Measures Of Dyssynchrony Research Articles

Left fascicular pacing is not inferior to left bundle branch pacing in preserving ventricular mechanical synchrony and cardiac function

Abstract Background Left bundle branch pacing (LBBP) has emerged as a more physiological alternative to right ventricular pacing.However, capturing the pre-divisional LBB is not easy to accomplish. This study investigates if left fascicular pacing(LFP), defined as the capture of one of the LBB fascicles, could achieve comparable left ventricular (LV) mechanical synchronicity and cardiac function compared to LBBP. Methods Thirty-one patients with pacing indication for bradycardia were retrospectively collected: LBBP was successfully performed in 13 patients and 18 achieved LFP. All patients underwent echocardiography before and after implantation and at one-year follow-up. Left ventricular (LV) volumes, ejection fraction (EF) and global longitudinal strain (GLS) were measured. The lateral-septal (LW-SW) work difference was used as a measure of mechanical dyssynchrony. Septal flash, apical rocking and septal strain patterns were also assessed. Results Although LW-SW work difference were significantly higher in the LBBP groups than that in the LFP group at baseline(272±269 mmHg*% vs 25±279mmHg*%,p=0.02), a similar increase in LW-SW work difference was observed during follow-up(199±342 mmHg*% vs 371±384mmHg*%,p=0.21). In addition, both LFP and LBBP induced septal flash or apical rocking in some patients, and resulted in subtle changes in strain patterns, which were not significantly different between groups. At one year follow-up, LV ejection fraction (EF) remained almost unchanged in both LBBP and LFP patients(ΔLVEF: 1.1+3.1% vs -0.3±4.8%,p=0.35) , and global longitudinal strain (GLS) was slightly and equally decreased in LFP compared to LBBP (ΔLVGLS: -1.6±2.3% vs -1.2±2.7%,p=0.69). Conclusion LFP and LBBP did not differ in mechanical dyssynchrony or LV remodelling.

Assessment of ventricular electrical heterogeneity in left bundle branch pacing and left ventricular septal pacing by using various electrophysiological methods.

Left bundle branch area pacing (LBBAP) comprises pacing at the left ventricular septum (LVSP) or left bundle branch (LBBP). The aim of the present study was to investigate the differences in ventricular electrical heterogeneity between LVSP, LBBP, right ventricular pacing (RVP) and intrinsic conduction with different dyssynchrony measures using the ECG, vectorcardiograpy, ECG belt, and Ultrahigh frequency (UHF-)ECG. Thirty-seven patients with a pacemaker indication for bradycardia or cardiac resynchronization therapy underwent LBBAP implantation. ECG, vectorcardiogram, ECG belt and UHF-ECG signals were recorded during RVP, LVSP and LBBP, and intrinsic activation. QRS duration (QRSd) was measured from the ECG, QRS area was calculated from the vectorcardiogram, LV activation time (LVAT) and standard deviation of activation time (SDAT) from ECG belt and electrical dyssynchrony (e-DYS16) from UHF-ECG. Both LVSP and LBBP significantly reduced ventricular electrical heterogeneity as compared to underlying LBBB and RV pacing in terms of QRS area (p < .001), SDAT (p < .001), LVAT (p < .001) and e-DYS16 (p < .001). QRSd was only reduced as compared to RV pacing(p < .001). QRS area was similar during LBBP and normal intrinsic conduction, e-DYS16 was similar during LVSP and normal intrinsic conduction, whereas SDAT was similar for LVSP, LBBP and normal intrinsic conduction. For all these variables there was no significant difference between LVSP and LBBP. Both LVSP and LBBP resulted in a more synchronous LV activation than LBBB and RVP. Especially LBBP resulted in levels of LV synchrony comparable to normal intrinsic conduction.

The electrical substrate of vectorcardiographic QRS area in cardiac resynchronization therapy: insights from ECG-imaging

Abstract Background The QRS area shows promise as a vectorcardiographic (VCG) marker for electrical dyssynchrony in patient selection for cardiac resynchronization therapy (CRT). Nevertheless, little information is known about the underlying cardiac electrical substrate it may reflect. Purpose The aim of this study was to compare the VCG QRS area with measures of cardiac electrical dyssynchrony derived from electrocardiographic imaging (ECG-imaging). Methods QRS area from the synthesized VCG (Kors transformation matrix from the 12-lead ECG) was computed for 27 patients who underwent ECG-imaging (11 patients with no history of structural heart disease and 16 consecutive CRT patients). ECG-imaging measures for electrical dyssynchrony analyzed were: ventricular electrical uncoupling (VEU) computed as the difference between the average LV and RV activation times from ECG-imaging, standard deviation of activation times from the left ventricle (LV SDAT, and the maximal activation (Max AT). Pearson correlation analyses between VCG QRS area and ECG-imaging measures of dyssynchrony were carried out for the entire cohort and for patients with a wide-QRS only. Results ECG-imaging measures of dyssynchrony compared with QRS area in 11 patients with no structural heart disease with narrow-QRS (blue) and 16 candidates for CRT with heart failure (HF) and predominantly wide-QRS (LBBB [n=6], IVCD [n=8], RVpaced [n=1], and nQRS-HF [n=1]) are provided in Figure 1. QRS area were associated with all ECG-imaging measures of dyssynchrony. However, sub-analysis in only the wide-QRS patients revealed that QRS area exhibited the strongest association with VEU. Conclusion Vectorcardiographic QRS area is associated with cardiac electrical dyssynchrony on ECG-imaging, exhibiting a particularly strong association with ventricular electrical uncoupling.

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

Correlates of markers of dyssynchrony in patients with STEMI and multivessel disease: an analysis from the IAEA SPECT STEMI trial.

In this substudy of the Value of Gated-SPECT MPI for Ischemia- Guided PCI of non-culprit vessels in STEMI Patients with Multi vessel Disease after primary PCI trial after primary PCI we aim to assess if infarct size affects conventional measures of dyssynchrony at rest. Additionally, we explore if there is an independent correlation of stress-inducible ischemia with dyssynchrony at rest. The 48 patients with imaging at randomization were analyzed. Gated-single-photon emission computed tomography (SPECT) MPI with vasodilator stress and technetium-99m-labeled tracers was performed. The phase histogram bandwidth (HBW), phase SD, and entropy were obtained with the QGS software. Correlation between dyssynchrony at rest and infarct size and inducible ischemia was performed using the Spearman test. According to normal database limits dyssynchrony parameters at rest were abnormal for men. In women only HBW was abnormal. Correlation between the summed rest score with dyssynchrony was significant only for entropy ( P = 0.035). No correlation was observed for dyssynchrony and stress-induced ischemia. Entropy, as a measure of dyssynchrony, has potential in the assessment of patients with STEMI and multivessel disease after primary PCI. Smaller residual myocardial scars in PCI-reperfused patients with STEMI may contribute to the lack of correlation between dyssynchrony at rest and infarct size and stress-induced ischemia, respectively.

Impact of Neonatal Intervention on Left Ventricular Performance in Ebstein’s Anomaly and Tricuspid Valve Dysplasia

Severe neonatal Ebstein's anomaly (EA) and tricuspid valve dysplasia (TVD) are associated with high perinatal morbidity and mortality. The authors recently demonstrated left ventricular (LV) dysfunction and dyssynchrony to be prevalent in affected newborns and to contribute to poor outcomes. The aim of this study was to investigate the impact of patent ductus arteriosus (PDA) closure, spontaneous or surgical ligation, or right ventricular exclusion (Starnes procedure) on LV performance in neonatal EA and TVD. Neonates with EA or TVD encountered from 2004 to 2018 at three institutions were identified. Pre-and postoperative LV function was assessed using two-dimensional, Doppler-derived deformation (six-segment vector velocity imaging) and two measures of mechanical dyssynchrony (the SD of time to peak and global dyssynchrony index), and values were compared using paired t test analysis or the Wilcoxon rank sum test. Before the intervention, LV function was impaired in the PDA (n=18) and Starnes (n=6) groups and was similar between groups. After PDA closure, LV performance did not change. After the Starnes procedure, however, LV function, including synchrony, improved significantly: fractional area change from 45±5% to 58±8% (P=.003), global circumferential strain from -18.2±5.0% to -32.5±5.5% (P=.01), cardiac index from 1.9±0.3 to 3.9±1.5L/min/m2 (P=.05), and circumferential strain dyssynchrony (dyssynchrony index from 0.19±0.09 to 0.04±0.02 [P=.009] and SD of time to peak from 59.8±18.5 to 29.9±8.2 [P=.02]). The Starnes procedure results in early improvements in LV dysfunction and dyssynchrony, not observed after PDA closure in neonatal severe EA and TVD, which may benefit critically unwell neonates.

Left bundle branch pacing better preserves ventricular mechanical synchrony than right ventricular pacing: a two-centre study.

Left bundle branch pacing (LBBP) has been shown to better maintain electrical synchrony compared with right ventricular pacing (RVP), but little is known about its impact on mechanical synchrony. This study investigates whether LBBP better preserves left ventricular (LV) mechanical synchronicity and function compared with RVP. Sixty patients with pacing indication for bradycardia were included: LBBP (n = 31) and RVP (n = 29). Echocardiography was performed before and shortly after pacemaker implantation and at 1-year follow-up. The lateral wall-septal wall (LW-SW) work difference was used as a measure of mechanical dyssynchrony. Septal flash, apical rocking, and septal strain patterns were also assessed. At baseline, LW-SW work difference was small and similar in two groups. SW was markedly decreased, while LW work remained mostly unchanged in RVP, resulting in a larger LW-SW work difference compared with LBBP (1253 ± 687 mmHg·% vs. 439 ± 408 mmHg·%, P < 0.01) at last follow-up. In addition, RVP more often induced septal flash or apical rocking and resulted in more advanced strain patterns compared with LBBP. At 1 year follow-up, LV ejection fraction (EF) and global longitudinal strain (GLS) were more decreased in RVP compared with LBBP (ΔLVEF: -7.4 ± 7.0% vs. 0.3 ± 4.1%; ΔLVGLS: -4.8 ± 4.0% vs. -1.4 ± 2.5%, both P < 0.01). In addition, ΔLW-SW work difference was independently correlated with LV adverse remodelling (r = 0.42, P < 0.01) and LV dysfunction (ΔLVEF: r = -0.61, P < 0.01 and ΔLVGLS: r = -0.38, P = 0.02). LBBP causes less LV mechanical dyssynchrony than RVP as it preserves a more physiologic electrical conduction. As a consequence, LBBP appears to preserve LV function better than RVP.

Comparison of serum N-terminal pro-brain natriuretic peptide levels, conventional echocardiography, exercise parameters, and dyssynchrony measurements in Fontan patients.

Little data are available concerning the methods used in the long-term follow-up of Fontan patients. We analyzed the association between serum N-terminal pro-brain natriuretic peptide levels, conventional echocardiography findings, exercise parameters, and dyssynchrony measurements in patients who underwent Fontan surgery. This study included 28 patients who underwent Fontan surgery (mean age 12.8 ± 4.36 years) and 27 healthy controls (mean age 12.5 ± 3.76 years). Echocardiography examinations and exercise tests were performed in both groups. The systemic ventricle was examined via echocardiography, dyssynchrony measurement was performed, the systemic ventricular myocardial performance index was calculated, and serum N-terminal pro-brain natriuretic peptide levels were measured for all subjects. Lower cardiac output, stroke volume, maximal work, chronotropic index, maximal oxygen uptake, and higher N-terminal pro-brain natriuretic peptide levels were observed in the Fontan group than in the control group (p < 0.05). A negative correlation was found between physical exercise parameters and N-terminal pro-brain natriuretic peptide levels and dyssynchrony measurements. Measurements of exercise capacity, serum N-terminal pro-brain natriuretic peptide levels, and dyssynchrony measurement were more valuable than conventional methods for assessing patients' clinical and functional status. Dyssynchrony measurements provided better information about ventricular status than did conventional echocardiography studies. While patients' systolic function determined by conventional echocardiography was normal, dyssynchrony measurements showed the opposite result. The negative relationship between serum N-terminal pro-brain natriuretic peptide levels, dyssynchrony measurements, and exercise capacity suggests that these parameters should be investigated further in Fontan patients.

Diastolic dysfunction inhibits mechanical dyssynchrony in cardiac resynchronization therapy patients: a combined clinical-computational study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported by the European Union's Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie grant agreement No. 860745. Background In heart failure patients treated with cardiac resynchronization therapy (CRT), both the presence of typical left bundle branch block (LBBB) mechanics and a relatively preserved diastolic function are associated with better clinical outcomes. However, the mechanistic interaction between both phenomena has never been investigated. Aim In this combined clinical-computational study, we explored the potential interaction between LBBB mechanics and the severity of diastolic dysfunction. Methods In 219 CRT candidates, left atrial pressure (LAP) was retrospectively estimated using the multiparametric guideline approach, where patients were classified into elevated (eLAP, 49%), normal (nLAP, 40%) and undetermined (uLAP, 11%) LAP. nLAP and uLAP were together referred to as non-elevated LAP (non-eLAP, 51%). Typical LBBB mechanical behavior was quantified using two speckle-tracking echocardiography-based indices, being systolic stretch index (SSI) and global myocardial wasted work (GWW). Both indices positively correlate with the mechanical interaction between septal and lateral walls in typical LBBB as previously shown. CRT response was quantified as change of LV end-systolic volume (LVESV) at follow-up (12±6 months) relative to baseline. We used the CircAdapt computer model of the human heart and circulation to investigate the effects of eccentric remodeling and diastolic dysfunction (i.e. myocardial stiffening) on SSI and GWW in virtual hearts with a constant LBBB-like septal-to-lateral conduction delay, i.e. a 25-ms and 75-ms mechanical activation delay of the septum and LV free wall with respect to the right ventricular free wall. Results Before CRT, patients with non-eLAP showed more typical LBBB mechanical behavior (Fig. 1), as suggested by higher SSI and higher GWW compared to patients with non-eLAP (SSI: 4.6±3.2 vs 3.4±3.5 %, P=0.02, GWW: 368±131 vs 309±127 mmHg*%, P=0.03). At follow-up, patients with eLAP showed significantly less LV reverse remodeling compared to patients with non-eLAP (relative decrease of LVESV: 30±26% vs 46±34 P=0.001). Our simulations (Fig. 2) revealed that eccentric remodeling amplifies mechanical dyssynchrony, characterized by increased septal rebound stretch (second row) and increased wasted work (third and bottom rows), while LAP remained normal (top row). In contrast, increasing myocardial stiffness led to elevated LAP (top row), but a pronounced reduction of mechanical dyssynchrony (second, third and bottom rows). Conclusion The presented combination of clinical data and virtual patient simulations revealed that diastolic dysfunction, in particular myocardial stiffening, inhibits mechanical dyssynchrony induced by LBBB. In contrast, eccentric remodeling amplifies the LBBB mechanical substrate. These data further explain why baseline dyssynchrony measures like septal rebound stretch and wasted work are well associated with reverse remodeling and clinical outcome after CRT.

Feasibility of CMR Imaging during Biventricular Pacing: Comparison with Invasive Measurement as a Pathway towards a Novel Optimization Strategy.

This prospective pilot study assessed the feasibility of cardiovascular magnetic resonance (CMR) imaging during biventricular (BIV) pacing in patients with a CMR conditional cardiac resynchronization therapy defibrillator (CRT-D) and compared the results with invasive volume measurements. Ten CRT-D patients underwent CMR imaging prior to device implantation (baseline) and six weeks after device implantation, including CRT-on and CRT-off modes. Left ventricular (LV) function, volumes, and strain measurements of LV dyssynchrony and dyscoordination were assessed. Invasive pressure-volume measurements were performed, matching the CRT settings used during CMR. Post-implantation imaging enabled reliable cine assessment, but showed artefacts on late gadolinium enhancement images. After six weeks of CRT, significant reverse remodeling was observed, with a 22.7 ± 11% reduction in LV end-systolic volume during intrinsic rhythm (CRT-off). During CRT-on, the LV ejection fraction significantly improved from 27.4 ± 5.9% to 32.2 ± 8.7% (p < 0.01), and the strain assessment showed the abolition of the left bundle branch block contraction pattern. Invasively measured and CMR-assessed LV hemodynamics during BIV pacing were significantly associated. Post-CRT implantation CMR assessing acute LV pump function is feasible and provides important insights into the effects of BIV pacing on cardiac function and contraction patterns. LV assessment during CMR may constitute a future CRT optimization strategy.

Effects of Atrioventricular Optimization on Left Ventricular Reverse Remodeling With Cardiac Resynchronization Therapy: Results of the SMART-CRT Trial.

The role of atrioventricular optimization (AVO) to improve cardiac resynchronization therapy outcomes remains controversial. Previous post hoc analyses of a multicenter trial showed that measures of electrical dyssynchrony (right ventricular-left ventricular [LV] or QLV durations) are associated with patients who benefit from AVO. This was a global, multicenter, prospective, randomized trial of de novo cardiac resynchronization therapy implant patients with an right ventricular-LV duration ≥70 ms to determine whether AVO results in greater reverse remodeling. Patients were randomized 1:1 for either an AVO algorithm (SmartDelay) that determines atrioventricular delay and pacing chamber, biventricular or LV only, or a fixed atrioventricular delay of 120 ms with biventricular pacing. Paired echocardiograms performed at baseline and 6 months were evaluated. The primary end point was echocardiographic cardiac resynchronization therapy response, defined dichotomously as a >15% reduction in LV end-systolic volume. A total of 310 patients (n=120 women) were randomized and had completed 6 months of follow-up. The echocardiographic cardiac resynchronization therapy response rate did not statistically differ between the groups (SmartDelay, 74.8%; fixed, 67.7%; P=0.17). Analyses of prespecified secondary end points demonstrated significant improvements in the absolute (median: SmartDelay, -41.0 mL; fixed, -33.0 mL; P=0.01) and relative change in LV end-systolic volume (SmartDelay, -38.3%; fixed, -27.8%; P=0.03) for patients with SmartDelay optimization. Similar results were observed for the relative improvement in LV ejection fraction (SmartDelay, 46.7%; fixed, 32.1%; P=0.050); absolute improvement in LV ejection fraction trended to be higher with SmartDelay (P=0.06). Analysis of reverse remodeling parameters demonstrated that AVO via SmartDelay, relative to the nonoptimized fixed atrioventricular delay comparator group, improved absolute and relative changes in LV function in patients with longer right ventricular-LV duration. URL: https://www. gov; Unique identifier: NCT03089281.

PO-03-109 RIGHT VENTRICULAR PACING EXACERBATE ELECTRICAL DYSSYNCHRONY BEYOND INTRINSIC LEFT BUNDLE BRANCH BLOCK

Right ventricular (RV) pacing produces an iatrogenic form of left bundle branch block (LBBB). Intrinsic LBBB (I-LBBB) can cause adverse hemodynamic effects due to ventricular dyssynchrony, mainly in patients with heart failure and reduced ejection fraction (HFrEF). Although RV pacing is thought to create a similar activation pattern as LBBB, some studies suggest RV apical pacing can be harmful even in patients with I-LBBB. Currently, the mechanism responsible for this harm is not fully understood. We aimed to quantify and compare the degree of ventricular electrical dyssynchrony, as measured on the surface ECG, during I-LBBB, and RV pacing in patients with HFrEF (left ventricular EF ≤40%) and I-LBBB. Patients with HFrEF and prophylactic defibrillator therapy were prospectively recruited. For each patient, 3-minute, high-resolution (1024 Hz), digital 12-lead ECGs were recorded during I-LBBB rhythm and then RV pacing at 60 bpm or intrinsic heart rate (whichever was higher). High-resolution ECGs were analyzed to quantify abnormal intra-QRS peaks (QRSp) as a measure of ventricular electrical dyssynchrony. QRSp was defined as the mean number of peaks detected in the QRS complex that deviated from a smoothing-filtered version of the QRS. QRSp was automatically quantified for each precordial lead using validated custom software. Mean QRSp was defined as the average of QRSp in precordial leads. Thirty patients with HFrEF (66±9 yrs, 50% male, LVEF 30±8%) and I-LBBB (QRS duration [QRSd]: 172±22 ms) were included. Changes in mean QRSp between I-LBBB and RV apical pacing are shown in (Figure1A). RV pacing increased the mean QRSp in 27 patients (90%) as compared to I-LBBB, suggesting overall more electrical dyssynchrony during RV pacing. Changes in QRSd between I-LBBB and RV pacing are shown in (Figure 1B). RV pacing resulted in QRSd widening beyond I-LBBB QRSd in 18 patients (60%), while QRSd did not change in the remaining patients. During RV pacing (versus I-LBBB), Mean QRSp changed in more patients as compared to QRSd (27 patients versus 18 patients; p = 0.007). Although RV pacing produces an iatrogenic form of LBBB, ventricular electrical activation is more dyssynchronous during RV pacing as measured by changes in mean QRSp and QRSd. Compared to QRSd, mean QRSp is a more sensitive marker of change in ventricular electrical dyssynchrony between RV pacing and I-LBBB. Our results suggest RV pacing can exacerbate ventricular electrical dyssynchrony in those with I-LBBB.

Beta-blockers and mechanical dyssynchrony in heart failure assessed by radionuclide ventriculography

BackgroundRadionuclide ventriculography (RNVG) can be used to quantify mechanical dyssynchrony and may be a valuable adjunct in the assessment of heart failure with reduced ejection fraction (HFrEF). The study aims to investigate the effect of beta-blockers on mechanical dyssynchrony using novel RNVG phase parameters. MethodsA retrospective study was carried out in a group of 98 patients with HFrEF. LVEF and dyssynchrony were assessed pre and post beta-blockade. Dyssynchrony was assessed using synchrony, entropy, phase standard deviation, approximate entropy, and sample entropy from planar RNVG phase images. Subgroups split by ischemic etiology were also investigated. ResultsAn improvement in dyssynchrony and LVEF was measured six months post beta-blockade for both ischemic and non-ischemic groups. ConclusionsA significant improvement in dyssynchrony and LVEF was measured post beta-blockade using novel measures of dyssynchrony.

Left bundle branch pacing is superior in preserving ventricular mechanical synchrony and cardiac function than right ventricular pacing: a two-center experience

Abstract Background Left bundle branch pacing (LBBP) has emerged as a novel pacing modality. Although it has been proved to maintain electrical synchrony better than right ventricular pacing (RVP), little is known about the impact on mechanical synchrony. This study investigates if LBBP preserves mechanical synchrony and cardiac function better compared to conventional (CRVP) and leadless (LRVP) RVP. Methods Sixty-five patients with pacing indication for bradycardia were prospectively enrolled: Twenty-two were treated with LBBP, 23 with CRVP and 20 with LRVP. All patients underwent echocardiography before and after implantation and at one-year follow-up. Left ventricular (LV) volumes, ejection fraction (EF) and global longitudinal strain (GLS) were measured. Regional septal (SW) and lateral wall work (LW) was calculated as the average from the respective basal and mid-ventricular segments in the apical four-chamber and three-chamber view. The lateral-septal work difference (LSWD) was used as a measure of mechanical dyssynchrony. Results At baseline, the QRS duration and LSWD were similar in all three groups. During follow-up, the QRS duration increased least in LBBP compared to CRVP and LRVP (+28.1±18.3ms vs +58.2±31.4 and 47.1±26.1ms, both P&amp;lt;0.01). SW was markedly decreased in CRVP and LRVP while LW work remained unchanged, resulting in a large LSWD compared to LBBP (1308.4±732.9 mmHg*% and 1451.3±606.1 mmHg*% vs. 286.0±479.9mmHg*%, both P&amp;lt;0.001). During one year follow-up, LVEF and LV GLS decreased more in CRVP compared to LBBP (both P&amp;lt;0.05). Conclusion LBBP causes less LV dyssynchrony than CRVP and LRVP as it preserves a more physiologic conduction pattern. With this, LBBP appears to preserve LV function better than CRVP. CRVP and LRVP did not differ in mechanical dyssynchrony or LV remodelling. Funding Acknowledgement Type of funding sources: None.

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&amp;lt;0.01 and EDV; 236.2±31.8ml vs. 268.1±42.3ml, p&amp;lt;0.01). A significant improvement in LVEF was observed during BIV-pacing (32.2±8.7% vs. 27.4±5.9%, p&amp;lt;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&amp;lt;0.01 and SRSseptal; 2.1±2.6% vs. 6.0±3.0%, p&amp;lt;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)

Assessment of electrical dyssynchrony in cardiac resynchronization therapy: 12-lead electrocardiogram vs. 96-lead body surface map.

The standard deviation of activation time (SDAT) derived from body surface maps (BSMs) has been proposed as an optimal measure of electrical dyssynchrony in patients with cardiac resynchronization therapy (CRT). The goal of this study was two-fold: (i) to compare the values of SDAT in individual CRT patients with reconstructed myocardial metrics of depolarization heterogeneity using an inverse solution algorithm and (ii) to compare SDAT calculated from 96-lead BSM with a clinically easily applicable 12-lead electrocardiogram (ECG). Cardiac resynchronization therapy patients with sinus rhythm and left bundle branch block at baseline (n = 19, 58% males, age 60 ± 11 years, New York Heart Association Classes II and III, QRS 167 ± 16) were studied using a 96-lead BSM. The activation time (AT) was automatically detected for each ECG lead, and SDAT was calculated using either 96 leads or standard 12 leads. Standard deviation of activation time was assessed in sinus rhythm and during six different pacing modes, including atrial pacing, sequential left or right ventricular, and biventricular pacing. Changes in SDAT calculated both from BSM and from 12-lead ECG corresponded to changes in reconstructed myocardial ATs. A high degree of reliability was found between SDAT values obtained from 12-lead ECG and BSM for different pacing modes, and the intraclass correlation coefficient varied between 0.78 and 0.96 (P < 0.001). Standard deviation of activation time measurement from BSM correlated with reconstructed myocardial ATs, supporting its utility in the assessment of electrical dyssynchrony in CRT. Importantly, 12-lead ECG provided similar information as BSM. Further prospective studies are necessary to verify the clinical utility of SDAT from 12-lead ECG in larger patient cohorts, including those with ischaemic cardiomyopathy.

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.

Vectorcardiography-derived index allows a robust quantification of ventricular electrical synchrony

Alteration of muscle activation sequence is a key mechanism in heart failure with reduced ejection fraction. Successful cardiac resynchronization therapy (CRT), which has become standard therapy in these patients, is limited by the lack of precise dyssynchrony quantification. We implemented a computational pipeline that allows assessment of ventricular dyssynchrony by vectorcardiogram reconstruction from the patient’s electrocardiogram. We defined a ventricular dyssynchrony index as the distance between the voltage and speed time integrals of an individual observation and the linear fit of these variables obtained from a healthy population. The pipeline was tested in a 1914-patient population. The dyssynchrony index showed minimum values in heathy controls and maximum values in patients with left bundle branch block (LBBB) or with a pacemaker (PM). We established a critical dyssynchrony index value that discriminates electrical dyssynchronous patterns (LBBB and PM) from ventricular synchrony. In 10 patients with PM or CRT devices, dyssynchrony indexes above the critical value were associated with high time to peak strain standard deviation, an echocardiographic measure of mechanical dyssynchrony. Our index proves to be a promising tool to evaluate ventricular activation dyssynchrony, potentially enhancing the selection of candidates for CRT, device configuration during implantation, and post-implant optimization.

Measurement of electrical dyssynchrony in CRT patients: 12-lead ECG versus 96-lead body surface map

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant agency AZV, Ministry of Health of the Czech Republic Background Quantification of electrical dyssynchrony would allow optimization of lead placement and timing in patients with CRT. The standard deviation of activation times (SDAT) derived from body surface maps (BSM) was proposed as a measure of electrical dyssynchrony in CRT patients. However, SDAT derived from standard 12-lead ECG would be clinically preferred. Objective To evaluate and compare the SDAT measured from BSM and 12-lead ECG for assessment of electrical resynchronization in patients with implanted CRT. Methods CRT patients with sinus rhythm and LBBB at baseline (n=19, 58% males; age 60±11 years; NYHA class II-III; QRS 160±29) were studied using 96-lead BSM. For each ECG lead, the activation time was automatically detected and SDAT was calculated using either 96 leads or standard 12 leads. Electrical dyssynchrony was assessed during native sinus rhythm and 6 different pacing modes (see figure). Results SDAT calculated from BSM and 12-lead ECG decreased during optimal BiV pacing as compared to sinus rhythm by 26% (p=0.006) and 30% (p=0.003), respectively. The two other BiV setups showed also a decrease in SDAT values. Importantly, a high degree of reliability was found between values of SDAT obtained from12-lead ECG and 96-lead BSM for different pacing modes, the intraclass correlation coefficient was 0.8 to 0.9 (95% CI 0.7 - 0.9, p&amp;lt;0.001). Conclusion SDAT assessment is considered an important metric of electrical dyssynchrony in CRT. Our results suggest that 12-lead ECG provides similar results as BSM and thus, allows simplification of the measurement. Further prospective studies are necessary to verify the clinical utility of SDAT from 12-lead ECG.

Evolving concept of dyssynchrony and its utility.

The role of electromechanical dyssynchrony in heart failure gained prominence in literature with the results of trials of cardiac resynchronization therapy (CRT). CRT has shown to significantly decrease heart failure hospitalization and mortality in heart failure patients with dyssynchrony. Current guidelines recommend the use of electrical dyssynchrony based on a QRS > 150 ms and a left bundle branch block pattern on surface electrocardiogram to identify dyssynchrony in patients who will benefit from CRT implantation. However, predicting response to CRT remains a challenge with nearly one-third of patients gaining no benefit from the device. Multiple echocardiographic measures of mechanical dyssynchrony have been studied over the past two decade. However, trials where mechanical dyssynchrony used as an additional or lone criteria for CRT failed to show any benefit in the response to CRT. This shows that a deeper understanding of cardiac mechanics should be applied in the assessment of dyssynchrony. This review discusses the evolving role of imaging techniques in assessing cardiac dyssynchrony and their application in patients considered for device therapy.