Ventricular Activation Sequence Research Articles

Ventricular activation pattern of left ventricular septal pacing in a canine model.

Left bundle branch pacing (LBBP) is a feasible and effective physiological pacing technique. The QRS morphology of left ventricular septal pacing (LVSP) is similar to that of LBBP. The ventricular activation pattern of LBBP is well-known, whereas the pattern of LVSP still needs further investigation. The present study aimed to determine ventricular activation pattern difference between LVSP and LBBP in a canine model. All six canines underwent successful LBBP and LVSP through trans-ventricular septum using intracardiac echocardiography and intracardiac electrogram. Their hearts were isolated and stained with Lugol's iodine to determine the position of the pacing lead. The activation sequences of the left ventricular myocardium and His-Purkinje system were recorded by placing multiple electrode catheters. First, the left His-Purkinje system in LVSP was activated simultaneously from apical and basal regions to the left ventricular middle septal region, whereas the left ventricular septal myocardium was activated from the apical to basal region. The left His-Purkinje system activation in LBBP occurred in the direction of the apex from the pacing lead, but the left ventricular septal myocardium was activated in the apical to basal direction. Furthermore, the left intraventricular electrical synchrony was similar between LVSP and LBBP as determined by mapping the left ventricular septal to free wall activation time (46.7 ± 1.8ms vs. 45.0 ± 1.4ms, p = 0.11). The ventricular activation sequence of LVSP was similar to LBBP. LVSP can capture LBB due to the wide distribution of LBB. These findings suggest a rationale for clinical application of LVSP.

Abstract Mo058: Cellular and Subcellular Ventricular Localization of the Fast Transient Outward Potassium Channels in the Murine Heart

Introduction: Cardiac fast transient outward potassium currents (I to,f ) are formed by KCND2 (Kv4.2) and KCND3 (Kv4.3) channels in mice and primarily KCND3 in humans. Rapid I to,f activation induces early phase 1 repolarization of action potentials (APs), which has been linked strongly to the modulation of excitation-contraction coupling (ECC). Consequently, variations in I to,f densities underlie regional differences in ventricular APs and myocardial contractile properties. To investigate further the role of I to,f in cardiac function, we created mice with fluorescently labelled KCND2 (KCND2-GFP) and KCND3 (KCND3-RFP). Methods and Results: The expression patterns of I to,f in the ventricles were examined using frozen histological sections. Remarkably, KCND2 and KCND3 were preferentially localized to the intercalated discs (ICDs) by >50%, with expression also in lateral membranes and within t-tubules (i.e. a sarcomeric pattern), yet KCND3 showed a greater t-tubule localization. Additionally, KCND2 expression was, as expected, greater ( P <0.048, two-way ANOVA; n=3) in the epi- versus endo-myocardium of both ventricles, whereas KCND3 lacked ( P >0.172; n=3) a distinct gradient. Moreover, KCND2 expression inversely correlated with the temporal sequence of ventricular activation, whereby the posterobasal regions that depolarize last show elevated Kv4.2 ( P =0.009, unpaired t-test; n=3) compared to the anterolateral endocardium activated first. In contrast, Kv4.3 demonstrates a relatively uniform expression. Conclusions: The regional expression patterns of I to,f in ventricles and preferential I to,f expression in t-tubules support previous studies suggesting that I to,f controls the regional variations in the timing and amplitude of ECC. We are currently exploring the possible differential actions of KCND2 versus KCND3 in ECC and the potential consequence of ICD localization of I to,f on ephaptic coupling.

Precordial activation sequences from low frequency analysis in left bundle branch block patients: left bundle branch area pacing vs right ventricular pacing

Abstract Introduction Left bundle branch area pacing (LBBAP) provides a more synchronous and physiological ventricular activation than conventional right ventricular pacing (RVP) in LBBB patients. QRS duration (QRSd) is the standard measurement for assessing depolarization synchrony, but it only provides information about the activation time and not about the activation sequence. Purpose Our aim is to assess the activation sequence by precordial activation delay (pAD) using a low-frequency (LF) ECG method comparing baseline and paced ECG in LBBAP and RVP patients. Methods Twelve-lead ECGs recordings were acquired from 29 patients with LBBB (16 LBBAP and 13 RVP) after 24 hours of sequential LBBAP or RVP. LF-ECG was employed for QRS-complex analysis. The activation time for each lead was computed and an activation sequence constructed by linking them. pAD was calculated as the time between the first and the last lead activation. pAD provides information about both, the delay in ventricular depolarization as indicated by its magnitude, and the depolarization direction (as it can take a positive or negative value indicating a left or right ventricle delay, respectively). Results At baseline, both groups (LBBAP and RVP) showed the latest activation at V5-V6, supported by positive median pAD values with no statistically significant differences between both groups (50 (21, 65) vs. 54 (17, 67) ms, p=0.93). LBBAP reduced V6 delay and pAD values compared to the baseline QRS (basal: 50 (21, 65) vs. paced: 2 (-18, 25) ms, p<0.001) while RVP did not exhibit any difference (basal: 54 (17, 67) vs. paced: 36 (19, 53) ms, p=0.33). LBBAP provided lower pAD values when compared to RVP (2 (-18, 25) vs. 36 (19, 53) ms, p<0.01). Conclusions pAD measured using a LF-ECG analysis is a feasible method to evaluate depolarization synchrony and provides complementary information to QRSd. In contrast to RVP, LBBAP generates a physiological ventricular activation sequence in patients with LBBB.Baseline patients characteristicsVentricular activation sequences and pAD

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 <0.0001) and interventricular e-DYS for 24 ± 5 ms (p <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<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

Activation pattern of the coronary sinus facilitates the differentiation for ventricular outflow tract arrhythmias.

The accuracy of surface ECG algorithms for predicting the origin of outflow tract ventricular arrhythmias (OT-VAs) might be questioned. Intracardiac electrograms recorded at anatomic landmarks could provide new predictive insights. We aim to evaluate the efficacy of a novel criterion utilizing the activation pattern of the coronary sinus (CS) in localizing OT-VAs, including VAs originating from the right ventricular outflow tract (RVOT), endocardial left ventricular outflow tract (Endo-LVOT), and epicardial left ventricular outflow tract (Epi-LVOT). We measured the ventricular activation time of the mitral annulus (MA) from the onset of the earliest QRS complex of VAs to the initial deflection over the isoelectric line at local signals, namely the QRS-MA interval. The activation at 3 and 12 o'clock of the MA was recorded as the QRS-MA3 and QRS-MA12 intervals, respectively. Their predictive values were compared to previous ECG algorithms. A total of 68 patients with OT-VAs were enrolled (51 for development and 17 for validation). From early to late, the ventricular activation sequences at MA12 were as follows: Epi-LVOT, Endo-LVOT, and RVOT. In LBBB morphology OT-VAs, the QRS-MA12 interval was significantly earlier for LVOT origins than RVOT origins. In the combined cohort of development and validation cohort, a cut-off value of ≤10 ms predicted the LVOT origin with a sensitivity of 100% and specificity of 78%. The QRS-MA12 interval ≤ -24 ms additionally predicted epicardial LVOT sites of origin. The QRS-MA interval could accurately differentiate the OT-VAs localization.

Concepts of Cardiac Dyssynchrony and Dynamic Approach.

Cardiac conduction involves electrical activity from one myocyte to another, creating coordinated contractions in each. Disruptions in the conducting system, such as left bundle branch block (LBBB), can result in premature activation of specific regions of the heart, leading to heart failure and increased morbidity and mortality. Structural alterations in T-tubules and the sarcoplasmic reticulum can lead to dyssynchrony, a condition that can be treated by cardiac resynchronization therapy (CRT), which stands as a cornerstone in this pathology. The heterogeneity in patient responses underscored the necessity of improving the diagnostic approach. Vectocardiography, ultra-high-frequency ECG, 3D echocardiography, and electrocardiographic imaging seem to offer advanced precision in identifying optimal candidates for CRT in addition to the classic diagnostic methods. The advent of His bundle pacing and left bundle branch pacing further refined the approach in the treatment of dyssynchrony, offering more physiological pacing modalities that promise enhanced outcomes by maintaining or restoring the natural sequence of ventricular activation. HOT-CRT emerges as a pivotal innovation combining the benefits of CRT with the precision of His bundle or left bundle branch area pacing to optimize cardiac function in a subset of patients where traditional CRT might fall short.

Digital twinning of the human ventricular activation sequence to Clinical 12-lead ECGs and magnetic resonance imaging using realistic Purkinje networks for in silico clinical trials

Cardiac in silico clinical trials can virtually assess the safety and efficacy of therapies using human-based modelling and simulation. These technologies can provide mechanistic explanations for clinically observed pathological behaviour. Designing virtual cohorts for in silico trials requires exploiting clinical data to capture the physiological variability in the human population. The clinical characterisation of ventricular activation and the Purkinje network is challenging, especially non-invasively. Our study aims to present a novel digital twinning pipeline that can efficiently generate and integrate Purkinje networks into human multiscale biventricular models based on subject-specific clinical 12-lead electrocardiogram and magnetic resonance recordings. Essential novel features of the pipeline are the human-based Purkinje network generation method, personalisation considering ECG R wave progression as well as QRS morphology, and translation from reduced-order Eikonal models to equivalent biophysically-detailed monodomain ones. We demonstrate ECG simulations in line with clinical data with clinical image-based multiscale models with Purkinje in four control subjects and two hypertrophic cardiomyopathy patients (simulated and clinical QRS complexes with Pearson's correlation coefficients > 0.7). Our methods also considered possible differences in the density of Purkinje myocardial junctions in the Eikonal-based inference as regional conduction velocities. These differences translated into regional coupling effects between Purkinje and myocardial models in the monodomain formulation. In summary, we demonstrate a digital twin pipeline enabling simulations yielding clinically consistent ECGs with clinical CMR image-based biventricular multiscale models, including personalised Purkinje in healthy and cardiac disease conditions.

Abstract 11698: Torsades de Aortique Pustule: A Case of Aortic Abscess Leading to 2:1 AV Block and Torsades de Pointes

Introduction: Endocarditis of the aortic valve has a propensity to create A-V conduction disturbances in up to 10% of cases. Torsades de pointes (TdP) is polymorphic ventricular tachycardia in the setting of prolonged QT interval and bradycardia that is typically preceded by a short-long-short sequence of ventricular activation. We present a case of infective endocarditis with aortic root abscess leading to acute 2:1 A-V conduction and culminating in TdP. Case Summary: A 30-year-old male with history of IV drug use and bioprosthetic aortic valve repair presented with pleuritic chest pain, nausea and vomiting. He was febrile and tachycardic with a systolic murmur at the right upper sternal border. Initial electrocardiogram showed sinus rhythm with no conduction abnormalities. A Transthoracic echocardiography showed a large aortic valve vegetation with an abscess cavity. E Blood cultures grew Streptococcus oralis. Two days later, he developed VT/VF arrest requiring external defibrillation. Preceding ECGs and telemetry showed sinus tachycardia with new left bundle branch block and prolonged QTc. B This progressed to 2:1 AV block C with abrupt transition to relative bradycardia and ventricular ectopy leading to short-long-short ventricular intervals and subsequent TdP. D A temporary pacemaker was placed, and he underwent an aortic root reconstruction with valve replacement. Discussion: While both the etiology of TdP and aortic root abscesses leading to conduction system disease are well described, this case exhibits the real time progression of aortic abscess involvement. The patient presented with a normal QRS morphology. During hospitalization, he developed new LBBB, and the appropriate sinus tachycardia then deteriorated into 2:1 AV conduction leading to relative bradycardia. This abrupt transition with QTc prolongation sets up the nidus for ventricular ectopy (due to early after depolarizations) with salvos of short-long-short sequences causing TdP.

Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats.

Transmural action potential duration differences and transmural conduction gradients aid the synchronization of left ventricular repolarization, reducing vulnerability to transmural reentry and arrhythmias. A high-fat diet and the associated accumulation of pericardial adipose tissue are linked with conduction slowing and greater arrhythmia vulnerability. It is predicted that cardiac adiposity may more readily influence epicardial conduction (versus endocardial) and disrupt normal transmural activation/repolarization gradients. The aim of this investigation was to determine whether transmural conduction gradients are modified in a rat model of pericardial adiposity. Adult Sprague-Dawley rats were fed control/high-fat diets for 15 wk. Left ventricular 300 µm tangential slices were generated from the endocardium to the epicardium, and conduction was mapped using microelectrode arrays. Slices were then histologically processed to assess fibrosis and cardiomyocyte lipid status. Conduction velocity was significantly greater in epicardial versus endocardial slices in control rats, supporting the concept of a transmural conduction gradient. High-fat diet feeding increased pericardial adiposity and abolished the transmural conduction gradient. Slowed epicardial conduction in epicardial slices strongly correlated with an increase in cardiomyocyte lipid content, but not fibrosis. The positive transmural conduction gradient reported here represents a physiological property of the ventricular activation sequence that likely protects against reentry. The absence of this gradient, secondary to conduction slowing and cardiomyocyte lipid accumulation, specifically in the epicardium, indicates a novel mechanism by which pericardial adiposity may exacerbate ventricular arrhythmias.

Left ventricular endocardial activation maps during right ventricular pacing in pediatric patients.

Cardiac pacing from right ventricular (RV) sites may cause electromechanical ventricular dyssynchrony. Invasive and noninvasive mapping studies showed left ventricular (LV) activation sequence in adults. Aim of this study was to seek out the LV endocardial activation (LVEA) in pediatric patients who underwent RV pacing. Single-center, prospective study conducted on pediatric patients who underwent left sided catheter ablation of accessory pathways with the Carto Univu mapping system. After successful ablation procedures, LVEA was recorded by the ablation catheter during sinus rhythm (SR) and during para-hisian (PHP), midseptum (MSP), and apical (RVAP) pacing. Seventeen patients, 13 males, aged 12 (10-15) years, registered LV activation maps and times (LVAT). SR showed significantly shorter LVAT than during pacing. LVAT of PHP was shorter than MSP, while there were not significant differences among PHP and MSP versus RVAP. In SR initial LV endocardial activation occurred in two midseptum sites, inferior-posterior and superior-anterior. During PHP, initial activation occurred at parahisian basal septum, rapidly followed by midseptum as in SR. During MSP and RVAP initial activation occurred at midseptum and apex, respectively. From all initial sites, the excitation spreads toward the base of the lateral LV free wall. A mild linear correlation was found between QRS duration and LVAT for MSP and for PHP. In pediatric patients LVEA maps during RV pacing showed that the shortest LVAT was obtained with PHP. The LV activation pattern seemed similar in sinus rhythm, PHP and MSP, from midseptum to LV lateral base.

Estimation of left ventricular activation sequence in patients with heart failure using two-dimensional speckle tracking echocardiography

Evaluation of longitudinal strain (LS) from two-dimensional echocardiography is useful for global and regional left ventricular (LV) dysfunction assessment. We determined whether the LS reflects contraction process in patients with asynchronous LV activation. We studied 144 patients with an ejection fraction ≤ 35%, who had left bundle branch block (LBBB, n = 42), right ventricular apical (RVA) pacing (n = 34), LV basal- or mid-lateral pacing (n = 23), and no conduction block (Narrow-QRS, n = 45). LS distribution maps were constructed using 3 standard apical views. The times from the QRS onset-to-early systolic positive peak (Q-EPpeak) and late systolic negative peak (Q-LNpeak) were measured to determine the beginning and end of contractions in each segment. Negative strain in LBBB initially appeared in the septum and basal-lateral contracted late. In RVA and LV pacing, the contracted area enlarged centrifugally from the pacing site. Narrow-QRS showed few regional differences in strain during the systolic period. The Q-EPpeak and Q-LNpeak exhibited similar sequences characterized by septum to basal-lateral via the apical regions in LBBB, apical to basal regions in RVA pacing, and lateral to a relatively large delayed contracted area between the apical- and basal-septum in LV pacing. Differences in Q-LNpeaks between the apical and basal segments in delayed contracted wall were 107 ± 30 ms in LBBB, 133 ± 46 ms in RVA pacing, and 37 ± 20 ms in LV pacing (p < 0.05, between QRS groups). Specific LV contraction processes were demonstrated by evaluating the LS distribution and time-to-peak strain. These evaluations may have potential to estimate the activation sequence in patients with asynchronous LV activation.

CineECG illustrating the ventricular activation sequence in progressive AV-junctional conduction block

We present the use of CineECG in visualizing abnormal ventricular activation in a case of a complex conduction disorder. CineECG combines the standard 12‑lead surface ECG with a 3D anatomical model of the heart. It projects the location and direction of the average ventricular activation and recovery on the heart model over time. In this case, CineECG was able to visualize the different type of fascicular conduction in this progressive conduction block. This novel imaging technique was able to provide additional insight in this complex case, and might be of use in other complex ECG patterns.

A computational model of rabbit geometry and ECG: Optimizing ventricular activation sequence and APD distribution.

Computational modeling of electrophysiological properties of the rabbit heart is a commonly used way to enhance and/or complement findings from classic lab work on single cell or tissue levels. Yet, thus far, there was no possibility to extend the scope to include the resulting body surface potentials as a way of validation or to investigate the effect of certain pathologies. Based on CT imaging, we developed the first openly available computational geometrical model not only of the whole heart but also the complete torso of the rabbit. Additionally, we fabricated a 32-lead ECG-vest to record body surface potential signals of the aforementioned rabbit. Based on the developed geometrical model and the measured signals, we then optimized the activation sequence of the ventricles, recreating the functionality of the Purkinje network, and we investigated different apico-basal and transmural gradients in action potential duration. Optimization of the activation sequence resulted in an average root mean square error between measured and simulated signal of 0.074 mV/ms for all leads. The best-fit T-Wave, compared to measured data (0.038 mV/ms), resulted from incorporating an action potential duration gradient from base to apex with a respective shortening of 20 ms and a transmural gradient with a shortening of 15 ms from endocardium to epicardium. By making our model and measured data openly available, we hope to give other researchers the opportunity to verify their research, as well as to create the possibility to investigate the impact of electrophysiological alterations on body surface signals for translational research.

PO-640-05 GLOBAL ELECTRICAL HETEROGENEITY AND CARDIAC MEMORY CHANGES DISTINGUISH ACUTE FROM CHRONIC LEFT BUNDLE BRANCH BLOCK

Time-dependent electrical remodeling due to ventricular activation sequence changes (cardiac memory), measured as peak QRS/T ratio, has been used to differentiate acute and chronic LBBB. The association between cardiac memory and the spatial ventricular gradient (SVG), a measure of myocardial global electrical heterogeneity (GEH), is unknown.

Ventricular Dyssynchrony and Pacing-induced Cardiomyopathy in Patients with Pacemakers, the Utility of Ultra-high-frequency ECG and Other Dyssynchrony Assessment Tools.

The majority of patients tolerate right ventricular pacing well; however, some patients manifest signs of heart failure after pacemaker implantation and develop pacing-induced cardiomyopathy. This is a consequence of non-physiological ventricular activation bypassing the conduction system. Ventricular dyssynchrony was identified as one of the main factors responsible for pacing-induced cardiomyopathy development. Currently, methods that would allow rapid and reliable ventricular dyssynchrony assessment, ideally during the implant procedure, are lacking. Paced QRS duration is an imperfect marker of dyssynchrony, and methods based on body surface mapping, electrocardiographic imaging or echocardiography are laborious and time-consuming, and can be difficult to use during the implantation procedure. However, the ventricular activation sequence can be readily displayed from the chest leads using an ultra-high-frequency ECG. It can be performed during the implantation procedure to visualise ventricular depolarisation and resultant ventricular dyssynchrony during pacing. This information can assist the electrophysiologist in selecting a pacing location that avoids dyssynchronous ventricular activation.

Differentiating left bundle branch pacing and left ventricular septal pacing: An algorithm based on intracardiac electrophysiology.

Left bundle branch pacing (LBBP) is a new near-physiological pacing modality. Distinguishing left ventricular septal only pacing (LVSP) from nonselective LBBP still needs clarification. This prospective study sought to establish a differentiation algorithm to confirm LBBP. LBBP was attempted in consecutive patients. If direct LBB capture (LBBP) could not be confirmed, LVSP was considered to have been achieved. Intracardiac left ventricular (LV) activation sequence and activation time were analyzed using coronary sinus (CS) electrogram mapping. Electrophysiological parameters including S-CSmax, S-CSmin, LV lateral wall activation time, ΔLV, and LBB potential were compared between LBBP and LVSP. Stimulated LV activation time (S-LVAT) and stimulated QRS duration (S-QRSd) were also compared between the two groups. Multivariate logistic regression analysis was used to develop a prediction algorithm for LBBP. Of the 43 prospectively enrolled patients, 27 underwent LBBP and 16 underwent LVSP. All LBBP patients showed identical LV activation sequences to their intrinsic rhythm while no LVSP patients maintained their intrinsic sequence. S-CSmax, ΔLV, LV lateral wall activation time, and S-LVAT during LBBP were significantly shorter than those during LVSP. Combining LBB potential with S-LVAT had the largest area under the curve (AUC) of 0.985 for confirming LBBP with a sensitivity of 95.2% and a specificity of 93.7%. Compared with LVSP, LBBP preserves a normal LV activation sequence and better electrical synchrony. A combination of LBB potential with S-LVAT can be an effective and practical model to distinguish LBBP from LVSP during implantation in patients with normal LBB activation.

Pacing therapy for atrioventricular dromotropathy: a combined computational-experimental-clinical study.

AimsInvestigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational–experimental–clinical study.Methods and resultsComputer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure (HF) patients (LV ejection fraction <35%) with prolonged PR interval (>230 ms) and narrow or non-left bundle branch block QRS complex. Computer simulations and animal studies in normal hearts showed that restoring of AV-coupling with unchanged ventricular activation sequence significantly increased LV filling, mean arterial pressure, and cardiac output by 10–15%. In computer simulations of failing hearts and in HF patients, reducing PR interval by biventricular (BiV) pacing (patients: from 300 ± 61 to 137 ± 30 ms) resulted in significant increases in LV stroke volume and stroke work (patients: 34 ± 40% and 26 ± 31%, respectively). However, worsening of ventricular dyssynchrony by using right ventricular (RV) pacing abrogated the benefit of restoring AV-coupling. In model simulations, animals and patients, the increase of LV filling and associated improvement of LV pump function coincided with both larger mitral inflow (E- and A-wave area) and reduction of diastolic mitral regurgitation.ConclusionRestoration of AV-coupling by BiV pacing in normal and failing hearts with prolonged AV conduction leads to considerable haemodynamic improvement. These results indicate that BiV or physiological pacing, but not RV pacing, may improve cardiac function in patients with HF and prolonged PR interval.

High frame rate speckle tracking echocardiography to assess diastolic function

Abstract Background Left ventricular (LV) strain rate (SR) during isovolumic relaxation (SRIVR) and early diastolic filling (SRe) has previously been shown to correlate with the invasive gold standard for LV diastolic function (i.e. the time constant of LV pressure decay tau). However, the translation of these biomarkers to the clinic has been hampered by technical limitations. Indeed, conventional speckle tracking (STE) is limited by its temporal resolution, whereas tissue Doppler imaging (TDI) is angle-dependent, labor-intensive and thus rarely used clinically nowadays. Purpose The aim of this study was to show that these limitations could be overcome by using a recently proposed STE algorithm operating on high frame rate (HFR) imaging data. Methods 37 subjects (age: 64±12, 81% male) were included in the study; 16 had cardiac amyloidosis, 12 were undergoing clinically indicated left and/or right heart cardiac catheterization and 9 were healthy volunteers. Since the sequence of left ventricular activation and thus the repolarization process (i.e. relaxation) starts at mid septum, we measured SRIVR and SRe in the mid septal segment in an apical 4 chamber view using a commercially available clinical system with: (1) TDI (frame rate (FR) ∼142 Hz); (2) STE (FR ∼65 Hz). Moreover, subjects were scanned with HD-PULSE, an experimental high frame ultrasound scanner (FR ∼915 Hz) and then a manually placed contour was tracked during the cardiac cycle by a custom-made 2D HFR STE algorithm, to compute and extract SRIVR and SRe from the mid septum. Since TDI is considered the reference method to assess SR, conventional as well as HFR STE values were correlated against the TDI SR values. Results In 3 subjects, SRIVR could not be reliably assessed with the clinical STE approach, which we attributed to the relatively low temporal resolution of the images; all other measurements could be made in all subjects. For both biomarkers, HFR STE values correlated better with the TDI reference measurements than the clinical STE estimates (Fig.1). The latter estimates showed a systematic underestimation (bias −0.19 1/s (p&amp;lt;0.01) and −0.46 1/s (p&amp;lt;0.01) for SRIVR and SRe respectively) while no significant bias was observed for the HFR STE values. Similarly, the limits of agreement of the HFR STE values were narrower (−0.45 to +0.54 1/s and −0.94 to +0.86 1/s) than those of the clinical STE measurements (−0.85 to +0.48 1/s and −1.32 to +0.41 1/s). Conclusions These results show that HFR STE offers a reliable way to assess novel biomarkers of diastolic function in a user-friendly manner and can therefore facilitate their incorporation to the clinical practice. Funding Acknowledgement Type of funding sources: None.

Comparing Non-invasive Inverse Electrocardiography With Invasive Endocardial and Epicardial Electroanatomical Mapping During Sinus Rhythm.

This study presents a novel non-invasive equivalent dipole layer (EDL) based inverse electrocardiography (iECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our iECG approach with invasive electro-anatomical mapping (EAM) during sinus rhythm with the objective of enabling functional substrate imaging and sudden cardiac death risk stratification in patients with cardiomyopathy. Thirteen patients (77% males, 48 ± 20 years old) referred for endocardial and epicardial EAM underwent 67-electrode body surface potential mapping and CT imaging. The EDL-based iECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with iECG-LAT maps using absolute differences and Pearson’s correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between iECG-LAT maps and EAM was 0.54 ± 0.19 [0.49–0.59] for epicardial activation, 0.50 ± 0.27 [0.41–0.58] for right ventricular endocardial activation and 0.44 ± 0.29 [0.32–0.56] for left ventricular endocardial activation. The absolute difference in timing between iECG maps and EAM was 17.4 ± 7.2 ms for epicardial maps, 19.5 ± 7.7 ms for right ventricular endocardial maps, 27.9 ± 8.7 ms for left ventricular endocardial maps. The absolute distance between right ventricular endocardial breakthrough sites was 30 ± 16 mm and 31 ± 17 mm for the left ventricle. The absolute distance for latest epicardial activation was median 12.8 [IQR: 2.9–29.3] mm. This first in-human quantitative comparison of iECG and invasive LAT-maps on both the endocardial and epicardial surface during sinus rhythm showed improved agreement, although with considerable absolute difference and moderate correlation coefficient. Non-invasive iECG requires further refinements to facilitate clinical implementation and risk stratification.

Automated Framework for the Inclusion of a His\u2013Purkinje System in Cardiac Digital Twins of Ventricular Electrophysiology

Personalized models of cardiac electrophysiology (EP) that match clinical observation with high fidelity, referred to as cardiac digital twins (CDTs), show promise as a tool for tailoring cardiac precision therapies. Building CDTs of cardiac EP relies on the ability of models to replicate the ventricular activation sequence under a broad range of conditions. Of pivotal importance is the His–Purkinje system (HPS) within the ventricles. Workflows for the generation and incorporation of HPS models are needed for use in cardiac digital twinning pipelines that aim to minimize the misfit between model predictions and clinical data such as the 12 lead electrocardiogram (ECG). We thus develop an automated two stage approach for HPS personalization. A fascicular-based model is first introduced that modulates the endocardial Purkinje network. Only emergent features of sites of earliest activation within the ventricular myocardium and a fast-conducting sub-endocardial layer are accounted for. It is then replaced by a topologically realistic Purkinje-based representation of the HPS. Feasibility of the approach is demonstrated. Equivalence between both HPS model representations is investigated by comparing activation patterns and 12 lead ECGs under both sinus rhythm and right-ventricular apical pacing. Predominant ECG morphology is preserved by both HPS models under sinus conditions, but elucidates differences during pacing.