Left Ventricular Dyssynchrony Research Articles

Acute hemodynamic effects of biventricular pacing studied during cardiovascular magnetic resonance imaging: the PICARIA Trial

Abstract Background Cardiac resynchronization therapy (CRT) is hampered by a relative high rate of non-response whereby device optimization could aid in improving benefit from CRT. Nonetheless, a non-invasive and reproducible clinical tool for device optimization is currently lacking. Recently introduced cardiovascular magnetic resonance (CMR) compatible CRT devices may allow for patient follow-up and device optimization as biventricular (BIV) pacing can be performed during the CMR exam. However, to date, CMR evaluation of acute pump function changes during CRT is limited. Purpose To assess the effects of BIV-pacing on change in left ventricular (LV) function and contraction patterns using CMR. Methods Ten patients were included in this prospective pilot study. All patients underwent CMR imaging (1.5T system) prior to device implantation (baseline), and 6 weeks after device implantation (CRT-on and CRT-off). LV end systolic volume (ESV), end diastolic volume (EDV), ejection fraction (LVEF), and measures of LV dyssynchrony and dyscoordination (septal systolic rebound stretch (SRSseptal)) were assessed on cine images. Results LV function and contraction patterns before and after device implantation are compared and displayed in the figure. LV ESV and EDV decreased in all patients during BIV-pacing as compared to intrinsic rhythm (CRT-off) (ESV; 161.4±36.3ml vs. 194.9±37.1ml, p<0.01 and EDV; 236.2±31.8ml vs. 268.1±42.3ml, p<0.01). A significant improvement in LVEF was observed during BIV-pacing (32.2±8.7% vs. 27.4±5.9%, p<0.01). Both, regional dyssynchrony and regional dyscoordination significantly improved during CRT-on compared to CRT-off (peakseptal-peaklateral; 57±46ms vs. 183±86ms, p<0.01 and SRSseptal; 2.1±2.6% vs. 6.0±3.0%, p<0.01). Conclusions Post-CRT implantation CMR assessing acute pump function changes to different CRT pacing settings is feasible and provides important insights in the effects of BIV-pacing on cardiac function and contraction patterns. LV assessment using CMR, potentially in combination with non-invasive pressure measurements, may constitute a future CRT optimization strategy. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Biotronik (Berlin, Germany)

Clinical impacts of scar reduction on gated myocardial perfusion SPECT after cardiac resynchronization therapy

BackgroundIt had not been reported that myocardial scar shown on gated myocardial perfusion SPECT (GMPS) might reduce after cardiac resynchronization therapy (CRT). In this study, we aim to investigate the clinical impact and characteristic of scar reduction (SR) after CRT. Methods and ResultsSixty-one heart failure patients following standard indication for CRT received twice GMPS as pre- and post-CRT evaluations. The patients with an absolute reduction of scar ≥ 10% after CRT were classified as the SR group while the rest were classified as the non-SR group. The SR group (N = 22, 36%) showed more improvement on LV function (∆LVEF: 18.1 ± 12.4 vs 9.4 ± 9.9 %, P = 0.007, ∆ESV: − 91.6 ± 52.6 vs − 38.1 ± 46.5 mL, P < 0.001) and dyssynchrony (ΔPSD: − 26.19 ± 18.42 vs − 5.8 ± 23.0°, P < 0.001, Δ BW: − 128.7 ± 82.8 vs − 25.2 ± 109.0°, P < 0.001) than non-SR group (N = 39, 64%). Multivariate logistic regression analysis showed baseline QRSd (95% CI 1.019-1.100, P = 0.006) and pre-CRT Reduced Wall Thickening (RWT) (95% CI 1.016-1.173, P = 0.028) were independent predictors for the development of SR. ConclusionMore than one third of patients showed SR after CRT who had more post-CRT improvement on LV function and dyssynchrony than those without SR. Wider QRSd and higher RWT before CRT were related to the development of SR after CRT.

Predictive values of left ventricular mechanical dyssynchrony for CRT response in heart failure patients with different pathophysiology

BackgroundCardiac resynchronization therapy (CRT) patients with different pathophysiology may influence mechanical dyssynchrony and get different ventricular resynchronization and clinical outcomes. MethodsNinety-two dilated cardiomyopathy (DCM) and fifty ischemic cardiomyopathy (ICM) patients with gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) were included in this retrospective study. Patients were classified based on the concordance between the left ventricular (LV) lead and the latest contraction or relaxation position. If the LV lead was located on or adjacent to both the latest contraction and relaxation position, the patient was categorized into the both match group; if the LV lead was located on or adjacent to the latest contraction or relaxation position, the patient was classified into the one match group; if the LV lead was located on or adjacent to neither the latest contraction nor relaxation position, the patient was categorized to the neither group. CRT response was defined as ≥5% improvement of LV ejection fraction at the 6-month follow-up. Variables with P < .05 in the univariate analysis were included in the stepwise multivariate model. ResultsDuring the follow-up period, 58.7% (54 of 92) for DCM patients and 54% (27 of 50) for ICM patients were CRT responders. The univariate analysis and stepwise multivariate analysis showed that QRS duration, systolic phase bandwidth (PBW), diastolic PBW, diastolic phase histogram standard deviation (PSD), and left ventricular mechanical dyssynchrony (LVMD) concordance were independent predictors of CRT response in DCM patients; diabetes mellitus and left ventricular end-systolic volume were significantly associated with CRT response in ICM patients. The intra-group comparison revealed that the CRT response rate was significantly different in the both match group of DCM (N = 18, 94%) and ICM (N = 24, 62%) patients (P = .016). However, there was no significant difference between DCM and ICM in the one match and neither group. For the inter-group comparison, Kruskal-Wallis H-test revealed that CRT response was significantly different in all the groups of DCM patients (P < .001), but not in ICM patients (P = .383). ConclusionsCompared with ICM patients, systolic PBW, diastolic PBW and PSD have better predictive and prognostic values for the CRT response in DCM patients. Placing the LV lead in or adjacent to the latest contraction and relaxation position can improve the clinical outcomes of DCM patients, but it does not apply to ICM patients.

The assessment of left ventricular mechanical dyssynchrony from gated 99mTc-tetrofosmin SPECT and gated 18F-FDG PET by QGS: a comparative study

BackgroundDue to partly conflicting studies, further research is warranted with the QGS software package, with regard to the performance of gated FDG PET phase analysis as compared to gated MPS as well as the establishment of possible cut-off values for FDG PET to define dyssynchrony. MethodsGated MPS and gated FDG PET datasets of 93 patients were analyzed with the QGS software. BW, Phase SD, and Entropy were calculated and compared between the methods. The performance of gated PET to identify dyssynchrony was measured against SPECT as reference standard. ROC analysis was performed to identify the best discriminator of dyssynchrony and to define cut-off values. ResultsBW and Phase SD differed significantly between the SPECT and PET. There was no significant difference in Entropy with a high linear correlation between methods.There was only moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony with a cut-off point at 62%. ConclusionGated MPS and gated FDG PET can assess LVMD. The methods cannot be used interchangeably. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. Further prospective research is necessary.

Impact of left bundle branch block in Takotsubo Syndrome.

BackgroundLeft bundle branch block (LBBB) causes left ventricular dyssynchrony, and its presence with concomitant left ventricular dysfunction has been proven to play a synergistic role, worsening ventricular function. Our study seeks to further explore the association between LBBB and various in-hospital outcomes in patients with takotsubo syndrome (TTS).MethodsThe national inpatient sample was queried from 2016 to 2019 to identify all admissions with a primary diagnosis of TTS. International classification of diseases, tenth revision codes were used to divide patients based on the presence or absence of LBBB. Multivariate regression analysis was performed to assess the effect of LBBB among all the pre-specified outcomes.ResultsA total of 26,615 admissions were included in the analysis. Admissions with LBBB were more likely to be older (72.2 vs. 66.2 years) and have a higher burden of comorbidities. The presence of a LBBB was associated with ventricular arrhythmias (OR = 1.97, 95% CI 1.08–3.61, p = 0.028) but not with sudden cardiac arrest (SCA), acute heart failure, cardiogenic shock, and all-cause intra-hospital mortality.ConclusionsIntraventricular dyssynchrony appears to play a significant role in ventricular arrhythmogenesis and SCA, as several trials have demonstrated that cardiac resynchronization therapy alone without defibrillator function reduces the rate of ventricular arrhythmias and SCA in patients with heart failure with systolic dysfunction and a widened QRS complex. The most likely mechanism of arrhythmia development in TTS is related to the elevated plasma levels of catecholamines and their proarrhythmic effects in the ventricular myocardium.

The Balance between the Left and Right Ventricular Deformation Evaluated by Speckle Tracking Echocardiography Is a Great Predictor of the Major Adverse Cardiac Event in Patients with Pulmonary Hypertension

Cardiovascular failure is one of the most relevant causes of death in pulmonary hypertension (PH). With progressive increases of right ventricular (RV) afterload in PH patients, both RV and left ventricular (LV) function impair and RV–LV dyssynchrony develop in parallel. We aimed to analyze the balance between the left and right ventricular deformation to assess the outcome of patients with pulmonary hypertension by means of speckle tracking echocardiography. In this prospective study, 54 patients with invasively diagnosed pulmonary hypertension, and 26 healthy volunteers were included and underwent a broad panel of noninvasive assessment including 2D-echocardiography, 2D speckle tracking, 6-minute walking test and BNP. Patients were followed up for 338.7 ± 131.1 (range 60 to 572) days. There were significant differences in |LVGLS/RVFLS-1| and |LASc/RASc-1| between PH patients and the control group. During the follow up, 13 patients experienced MACEs, which included 7 patients with cardiac death and 6 patients with re-admitted hospital due to right ventricular dysfunction. In the multivariate Cox model analysis, |LVGLS/RVFLS-1| remained independent prognosis of markers (HR = 4.03). Our study findings show that |LVGLS/RVFLS-1| is of high clinical and prognostic relevance in pulmonary hypertension patients and reveal the importance of the balance between the left and right ventricular deformation.

Left ventricular dyssynchrony as marker of early dysfunction in premature ventricular contraction-induced cardiomyopathy.

BackgroundStrain imaging has been suggested as a tool to detect early left ventricular (LV) dysfunction due to frequent premature ventricular contractions (PVCs) in patients with preserved LV ejection fraction (EF). However, the progression of intraventricular dyssynchrony (IVD), radial, and circumferential strain (RS, CS) in PVC-cardiomyopathy (CM) are unknown. The aim of this study was to elucidate the progression patterns of CS, IVD, and electro-mechanical latency (EML) in PVC-CM.Methods and resultsPacemakers were implanted in 20 canines to reproduce ventricular bigeminy at 200ms (PVCs n = 11) for 12 weeks and compared to a sham group (n = 9). We obtained echocardiograms at baseline, 4-, 8- and 12-weeks. RS and CS were obtained at the LV mid-cavitary level. IVD was defined as the time between the earliest and latest peak RS. EML was defined as the time between the onset of QRS and the earliest peak RS. LVEF (62 ± 5 to 42 ± 7%, p < 0.01), CS (–18 ± 3 to –12 ± 3, p < 0.01), and EML (219 ± 37 to 283 ± 46ms, p = 0.02) changed significantly in the PVC group. Peak CS (–18 ± 3 to –14 ± 4, p = 0.02) and IVD (49 ± 31 to 122 ± 103, p = 0.05) had a significant change at 4-weeks despite preserved LVEF (51 ± 5%). IVD normalized while EML increased at weeks 8 and 12.ConclusionOur findings consolidate the existing theory that changes in strain precede changes in LVEF in PVC-CM. While IVD becomes abnormal early in the development of PVC-CM, it pseudo-normalizes at advanced stages due to further increases in EML suggestive of cardiac contractility remodeling. These findings are consistent with recent published data where abnormal LV mechanics could be part of a substrate that can predispose to worse outcome in PVC-Cardiomyopathy.

Prognostic risk stratification based on left ventricular mechanical dyssynchrony in patients at low or intermediate risk of major cardiac events using the J-ACCESS risk model.

There have been no reports on prognostic prediction and risk stratification based on stress phase bandwidth (SPBW), or a left ventricular (LV) mechanical dyssynchrony index, in patients with known or suspected stable coronary artery disease (CAD) at low or intermediate risk of major cardiac events (MCEs) using the J-ACCESS risk model. We retrospectively investigated 4,996 consecutive patients with known or suspected CAD who underwent rest 201Tl and stress 99mTc-tetrofosmin electrocardiogram (ECG)-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) and followed up for 3 years to confirm their prognosis. MCE risk over 3 years was estimated using an equation based on that used in the J-ACCESS study. The composite endpoint was the onset of MCEs consisting of cardiac death, non-fatal myocardial infarction (MI), and severe heart failure requiring hospitalization. SPBW was calculated by phase analysis with the Heart Risk View-F software and its normal upper limit was set to 38°. Based on the estimated 3-year incidence of MCEs obtained from the J-ACCESS risk model, 4,123 of the 4,996 consecutive patients were classified as low (n = 2,653) or intermediate risk (n = 1,470) and they were analyzed for follow-up. During the follow-up, 153 patients experienced MCEs: cardiac death (n = 38), non-fatal MI (n = 45), and severe heart failure (n = 70). The results of the multivariate analysis showed age, estimated glomerular filtration rate (eGFR), stress LV ejection fraction, and stress SPBW to be independent predictors of MCEs. The actual 3-year MCE rate in patients at intermediate risk was significantly higher than in those at low risk (6.7% vs. 2.1%, P < 0.0001). However, the actual 3-year MCE rate in patients with abnormal SPBW (> 38°) was 4.0% and 9.2% in low- and intermediate-risk patients, respectively, which corresponded to intermediate and high risk. Kaplan-Meier analysis also showed significant risk stratification by normal SPBW values for both low- and intermediate-risk patients. LV mechanical dyssynchrony assessed with ECG-gated SPECT MPI is useful for risk stratification of known or suspected stable CAD patients at low or intermediate risk of MCEs and may help identify higher risk patients who could not be identified as being at risk based on J-ACCESS risk assessment.

Outcomes in patients with electrocardiographic left ventricular dyssynchrony following transcatheter aortic valve replacement

Left bundle branch block (LBBB) and atrioventricular (AV) conduction abnormalities requiring permanent pacemaker (PPM) implantation occur frequently following transcatheter aortic valve replacement (TAVR). The resultant left ventricular (LV) dyssynchrony may be associated with adverse clinical events. The purpose of this study was to assess the adverse outcomes associated with LV dyssynchrony due to high-burden right ventricular (RV) pacing or permanent LBBB following TAVR in patients with preserved left ventricular ejection fraction (LVEF). Consecutive TAVR patients at the University of Michigan from January 2012 to June 2017 were included. Pre-existing cardiac implantable electronic device, previous LBBB, LVEF <50%, or follow-up period <1 year were excluded. The primary outcome was all-cause mortality. Secondary outcomes included cardiomyopathy (defined as LVEF ≤45%), a composite endpoint of cardiomyopathy or all-cause mortality, and the change in LVEF at 1-year follow-up. A total of 362 patients were analyzed (mean age 77 years). LV dyssynchrony group (n = 91 [25.1%]) included 56 permanent LBBB patients, 12 permanent LBBB patients with PPM, and 23 non-LBBB patients with PPM and high-burden RV pacing. Remaining patients served as control (n = 271 [74.9%]). After adjusted analysis, LV dyssynchrony had significantly higher all-cause mortality (adjusted hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.07-4.37) and cardiomyopathy (adjusted HR 14.80; 95% CI 6.31-14.69). The LV dyssynchrony group had mean LVEF decline of 10.5% ± 10.2% compared to a small increase (0.5% ± 7.7%) in control. Among TAVR patients with preserved LVEF and normal AV conduction, development of postprocedural LV dyssynchrony secondary to high-burden RV pacing or permanent LBBB was associated with significantly higher risk of death and cardiomyopathy at 1-year follow-up.

Cardiac resynchronization therapy optimization in nonresponders and incomplete responders using electrical dyssynchrony mapping

Nonresponse to cardiac resynchronization therapy (CRT) occurs in ∼30%-50% of patients. There are no well-accepted clinical approaches for optimizing CRT in nonresponders. The purpose of this study was to demonstrate the effect of CRT optimization using electrical dyssynchrony mapping on left ventricular (LV) function, size, and dyssynchrony in selected patients with nonresponse/incomplete response to CRT. We studied 39 patients with underlying left bundle branch block or interventricular conduction delay who had an LV ejection fraction of ≤40% after receiving CRT and had significant electrical dyssynchrony. Electrical dyssynchrony was measured at multiple atrioventricular delays and interventricular delays. The QRS area between combinations of 9 anterior and 9 posterior electrograms (QRS area under the curve) was calculated, and cardiac resynchronization index (CRI) was defined as the percent change in QRS area under the curve compared to native conduction. Electrical dyssynchrony maps depicted CRI over the wide range of settings tested. Patients were programmed to an optimal device setting, and echocardiograms were recorded 5.9 ± 3.7 months postoptimization. CRI increased from 49.4% ± 24.0% to 90.8% ± 10.5%. CRT optimization significantly improved LV ejection fraction from 31.8% ± 4.7% to 36.3% ± 5.9% (P < .001) and LV end-systolic volume from 108.5 ± 37.6 to 98.0 ± 37.5 mL (P = .009). Speckle-tracking measures of LV strain significantly improved by 2.4% ± 4.5% (transverse; P = .002) and 1.0% ± 2.6% (longitudinal; P = .017). Aortic to pulmonic valve opening time, a measure of interventricular dyssynchrony, significantly (P = .040) decreased by 14.9 ± 39.4 ms. CRT optimization of electrical dyssynchrony using a novel electrical dyssynchrony mapping technology significantly improves LV systolic function, LV end-systolic volume, and mechanical dyssynchrony. This methodology offers a noninvasive, practical clinical approach to treating nonresponders and incomplete responders to CRT.

Premature Ventricular Contractions Are Presaged by a Mechanically Abnormal Sinus Beat.

Frequent premature ventricular contractions (PVCs) can lead to cardiomyopathy; it is unclear if there are abnormal myocardial mechanics operative in the PVC and non-PVC beats. The aim of this study was to investigate regional and global myocardial mechanics, including dyssynchrony, in patients with frequent PVCs. Fifty-six consecutive patients referred for PVC ablation were prospectively studied. During sinus rhythm (SR) and PVC beats, left ventricular (LV) global longitudinal strain (GLS), LV dyssynchrony (measured as the SD of time to peak GLS), and dyssynergy (measured as maximum regional strain minus minimum regional strain at aortic valve closure) were quantified using 2-dimensional strain echocardiography. GLS, dyssynchrony, and dyssynergy were compared in remote SR, pre-PVC SR, PVC, and post-PVC SR beats. In SR beats remote from the PVC, GLS was-17.3% ± 4%, dyssynchrony was 49 ± 14ms, and dyssynergy was22% ± 9%. Myocardial mechanics were significantly abnormal during PVCs compared with remote SR beats (GLS-7.7% ± 3% [P< 0.001], dyssynchrony 115 ± 37 milliseconds [P< 0.001], and dyssynergy 26% ± 10% [P<0.001]). There were significant mechanical abnormalities in the SR beat preceding the PVC, which demonstrated significantly lower LV strain (pre-PVC SR,-13% ± 4%; P< 0.001) and more dyssynchrony (pre-PVC SR, 63 ± 19 milliseconds; P< 0.001) compared with remote SR beats. Dyssynergy was significantly higher for pre-PVC SR and PVC beats compared with remote SR (pre-PVC SR, 25% ± 8% [P< 0.001]; PVC, 26% ± 10% [P< 0.001]). In patients with frequent PVCs, the SR beat preceding the PVC demonstrates significant mechanical abnormalities. This finding suggests that perturbations in cellular physiological processes such as excitation-contraction coupling may underlie the generation of frequent PVCs.

Longitudinal evaluation of diastolic dyssynchrony by SPECT gated myocardial perfusion imaging early after acute myocardial infarction and the relationship with left ventricular remodeling progression in a swine model

BackgroundLeft ventricular diastolic dyssynchrony (LVDD), a dyssynchronous relaxation pattern, has been known to develop after myocardial damage. We aimed to evaluate the dynamic changes in LVDD in the early stage of acute myocardial infarction (AMI) by phase analysis of 99mtechnetium methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography (SPECT) gated myocardial perfusion imaging (GMPI) and explore its relationship with the progression of left ventricular remodeling (LVR). MethodsThe left anterior descending coronary arteries of 16 Bama miniature swine were occluded with a balloon to build AMI models. Animals were imaged by SPECT GMPI before AMI and at 1 day, 1 week and 4 weeks after AMI, and quantitative analysis was performed to determine the extent of left ventricle (LV) perfusion defects, left ventricular systolic dyssynchrony (LVSD) and the LVDD parameters: phase histogram bandwidth (PBW) and phase standard deviation (PSD). Echocardiography was simultaneously applied to evaluate left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the LVDD parameters: Te-12-diff and Te-12-SD. Myocardial injury markers were measured, and 12-lead ECGs were performed. The degree of LVR progression was defined as ΔLVESV (%) = (LVESVAMI4weeks − LVESVAMI1day)/LVESVAMI1day. ResultsThirteen swine completed the study. LVDD parameters changed dynamically at different time points after AMI. LVDD occurred as early as 1 day after AMI, peaked at 1 week, and trended toward a partial recovery at 4 weeks. Phase analysis on SPECT GMPI showed a significant correlation with tissue Doppler imaging for the assessment of LVDD during the longitudinal evaluation (r = 0.569 to 0.787, both P <0.05). During the univariate and multivariate regression analyses, the LVDD parameters PBW and PSD as of 1 day after AMI were significantly associated with the progression of LVR, respectively (PBW, β = 0.004, 95% CI 0.001 to 0.007, P = 0.024; PSD, β = 0.008, 95% CI 0.000 to 0.017, P = 0.049). Adjusted smooth curve fitting and threshold effect analysis indicated PBW and PSD break-point values of 142° and 60.4°, respectively, to predict the progression of LVR after AMI. ConclusionsPhase analysis of SPECT GMPI can accurately and reliably characterize LVDD. LVDD occurred on the first day after AMI, reached its peak at 1 week, and partially recovered at 4 weeks after AMI. LVDD as evaluated by phase analysis of SPECT GMPI early after AMI was significantly associated with the progression of LVR. The early assessment of LVDD after AMI may provide helpful information for predicting the progression of LVR in the future.

Improved risk-stratification in heart failure patients with mid-range to severe abnormalities of QRS duration and systolic function using mechanical dyssynchrony assessed by myocardial perfusion-gated SPECT

BackgroundThe use of left ventricular mechanical dyssynchrony (LVMD), which has been reported to be responsible for unfavorable outcomes, might improve conventional risk-stratification by clinical indices including QRS duration (QRSd) and systolic dysfunction in patients with heart failure (HF). Methods and resultsFollowing measurements of 12-lead QRSd and left ventricular ejection fraction (LVEF), three-dimensional (3-D) LVMD was evaluated as a standard deviation (phase SD) of regional mechanical systolic phase angles by gated myocardial perfusion imaging in 829 HF patients. Patients were followed up for a mean period of 37 months with a primary endpoint of lethal cardiac events (CEs). In an overall multivariate Cox proportional hazards model, phase SDs were identified as significant prognostic determinants independently. The patients were divided into 4 groups by combining with the cut-off values of LVEF (35% and 50%) and QRSd (130 ms and 150 ms). The groups with lower LVEF and prolonged QRSd more frequently had CEs than did the other groups. Patient groups with LVEF < 35% and with 35% ≦ LVEF < 50% were differentiated into low-risk and high-risk categories by using an optimal phase SD cut-off value of both QRSd thresholds. Conclusions3-D LVMD can risk-stratify HF patients with mid-range as well as severe abnormalities of QRSd and systolic dysfunction.

A method using deep learning to discover new predictors from left-ventricular mechanical dyssynchrony for CRT response

BackgroundStudies have shown that the conventional parameters characterizing left ventricular mechanical dyssynchrony (LVMD) measured on gated SPECT myocardial perfusion imaging (MPI) have their own statistical limitations in predicting cardiac resynchronization therapy (CRT) response. The purpose of this study is to discover new predictors from the polarmaps of LVMD by deep learning to help select heart failure patients with a high likelihood of response to CRT. MethodsOne hundred and fifty-seven patients who underwent rest gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at 6 ± 1 month follow up. The autoencoder (AE) technique, an unsupervised deep learning method, was applied to the polarmaps of LVMD to extract new predictors characterizing LVMD. Pearson correlation analysis was used to explain the relationships between new predictors and existing clinical parameters. Patients from the IAEA VISION-CRT trial were used for an external validation. Heatmaps were used to interpret the AE-extracted feature. ResultsComplete data were obtained in 130 patients, and 68.5% of them were classified as CRT responders. After variable selection by feature importance ranking and correlation analysis, one AE-extracted LVMD predictor was included in the statistical analysis. This new AE-extracted LVMD predictor showed statistical significance in the univariate (OR 2.00, P = .026) and multivariate (OR 1.11, P = .021) analyses, respectively. Moreover, the new AE-extracted LVMD predictor not only had incremental value over PBW and significant clinical variables, including QRS duration and left ventricular end-systolic volume (AUC 0.74 vs 0.72, LH 7.33, P = .007), but also showed encouraging predictive value in the 165 patients from the IAEA VISION-CRT trial (P < .1). The heatmaps for calculation of the AE-extracted predictor showed higher weights on the anterior, lateral, and inferior myocardial walls, which are recommended as LV pacing sites in clinical practice. ConclusionsAE techniques have significant value in the discovery of new clinical predictors. The new AE-extracted LVMD predictor extracted from the baseline gated SPECT MPI has the potential to improve the prediction of CRT response.

Cardiac remodelling in association with left ventricular dyssynchrony and systolic dysfunction in patients with coronary artery disease.

In patients with coronary artery disease (CAD), ischaemic cardiomyopathy may result in progressive cardiac remodelling and left ventricular (LV) dysfunction. Myocardial perfusion imaging (MPI) can be used to quantify LV size and shape, mechanical dyssynchrony (LVMD) and ejection fraction (EF) as well as myocardial ischaemia and injury extents. We investigated the prevalence of LV remodelling (LVR) in patients with CAD and the relationship between LVR, LVMD and EF. Three hundred twenty-sixpatients with CAD were evaluated. The EF and end-diastolic volume (EDV) were measured using MPI. LVMD was assessed using phase analysis. LVR was characterised according to LV dilatation or increased shape indices (systolic shape index[SIES] anddiastolic shape index [SIED]). LVR were observed in 41% of CAD patients. EDV, SIES and SIED were larger in patients with LVMD or low EF. After adjustment for age, sex and infarct and ischaemia extents, phase histogram bandwidth correlated with EDV (r = 0.218) and SIES (r = 0.266) and EF correlated with EDV (r = -0.535), SIES (r = -0.554) and SIED (r = -0.217, p < 0.001 for all). LVR is frequently seen in patients with CAD and may be detected even before the development of symptomatic heart failure. A large LV volume and a more spherical-shaped LV were associated with LVMD and low EF, highlighting the close relationships between remodelling and systolic dyssynchrony and dysfunction. MPI is useful for assessing LVR by providing information about LV size and shape, which changes from an ellipsoid towards a spherical form in the development of ischaemic cardiomyopathy.

Comparison of left ventricle mechanical dyssynchrony parameters in ischemic and non-ischemic patients using 13N-NH3 PET/CT

Background-AimThe relationship between perfusion pattern and stress-induced changes in Left Ventricular Mechanical Dyssynchrony (LVMD) has been previously described with controversial results using stress-rest perfusion imaging studies. The aim of this study was to assess the relationship between perfusion pattern and stress-induced changes in LVMD usingo regadenoson/rest13N-NH3 PET/CT. MethodsThere were 74 patients who underwent stress-rest 13N-NH PET/CT from January 2014 to October 2018 excluding patients with left bundle branch block, ventricular pacing and myocardial necrosis. The patients were divided into those with reversible perfusion defects at stress (Ischemic group, n = 18) and patients without reversible perfusion defects (non-ischemic group, n = 56). The LVMD parameters included: phase standard deviation (PSD) and phase histogram bandwidth (PHB), after stress and at rest. The ΔPSD (post-stressPSD-restPSD) and ΔPHB (post-stressPHB—restPHB) were calculated to measure stress-induced changes in LVMD. ResultsThere were no significant differences in LVMD parameters between post-stress and at rest in both groups. The PSD post-stress, ΔPSD and PHB post-stress were significantly higher in the ischemic group. ConclusionsUsing a vasodilator as a stress, the PSD and PHB post-stress and ΔPSD were significantly higher in the ischemic patients than the non-ischemic group, while there were no significant differences in each cohort between stress and rest indices.

Reproducibility of global LV function and dyssynchrony parameters derived from phase analysis of gated myocardial perfusion SPECT: A multicenter comparison with core laboratory setting

BackgroundGated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population. MethodsThis is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab. Results276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland–Altman plots demonstrated good agreement. ConclusionsThe presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.

Prognostic value of left ventricular mechanical dyssynchrony induced by exercise stress in patients with normal myocardial perfusion single-photon emission computed tomography

BackgroundLeft ventricular mechanical dyssynchrony (LVMD) induced by exercise stress was reported to be clinically useful in detecting multivessel coronary artery diseases. The aim of this study was to compare the prognostic value of LVMD induced by pharmacological stress with that induced by exercise stress. MethodsWe retrospectively examined 918 consecutive patients who underwent exercise (N = 310) or pharmacological stress (N = 608) 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) with normal myocardial perfusion. LVMD was evaluated by phase analysis as the indices of phase bandwidth and phase standard deviation (PSD). ResultsDuring the follow-up period (2.2 ± 1.9 years), 74 major cardiac events (MCEs) occurred (7 cases of cardiac death, 17 cases of heart failure, and 50 cases of coronary intervention). In global patients, the indices of LVMD on rest images were significantly greater in patients with MCEs (bandwidth (°): 51 ± 31 vs 37 ± 21, P = .001, PSD: 14 ± 9 vs 10 ± 6, P = .001). The exercise stress bandwidth was significantly higher in patients with MCEs (62 ± 37° vs 42 ± 21°, P = .026), as was the pharmacological stress bandwidth (57 ± 35° vs 43 ± 24°, P = .006). Multivariate analysis demonstrated the exercise stress bandwidth to be an independent predictor of MCEs (HR 1.017, CI 1.003 to 1.032, P = .019), but the pharmacological stress bandwidth had no influence on MCEs. ConclusionsLVMD induced by exercise stress was an independent predictor of MCEs in patients with normal perfusion SPECT, whereas that induced by pharmacological stress had no association with further events.

Evaluation of left ventricular dyssynchrony by ultra-high-frequency ECG in patients with non-LBBB conduction disorder treated with cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction LBBB is a reliable left ventricular (LV) electrical dyssynchrony indicator. Patients with RBBB/IVCD are a heterogeneous group, where even with "larger" QRS complex expansion, LV dyssynchrony may not be present. Ultra-high-frequency (UHF) 14-lead ECG is a non-invasive method based on signal averaging that allows better assessment of local electrical activation of the ventricles than standard ECG. Our study aims to test the hypothesis of the usefulness of UHF ECG to select non-LBBB patients for cardiac resynchronization therapy (CRT) based on evidence of electrical dyssynchrony. Methods Using UHF ECG we analysed patients who underwent CRT implantation. The groups of patients with RBBB, IVCD, and LBBB were compared and the presence of electrical dyssynchrony (e-DYS) as a parameter of global ventricular activation, and delayed activation of the left ventricular lateral wall (LVLWd) as a marker of LV intravenricular dyssynchrony was assessed. Results UHF ECG was recorded in 49 patients treated with CRT. IVCD patients had lower e-DYS compared to LBBB patients (26±17 ms vs. 86±20 ms; p&amp;lt;0.0001) and lower LVLWd (26±16 ms vs. 83±22 ms; p&amp;lt;0.0001). In RBBB patients, e-DYS was -52±22 ms, corresponding to right ventricular delay. Delayed left ventricular free wall activation ("RBBB masking LBBB" activation pattern) was not found in any RBBB patient. Conclusion UHF ECG appears to be a promising tool to detect LV electrical dyssynchrony in non-LBBB candidates for cardiac resynchronization therapy. Delayed left ventricular free wall activation was not found in any RBBB patient. Our findings are consistent with the lack of effect of CRT in this group of patients.

Left bundle branch pacing preserves ventricular mechanical synchrony better than right ventricular pacing-a two-center study

Abstract Funding Acknowledgements Type of funding sources: None. Background Left bundle branch pacing (LBBP) has emerged as a novel pacing method. We sought to evaluate left ventricular (LV) mechanical synchrony under permanent LBBP and compare it with conventional and leadless right ventricular pacing (CRVP, LRVP). Methods Sixty-four patients with pacing indication for bradycardia were prospectively enrolled. Twenty-two patients received LBBP in the basal ventricular septum. Twenty-three patients received CRVP and 19 LRVP. All patients underwent echocardiography before and after device implantation. Myocardial work was estimated by pressure-strain analysis. Regional work in the septum (SEP) and lateral wall (LW) was calculated as the average from the respective basal and mid-ventricular segments in the apical four-chamber and three-chamber view. The absolute difference between work in LW and SEP (LW-S-work difference) was used as a measure of asymmetry in workload. Results Baseline characteristics were similar among the three groups. The electrocardiogram during LBBP showed a right bundle branch block pattern; during CRVP and LRVP a left bundle branch block pattern. The paced QRS duration was 114.27±9.9 ms in the LBBP group, significantly shorter than that in the CRVP and LRVP groups (153.9±25.26 ms and 159.1±13.99ms, respectively, both p&amp;lt;0.001). The SEP work decreased in all groups during ventricular pacing (all P&amp;lt;0.05), while the LW work remained similar. The paced LW-S work difference and work difference change between pacing on and off were more significant in the CRVP (1012.9±566.0mmHg*%) and LRVP group (1066.1±472.6mmHg*%) than the LBBP group (260.5±239.8mmHg*%, both P&amp;lt;0.001). In addition, LW-S work difference during ventricular pacing and work difference change between pacing and baseline were comparable in CRVP and LRVP group. Conclusion LBBP causes less LV dyssynchrony than CRVP and LRVP as it preserves a more physiologic conduction pattern. CRVP and LRVP did not differ in this respect. Further studies need to prove that LBBP has advantages over RVP with regards to preservation of LV synchrony and contractility.