Publications by authors named "Jürgen Duchenne"

45 Publications

Can nuclear imaging accurately detect scar in ischemic cardiac resynchronization therapy candidates?

Nucl Med Commun 2022 Jan 17. Epub 2022 Jan 17.

Department of Imaging and Pathology, KU Leuven Nuclear Medicine and Molecular Imaging, University Hospitals Leuven Department of Cardiovascular Sciences, KU Leuven Department of Cardiovascular Diseases, University Hospitals Leuven Department of Radiology, University Hospitals Leuven, Leuven, Belgium Department of Radiology and Nuclear Medicine, Amsterdam UMC, location AMC, University of Amsterdam, The Netherlands Department of Nuclear Medicine, Cliniques Universitaires Saint-Luc, Brussel.

Background: Accurate scar assessment is crucial in cardiac resynchronization therapy (CRT) candidates, since its presence is a negative predictor for CRT response. Therefore, we assessed the performance of different PET parameters to detect scar in CRT candidates.

Methods: Twenty-nine CRT candidates underwent 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT), resting 13N-NH3-PET/CT and cardiac magnetic resonance (CMR) prior to CRT implantation. Segmental 18F-FDG uptake, late 13N-NH3 uptake and absolute myocardial blood flow (MBF) were evaluated for scar detection using late gadolinium enhancement (LGE) CMR as reference. A receiver operator characteristic (ROC) area under the curve (AUC) ≥0.8 indicated a good accuracy of the methods evaluated.

Results: Scar was present in 111 of 464 segments. None of the approaches could reliably identify segments with nontransmural scar, except for 18F-FDG uptake in the lateral wall (AUC 0.83). Segmental transmural scars could be detected with all methods (AUC ≥ 0.8), except for septal 18F-FDG uptake and MBF in the inferior wall (AUC < 0.8). Late 13N-NH3 uptake was the best parameter for transmural scar detection, independent of its location, with a sensitivity of 80% and specificity of 92% using a cutoff of 66% of the maximum tracer activity.

Conclusions: Late 13N-NH3 uptake is superior to 13N-NH3 MBF and 18F-FDG in detecting transmural scar, independently of its location. However, none of the tested PET parameters was able to accurately detect nontransmural scar.
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http://dx.doi.org/10.1097/MNM.0000000000001533DOI Listing
January 2022

Comparison between Nondedicated and Novel Dedicated Tracking Tool for Right Ventricular and Left Atrial Strain.

J Am Soc Echocardiogr 2021 Nov 17. Epub 2021 Nov 17.

Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Background: Recently, dedicated speckle-tracking solutions for right ventricular (RV) and left atrial (LA) strain assessment have become commercially available. The purpose of this study was to assess the level of agreement between nondedicated (left ventricular [LV] tracking software) and novel dedicated tracking software for RV and LA strain.

Methods: In 200 patients with various cardiovascular pathologies, we measured global longitudinal strain (GLS), free wall strain (FWS), and segmental values, as well as LA strain during reservoir, conduit, and contraction phases, by using the (1) LV-tracking software and (2) the novel dedicated tracking software for RV or LA strain analysis. Agreement between corresponding measurements obtained with the LV and dedicated RV or LA software was determined by using mean absolute difference (MAD) and Bland-Altman test. The intra- and interobserver reproducibility related to the nondedicated and novel dedicated tracking software was tested in 30 randomly selected subjects.

Results: The dedicated RV-tracking software provided slightly lower strain values without reaching statistical significance. The agreement between software was best for RV GLS (MAD, 2.4 ± 1.8) and significantly poorer for segmental values (MAD ranging from 4.5 ± 3.8 to 5.1 ± 4.0; analysis of variance, P < .05). The intra- and interobserver reproducibility for RV measurements was similar with both software (P > .05 for all parameters). Left atrial mean values showed no statistical difference when obtained with the two tracking tools. The use of LA dedicated tracking software increased significantly the intra- and interobserver reproducibility for LA strain during reservoir and atrial contraction (P < .01 for both).

Conclusions: Our results suggest that the choice of tracking software does not significantly impact RV strain measurements. Nonetheless, the use of the same tracking software is recommended when performing serial measurements. The use of the dedicated software for LA strain analysis significantly improved the intra- and interobserver reproducibility.
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http://dx.doi.org/10.1016/j.echo.2021.11.011DOI Listing
November 2021

Left Atrial Strain Determinants During the Cardiac Phases.

JACC Cardiovasc Imaging 2021 Oct 7. Epub 2021 Oct 7.

Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium; Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Objectives: The present study investigated the determinants of left atrial (LA) strain in all phases of the cardiac cycle.

Background: LA strain by speckle-tracking echocardiography allows the assessment of LA function in each phase of the cardiac cycle. However, its determinants and its relation with left ventricular (LV) function have not yet been fully described.

Methods: The authors performed a retrospective analysis in 127 patients with different cardiovascular pathologies. Using 2-dimensional speckle tracking in 4- and 2-chamber apical views we derived both LA and LV strain curves. Strain-strain loops were reconstructed using LV strain and the corresponding, synchronized LA strain data. Linear regressions were calculated for the entire strain-strain loop as well as for the 3 phases of the cardiac cycle (systole, and early and late diastole). The association between LA strain parameters and LV systolic and diastolic parameters was studied. The prediction of cardiovascular events was evaluated for both measured and predicted LA strain and other parameters.

Results: LA and LV strain curves presented excellent correlations with an R >0.9 for the cardiac cycle, and >0.97 for its phases. Moreover, the ratios of LV/LA maximal volumes and the slopes of the LA-LV strain-strain loops of the individual patients correlated well (R = 0.75). In each phase of the cardiac cycle, LA strain parameters correlated well with the corresponding LV strain and the LV-LA volume ratio (R >0.78). No significant difference in predictive ability of cardiovascular events or atrial fibrillation between the measured and predicted LA strain was observed (P > 0.05 for both).

Conclusions: In the absence of abnormal LA/LV volume exchange, LA strain is, to a large extent, determined by LV strain and further modulated by the ratio of LV and LA volumes. Nonetheless, measuring LA strain is of high clinical interest because it integrates several parameters into a single, robust, and reproducible measurement.
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http://dx.doi.org/10.1016/j.jcmg.2021.09.009DOI Listing
October 2021

Left atrial strain is a predictor of left ventricular systolic and diastolic reverse remodelling in CRT candidates.

Eur Heart J Cardiovasc Imaging 2021 Aug 25. Epub 2021 Aug 25.

Univ Rennes, CHU Rennes, Departement of Cardiology, Inserm, LTSI-UMR 1099, F-35000 Rennes, France.

Aims: The left atrium (LA) has a pivotal role in cardiac performance and LA deformation is a well-known prognostic predictor in several clinical conditions including heart failure with reduced ejection fraction. The aim of this study is to investigate the effect of cardiac resynchronization therapy (CRT) on both LA morphology and function and to assess the impact of LA reservoir strain (LARS) on left ventricular (LV) systolic and diastolic remodelling after CRT.

Methods And Results: Two hundred and twenty-one CRT-candidates were prospectively included in the study in four tertiary centres and underwent echocardiography before CRT-implantation and at 6-month follow-up (FU). CRT-response was defined by a 15% reduction in LV end-systolic volume. LV systolic and diastolic remodelling were defined as the percent reduction in LV end-systolic and end-diastolic volume at FU. Indexed LA volume (LAVI) and LV-global longitudinal (GLS) strain were the main parameters correlated with LARS, with LV-GLS being the strongest determinant of LARS (r = -0.59, P < 0.0001). CRT induced a significant improvement in LAVI and LARS in responders (both P < 0.0001). LARS was an independent predictor of both LV systolic and diastolic remodelling at follow-up (r = -0.14, P = 0.049 and r = -0.17, P = 0.002, respectively).

Conclusion: CRT induces a significant improvement in LAVI and LARS in responders. In CRT candidates, the evaluation of LARS before CRT delivery is an independent predictor of LV systolic and diastolic remodelling at FU.
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http://dx.doi.org/10.1093/ehjci/jeab163DOI Listing
August 2021

Lateral Wall Dysfunction Signals Onset of Progressive Heart Failure in Left Bundle Branch Block.

JACC Cardiovasc Imaging 2021 Nov 16;14(11):2059-2069. Epub 2021 Jun 16.

Institute for Surgical Research, Rikshospitalet, Oslo University Hospital and University of Oslo, Oslo, Norway; Department of Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address:

Objectives: This study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT).

Background: LBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT.

Methods: In 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EF), 36% to 49% (EF), and ≤35% (EF). Sixty-four patients underwent CRT and were re-examined after 6 months.

Results: Septal work was successively reduced from controls, through EF, EF, and EF (all p < 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p < 0.005). In contrast, LV lateral wall work was numerically increased in EF and EF versus controls, and did not significantly correlate with LVEF in these groups. In EF however, LV lateral wall work was substantially reduced (p < 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p < 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p < 0.005).

Conclusions: In early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT.
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http://dx.doi.org/10.1016/j.jcmg.2021.04.017DOI Listing
November 2021

Diastolic function assessment based on a semi-automated computing of strain-volume loops.

Eur Heart J Cardiovasc Imaging 2021 04;22(5):597-598

Department of Cardiovascular Diseases, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1093/ehjci/jeab004DOI Listing
April 2021

Cardiac Microvascular Endothelial Cells in Pressure Overload-Induced Heart Disease.

Circ Heart Fail 2021 01 19;14(1):e006979. Epub 2021 Jan 19.

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Background: Chronic pressure overload predisposes to heart failure, but the pathogenic role of microvascular endothelial cells (MiVEC) remains unknown. We characterized transcriptional, metabolic, and functional adaptation of cardiac MiVEC to pressure overload in mice and patients with aortic stenosis (AS).

Methods: In mice subjected to transverse aortic constriction or sham surgery, we performed RNA sequencing of isolated cardiac -MiVEC and validated the signature in freshly isolated MiVEC from left ventricle outflow tract and right atrium of patients with AS. We next compared their angiogenic and metabolic profiles and finally correlated molecular and pathological signatures with clinical phenotypes of 42 patients with AS (50% women).

Results: In mice, transverse aortic constriction induced progressive systolic dysfunction, fibrosis, and reduced microvascular density. After 10 weeks, 25 genes predominantly involved in matrix-regulation were >2-fold upregulated in isolated MiVEC. Increased transcript levels of (), , , and were confirmed by quantitative reverse transcription polymerase chain reaction and recapitulated in left ventricle outflow tract-derived MiVEC of AS (<0.05 versus right atrium-MiVEC). Fatty acid oxidation increased >2-fold in left ventricle outflow tract-MiVEC, proline content by 130% (median, IQR, 58%-474%; =0.008) and procollagen secretion by 85% (mean [95% CI, 16%-154%]; <0.05 versus right atrium-MiVEC for all). The altered transcriptome in left ventricle outflow tract-MiVEC was associated with impaired 2-dimensional-vascular network formation and 3-dimensional-spheroid sprouting (<0.05 versus right atrium-MiVEC), profibrotic ultrastructural changes, and impaired diastolic left ventricle function, capillary density and functional status, especially in female AS.

Conclusions: Pressure overload induces major transcriptional and metabolic adaptations in cardiac MiVEC resulting in excess interstitial fibrosis and impaired angiogenesis. Molecular rewiring of MiVEC is worse in women, compromises functional status, and identifies novel targets for intervention.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.006979DOI Listing
January 2021

Inter-vendor variability in strain measurements depends on software rather than image characteristics.

Int J Cardiovasc Imaging 2021 May 16;37(5):1689-1697. Epub 2021 Jan 16.

Department of Cardiovascular Diseases, University Hospital Leuven, Herestraat 49, 3000, Leuven, Belgium.

Despite standardization efforts, vendors still use specific proprietary software algorithms for echocardiographic strain measurements, which result in high inter-vendor variability. Using vendor-independent software could be one solution. Little is known, however, how vendor specific image characteristics can influence tracking results of such software. We therefore investigated the reproducibility, accuracy, and scar detection ability of strain measurements on images from different vendors by using a vendor-independent software. A vendor-independent software (TomTec Image Arena) was used to analyse datasets of 63 patients which were obtained on machines from four different ultrasound machine vendors (GE, Philips, Siemens, Toshiba). We measured the tracking feasibility, inter-vendor bias, the relative test-re-test variability and scar discrimination ability of strain measurements. Cardiac magnetic resonance delayed enhancement images were used as the reference standard of scar definition. Tracking feasibility on vendor datasets were significantly different (p < 0.001). Variability of global longitudinal strain (GLS) measurements was similar among the vendors whereas variability of segmental longitudinal strain (SLS) showed modest difference. Relative test-re-test variability of GLS and SLS showed no relevant differences. No significant difference in scar detection capability was observed. Average GLS and SLS values were similar among vendors. Reproducibility of GLS measurements showed no difference among vendors and was in acceptable range. SLS reproducibility was high but similar for all vendors. No relevant difference was found for identifying regional dysfunction. Tracking feasibility showed a substantial difference among images from different vendors. Our findings demonstrate that tracking results depend mainly on the software used and show little influence from vendor specific image characteristics.
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http://dx.doi.org/10.1007/s10554-020-02155-2DOI Listing
May 2021

Importance of Systematic Right Ventricular Assessment in Cardiac Resynchronization Therapy Candidates: A Machine Learning Approach.

J Am Soc Echocardiogr 2021 05 7;34(5):494-502. Epub 2021 Jan 7.

Université de Rennes, CHU Rennes, Inserm, LTSI - UMR 1099, Rennes, France. Electronic address:

Background: Despite all having systolic heart failure and broad QRS intervals, patients screened for cardiac resynchronization therapy (CRT) are highly heterogeneous, and it remains extremely challenging to predict the impact of CRT devices on left ventricular function and outcomes. The aim of this study was to evaluate the relative impact of clinical, electrocardiographic, and echocardiographic data on the left ventricular remodeling and prognosis of CRT candidates by the application of machine learning approaches.

Methods: One hundred ninety-three patients with systolic heart failure receiving CRT according to current recommendations were prospectively included in this multicenter study. A combination of the Boruta algorithm and random forest methods was used to identify features predicting both CRT volumetric response and prognosis. Model performance was tested using the area under the receiver operating characteristic curve. The k-medoid method was also applied to identify clusters of phenotypically similar patients.

Results: From 28 clinical, electrocardiographic, and echocardiographic variables, 16 features were predictive of CRT response, and 11 features were predictive of prognosis. Among the predictors of CRT response, eight variables (50%) pertained to right ventricular size or function. Tricuspid annular plane systolic excursion was the main feature associated with prognosis. The selected features were associated with particularly good prediction of both CRT response (area under the curve, 0.81; 95% CI, 0.74-0.87) and outcomes (area under the curve, 0.84; 95% CI, 0.75-0.93). An unsupervised machine learning approach allowed the identification of two phenogroups of patients who differed significantly in clinical variables and parameters of biventricular size and right ventricular function. The two phenogroups had significantly different prognosis (hazard ratio, 4.70; 95% CI, 2.1-10.0; P < .0001; log-rank P < .0001).

Conclusions: Machine learning can reliably identify clinical and echocardiographic features associated with CRT response and prognosis. The evaluation of both right ventricular size and functional parameters has pivotal importance for the risk stratification of CRT candidates and should be systematically performed in patients undergoing CRT.
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http://dx.doi.org/10.1016/j.echo.2020.12.025DOI Listing
May 2021

Left ventricular regional glucose metabolism in combination with septal scar extent identifies CRT responders.

Eur J Nucl Med Mol Imaging 2021 07 8;48(8):2437-2446. Epub 2021 Jan 8.

Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Background: Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain.

Purpose: We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT.

Methods: Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent.

Results: We evaluated 88 patients (67 ± 10 years, 72% males). F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively.

Conclusions: FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.
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http://dx.doi.org/10.1007/s00259-020-05161-7DOI Listing
July 2021

Shear Wave Elastography Using High-Frame-Rate Imaging in the Follow-Up of Heart Transplantation Recipients.

JACC Cardiovasc Imaging 2020 11 28;13(11):2304-2313. Epub 2020 Sep 28.

Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Objectives: The purpose of this study was to investigate whether propagation velocities of naturally occurring shear waves (SWs) at mitral valve closure (MVC) increase with the degree of diffuse myocardial injury (DMI) and with invasively determined LV filling pressures as a reflection of an increase in myocardial stiffness in heart transplantation (HTx) recipients.

Background: After orthotopic HTx, allografts undergo DMI that contributes to functional impairment, especially to increased passive myocardial stiffness, which is an important pathophysiological determinant of left ventricular (LV) diastolic dysfunction. Echocardiographic SW elastography is an emerging approach for measuring myocardial stiffness in vivo. Natural SWs occur after mechanical excitation of the myocardium, for example, after MVC, and their propagation velocity is directly related to myocardial stiffness, thus providing an opportunity to assess myocardial stiffness at end-diastole.

Methods: A total of 52 HTx recipients who underwent right heart catheterization (all) and cardiac magnetic resonance (CMR) (n = 23) during their annual check-up were prospectively enrolled. Echocardiographic SW elastography was performed in parasternal long axis views of the LV using an experimental scanner at 1,135 ± 270 frames per second. The degree of DMI was quantified with T1 mapping.

Results: SW velocity at MVC correlated best with native myocardial T1 values (r = 0.75; p < 0.0001) and was the best noninvasive parameter that correlated with pulmonary capillary wedge pressures (PCWP) (r = 0.54; p < 0.001). Standard echocardiographic parameters of LV diastolic function correlated poorly with both native T1 and PCWP values.

Conclusions: End-diastolic SW propagation velocities, as measure of myocardial stiffness, showed a good correlation with CMR-defined diffuse myocardial injury and with invasively determined LV filling pressures in patients with HTx. Thus, these findings suggest that SW elastography has the potential to become a valuable noninvasive method for the assessment of diastolic myocardial properties in HTx recipients.
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http://dx.doi.org/10.1016/j.jcmg.2020.06.043DOI Listing
November 2020

Imaging predictors of response to cardiac resynchronization therapy: left ventricular work asymmetry by echocardiography and septal viability by cardiac magnetic resonance.

Eur Heart J 2020 10;41(39):3813-3823

Institute for Surgical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.

Aims: Left ventricular (LV) failure in left bundle branch block is caused by loss of septal function and compensatory hyperfunction of the LV lateral wall (LW) which stimulates adverse remodelling. This study investigates if septal and LW function measured as myocardial work, alone and combined with assessment of septal viability, identifies responders to cardiac resynchronization therapy (CRT).

Methods And Results: In a prospective multicentre study of 200 CRT recipients, myocardial work was measured by pressure-strain analysis and viability by cardiac magnetic resonance (CMR) imaging (n = 125). CRT response was defined as ≥15% reduction in LV end-systolic volume after 6 months. Before CRT, septal work was markedly lower than LW work (P < 0.0001), and the difference was largest in CRT responders (P < 0.001). Work difference between septum and LW predicted CRT response with area under the curve (AUC) 0.77 (95% CI: 0.70-0.84) and was feasible in 98% of patients. In patients undergoing CMR, combining work difference and septal viability significantly increased AUC to 0.88 (95% CI: 0.81-0.95). This was superior to the predictive power of QRS morphology, QRS duration and the echocardiographic parameters septal flash, apical rocking, and systolic stretch index. Accuracy was similar for the subgroup of patients with QRS 120-150 ms as for the entire study group. Both work difference alone and work difference combined with septal viability predicted long-term survival without heart transplantation with hazard ratio 0.36 (95% CI: 0.18-0.74) and 0.21 (95% CI: 0.072-0.61), respectively.

Conclusion: Assessment of myocardial work and septal viability identified CRT responders with high accuracy.
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http://dx.doi.org/10.1093/eurheartj/ehaa603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599033PMC
October 2020

Speckle tracking deformation imaging to detect regional fibrosis in hypertrophic cardiomyopathy: a comparison between 2D and 3D echo modalities.

Eur Heart J Cardiovasc Imaging 2020 10;21(11):1262-1272

Department of Cardiovascular Diseases, University Hospital Leuven, Catholic University Leuven, Herestraat 49, 3000 Leuven, Belgium.

Aims: We aimed at directly comparing three-dimensional (3D) and two-dimensional (2D) deformation parameters in hypertrophic hearts and depict which may best reflect underlying fibrosis in hypertrophic cardiomyopathy (HCM), defined by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR).

Methods And Results: We included 40 HCM [54.1 ± 14.3 years, 82.5% male, maximum wall thickness (MWT) 19.3 ± 4.8 mm] and 15 hypertensive (HTN) patients showing myocardial hypertrophy (58.1 ± 15.6 years, 80% male, MWT 12.8 ± 1.4 mm) who have consecutively undergone 2D-, 3D-speckle tracking echocardiography and LGE CMR. Deformation parameters (2D and 3D) presented overall poor to moderate correlations, with 3D_longitudinal strain (LS) and 3D_circumferential strain (CS) values being constantly higher compared to 2D derivatives. By regression analysis, hypertrophy substrate (HCM vs. hypertension) and hypertrophy magnitude were the parameters to influence 2D-3D LS and CS strain correlations (R2 = 0.66, P < 0.001 and R2 = 0.5, P = 0.001 accordingly). Among segmental deformation indices, 2D_LS showed the best area under the curve [AUC = 0.78, 95% confidence intervals (CI) (0.75-0.81), P < 0.0005] to detect fibrosis, with 3D deformation parameters showing similar AUC (0.65) and 3D_LS presenting the highest specificity [93.1%, 95% CI (90.6-95.1)].

Conclusions: In hypertrophic hearts, 2D and 3D deformation parameters are not interchangeable, showing modest correlations. Thickness, substrate, and tracking algorithm calculating assumptions seem to induce this variability. Nevertheless, among HCM patients 2D_peak segmental longitudinal strain remains the best strain parameter for tissue characterization and fibrosis detection.
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http://dx.doi.org/10.1093/ehjci/jeaa057DOI Listing
October 2020

Acute redistribution of regional left ventricular work by cardiac resynchronization therapy determines long-term remodelling.

Eur Heart J Cardiovasc Imaging 2020 06;21(6):619-628

Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.

Aims: Investigating the acute impact of cardiac resynchronization therapy (CRT) on regional myocardial work distribution in the left ventricle (LV) and to which extent it is related to long-term reverse remodelling.

Methods And Results: One hundred and thirty heart failure patients, referred for CRT implantation, were recruited in our prospective multicentre study. Regional myocardial work was calculated from non-invasive segmental stress-strain loop area before and immediately after CRT. The magnitude of volumetric reverse remodelling was determined from the change in LV end-systolic volume, 11 ± 2 months after implantation. CRT caused acute redistribution of myocardial work across the LV, with an increase in septal work, and decrease in LV lateral wall work (all P < 0.05). Amongst all LV walls, the acute change in work in the septum and lateral wall of the four-chamber view correlated best and significantly with volumetric reverse remodelling (r = 0.62, P < 0.0001), with largest change seen in patients with most volumetric reverse remodelling. In multivariate linear regression analysis, including conventional parameters, such as pre-implant QRS morphology and duration, LV ejection fraction, ischaemic origin of cardiomyopathy, and the redistribution of work across the septal and lateral walls, the latter appeared as the strongest determinant of volumetric reverse remodelling after CRT (model R2 = 0.414, P < 0.0001).

Conclusion: The acute redistribution of regional myocardial work between the septal and lateral wall of the LV is an important determinant of reverse remodelling after CRT implantation. Our data suggest that the treatment of the loading imbalance should, therefore, be the main aim of CRT.
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http://dx.doi.org/10.1093/ehjci/jeaa003DOI Listing
June 2020

Mechanical Effects on Right Ventricular Function From Left Bundle Branch Block and Cardiac Resynchronization Therapy.

JACC Cardiovasc Imaging 2020 07 15;13(7):1475-1484. Epub 2020 Jan 15.

Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address:

Objectives: The purpose of this study was to investigate how LBBB and CRT modify RV free wall function by direct ventricular interaction.

Background: Right ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function.

Methods: In 24 patients with LBBB with nonischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers.

Results: Patients with LBBB demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall, which pushed the septum toward the RV. CRT reduced abnormal septal motion and increased RV free wall work because there was less inefficient shortening against low pressure.

Conclusions: LBBB reduces workload on the RV free wall because of abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185).
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http://dx.doi.org/10.1016/j.jcmg.2019.11.016DOI Listing
July 2020

Low septal to lateral wall F-FDG ratio is highly associated with mechanical dyssynchrony in non-ischemic CRT candidates.

EJNMMI Res 2019 Dec 9;9(1):105. Epub 2019 Dec 9.

Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Background: In order to better understand the concept of mechanical dyssynchrony, a promising hallmark of cardiac resynchronization therapy (CRT) response, we investigated its effect on regional myocardial metabolism and myocardial blood flow (MBF) in non-ischemic CRT candidates.

Results: Thirty consecutive non-ischemic CRT eligible patients underwent static F-FDG and resting dynamic N-NH PET/CT. F-FDG uptake and MBF for septal and lateral wall were analysed and septal-to-lateral wall ratios (SLR) were calculated. Based on the presence of mechanical dyssynchrony (septal flash and/or apical rocking) on echocardiography, patients were divided into 2 groups, with (n = 23) and without (n = 7) mechanical dyssynchrony. Patients with mechanical dyssynchrony had significantly lower F-FDG SUVmean in the septum compared with the lateral wall (5.58 ± 2.65 vs 11.19 ± 4.10, p < 0.0001), while patients without mechanical dyssynchrony had a more homogeneous F-FDG distribution (7.33 ± 2.88 vs 8.31 ± 2.50, respectively, p = 0.30). Similarly, MBF was significantly different between the septal and lateral wall in the dyssynchrony group (0.57 ± 0.11 ml/g/min vs 0.92 ± 0.23 ml/g/min, respectively, p < 0.0001), whereas no difference was observed in the non-dyssynchrony group (0.61 ± 0.23 ml/g/min vs 0.77 ± 0.21 ml/g/min, respectively, p = 0.16). F-FDG SLR, but not MBF SLR, was associated with the presence of mechanical dyssynchrony and showed a significant inverse correlation with volumetric reverse remodeling after CRT (r = - 0.62, p = 0.001).

Conclusions: Non-ischemic heart failure patients with mechanical dyssynchrony demonstrate heterogeneous regional metabolism and MBF compared with patients without dyssynchrony. However, only F-FDG SLR appeared to be highly associated with the presence of mechanical dyssynchrony.

Trial Registration: Clinicaltrials, NCT02537782. Registered 2 September 2015.
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http://dx.doi.org/10.1186/s13550-019-0575-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901655PMC
December 2019

Regional myocardial work by cardiac magnetic resonance and non-invasive left ventricular pressure: a feasibility study in left bundle branch block.

Eur Heart J Cardiovasc Imaging 2020 02;21(2):143-153

Center for Cardiological Innovation, Oslo University Hospital, Oslo, Norway.

Aims: Regional myocardial work may be assessed by pressure-strain analysis using a non-invasive estimate of left ventricular pressure (LVP). Strain by speckle tracking echocardiography (STE) is not always accessible due to poor image quality. This study investigated the estimation of regional myocardial work from strain by feature tracking (FT) cardiac magnetic resonance (CMR) and non-invasive LVP.

Methods And Results: Thirty-seven heart failure patients with reduced ejection fraction, left bundle branch block (LBBB), and no myocardial scar were compared to nine controls without LBBB. Circumferential strain was measured by FT-CMR in a mid-ventricular short-axis cine view, and longitudinal strain by STE. Segmental work was calculated by pressure-strain analysis. Twenty-five patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography. Segmental values were reported as percentages of the segment with maximum myocardial FDG uptake. In LBBB patients, net CMR-derived work was 51 ± 537 (mean ± standard deviation) in septum vs. 1978 ± 1084 mmHg·% in the left ventricular (LV) lateral wall (P < 0.001). In controls, however, there was homogeneous work distribution with similar values in septum and the LV lateral wall (non-significant). Reproducibility was good. Segmental CMR-derived work correlated with segmental STE-derived work and with segmental FDG uptake (average r = 0.71 and 0.80, respectively).

Conclusion: FT-CMR in combination with non-invasive LVP demonstrated markedly reduced work in septum compared to the LV lateral wall in patients with LBBB. Work distribution correlated with STE-derived work and energy demand as reflected in FDG uptake. These results suggest that FT-CMR in combination with non-invasive LVP is a relevant clinical tool to measure regional myocardial work.
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http://dx.doi.org/10.1093/ehjci/jez231DOI Listing
February 2020

Impact of left bundle branch block on myocardial perfusion and metabolism: A positron emission tomography study.

J Nucl Cardiol 2021 Aug 2;28(4):1730-1739. Epub 2019 Oct 2.

Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Background: Better understanding of pathophysiological changes, induced by left bundle branch block (LBBB), may improve patient selection for cardiac resynchronization therapy (CRT). Therefore, we assessed the effect of LBBB on regional glucose metabolism, N-NH-derived absolute and semiquantitative myocardial blood flow (MBF), and their relation in non-ischemic CRT candidates.

Methods: Twenty-five consecutive non-ischemic patients with LBBB underwent F-FDG and resting dynamic N-NH PET/CT prior to CRT implantation. Regional F-FDG uptake, absolute MBF, and late N-NH uptake were analyzed and corresponding septal-to-lateral wall ratios (SLR) were calculated. Segmental analysis was performed to evaluate "reverse mismatch," "mismatch," and "match" patterns, based on late N-NH/F-FDG uptake ratios.

Results: A significantly lower F-FDG uptake was observed in the septum compared to the lateral wall (SLR 0.53 ± 0.17). A similar pattern was observed for MBF (SLR 0.68 ± 0.18), whereas late N-NH uptake showed a homogeneous distribution (SLR 0.96 ± 0.13). N-NH/F-FDG "mismatch" and "reverse mismatch" segments were predominantly present in the lateral (52%) and septal wall (61%), respectively.

Conclusions: Non-ischemic CRT candidates with LBBB demonstrate lower glucose uptake and absolute MBF in the septum compared to the lateral wall. However, late static N-NH uptake showed a homogenous distribution, reflecting a composite measure of altered regional MBF and metabolism, induced by LBBB.
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http://dx.doi.org/10.1007/s12350-019-01900-yDOI Listing
August 2021

Interplay of cardiac remodelling and myocardial stiffness in hypertensive heart disease: a shear wave imaging study using high-frame rate echocardiography.

Eur Heart J Cardiovasc Imaging 2020 06;21(6):664-672

Department of Cardiovascular Sciences, University of Leuven, Herestraat 49, 3000 Leuven, Belgium.

Aims: To determine myocardial stiffness by means of measuring the velocity of naturally occurring myocardial shear waves (SWs) at mitral valve closure (MVC) and investigate their changes with myocardial remodelling in patients with hypertensive heart disease.

Methods And Results: Thirty-three treated arterial hypertension (HT) patients with hypertrophic left ventricular (LV) remodelling (59 ± 14 years, 55% male) and 26 aged matched healthy controls (55±15 years, 77% male) were included. HT patients were further divided into a concentric remodelling (HT1) group (13 patients) and a concentric hypertrophy (HT2) group (20 patients). LV parasternal long-axis views were acquired with an experimental ultrasound scanner at 1266 ± 317 frames per seconds. The SW velocity induced by MVC was measured from myocardial acceleration maps. SW velocities differed significantly between HT patients and controls (5.83 ± 1.20 m/s vs. 4.04 ± 0.96 m/s; P < 0.001). In addition, the HT2 group had the highest SW velocities (P < 0.001), whereas values between controls and the HT1 group were comparable (P = 0.075). Significant positive correlations were found between SW velocity and LV remodelling (interventricular septum thickness: r = 0.786, P < 0.001; LV mass index: r = 0.761, P < 0.001). SW velocity normalized for wall stress indicated that myocardial stiffness in the HT2 group was twice as high as in controls (P < 0.001), whereas values of the HT1 group overlapped with the controls (P = 1.00).

Conclusions: SW velocity as measure of myocardial stiffness is higher in HT patients compared with healthy controls, particularly in advanced hypertensive heart disease. Patients with concentric remodelling have still normal myocardial properties whereas patients with concentric hypertrophy show significant stiffening.
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http://dx.doi.org/10.1093/ehjci/jez205DOI Listing
June 2020

How Does Regional Hypertrophy Affect Strain Measurements With Different Speckle-Tracking Methods?

J Am Soc Echocardiogr 2019 11 31;32(11):1444-1450. Epub 2019 Jul 31.

Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. Electronic address:

Background: In this study, we evaluate the impact of abnormal myocardial shapes, such as regional hypertrophy, on longitudinal strain measurements with different tracking approaches.

Methods: We selected 40 patients with normal ejection fraction and prominent septal bulge. We assessed longitudinal strain with full wall (FW) tracking, (GE EchoPAC) as well as endo-, mid-, and epicardial (EME) tracking (Tomtec ImageArena), on the same image acquired with a GE machine (using raw data and full frame rate DICOM data, respectively). We used a region of interest (ROI) which follows precisely the endo- and epicardial contours (true contour ROI) and one where the bulging region was excluded (straight ROI).

Results: In segments with bulge, absolute segmental longitudinal strain values were in all myocardial layers significantly higher with a straight ROI compared to a true contour ROI, both with FW tracking and EME tracking. The highest difference was found in the endocardial layer (3.4 ± 2.5% and 7.7 ± 7.1%, respectively, both P < 0.001). In the bulged segments, the effect of ROI shape was more pronounced in EME tracking software compared to FW tracking software. Bulged segments also influenced global longitudinal strain measurements, mostly in the endocardial layer (P < 0.001). Global longitudinal strain values obtained with the straight ROI correlated better with longitudinal fractional shortening of the LV.

Conclusions: Regional bulging has a significant effect on both global and segmental strain measurements. Endocardial strain values obtained with EME tracking and a true contour ROI were most sensitive to bulging. Midwall strain values derived from FW tracking using a straight ROI were most robust.
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http://dx.doi.org/10.1016/j.echo.2019.06.008DOI Listing
November 2019

Impact of apical foreshortening on deformation measurements: a report from the EACVI-ASE Strain Standardization Task Force.

Eur Heart J Cardiovasc Imaging 2020 03;21(3):337-343

Department of Cardiovascular Diseases, University Hospital Leuven, Herestraat 49, 3000 Leuven, Belgium.

Aims: Foreshortening of apical views is a common problem in echocardiography. It results in an abnormally thick false apex and a shortened left ventricular (LV) long axis. We sought to evaluate the impact of foreshortened (FS) on LV ejection fraction (LVEF) and layer-specific 2D speckle tracking based segmental (S) and global (G) longitudinal strain (LS) measurements.

Methods And Results: We examined 72 participants using a GE Vivid E9 system. FS apical views were collected from an imaging window one rib-space higher than the optimal images. Ejection fraction as well as layer-specific GLS and SLS measurements were analysed by GE EchoPAC v201 and TomTec Image Arena 4.6 and compared between optimal and FS images. On average, LV long axis was 10% shorter in FS images than in optimal images. FS induced a relative change in LVEF of 3.3% and 6.9% for GE and TomTec, respectively (both, P < 0.001). Endocardial GLS was 9.0% higher with GE and 23.2% with TomTec (P < 0.001). Midwall GLS measurements were less affected (7.8% for GE and 14.1% for TomTec, respectively, both P < 0.001). Segmental strain analysis revealed that the mid-ventricular and apical segments were more affected by foreshortening, and endocardial measurements were more affected than midwall.

Conclusion: Optimal image geometry is crucial for accurate LV function assessment. Foreshorhening of apical views has a substantial impact on longitudinal strain measurements, predominantly in the apex and in the endocardial layer. Our data suggest that measuring midwall strain might therefore be the more robust approach for clinical routine use.
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http://dx.doi.org/10.1093/ehjci/jez189DOI Listing
March 2020

Non-invasive myocardial performance mapping using 3D echocardiographic stress-strain loops.

Phys Med Biol 2019 06 5;64(11):115026. Epub 2019 Jun 5.

Laboratory on Cardiovascular Imaging and Dynamics, Department of Cardiovascular Sciences, KU Leuven, Belgium.

Regional contribution to left ventricular (LV) ejection is of much clinical importance but its assessment is notably challenging. While deformation imaging is often used, this does not take into account loading conditions. Recently, a method for intraventricular pressure estimation was proposed, thus allowing for loading conditions to be taken into account in a non-invasive way. In this work, a method for 3D automatic myocardial performance mapping in echocardiography is proposed by performing 3D myocardial segmentation and tracking, thus giving access to local geometry and strain. This is then used to assess local LV stress-strain relationships which can be seen as a measure of local myocardial work. The proposed method was validated against F-fluorodeoxyglucose positron emission tomography, the reference method to clinically assess local metabolism. Averaged over all patients, the mean correlation between FDG-PET and the proposed method was [Formula: see text]. In conclusion, stress-strain loops were, for the first time, estimated from 3D echocardiography and correlated to the clinical gold standard for local metabolism, showing the future potential of real-time 3D echocardiography (RT3DE) for the assessment of local metabolic activity of the heart.
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http://dx.doi.org/10.1088/1361-6560/ab21f8DOI Listing
June 2019

Left Ventricular Remodeling Results in Homogenization of Myocardial Work Distribution.

Circ Arrhythm Electrophysiol 2019 05;12(5):e007224

Department of Cardiovascular Sciences (J.D., S.Ü., E.D.P., S.B., M.C., P.C., F.R., J.-U.V.), KU Leuven, Belgium.

Background: The interaction between regional left ventricular (LV) myocardial work and metabolism in remodeled hearts has not yet been well established. Our aim was to investigate the effect of inhomogeneous LV work distribution on regional metabolism and remodeling in our animal model with reversible dyssynchrony due to pacing.

Methods: In 12 sheep, 8 weeks of right atrial and right ventricular free wall (DDD) pacing lead to LV dilatation, a thinned septum, and thickened lateral wall. Left bundle branch block-like dyssynchrony caused by DDD pacing could be acutely reverted by right atrial pacing (AAI) only. Invasive hemodynamics and echocardiography were used to assess regional work by stress-strain loop area and compared with regional glucose metabolism measured by F-fluorodeoxyglucose positron emission tomography with and without improved spatial resolution by motion and anatomy correction on gated reconstructions.

Results: Glucose metabolism by positron emission tomography with anatomic correction on gated positron emission tomography reconstruction showed a different regional distribution than with clinical reconstructions and correlated best and significantly with regional myocardial work. At baseline, work was homogeneously distributed with normal conduction (AAI pacing), whereas during dyssynchrony (DDD pacing), the lateral wall was more loaded, and the septum was unloaded. After 8 weeks of remodeling under DDD pacing, however, an almost homogeneous work distribution was found with DDD pacing, whereas with AAI pacing, the thin septum showed exaggerated loading and the lateral walls a low load. Our experimental observations were confirmed in 5 patient responders to cardiac resynchronization therapy.

Conclusions: Regional LV glucose metabolism closely correlates with regional work. Our data indicate that regionally different LV remodeling after exposure to inhomogeneous loading conditions, such as during LV dyssynchrony, is an adaptive process that helps to equilibrate work distribution. Correction of the inhomogeneous loading conditions, such as during cardiac resynchronization therapy, then triggers a reverse LV remodeling through the same mechanism.
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http://dx.doi.org/10.1161/CIRCEP.118.007224DOI Listing
May 2019

Layer-Specific Segmental Longitudinal Strain Measurements: Capability of Detecting Myocardial Scar and Differences in Feasibility, Accuracy, and Reproducibility, Among Four Vendors A Report From the EACVI-ASE Strain Standardization Task Force.

J Am Soc Echocardiogr 2019 05 14;32(5):624-632.e11. Epub 2019 Mar 14.

Department of Cardiovascular Diseases, University Hospital Leuven, Leuven, Belgium. Electronic address:

Background: Segmental longitudinal strain (SLS) is reported to be vendor specific. Despite standardization efforts, vendors still use different myocardial layers for strain measurements. It is unclear, however, which layer is the most favorable for clinical purposes. Therefore, in this study we evaluated the reproducibility, accuracy, and scar detection ability of SLS measurements from different myocardial layers.

Methods: In data sets of 58 patients with prior myocardial infarction and five healthy volunteers, we measured the intervendor bias, the relative test-retest variability, and scar discrimination ability of endocardial and midwall SLS, using software packages from four different companies (GE, Siemens, Toshiba, and TomTec). Cardiac magnetic resonance delayed enhancement images were used as the reference standard of scar definition.

Results: Variability of SLS measurements was significant among the vendors for both midwall and endocardium. In addition, relative errors of SLS measurements varied considerably among vendors (P < .001 for both layers). Comparisons of test-retest errors from different layers for individual vendors did not show any significant differences. Regardless of the vendor, both endocardial and midwall strain values were decreased in scarred segments. Endocardial to midwall ratio of strain measurements showed no difference between scar-free and scarred segments. Endocardial and midwall strain parameters showed no significant difference in scar detection capability.

Conclusions: Layer-specific SLS measurements vary significantly among vendors. Endocardial and midwall SLS measurements have a high yet comparable test-retest variability. Combining layer-specific SLS measurements does not provide additional information for detection of regional functional abnormalities. Our results do not provide evidence to favor the use of one myocardial layer over another.
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http://dx.doi.org/10.1016/j.echo.2019.01.010DOI Listing
May 2019

Mechanism of Abnormal Septal Motion in Left Bundle Branch Block: Role of Left Ventricular Wall Interactions and Myocardial Scar.

JACC Cardiovasc Imaging 2019 12 13;12(12):2402-2413. Epub 2019 Feb 13.

Institute for Surgical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Oslo, Norway; Department of Cardiology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address:

Objectives: This study sought to investigate how regional left ventricular (LV) function modifies septal motion in left bundle branch block (LBBB).

Background: In LBBB, the interventricular septum often has marked pre-ejection shortening, followed by immediate relengthening (rebound stretch). This motion, often referred to as septal flash, is associated with positive response to cardiac resynchronization therapy (CRT).

Methods: In 10 anesthetized dogs, we induced LBBB by radiofrequency ablation and occluded the circumflex (CX) (n = 10) and left anterior descending (LAD) (n = 6) coronary arteries, respectively. Myocardial dimensions were measured by sonomicrometry and myocardial work by pressure-segment length analysis. In 40 heart failure patients with LBBB, including 20 with post-infarct scar and 20 with nonischemic cardiomyopathy, myocardial strain was measured by speckle-tracking echocardiography and myocardial work by pressure-strain analysis. Scar was assessed by cardiac magnetic resonance imaging with late gadolinium enhancement.

Results: During LBBB, each animal showed typical septal flash with pre-ejection shortening and rebound stretch, followed by reduced septal systolic shortening (p < 0.01). CX occlusion caused LV lateral wall dysfunction and abolished septal flash due to loss of rebound stretch (p < 0.0001). Furthermore, CX occlusion restored septal systolic shortening to a similar level as before induction of LBBB and substantially improved septal work (p < 0.001). LAD occlusion, however, accentuated septal flash by increasing rebound stretch (p < 0.05). Consistent with the experimental findings, septal flash was absent in patients with LV lateral wall scar due to lack of rebound stretch (p < 0.001), and septal systolic shortening and septal work far exceeded values in nonischemic cardiomyopathy (p < 0.0001). Septal flash was present in most patients with anteroseptal scar.

Conclusions: LV lateral wall dysfunction and scar abolished septal flash and markedly improved septal function in LBBB. Therefore, function and scar in the LV lateral wall should be taken into account when septal motion is used to evaluate dyssynchrony.
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http://dx.doi.org/10.1016/j.jcmg.2018.11.030DOI Listing
December 2019

Sex-specific difference in outcome after cardiac resynchronization therapy.

Eur Heart J Cardiovasc Imaging 2019 May;20(5):504-511

Department of Cardiovascular Diseases, University Hospitals Leuven, University of Leuven, Herestraat 49, Leuven, Belgium.

Aims: Observation of better outcome in women after cardiac resynchronization therapy (CRT) has led to controversies about a potential sex-specific response. In this study, we investigated to which extent this sex-specific difference in CRT outcome could be explained by differences in baseline characteristics between both sexes.

Methods And Results: We retrospectively analysed data from a multicentre registry of 1058 patients who received CRT. Patients were examined by echocardiography before and 12 ± 6 months after implantation. Response was defined as ≥15% reduction of left ventricular end-systolic volume at follow-up. Patient's characteristics at baseline, including New York Heart Association class, ejection fraction, QRS width and morphology, ischaemic aetiology of cardiomyopathy (ICM), number of scarred segments, age at implantation, atrial fibrillation, and mechanical dyssynchrony (Dyss) were analysed. Patients were followed for a median duration of 59 months. Primary end point was all-cause mortality. Women (24% of the population) had less ICM (23% vs. 49%, P < 0.0001), less scarred segments (0.4 ± 1.3 vs. 1.0 ± 2.1, P < 0.0001), more left bundle branch block (LBBB; 87% vs. 80%, P = 0.01), and more Dyss at baseline (78% vs. 57%, P < 0.0001). Without matching baseline differences, women showed better survival (log rank P < 0.0001). After matching, survival was similar (log rank P = 0.58). In multivariable analysis, female sex was no independent predictor of neither volumetric response (P = 0.06) nor survival (P = 0.31).

Conclusion: Our data suggest that the repeatedly observed better outcome in women after CRT is mainly due to the lower rate ICM and smaller scars. When comparing patients with similar baseline characteristics, the response of both sexes to CRT is similar.
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http://dx.doi.org/10.1093/ehjci/jey231DOI Listing
May 2019

Relation of regional myocardial structure and function in hypertrophic cardiomyopathy and amyloidois: a combined two-dimensional speckle tracking and cardiovascular magnetic resonance analysis.

Eur Heart J Cardiovasc Imaging 2019 04;20(4):426-437

Department of Cardiovascular Diseases, University Hospital Leuven, Catholic University Leuven, Herestraat 49, Leuven, Belgium.

Aims: We aimed at investigating the relationship between segmental morphology [wall thickness (WT) and WT location (LT: base-mid-apex)], loading conditions and underlying pathological substrate [histology (H), hypertrophy vs. infiltration] with segmental longitudinal (SLS) and circumferential (SCS) strain in a group of patients with hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA).

Methods And Results: We included 30 patients with biopsy-proven CA (65.4 ± 10.7 years, 66% male, 76.7% AL type) and 50 patients with HCM matched for maximum WT (60 ± 16 years, 80% male). SLS and SCS were assessed with speckle-tracking echocardiography in an 18-segment model of left ventricle, while morphological parameters were measured in short-axis cardiovascular magnetic resonance cine loops which corresponded with echo segments. In total, 1440 segments were evaluated of which 198 (36.7%) in CA and 252 (28%) in HCM had WT >12 mm (maximum WT 18.1 ± 3.7 mm in CA vs. 18.6 ± 4.1 in HCM, P = 0.59). SLS showed association with WT [beta 0.49, 95% confidence interval (CI) 0.37-0.6; P < 0.0005], LT and H (P < 0.0005 for both), with CA segments demonstrating 5.94% more impaired SLS compared with HCM segments with the same WT and LT. On the other hand, there was no linear association between SCS and WT, with SCS being dependent on LT, H (P < 0.0005) and preload (P < 0.002).

Conclusion: Our study indicates that regional myocardial mechanics are differentially influenced by local morphological parameters. While SLS is dominated by WT, SCS is more determined by LT and H. These findings may have an important role in diagnosis and prognosis of patients with thickened hearts.
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http://dx.doi.org/10.1093/ehjci/jey107DOI Listing
April 2019

Papillary muscles contribute significantly more to left ventricular work in dilated hearts.

Eur Heart J Cardiovasc Imaging 2019 01;20(1):84-91

Department of Cardiovascular Sciences, KU Leuven-University of Leuven, Herestraat 49, Leuven, Belgium.

Aims: Left ventricular (LV) dilatation results in increased sphericity and affects position and orientation of papillary muscles (PMs), which may influence their performed work. The aim of this study was to assess the contribution of PM to LV function and its changes with dilatation.

Methods And Results: Fifteen sheep were investigated. Ten animals were subjected to 8 weeks of rapid (180 bpm) pacing, inducing LV dilatation. Five animals served as controls. High-resolution gated computed tomography was performed to assess LV volumes, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), sphericity index, and PM angle, width and fractional shortening. 18F-fluorodeoxyglucose positron emission tomography (PET) was used to measure glucose metabolism as surrogate of regional myocardial work. Spatial resolution of PET images was maximized by electrocardiogram- and respiratory-gating. 18F-fluorodeoxyglucose uptake was measured in PM and compared with remaining left ventricular myocardium (MYO) to obtain a PM/MYO ratio. Animals with dilated heart had a more spherical left ventricle, with reduced LVEF (P < 0.0001) and GLS (P < 0.0001). In dilated hearts, PET analysis revealed a higher contribution of both PM to LV myocardial work (P < 0.0001); and PM angle towards LV wall correlated with PM work, together with PM width and the LV sphericity index. Sphericity index and posterior PM angle were strongest determinants of posterior PM/MYO ratio (R2 = 0.754; P < 0.0001), while anterior PM/MYO was mostly determined by sphericity index and the PM width (R2 = 0.805; P < 0.0001).

Conclusion: In dilated hearts, PM contribute relatively more to LV myocardial work. We hypothesize that this is caused by the more cross-sectional orientation of the subvalvular apparatus, which leads to a higher stress on the PM compared with the spherical LV walls. The reduced cross-sectional area of the PM may further explain their increased stress.
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http://dx.doi.org/10.1093/ehjci/jey043DOI Listing
January 2019

Sheep can be used as animal model of regional myocardial remodeling and controllable work.

Cardiol J 2019 23;26(4):375-384. Epub 2018 Mar 23.

Department of Cardiovascular Sciences and Department of Cardiovascular Diseases, KU Leuven - University of Leuven and University Hospitals Leuven, Leuven, Belgium.

Background: Pacing the right heart has been shown to induce reversible conduction delay and subse-quent asymmetric remodeling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore the aim of this study was to develop a more feasible and easy-to-use animal model in sheep.

Methods: Dual-chamber (DDD) pacemakers with epicardial leads on the right atrium and right ven-tricular free wall were implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm.

Results: DDD pacing acutely induced a left bundle branch block (LBBB) - like pattern with almost doubling in QRS width and the appearance of a septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodeling (confirmed with histology) with septal wall thinning (-30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (-31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD pacing decreased immediately work in the septum and increased it in the lateral wall (-69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (-27% and -25%, respectively, p < 0.05).

Conclusions: This study presents the development a new sheep model with an asymmetrically remod-eled LV. Simple pacemaker programing allows direct modulation of regional myocardial function and work. This animal model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodeling.
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http://dx.doi.org/10.5603/CJ.a2018.0007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084358PMC
July 2020
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