for ROC curve 0.91, 95% CI 0.78 – 1.00). A strong positive correlation between percentage TAT reduction and percentage LVEF improvement (Pearson R 0.70, p=0.001) was found. Conclusions ECGi guided CRT implantation in non-LBBB patients generates superior acute electrical resynchronization compared with BVP and is associated with favorable clinical and echocardiographic outcomes.