Ventricular Dyssynchrony Research Articles

Usefulness of left ventricular mechanical dyssynchrony for predicting atrial fibrillation and adverse outcomes following first atrial fibrillation event

Abstract Background Left ventricular mechanical dyssynchrony (LVMD) has shown to predict many cardiovascular outcomes including ventricular arrhythmias. Our hypothesis is that LVMD can reveal early atrial dysfunction. Purpose The aim of this study was to investigate whether LVMD can be used to predict atrial fibrillation (AF) and adverse outcomes following first AF event in individuals from the general population. Methods A total of 3785 individuals (mean age 55±17 years, 57% women) from the general population free of AF, heart failure (HF) and prior stroke had an echocardiographic examination performed including two-dimensional speckle tracking echocardiography. LVMD was calculated as the standard deviation of the regional time-to-peak strain from the three apical views. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or HF after the diagnosis of AF. Results During a median follow-up of 5 years (interquartile range, 4.4-6.2 years), 142 (4%) individuals were diagnosed with AF, and of these 22 (15%) individuals developed HF or stroke. LVMD was a univariable predictor of AF (per 10ms increase: HR 1.03; 95% CI (1.02-1.05), p<0.001, Figure). The association remained significant even after multivariable adjustment for age, sex, body mass index, diabetes, hypertension, heart rate, previous ischaemic heart disease, systolic blood pressure, diastolic blood pressure, smoking, left ventricular ejection fraction, global longitudinal strain, left atrial volume index (LAVI), and E/e’ (per 10ms increase: HR 1.02; 95% CI (1.00-1.04), p=0.042). LVMD also predicted complicated AF, and the association remained significant even after multivariable adjustment (per 10ms increase: HR 1.05; 95% CI (1.01-1.09), p=0.026). Furthermore, LVMD provided incremental prognostic information over the LAVI with regard to predicting AF (Harrell’s C-statistics 0.66 vs. 0.70, p=0.012). Conclusion In a low-risk general population, LVMD provides prognostic information on the risk of AF. Additionally, LVMD can identify individuals with complicated AF defined as occurrence of either stroke or HF following the diagnosis of incident AF. Furthermore, LVMD provides incremental prognostic information over the LAVI in predicting AF.

ECG as a screening tool for detection of significant functional mitral regurgitation in patients with left bundle branch block

Abstract Background Functional mitral regurgitation (FMR) may occur in the left bundle branch block (LBBB) due to mechanical left ventricular (LV) dyssynchrony, by the imbalance between the tethering and the closing forces exerted on the mitral apparatus1-3. Progressive FMR and LV remodeling result in a reciprocal worsening downward spiral and worse clinical outcomes1-3. Therefore, timely screening and follow-up of these patients to prevent the irreversible progression of FMR is required. To date, only LBBB morphology and QRS duration have been proven predictors of FMR4. Purpose This study aimed to assess the relationship between ECG parameters of LV dyssynchrony and the severity of FMR in patients with LBBB. Methods We retrospectively included 154 consecutive patients with LBBB, in sinus rhythm, who had an echocardiogram, with no more than mild organic valvular heart disease. We measured the following intraventricular dyssynchrony markers: LV activation times (LVAT), intrinsicoid deflection (ID) in lateral and aVF leads and a newly defined marker – the difference (Diff) between aVL and aVF ID’s (Diff_IDaVL_aVF). These two leads record the electrical activation of the two opposing myocardial segments adjacent to the posteromedial and anterolateral papillary muscles, respectively5 (Figure 1). Based on the severity of FMR, the patients were divided into two groups: no/mild FMR (grade II or less) (61%), and significant FMR (grade III and IV) (39%). Results In patients with significant FMR, the LVAT measured in lateral leads, the IDaVL and Diff_IDaVL_aVF were significantly longer, but IDaVF was significantly shorter compared to patients with no/mild FMR (p<0.001). Of all studied ECG parameters, the Diff_IDaVL_ aVF was the parameter that had the strongest correlation with significant FMR (r correlation coefficient 0.82, p < 0.001). In multivariable analysis the Diff_IDaVL_aVF (p = 0.010) was the only parameter independently correlated with significant FMR. On ROC analysis the best cut-off for significant FMR prediction was 55 ms (AUC of 0.99, sensitivity 90% and specificity 97%) (Figure 2). Conclusions In LBBB, a simple intraventricular dyssynchrony ECG parameter can provide insights into FMR severity. A 55 msec Diff_IDaVL_aVF identifies significant FMR that may benefit from early medical or CRT treatment to avoid progression and worse prognosis.

Myocardial single photon emission computed tomography imaging to identify non-responders to cardiac resynchronization therapy in patients with non-left bundle branch block

Abstract Background Non-response to cardiac resynchronization therapy (CRT) is an important issue in the treatment of heart failure with reduced ejection fraction (HFrEF) and non-left bundle branch block (LBBB). Although the QRS duration and morphology are crucial parameters for selecting CRT candidates, electrocardiogram (ECG) markers may inadequately represent the mechanical activation patterns within the heart. Owing to limitations associated with the ECG criteria, there is increasing interest in advanced multimodality imaging to improve patient selection. Recently, myocardial single-photon emission computed tomography imaging (G-MPI) is used for assessing left ventricular (LV) dyssynchrony. This technique is mostly automatic and has high intra- and inter-observer reproducibility and repeatability. Objectives This study aimed to examine whether preoperative G-MPI evaluation could predict non-responsiveness to CRT in patients with HFrEF with non-LBBB. Methods Between January 2021 and December 2022, 128 patients underwent CRT, of whom 73 with pre-operative evaluation using G-MPI were selected. Forty-three patients with non-LBBB (21 and 22 CRT responders and non-responders, respectively) were assessed. These patients were divided into CRT responder and non-responder groups. We evaluated the cut-off and clinical impact of pre-operative G-MPI parameters in predicting non-responsiveness to CRT. In addition, 30 patients with LBBB were analyzed. Results Among patients with non-LBBB, CRT responders and non-responders showed no significant differences in baseline characteristics, except for the LV dimension. A receiver operating characteristic curve analysis identified 108° and 27.7° as the optimal cut-offs for the bandwidth and phase standard deviation (SD), respectively, to predict non-responsiveness to CRT (area under the curve [AUC]=0.762; 95% confidence interval [CI]: 0.601–0.923 and AUC=0.742; 95% CI: 0.576–0.909, respectively). A multivariate analysis revealed that a cut-off bandwidth of ≥108° and phase SD of ≥27.7° are independent predictors of non-responsiveness to CRT in patients with non-LBBB (hazard ratios 5.65; 95% CI: 1.53–20.9; P=0.009). In contrast, there were no relationships between G-MPI parameters and non-responsiveness to CRT in patients with LBBB. Conclusions Pre-operative G-MPI findings were associated with non-responsiveness to CRT in patients with non-LBBB. The identification of potentially nonresponsive patients could influence patient management and alter outcomes.

Sex-specific prognostic implications of new-onset atrial fibrillation in patients treated with dual chamber pacemakers

Abstract Background Right ventricular pacing induces ventricular dyssynchrony, which over time may result in left ventricular dysfunction, increased left ventricular filling pressures, and ensuing left atrial dilatation, with increased risk of atrial arrhythmias. Atrial fibrillation (AF) prior to device implant is associated with worse prognosis, but the prognostic effects of new-onset AF during pacemaker treatment are less well described. Purpose To describe risk factors, incidence, and prognostic effects of new-onset AF after treatment is initiated with a dual chamber pacemaker. To evaluate mortality and risk of heart failure diagnosis or hospitalisation for heart failure in patients who develop AF, compared to those who do not develop AF. Methods All patients without pre-existing heart failure or atrial fibrillation, who received a dual chamber pacemaker at a large-volume tertiary care center during the period 2005–2020 were included. Data was crossmatched between the national pacemaker registry, the population registry and national disease registries. The primary outcome was 10-year mortality, and the secondary outcome was new-onset heart failure. Results 37127 patients were included in the study, of which 14760 (30%) were female. Median age was 76.4 years [interquartile range, IQR, 68.0–83.1] and the most common indication for pacemaker implant was AV block (57.7%), see Table 1. Overall, 10-year survival was higher for female patients, compared to male patients, p<0.0001 (see Kaplan-Meier curve in Figure 1A). Patients who developed new-onset AF had more comorbidities, were slightly older and a higher percentage were men. During follow-up 3661 (9.9%) developed atrial fibrillation within two years (9.1% of female and 10.3% of male patients, p<0.001), at a median of 291 [88–461] days after implant. In multivariable Cox regression analysis with new-onset AF as time dependent covariable and adjusted for clinically relevant covariables, AF was an independent predictor of higher all-cause mortality (HR 1.43 [1.37–1.49], p<0.0001). Risk factors for new-onset AF included increasing age, male sex, hypertension, malignancy, diabetes, chronic obstructive lung disease, chronic renal disease, and sick sinus syndrome indication (all p<0.01). In separate analyses for men and women, the risk factors and magnitude of odds ratios were the same. Conclusion In patients treated with dual chamber pacemakers due to bradycardia or AV block, development of new-onset AF within two years was associated with a higher 10-year mortality. The risk of developing AF was higher for men, but the negative prognostic effect was more pronounced for women.Figure 1A.-B. K-M survival curves

Changes and prognostic impact of noninvasive myocardial work indices in patients undergoing transcatheter aortic valve implantation.

The prognostic significance of noninvasive myocardial work (MW) indices in patients undergoing transcatheter aortic valve implantation (TAVI) has not been adequately examined. We retrospectively selected 88 consecutive patients (mean age 79.9 ± 6.4 years, 40% males) with severe aortic stenosis scheduled for TAVI enrolled in the EffecTAVI registry. Exclusion criteria were prior valve surgery, atrial fibrillation, and left bundle branch block (LBBB) at baseline. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were measured by echocardiography at baseline and at 30 days. Accuracy of the noninvasive measures was assessed by invasive evaluation of MW. In the overall population, a significant reduction in GWI (2406 ± 567 vs. 2063 ± 515 mmHg% before and after TAVI respectively, P < 0.001), GCW (2783 ± 616 vs. 2380 ± 495 mmHg%, P < 0.001) and GWW (238 ± 203 vs. 186 ± 135 mmHg%, P = 0.015) was observed at 30 days after TAVI. GWE improved only in patients who did not develop left ventricular dyssynchrony due to new-onset LBBB or pacemaker implantation following TAVI. In a multivariable Cox-regression analysis, GWE after TAVI (hazard ratio 0.892, 95% confidence interval 0.81-0.97; P = 0.011) was the strongest predictor of adverse events (a composite of all-cause death, worsening of dyspnea, or rehospitalization for cardiovascular events) at 1-year follow-up. TAVI results in significant changes in MW indices, including an early decrease in GWI, GCW and GWW, and an improvement in GWE in patients without left ventricle dyssynchrony. A GWE equal or less than 92% at 30 days is indicative of poor clinical outcomes at 1 year.

Association between an early revascularization strategy and major cardiac events based on left ventricular dyssynchrony in patients at intermediate risk of major cardiac events using the J-ACCESS risk model.

Objective This retrospective study aimed to investigate the association between therapeutic strategies and the development of major cardiac events (MCEs) in intermediate-risk patients by using the J-ACCESS risk model in combination with the stress phase bandwidth (SPBW), an index of left ventricular dyssynchrony. Methods Patients were followed-up for three years to confirm their prognosis. Based on the estimated propensity scores, the patients who underwent revascularization within the first 60 days after SPECT and those who did not were matched 1:1 (n = 367 per group). The composite endpoint was the occurrence of MCEs, consisting of cardiac death, non-fatal myocardial infarction, and severe heart failure. SPBW was calculated by a phase analysis using the Heart Risk View-F software program, and the MCE rate was compared between the two groups by applying the normal value of SPBW (38°). Patients The study included 2,053 patients with either known or suspected CAD who underwent electrocardiogram-gated single-photon emission computed tomography myocardial perfusion imaging and were at intermediate risk of MCE according to the J-ACCESS risk model. Results During follow-up, 54 of the 734 patients (7.4%) experienced MCEs. The overall incidence of MCE in intermediate-risk patients was not significantly different between the two groups. However, the incidence of MCE in patients with an abnormal SPBW was significantly lower in those who underwent early revascularization (4.8% vs. 11.9%, P = 0.0407). Conclusion The combination of the J-ACCESS risk model and the SPBW is thus considered to be an optimal treatment strategy for patients at intermediate risk of MCE, and early revascularization may lead to an improved prognosis in intermediate-risk patients with an abnormal SPBW.

Mechanical dyssynchrony in patients with chronic heart failure and left bundle branch block

Background. The main problem in patient selection for cardiac resynchronization therapy (CRT) is the lack of unified approaches to the definition of mechanical dyssynchrony (MD) and selection criteria, particularly, in patients with left bundle branch block (LBBB).Aim: To study mechanical dyssynchrony indices and three-dimensional Echo (3DE) criteria of global and local contractility function in patients with chronic heart failure (CHF) and LBBB during different types of isolated left ventricle (LV) pacing.Methodology and Research Methods. The experimental intraoperative study involved 88 points obtained from 12 patients with CRT class IA indications and LBBB. During isolated LV pacing as part of CRT implantation procedure endocardial and epicardial pacing were obtained. Transesophageal Echo (TEE) cineloops recording and paced QRS complex morphology registrations by means of LabSystem Pro Electrophysiological Recording System (Bard Electrophysiology, USA) were performed during each stimulation episode. Philips Qlab 10 software was used for TEE data analysis.Results. The global (3D EF, 23.8 [22; 28.4], GLS, –5.33% [10.90%; –15.4%]) and local contractility (ExсAvg 3.5 [2.1; 5.6]) criteria and dyssyncrony indices (SDI-16, 14.9 [8.9; 23.1]) showed severe systolic dysfunction and intraventricular dyssynchrony – typical signs in this patient group, and differed significantly (3D EF, p = 0.003; GLS, p = 0.004; ExcAvg, p &lt; 0.001; Tmsv-6 SD, р = 0.03) depending on the stimulation method and site. A moderate direct correlation between SDI-16 and the QRS duration (common electical dyssynchrony criterium) and inverse correlation with ExcAvg and 3D LVEF also describes LV response.

Right ventricular dyssynchrony predicts outcome in pulmonary arterial hypertension when assessed in multiple CMR views

BackgroundRight ventricular (RV) dyssynchrony or post systolic contraction (PSC) cause inefficient pumping and have not been investigated as prognostic markers in pulmonary arterial hypertension (PAH). ObjectivesTo investigate if RV dyssynchrony and PSC are prognostic markers of transplantation-free survival in PAH and if multiple RV views improve the prognostication. MethodsPatients with PAH undergoing cardiac magnetic resonance (CMR) between 2003-2021 were included. For strain analysis, endocardial end-diastolic RV contours were delineated in RV 3-chamber (RV3ch), 4-chamber (4ch) and midventricular short axis slice (SAX). RV dyssynchrony was defined as standard deviation of time to peak strain in the walls from one (4ch), two (4ch and SAX) or three views (4ch, SAX and RV3ch). PSC was defined as peak strain occurring after pulmonary valve closure. Outcome was defined as death or lung transplantation. ResultsOne hundred-one patients (58±19 years, 66% women) were included. Median follow-up was 37 [51] months. There were 60 events (55 deaths and 5 lung transplantations). Outcome was associated with RV dyssynchrony from three views and with RV strain in 4ch. An increase of RV dyssynchrony - from 3 views - by 1% was associated with a 10% increased risk of lung transplantation or death. There was no association between outcome and RV dyssynchrony in one or two views nor with PSC. ConclusionRight ventricular dyssynchrony from three views were associated with outcome in PAH, whereas assessing dyssynchrony from one or two views and PSC were not. This implies that assessment of multiple instead of single RV views potentially could be used for prognostication in PAH.

Вплив реваскуляризації коронарних артерій на механічну дисинхронію міокарду лівого шлуночка у хворих з коронарною хворобою серця

Introduction. Defining a treatment strategy for patients with stable coronary heart disease will require the development of personalized criteria, among which the assessment of myocardial dyssynchrony is considered promising. The aim of the study was to evaluate the effect of revascularization of coronary arteries on indicators of mechanical myocardial dyssynchrony in patients with stable coronary heart disease. Materials and methods. The study included 121 patients with coronary heart disease, who were assessed for mechanical myocardial dyssynchrony before and 2 weeks after revascularization. The main group included 48 patients with myocardial dyssynchrony, and the comparison group included 73 patients without myocardial dyssynchrony. Complete occlusion and lesions of 3 coronary arteries were found more often in the group with myocardial dyssynchrony, and the main group also had a higher SYNTAX SCORE. The results. Mechanical dyssynchrony of the myocardium was found in 39% of patients with coronary heart disease. Before revascularization, a signifiant increase in SPWMD, APEI, IVMD, and a decrease in LVFT and LVET were found in the group of patients with myocardial dyssynchrony. After revascularization in the main group, in 9 patients out of 48 (18.7%), indicators of myocardial dyssynchrony returned to normal values. LVFT in the group of patients with myocardial dyssynchrony significantly increased, as well as left ventricular ejection time (LVET) (from 318.5±9.6 ms to 344.9±23.2 ms, p&lt;0.01). Conclusions. After revascularization, the number of patients with myocardial dyssynchrony significantly decreased due to the improvement of interventricular and intraventricular dyssynchrony indicators. Key words: myocardial dyssynchrony, coronary heart disease, revascularization, coronary angiography, SYNTAX SCORE.

SPECT myocardial perfusion imaging for the evaluation of left ventricular mechanical dyssynchrony in obese patients.

Left ventricular dyssynchrony (LVD), the loss of coordinated contraction in the left ventricle, is an early sign of heart failure. LVD can be assessed using phase analysis techniques with gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). This study aimed to investigate the impact of obesity on LVD through phase analysis. We retrospectively enrolled 152 obese patients and 80 age- and sex-matched nonobese patients who showed normal myocardial perfusion and normal left ventricular ejection fraction (LVEF) on MPI. Phase standard deviation (PSD) and phase histogram bandwidth (PBW), as phase analysis parameters, were compared between patients with and without obesity. Although PSD values were within the normal range (cut-off value >23) for both groups, the PSD values of obese patients were higher than those of the nonobese (20.49 ± 8.66 vs. 14.81 ± 4.93; p < 0.05). PBW values of obese patients were statistically significantly higher than those of the nonobese (57.03 ± 23.17 vs. 41.40 ± 9.96; p < 0.05). The PBW values of obese patients exceeded the normal limits (cut-off value >49). A weak positive correlation was observed between body mass index (BMI) and PBW values in obese patients (r = 0.181, p < 0.05). In patients of normal weight, no correlations were found between BMI and phase analysis parameters. LVD may develop in obese patients, even when myocardial perfusion and ejection fraction are preserved. The use of phase analysis with gated SPECT could be an additional finding improving the early detection of left ventricular dyssynchrony in obese patients.

Outcomes with physiologic His bundle pacing in patients with narrow QRS complex

BackgroundIn patients with narrow QRS complex, both ventricular and biventricular pacing is associated with increased cardiac morbidity and mortality. This risk is not decreased by ventricular pacing avoidance algorithms, which cause nonphysiologic atrioventricular (AV) delays. ObjectiveThis study aimed to report outcomes in patients with narrow QRS complex when the paced complex is in normal range and physiologic AV delays are programmed. MethodsIn 196 patients with QRS duration of 92 ± 10 ms, permanent pacing was done at the site of the His bundle electrogram. The pacemakers were then programmed to maintain physiologic AV delays and to increase heart rates in response to exercise. Patients received usual care and were observed for 3 years. ResultsThe paced complex exhibited a delta wave, and the ventricular activation time, QRS axis, and lead I voltage remained in normal range. Physiologic programming resulted in His bundle pacing burden of 92%. In patients with decreased ejection fraction, there was significant improvement in left ventricular function, left ventricular dilation, and mitral regurgitation (P < .003). In patients with normal ejection fraction, left ventricular function remained normal without new valvular abnormalities. The 3-year all-cause mortality was 10%, and there was no increase in heart failure admissions. ConclusionIn patients with narrow QRS complex, when paced QRS morphology is maintained in normal range and AV dyssynchrony is avoided, His bundle pacing is associated with low all-cause mortality and improvement in abnormal echocardiographic parameters. The paced QRS morphology and physiologic AV delays may be important factors to evaluate in future trials of conduction system pacing.

Mitral regurgitation increases systolic strains in remote zone and worsens left ventricular dyssynchrony in a swine model of ischemic cardiomyopathy.

Ischemic mitral regurgitation (IMR) imposes volume overload on the left ventricle (LV), accelerating adverse LV remodeling. In this study, we sought to investigate the impact of volume overload due to IMR on regional myocardial contractile mechanics. Ten Yorkshire swine were induced with myocardial infarction (MI) by occluding the left circumflex coronary artery (LCx). Cardiac MRI was performed at baseline (BL) and 2.5 months (2.5M) post-MI. IMR was quantified with epicardial echocardiography 3 months post-MI. The animals were then assigned to 2 groups: no/mild MR (nmMR, n = 4) and moderate/severe MR (msMR, n = 6). MRI images were analyzed to assess infarction size, end-diastolic and end-systolic volume (EDV and ESV, respectively), ejection fraction (EF), longitudinal strain (LS), circumferential strain (CS), and systolic dyssynchrony index (SDI). The myocardial region was divided into infarction, border, and remote zones based on the LCx-supplied region. There was no difference in the infarction size. Group-wise comparison of LS and CS between BL and 2.5M demonstrated that LS and CS in the infarction zone and the border zone decreased at 2.5M in both groups. However, LS and CS in the remote zone were elevated only in the msMR group (LS: -9.81 ± 3.96 vs. -12.58 ± 5.07, p < 0.01; CS; -12.78 ± 3.81 vs. -16.09 ± 3.33, p < 0.01) at 2.5M compared to BL. The SDI of CS was significantly elevated in the msMR group (0.1255 vs. 0.0974, p = 0.015) at 2.5M compared to BL. Elevated LS and CS in the remote zone were observed in moderate/severe MR and ventricular dyssynchrony. These elevated cardiac strains, coupled with ventricular dyssynchrony, may contribute to the progression of MR, thereby accelerating heart failure.

A Comparative Analysis of Apical Rocking and Septal Flash: Two Views of the Same Systole?

Heart failure (HF) is a complex medical condition characterized by both electrical and mechanical dyssynchrony. Both dyssynchrony mechanisms are intricately linked together, but the current guidelines for cardiac resynchronization therapy (CRT) rely only on the electrical dyssynchrony criteria, such as the QRS complex duration. This possible inconsistency may result in undertreating eligible individuals who could benefit from CRT due to their mechanical dyssynchrony, even if they fail to fulfill the electrical criteria. The main objective of this literature review is to provide a comprehensive analysis of the practical value of echocardiography for the assessment of left ventricular (LV) dyssynchrony using parameters such as septal flash and apical rocking, which have proven their relevance in patient selection for CRT. The secondary objectives aim to offer an overview of the relationship between septal flash and apical rocking, to emphasize the primary drawbacks and benefits of using echocardiography for evaluation of septal flash and apical rocking, and to offer insights into potential clinical applications and future research directions in this area. Conclusion: there is an opportunity to render resynchronization therapy more effective for every individual; septal flash and apical rocking could be a very useful and straightforward echocardiography resource.

Conduction system pacing preserves both electrical and mechanical interventricular synchrony, a UHF ECG validation study

Abstract Background Interventricular mechanical delay (IVMD) is an established echocardiographic risk factor for pacing-induced cardiomyopathy development. Ultra-high-frequency ECG (UHF-ECG) is a non-invasive tool visualizing the ventricular activation sequence. Purpose To compare UHF-ECG interventricular dyssynchrony with echocardiography and to establish interventricular dyssynchrony related to conductive system pacing (CSP) and right ventricular myocardial pacing (RVP). Methods 53 patients with advanced AV conduction disease, without organic heart disease, and preserved LV systolic function were prospectively included. Thirty-two had RVP, and twenty-one had CSP. CSP included both His bundle pacing (n=5) and left bundle branch area pacing (n=16). UHF-ECG and echocardiography were obtained at the baseline (during spontaneous rhythm) and after 1 year (during pacing). IVMD was manually calculated as a difference between the time from a distinct point of the QRS until the onset of the flow through LV and RV outflow tract using pulsed wave doppler imaging. Analysis was performed by two experienced and blinded cardiologists. Interventricular e-DYS was calculated automatically by a software as a time difference between activation in V8 (LV free wall) and V1 electrode (RV free wall). Results The average age of all included patients was 76 ± 6 years old and patients in both RVP and CSP group had similar clinical characteristics. The values of IVMD and interventricular e-DYS were similar in the whole study population both before the pacemaker implantation (-2 ± 21 ms for IVMD vs. 0 ± 20 ms for interventricular e-DYS; p=0.31) and after one year (14 ± 23 ms for IVMD vs. 14 ± 24 ms for UHF; p = 0.7). There were no significant differences in the baseline IVMD and interventricular e-DYS between those receiving CSP vs. RVP (IVMD -6 ± 22 ms for CSP vs 2 ± 20 ms for RVP, p=0.22) and interventricular e-DYS (e-DYS -5 ± 20 ms for CSP vs. 3 ± 20 ms for RVP, p=0.34). After one year of pacing, the patients with CSP preserved similar levels of both IVMD (mean change -2 ± 5 ms, p=0.74) and interventricular e-DYS V8-V1 (mean change 0 ± 4 ms, p = 0.95) – Figure 1. There was no difference between IVMD and interventricular e-DYS in CSP patients after one year (p=0.92). On the contrary, in the RVP group IVMD increased for 27 ± 5 ms (p &amp;lt;0.0001) and interventricular e-DYS for 24 ± 5 ms (p &amp;lt;0.0001) compared to the baseline - Figure 1. There was no difference between IVMD and interventricular e-DYS in RVP patients after one year (p=0.75). There was a moderate overall correlation between IVMD and e-DYS V8-V1 in all studied ventricular rhythms (R=0.73, p&amp;lt;0.0001) – Figure 2. Conclusions UHF-ECG expresses the interventricular dyssynchrony noninvasively by measuring the activation difference between V8-V1 chest leads. RV myocardial pacing increases interventricular dyssynchrony, while CSP preserves synchronous ventricular activation.CSP vs RVPcorrelation of dyssynchrony

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&amp;lt;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&amp;lt;0.001]) and QRS area (from 100.5 ms*mV (or µVs) during AAI pacing to 65.6 ms during CRT [P&amp;lt;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.

ECG imaging as a real time tool to guide left bundle branch pacing implant in patients with left bundle branch block and resynchronization therapy indication

Abstract Background Left bundle branch pacing (LBBP) has emerged as a promising alternative technique for cardiac resynchronization therapy (CRT). ECG imaging (ECGI) may provide an accurate assessment of electrical resynchronization using real-time maps during LBBP implant. Purpose To evaluate the usefulness of ECGI to guide LBBP implant, by analyzing the ventricular activation times and the degree of resynchronization at each screwing step during the lead implant. Methods Four patients with CRT indication and left bundle branch block (LBBB) referred for LBBP were prospectively enrolled. ECGI was performed during the implant procedure. Cardiac signals were recorded using ECGI and projected into an artificial intelligence-derived geometric model. Thus, generating imageless and non-invasive activation maps at defined stages during lead screwing: basal rhythm (LBBB), right ventricular (RV) septum, mid-septal, deep-septal, and finally pacing from the left bundle branch (according with guidelines ECG criteria). The following parameters were measured: a) total activation time (TAT); b) left ventricular activation time (LVAT); c) left ventricular dyssynchrony index (LVDI) (as a quantifier of intraventricular dyssynchrony); d) ventricular electrical uncoupling (VEU); and e) histogram overlap between LV and RV distribution (the last 2 markers of interventricular dyssynchrony). Results The study cohort comprised men with a median age of 68 [Q1 59- Q3 79], with a median basal LBBB QRS duration of 175 ms [160-188] and a median LVEF of 32% [28-39]. A shortening of the activation times and a decrease in intra and interventricular dyssynchrony was achieved when the final lead position was reached. See the results in Figure 2. Conclusion Real-time and imageless ECGI system may offer a novel approach for guiding LBBP and it is useful to ensure left ventricular resynchronization.ECGI to guide LBBP implantActivation and dyssynchrony measurements

Real-time assessment of LV synchrony in AV block population undergoing LBB pacing using ECG Imaging

Abstract Background Left bundle branch pacing (LBBP) may prevent right ventricular (RV) pacing-induced dyssynchrony (DYS). Nowadays, real-time assessment of DYS correction is indirectly measured with QRS narrowing. Non-invasive ECG imaging (ECGI) technique may provide an evaluation of electrical resynchronization based on quantitative assessment of ventricular local activation time (LAT) maps. Purpose To assess whether real-time ECGI could evaluate LV synchrony achieved through LBBP, in a consecutive AV block (AVB) population. Methods A cohort of 12 patients with AVB were included. ECGI was performed during the implant procedure. ECGI signals were computed using an artificial intelligence derived cardiac geometry model. Ventricular LAT maps were obtained when pacing from septal RV and with LBBP (lead placed according to guidelines ECG criteria) for each of the patients. The following parameters were obtained from ECGI LAT maps to assess intra and interventricular DYS pacing at the RV septal and LBB locations: total activation time (TAT), left ventricular activation time (LVAT), left ventricular dyssynchrony index (LVDI), ventricular electrical uncoupling (VEU = mean LVAT – mean RV activation time) and histogram overlap between LV and RV activation times distribution. RESULTS: Nine of the 12 patients were men (75%), with a median age of 79[Q1 75-Q3 82]. QRS duration during RV septal pacing was 150 ms [138-172]. Median LVEF was 47% [26-59]. In Figure 1, it can be observed that dyssynchrony variables are corrected across all patients when reaching LBBP. Figure 2 shows activation maps during RV septal pacing and during LBBP, along with the QRS duration, and the RV and LV histogram of activation times. Conclusion ECGI is useful for assessing the LV synchrony correction during LBBP in an AV block population.Dyssynchrony variablesActivation maps with QRS and histograms

Predicting the response to cardiac resynchronization therapy using in silico heart models: pilot study of comparison between in silico and real cardiac resynchronization therapy outcomes

Abstract Background Cardiac resynchronization therapy (CRT) is treatment for patients with heart failure and left ventricular (LV) dyssynchrony. The objective of this study is to evaluate the feasibility of an in silico electromechanical heart model to predict CRT outcomes. Methods The three-dimensional heart geometries of 11 patients (age, 64.0±10.7 years, 4 men) with CRT were constructed from cardiac computed tomography images. We coupled cardiac electrical excitation and mechanical contraction with vascular hemodynamics using a lumped parameter model. We predicted the LV end-diastolic and end-systolic volumes and LV ejection fraction (LVEF) after CRT implantation using the in silico CRT simulation model. We compared the in silico CRT outcomes with the real CRT outcomes. Results Two patients were in silico CRT responders, and those 2 patients were also real CRT responders. Nine patients were in silico CRT non-responders, 8 who were real CRT non-responders, and 1 who was a real CRT responder. The in silico CRT outcomes agreed with the real CRT outcomes in 10 of 11 patients. The positive and negative predictive values and accuracy of the in silico CRT model were 100%, 88.9%, and 90.9%, respectively. Conclusion The in silico CRT simulation model is feasible for predicting real CRT outcomes.In silico CRT simulation model generatioAn example (patient No. 2) of LV (black

Electrocardiographic predictors of haemodynamic benefit from biventricular pacing: the role of atrioventricular timing measures

Abstract Background Patients with heart failure (HF) and left bundle branch block (LBBB) are selected for biventricular pacing (BVP) cardiac resynchronisation therapy (CRT) based on their 12-lead ECG QRS complex duration (QRSd). This is due to the long-held belief that BVP delivers its beneficial effects almost exclusively by reducing ventricular dyssynchrony. Recent work (1) suggests that atrioventricular delay (AVD) shortening is another key mechanism of benefit and, therefore, that atrioventricular timing may be an important CRT substrate. The ideal 12-lead ECG measure to facilitate patient selection that yields benefits from this mechanism is yet to be elucidated. Purpose We set out to establish whether incorporating a measure of AV delay provides additional benefit over and above using QRSd when using the 12-lead ECG to select patients who are likely to obtain haemodynamic benefit from BVP. Methods We identified patients in sinus rhythm with HF and LBBB meeting clinical criteria for CRT who had undergone implantation of a BVP device and had also undergone high-precision haemodynamic assessment of BVP. This is where pacing is alternated between atrium-only pacing (AAI) and DDD pacing using BVP multiple times for each of a full range of AVDs during continuous beat-by-beat blood pressure recording to determine the peak haemodynamic benefit of BVP in each patient. We extracted potentially predictive, pre-specified intrinsic (unpaced) ECG features that incorporated left or right AV timing to varying extents: PR interval (PR), end-of-p-wave-to-R-wave-peak-time-V6 (Pend-RWPTV6), start-of-p-wave-to-end-of-QRS (P-QRSend) as well as conventional QRSd. Pearson's test assessed the unadjusted correlation between intrinsic ECG intervals and BVP haemodynamic benefit(∆SBP). A multiparametric regression analysis model was constructed to account for confounders and interactions between different ECG features. Results 53 eligible patients were identified. 39 were male (73.6%), 31 had non-ischaemic aetiology (58.5%), mean LVEF was 27.6% ± SD 4.79 and mean LVEDD was 57.9± SD 9.4mm. Unadjusted correlations between intrinsic ECG features were not strong but favoured P-QRSend as a potentially predictive feature; R2 values: PR 0.28 (p=0.04), Pend-RWPTV6 0.19 (p=0.18), P-QRSend 0.27 (p=0.054), QRSd 0.045 (p=0.75). However, the multiparametric model revealed that utilising both PR interval and Pend-RWPTV6 in a predictive model showed better-adjusted correlation with BVP haemodynamic benefit (R2 0.54, p=0.04). Conclusion ECG features that incorporate either right (PR interval) or left (Pend-RWPTV6) AVD or both (P-QRSend) are superior to QRSd for predicting haemodynamic benefit from BVP in patients with HF and LBBB. This further reinforces the role of AVD shortening as a mechanism of benefit of BVP and suggests that selecting patients on the basis of AV timing may yield more overall benefit from CRT delivered by BVP or potentially conduction system pacing.ECG interval measurementCorrelation Graphs

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 (CRT) techniques is unreported. 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 1-year follow-up. 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 rebound, global longitudinal 'strain' (GLS), LBBB pattern, and mechanical dispersion). Baseline left ventricular ejection fraction (LVEF) was 27.5 ± 7%, and LV 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 and 49.3%) vs. 43% with BiVP (95% CI 39.6 and 45.8%), (P = 0.31), and LVESV was 80 mL (95% CI 55.3 and 104.5 mL) vs. 100 mL (95% CI 78.7 and 121.6 mL), respectively (P = 0.66). Longitudinal analysis showed a significant 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. CSP and BiVP provided similar dyssynchrony and 'strain' correction over time. Baseline global longitudinal 'strain' predicted ventricular remodelling at 12-month follow-up.