Quantification of left ventricular myocardial strain: Comparison between MRI tagging, MRI feature tracking, and ultrasound speckle tracking.

Ultrasound speckle tracking is frequently used to quantify myocardial strain, and magnetic resonance imaging (MRI) feature tracking is rapidly gaining interest. Our aim is to validate cardiac MRI feature tracking by comparing it with the gold standard method (i.e., MRI tagging) in healthy subjects and patients. Furthermore, we aim to perform an indirect validation by comparing ultrasound speckle tracking with MRI feature tracking. Forty-two subjects (17 formerly preeclamptic women, three healthy women, and 22 left bundle branch block patients of both sexes) received 3-T cardiac MRI and echocardiography. Cine and tagged MRI, and B-mode ultrasound images, were acquired. Intrapatient global and segmental left ventricular circumferential (MRI tagging vs. MRI feature tracking) and longitudinal (MRI feature tracking vs. ultrasound speckle tracking) peak strain and time to peak strain were compared between the three techniques. Intraclass correlation coefficient (ICC) (< 0.50 = poor, 0.50-0.75 = moderate, > 0.75-0.90 = good, > 0.90 = excellent) and Bland-Altman analysis were used to assess correlation and bias; p less than 0.05 indicates a significant ICC or bias. Global peak strain parameters showed moderate-to-good correlations between methods (ICC = 0.71-0.83, p < 0.01) with no significant biases. Global time to peak strain parameters showed moderate-to-good correlations (ICC = 0.56-0.82, p < 0.01) with no significant biases. Segmental peak strains showed significant biases in all parameters and moderate-to-good correlation (ICC = 0.62-0.77, p < 0.01), except for lateral longitudinal peak strain (ICC = 0.23, p = 0.22). Segmental time to peak strain parameters showed moderate-to-good correlation (ICC = 0.58-0.74, p < 0.01) with no significant biases. MRI feature tracking is a valid method to examine myocardial strain, but there is bias in absolute segmental strain values between imaging techniques. MRI feature tracking shows adequate comparability with ultrasound speckle tracking.

Ultra-High-Frequency ECG in Cardiac Pacing and Cardiac Resynchronization Therapy: From Technical Concept to Clinical Application.

Identifying electrical dyssynchrony is crucial for cardiac pacing and cardiac resynchronization therapy (CRT). The ultra-high-frequency electrocardiography (UHF-ECG) technique allows instantaneous dyssynchrony analyses with real-time visualization. This review explores the physiological background of higher frequencies in ventricular conduction and the translational evolution of UHF-ECG in cardiac pacing and CRT. Although high-frequency components were studied half a century ago, their exploration in the dyssynchrony context is rare. UHF-ECG records ECG signals from eight precordial leads over multiple beats in time. After initial conceptual studies, the implementation of an instant visualization of ventricular activation led to clinical implementation with minimal patient burden. UHF-ECG aids patient selection in biventricular CRT and evaluates ventricular activation during various forms of conduction system pacing (CSP). UHF-ECG ventricular electrical dyssynchrony has been associated with clinical outcomes in a large retrospective CRT cohort and has been used to study the electrophysiological differences between CSP methods, including His bundle pacing, left bundle branch (area) pacing, left ventricular septal pacing and conventional biventricular pacing. UHF-ECG can potentially be used to determine a tailored resynchronization approach (CRT through biventricular pacing or CSP) based on the electrical substrate (true LBBB vs. non-specified intraventricular conduction delay with more distal left ventricular conduction disease), for the optimization of CRT and holds promise beyond CRT for the risk stratification of ventricular arrhythmias.

The association between coronary artery calcification and vectorcardiography in mechanically ventilated COVID-19 patients: the Maastricht Intensive Care COVID cohort.

BACKGROUND: Coronary artery calcification (CAC) is associated with poor outcome in critically ill patients. A deterioration in cardiac conduction and loss of myocardial tissue could be an underlying cause. Vectorcardiography (VCG) and cardiac biomarkers provide insight into these underlying causes. The aim of this study was to investigate whether a high degree of CAC is associated with VCG-derived variables and biomarkers, including high-sensitivity troponin-T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). METHODS: Mechanically ventilated coronavirus-19 (COVID-19) patients with an available chest computed tomography (CT) and 12-lead electrocardiogram (ECG) were studied. CAC scores were determined using chest CT scans. Patients were categorized into 3 sex-specific tertiles: low, intermediate, and high CAC. Daily 12 leads-ECGs were converted to VCGs. Daily hs-cTnT and NT-proBNP levels were determined. Linear mixed-effects regression models examined the associations between CAC tertiles and VCG variables, and between CAC tertiles and hs-cTnT or NT-proBNP levels. RESULTS: In this study, 205 patients (73.2% men, median age 65 years [IQR 57.0; 71.0]) were included. Compared to the lowest CAC tertile, the highest CAC tertile had a larger QRS area at baseline (6.65 µVs larger [1.50; 11.81], p = 0.012), which decreased during admission (- 0.27 µVs per day [- 0.43; - 0.11], p = 0.001). Patients with the highest CAC tertile also had a longer QRS duration (12.02 ms longer [4.74; 19.30], p = 0.001), higher levels of log hs-cTnT (0.79 ng/L higher [0.40; 1.19], p < 0.001) and log NT-proBNP (0.83 pmol/L higher [0.30; 1.37], p = 0.002). CONCLUSION: Patients with a high degree of CAC had the largest QRS area and higher QRS amplitude, which decreased more over time when compared to patients with a low degree of CAC. These results suggest that CAC might contribute to loss of myocardial tissue during critical illness. These insights could improve risk stratification and prognostication of patients with critical illness.

Left ventricular lead placement in cardiac resynchronization therapy: Current data and potential explanations for the lack of benefit.

The present article reviews the literature on image-guided cardiac resynchronization therapy (CRT) studies. Improved outcome to CRT has been associated with the placement of a left ventricular (LV) lead in the latest activated segment free from scar. The majority of randomized controlled trials investigating guided LV lead implantation did not show superiority over conventional implantation approaches. Several factors may contribute to this paradoxical observation, including inclusion criteria favoring patients with left bundle branch block who already respond well to conventional anatomical LV lead implantation, differences in activation wavefronts during simultaneous right ventricular and LV pacing, incorrect definition of target regions, and limitations in coronary venous anatomy that prevent access to target regions that are detected by imaging. It is imperative that exclusion of patients lacking access to target regions from these studies would lead to larger benefit of image-guided CRT.

Association of vectorcardiographic T-wave area with clinical and echocardiographic outcomes in cardiac resynchronization therapy.

AIMS: Data on repolarization parameters in cardiac resynchronization therapy (CRT) are scarce. We investigated the association of baseline T-wave area, with both clinical and echocardiographic outcomes of CRT in a large, multi-centre cohort of CRT recipients. Also, we evaluated the association between the baseline T-wave area and QRS area. METHODS AND RESULTS: In this retrospective study, 1355 consecutive CRT recipients were evaluated. Pre-implantation T-wave and QRS area were calculated from vectorcardiograms. Echocardiographic response was defined as a reduction of ≥15% in left ventricular end-systolic volume between 3 and 12 months after implantation. The clinical outcome was a combination of all-cause mortality, heart transplantation, and left ventricular assist device implantation. Left ventricular end-systolic volume reduction was largest in patients with QRS area ≥ 109 µVs and T-wave area ≥ 66 µVs compared with QRS area ≥ 109 µVs and T-wave area < 66 µVs (P = 0.004), QRS area < 109 µVs and T-wave area ≥ 66 µVs (P < 0.001) and QRS area < 109 µVs and T-wave area < 66 µVs (P < 0.001). Event-free survival rate was higher in the subgroup of patients with QRS area ≥ 109 µVs and T-wave area ≥ 66 µVs (n = 616, P < 0.001) and QRS area ≥ 109 µVs and T-wave area < 66 µVs (n = 100, P < 0.001) than the other subgroups. In the multivariate analysis, T-wave area remained associated with echocardiographic response (P = 0.008), but not with the clinical outcome (P = 0.143), when QRS area was included in the model. CONCLUSION: Baseline T-wave area has a significant association with both clinical and echocardiographic outcomes after CRT. The association of T-wave area with echocardiographic response is independent from QRS area; the association with clinical outcome, however, is not.

Impact of Estimated Left Atrial Pressure on Cardiac Resynchronization Therapy Outcome.

BACKGROUND: We investigated the impact of baseline left atrial (LA) strain data and estimated left atrial pressure (LAP) by applying the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACVI) guidelines on cardiac resynchronization therapy (CRT) outcomes. METHODS: Datasets of 219 CRT patients were retrospectively analysed. All patients had full echocardiographic diastolic function assessment before CRT and were classified based on the guideline algorithm into normal LAP (nLAP = 40%), elevated LAP (eLAP = 49%) and indeterminate LAP (iLAP = 11%). All relevant baseline characteristics were analysed. CRT-induced left ventricular (LV) reverse remodeling was measured as the relative change of LV end-systolic volume (LVESV) at 12 ± 6 months after CRT compared to baseline. Patients were followed up for all-cause mortality for a mean of 4.8 years [interquartile range (IQR): 2.7-6.0 years]. RESULTS: At follow-up, CRT resulted in more pronounced reduction of LVESV in patients with nLAP than in patients with eLAP. In univariate analysis, nLAP was associated with LV reverse remodelling (p < 0.001), as well as long-term survival after CRT (p < 0.01). However, multivariable analysis showed that only the association between nLAP and LV reverse remodelling after CRT is independent (p < 0.01). Adding LA strain analysis to the guideline algorithm improved the feasibility of LAP estimation without affecting the association between estimated LAP and CRT outcome. CONCLUSION: Normal LAP before CRT, estimated using the 2016 ASE/EACVI guideline algorithm, is associated with LV reverse remodelling and long-term survival after CRT. Albeit non-independent, it can serve as a non-invasive imaging-based predictor of effective therapy. Furthermore, the inclusion of LA reservoir strain in the guideline algorithm can enhance the feasibility of LAP estimation without affecting the association between LAP and CRT outcome.

Myocardial perfusion and flow reserve in the asynchronous heart: mechanistic insight from a computational model.

The tight coupling between myocardial oxygen demand and supply has been recognized for decades, but it remains controversial whether this coupling persists under asynchronous activation, such as during left bundle branch block (LBBB). Furthermore, it is unclear whether the amount of local cardiac wall growth, following longer-lasting asynchronous activation, can explain differences in myocardial perfusion distribution between subjects. For a better understanding of these matters, we built upon our existing modeling framework for cardiac mechanics-to-perfusion coupling by incorporating coronary autoregulation. Regional coronary flow was regulated with a vasodilator signal based on regional demand, as estimated from regional fiber stress-strain area. Volume of left ventricular wall segments was adapted with chronic asynchronous activation toward a homogeneous distribution of myocardial oxygen demand per tissue weight. Modeling results show that 1) both myocardial oxygen demand and supply are decreased in early activated regions and increased in late-activated regions; 2) but that regional hyperemic flow remains unaffected; while 3) regional myocardial flow reserve (the ratio of hyperemic to resting myocardial flow) decreases with increases in absolute regional myocardial oxygen demand as well as with decreases in wall thickness. These findings suggest that septal hypoperfusion in LBBB represents an autoregulatory response to reduced myocardial oxygen demand. Furthermore, oxygen demand-driven remodeling of wall mass can explain asymmetric hypertrophy and the related homogenization of myocardial perfusion and flow reserve. Finally, the inconsistent observations of myocardial perfusion distribution can primarily be explained by the degree of dyssynchrony, the degree of asymmetric hypertrophy, and the imaging modality used.NEW & NOTEWORTHY This versatile modeling framework couples myocardial oxygen demand to oxygen supply and myocardial growth, enabling simulation of resting and hyperemic myocardial flow during acute and chronic asynchronous ventricular activation. Model-based findings suggest that reported inconsistencies in myocardial perfusion and flow reserve responses with asynchronous ventricular activation between patients can primarily be explained by the degree of dyssynchrony and wall mass remodeling, which together determine the heterogeneity in regional oxygen demand and, hence, supply with autoregulation.

Erratum to: Electro-energetics of Biventricular, Septal and Conduction System Pacing.

[This corrects the article DOI: 10.15420/aer.2021.30.].

Comparison of novel ventricular pacing strategies using an electro-mechanical simulation platform.

AIMS: Focus of pacemaker therapy is shifting from right ventricular (RV) apex pacing (RVAP) and biventricular pacing (BiVP) to conduction system pacing. Direct comparison between the different pacing modalities and their consequences to cardiac pump function is difficult, due to the practical implications and confounding variables. Computational modelling and simulation provide the opportunity to compare electrical, mechanical, and haemodynamic consequences in the same virtual heart. METHODS AND RESULTS: Using the same single cardiac geometry, electrical activation maps following the different pacing strategies were calculated using an Eikonal model on a three-dimensional geometry, which were then used as input for a lumped mechanical and haemodynamic model (CircAdapt). We then compared simulated strain, regional myocardial work, and haemodynamic function for each pacing strategy. Selective His-bundle pacing (HBP) best replicated physiological electrical activation and led to the most homogeneous mechanical behaviour. Selective left bundle branch (LBB) pacing led to good left ventricular (LV) function but significantly increased RV load. RV activation times were reduced in non-selective LBB pacing (nsLBBP), reducing RV load but increasing heterogeneity in LV contraction. LV septal pacing led to a slower LV and more heterogeneous LV activation than nsLBBP, while RV activation was similar. BiVP led to a synchronous LV-RV, but resulted in a heterogeneous contraction. RVAP led to the slowest and most heterogeneous contraction. Haemodynamic differences were small compared to differences in local wall behaviour. CONCLUSION: Using a computational modelling framework, we investigated the mechanical and haemodynamic outcome of the prevailing pacing strategies in hearts with normal electrical and mechanical function. For this class of patients, nsLBBP was the best compromise between LV and RV function if HBP is not possible.

Machine learning-powered, device-embedded heart sound measurement can optimize AV delay in patients with CRT.

BACKGROUND: Continuous optimization of atrioventricular (AV) delay for cardiac resynchronization therapy (CRT) is mainly performed by electrical means. OBJECTIVE: The purpose of this study was to develop an estimation model of cardiac function that uses a piezoelectric microphone embedded in a pulse generator to guide CRT optimization. METHODS: Electrocardiogram, left ventricular pressure (LVP), and heart sounds were simultaneously collected during CRT device implantation procedures. A piezoelectric alarm transducer embedded in a modified CRT device facilitated recording of heart sounds in patients undergoing a pacing protocol with different AV delays. Machine learning (ML) was used to produce a decision-tree ensemble model capable of estimating absolute maximal LVP (LVPmax) and maximal rise of LVP (LVdP/dtmax) using 3 heart sound-based features. To gauge the applicability of ML in AV delay optimization, polynomial curves were fitted to measured and estimated values. RESULTS: In the data set of ∼30,000 heartbeats, ML indicated S1 amplitude, S2 amplitude, and S1 integral (S1 energy for LVdP/dtmax) as most prominent features for AV delay optimization. ML resulted in single-beat estimation precision for absolute values of LVPmax and LVdP/dtmax of 67% and 64%, respectively. For 20-30 beat averages, cross-correlation between measured and estimated LVPmax and LVdP/dtmax was 0.999 for both. The estimated optimal AV delays were not significantly different from those measured using invasive LVP (difference -5.6 ± 17.1 ms for LVPmax and +5.1 ± 6.7 ms for LVdP/dtmax). The difference in function at estimated and measured optimal AV delays was not statiscally significant (1 ± 3 mm Hg for LVPmax and 9 ± 57 mm Hg/s for LVdP/dtmax). CONCLUSION: Heart sound sensors embedded in a CRT device, powered by a ML algorithm, provide a reliable assessment of optimal AV delays and absolute LVPmax and LVdP/dtmax.

Mechanoelectric effects in healthy cardiac function and under Left Bundle Branch Block pathology.

Mechanoelectric feedback (MEF) in the heart operates through several mechanisms which serve to regulate cardiac function. Stretch activated channels (SACs) in the myocyte membrane open in response to cell lengthening, while tension generation depends on stretch, shortening velocity, and calcium concentration. How all of these mechanisms interact and their effect on cardiac output is still not fully understood. We sought to gauge the acute importance of the different MEF mechanisms on heart function. An electromechanical computer model of a dog heart was constructed, using a biventricular geometry of 500K tetrahedral elements. To describe cellular behavior, we used a detailed ionic model to which a SAC model and an active tension model, dependent on stretch and shortening velocity and with calcium sensitivity, were added. Ventricular inflow and outflow were connected to the CircAdapt model of cardiovascular circulation. Pressure-volume loops and activation times were used for model validation. Simulations showed that SACs did not affect acute mechanical response, although if their trigger level was decreased sufficiently, they could cause premature excitations. The stretch dependence of tension had a modest effect in reducing the maximum stretch, and stroke volume, while shortening velocity had a much bigger effect on both. MEF served to reduce the heterogeneity in stretch while increasing tension heterogeneity. In the context of left bundle branch block, a decreased SAC trigger level could restore cardiac output by reducing the maximal stretch when compared to cardiac resynchronization therapy. MEF is an important aspect of cardiac function and could potentially mitigate activation problems.

Comparison of the relation of the ESC 2021 and ESC 2013 definitions of left bundle branch block with clinical and echocardiographic outcome in cardiac resynchronization therapy.

INTRODUCTION: We aimed to investigate the impact of the 2021 European Society of Cardiology (ESC) guideline changes in left bundle branch block (LBBB) definition on cardiac resynchronization therapy (CRT) patient selection and outcomes. METHODS: The MUG (Maastricht, Utrecht, Groningen) registry, consisting of consecutive patients implanted with a CRT device between 2001 and 2015 was studied. For this study, patients with baseline sinus rhythm and QRS duration ≥ 130ms were eligible. Patients were classified according to ESC 2013 and 2021 guideline LBBB definitions and QRS duration. Endpoints were heart transplantation, LVAD implantation or mortality (HTx/LVAD/mortality) and echocardiographic response (LVESV reduction ≥15%). RESULTS: The analyses included 1.202, typical CRT patients. The ESC 2021 definition resulted in considerably less LBBB diagnoses compared to the 2013 definition (31.6% vs. 80.9%, respectively). Applying the 2013 definition resulted in significant separation of the Kaplan-Meier curves of HTx/LVAD/mortality (p < .0001). A significantly higher echocardiographic response rate was found in the LBBB compared to the non-LBBB group using the 2013 definition. These differences in HTx/LVAD/mortality and echocardiographic response were not found when applying the 2021 definition. CONCLUSION: The ESC 2021 LBBB definition leads to a considerably lower percentage of patients with baseline LBBB then the ESC 2013 definition. This does not lead to better differentiation of CRT responders, nor does this lead to a stronger association with clinical outcomes after CRT. In fact, stratification according to the 2021 definition is not associated with a difference in clinical or echocardiographic outcome, implying that the guideline changes may negatively influence CRT implantation practice with a weakened recommendation in patients that will benefit from CRT.

Association between phonocardiography and echocardiography in heart failure patients with preserved ejection fraction.

Aims: Heart failure with preserved ejection fraction (HFpEF) is associated with stiffened myocardium and elevated filling pressure that may be captured by heart sound (HS). We investigated the relationship between phonocardiography (PCG) and echocardiography in symptomatic patients suspected of HFpEF. Methods and results: Consecutive symptomatic patients with sinus rhythm and left ventricular ejection fraction >45% were enrolled. Echocardiography was performed to evaluate the patients' diastolic function, accompanied by PCG measurements. Phonocardiography features including HS amplitude, frequency, and timing intervals were calculated, and their abilities to differentiate the ratio between early mitral inflow velocity and early diastolic mitral annular velocity (E/e') were investigated. Of 45 patients, variable ratio matching was applied to obtain two groups of patients with similar characteristics but different E/e'. Patients with a higher E/e' showed higher first and second HS frequencies and more fourth HS and longer systolic time intervals. The interval from QRS onset to first HS was the best feature for the prediction of E/e' > 9 [area under the curve (AUC): 0.72 (0.51-0.88)] in the matched patients. In comparison, N-terminal pro-brain natriuretic peptide (NT-proBNP) showed an AUC of 0.67 (0.46-0.85), a value not better than any PCG feature (P > 0.05). Conclusion: Phonocardiography features stratify E/e' in symptomatic patients suspected of HFpEF with a diagnostic performance similar to NT-proBNP. Heart sound may serve as a simple non-invasive tool for evaluating HFpEF patients.

Plasma Extracellular Vesicles as Liquid Biopsy to Unravel the Molecular Mechanisms of Cardiac Reverse Remodeling Following Resynchronization Therapy?

Cardiac resynchronization therapy (CRT) has become a valuable addition to the treatment options for heart failure, in particular for patients with disturbances in electrical conduction that lead to regionally different contraction patterns (dyssynchrony). Dyssynchronous hearts show extensive molecular and cellular remodeling, which has primarily been investigated in experimental animals. Evidence showing that at least several miRNAs play a role in this remodeling is increasing. A comparison of results from measurements in plasma and myocardial tissue suggests that plasma levels of miRNAs may reflect the expression of these miRNAs in the heart. Because many miRNAs released in the plasma are included in extracellular vesicles (EVs), which protect them from degradation, measurement of myocardium-derived miRNAs in peripheral blood EVs may open new avenues to investigate and monitor (reverse) remodeling in dyssynchronous and resynchronized hearts of patients.

Histopathological validation of semi-automated myocardial scar quantification techniques for dark-blood late gadolinium enhancement magnetic resonance imaging.

AIMS: To evaluate the performance of various semi-automated techniques for quantification of myocardial infarct size on both conventional bright-blood and novel dark-blood late gadolinium enhancement (LGE) images using histopathology as reference standard. METHODS AND RESULTS: In 13 Yorkshire pigs, reperfused myocardial infarction was experimentally induced. At 7 weeks post-infarction, both bright-blood and dark-blood LGE imaging were performed on a 1.5 T magnetic resonance scanner. Following magnetic resonance imaging (MRI), the animals were sacrificed, and histopathology was obtained. The percentage of infarcted myocardium was assessed per slice using various semi-automated scar quantification techniques, including the signal threshold vs. reference mean (STRM, using 3 to 8 SDs as threshold) and full-width at half-maximum (FWHM) methods, as well as manual contouring, for both LGE methods. Infarct size obtained by histopathology was used as reference. In total, 24 paired LGE MRI slices and histopathology samples were available for analysis. For both bright-blood and dark-blood LGE, the STRM method with a threshold of 5 SDs led to the best agreement to histopathology without significant bias (-0.23%, 95% CI [-2.99, 2.52%], P = 0.862 and -0.20%, 95% CI [-2.12, 1.72%], P = 0.831, respectively). Manual contouring significantly underestimated infarct size on bright-blood LGE (-1.57%, 95% CI [-2.96, -0.18%], P = 0.029), while manual contouring on dark-blood LGE outperformed semi-automated quantification and demonstrated the most accurate quantification in this study (-0.03%, 95% CI [-0.22, 0.16%], P = 0.760). CONCLUSION: The signal threshold vs. reference mean method with a threshold of 5 SDs demonstrated the most accurate semi-automated quantification of infarcted myocardium, without significant bias compared to histopathology, for both conventional bright-blood and novel dark-blood LGE.

Heart sound-derived systolic time intervals for atrioventricular delay optimization in cardiac resynchronization therapy.

BACKGROUND: Phonocardiography (PCG) can be used to determine systolic time intervals (STIs) from ventricular pacing spike to the first heart sound (VS1) and from the first to the second heart sound (S1S2). OBJECTIVE: The purpose of this study was to investigate the relations between STIs and hemodynamics during atrioventricular (AV) delay optimization of biventricular pacing (BiVP) in animals and patients. METHODS: Five pigs with AV block underwent BiVP, while PCG was collected from an epicardial accelerometer. In 21 patients undergoing cardiac resynchronization therapy device implantation, PCG was recorded with a pulse generator-embedded microphone. Optimal AV delays derived from shortest VS1 and longest S1S2 were compared with AV delays derived from highest left ventricular pressure (LVP), maximal rate of rise in LVP, and stroke work. RESULTS: In pigs, VS1 and S1S2 predicted the AV delays with optimal hemodynamics (highest LVP, maximal rate of rise in LVP, and stroke work) by a median error of 2-28 ms, resulting in a median loss of <2% of pump function. In patients, VS1 and S1S2 predicted the optimal AV delay by errors of 32.5 and 37.5 ms, respectively, resulting in 0.2%-0.9% lower LVP and stroke work, which were reduced to 21 and 24 ms in 8 patients with a full-capture AV delay of >180 ms. CONCLUSION: During BiVP with varying AV delays, close relations exist between PCG-derived STIs and hemodynamic parameters. AV delays advised by PCG-derived STIs cause only a minimal loss of pump function compared with those based on invasive hemodynamic measurements. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01832493.

Electromechanical factors associated with favourable outcome in cardiac resynchronization therapy.

AIMS: Electromechanical coupling in patients receiving cardiac resynchronization therapy (CRT) is not fully understood. Our aim was to determine the best combination of electrical and mechanical substrates associated with effective CRT. METHODS AND RESULTS: Sixty-two patients were prospectively enrolled from two centres. Patients underwent 12-lead electrocardiogram (ECG), cardiovascular magnetic resonance (CMR), echocardiography, and anatomo-electromechanical mapping (AEMM). Remodelling was measured as the end-systolic volume (ΔESV) decrease at 6 months. CRT was defined effective with ΔESV ≤ -15%. QRS duration (QRSd) was measured from ECG. Area strain was obtained from AEMM and used to derive systolic stretch index (SSI) and total left-ventricular mechanical time. Total left-ventricular activation time (TLVAT) and transeptal time (TST) were derived from AEMM and ECG. Scar was measured from CMR. Significant correlations were observed between ΔESV and TST [rho = 0.42; responder: 50 (20-58) vs. non-responder: 33 (8-44) ms], TLVAT [-0.68; 81 (73-97) vs. 112 (96-127) ms], scar [-0.27; 0.0 (0.0-1.2) vs. 8.7 (0.0-19.1)%], and SSI [0.41; 10.7 (7.1-16.8) vs. 4.2 (2.9-5.5)], but not QRSd [-0.13; 155 (140-176) vs. 167 (155-177) ms]. TLVAT and SSI were highly accurate in identifying CRT response [area under the curve (AUC) > 0.80], followed by scar (AUC > 0.70). Total left-ventricular activation time (odds ratio = 0.91), scar (0.94), and SSI (1.29) were independent factors associated with effective CRT. Subjects with SSI >7.9% and TLVAT <91 ms all responded to CRT with a median ΔESV ≈ -50%, while low SSI and prolonged TLVAT were more common in non-responders (ΔESV ≈ -5%). CONCLUSION: Electromechanical measurements are better associated with CRT response than conventional ECG variables. The absence of scar combined with high SSI and low TLVAT ensures effectiveness of CRT.

Electrocardiogram-based deep learning improves outcome prediction following cardiac resynchronization therapy.

AIMS: This study aims to identify and visualize electrocardiogram (ECG) features using an explainable deep learning-based algorithm to predict cardiac resynchronization therapy (CRT) outcome. Its performance is compared with current guideline ECG criteria and QRSAREA. METHODS AND RESULTS: A deep learning algorithm, trained on 1.1 million ECGs from 251 473 patients, was used to compress the median beat ECG, thereby summarizing most ECG features into only 21 explainable factors (FactorECG). Pre-implantation ECGs of 1306 CRT patients from three academic centres were converted into their respective FactorECG. FactorECG predicted the combined clinical endpoint of death, left ventricular assist device, or heart transplantation [c-statistic 0.69, 95% confidence interval (CI) 0.66-0.72], significantly outperforming QRSAREA and guideline ECG criteria [c-statistic 0.61 (95% CI 0.58-0.64) and 0.57 (95% CI 0.54-0.60), P < 0.001 for both]. The addition of 13 clinical variables was of limited added value for the FactorECG model when compared with QRSAREA (Δ c-statistic 0.03 vs. 0.10). FactorECG identified inferolateral T-wave inversion, smaller right precordial S- and T-wave amplitude, ventricular rate, and increased PR interval and P-wave duration to be important predictors for poor outcome. An online visualization tool was created to provide interactive visualizations (https://crt.ecgx.ai). CONCLUSION: Requiring only a standard 12-lead ECG, FactorECG held superior discriminative ability for the prediction of clinical outcome when compared with guideline criteria and QRSAREA, without requiring additional clinical variables. End-to-end automated visualization of ECG features allows for an explainable algorithm, which may facilitate rapid uptake of this personalized decision-making tool in CRT.

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

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

Virtual pacing of a patient's digital twin to predict left ventricular reverse remodelling after cardiac resynchronization therapy.

AIMS: Identifying heart failure (HF) patients who will benefit from cardiac resynchronization therapy (CRT) remains challenging. We evaluated whether virtual pacing in a digital twin (DT) of the patient's heart could be used to predict the degree of left ventricular (LV) reverse remodelling post-CRT. METHODS AND RESULTS: Forty-five HF patients with wide QRS complex (≥130 ms) and reduced LV ejection fraction (≤35%) receiving CRT were retrospectively enrolled. Echocardiography was performed before (baseline) and 6 months after CRT implantation to obtain LV volumes and 18-segment longitudinal strain. A previously developed algorithm was used to generate 45 DTs by personalizing the CircAdapt model to each patient's baseline measurements. From each DT, baseline septal-to-lateral myocardial work difference (MWLW-S,DT) and maximum rate of LV systolic pressure rise (dP/dtmax,DT) were derived. Biventricular pacing was then simulated using patient-specific atrioventricular delay and lead location. Virtual pacing-induced changes ΔMWLW-S,DT and ΔdP/dtmax,DT were correlated with real-world LV end-systolic volume change at 6-month follow-up (ΔLVESV). The DT's baseline MWLW-S,DT and virtual pacing-induced ΔMWLW-S,DT were both significantly associated with the real patient's reverse remodelling ΔLVESV (r = -0.60, P < 0.001 and r = 0.62, P < 0.001, respectively), while correlation between ΔdP/dtmax,DT and ΔLVESV was considerably weaker (r = -0.34, P = 0.02). CONCLUSION: Our results suggest that the reduction of septal-to-lateral work imbalance by virtual pacing in the DT can predict real-world post-CRT LV reverse remodelling. This DT approach could prove to be an additional tool in selecting HF patients for CRT and has the potential to provide valuable insights in optimization of CRT delivery.