Publications by authors named "Bart Bijnens"

198 Publications

Understanding right ventricular dyssynchrony: Its myriad determinants and clinical relevance.

Exp Physiol 2021 Apr 2;106(4):797-800. Epub 2021 Mar 2.

Labatt Family Heart Centre, Division of Cardiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1113/EP089366DOI Listing
April 2021

Septal curvature as a robust and reproducible marker for basal septal hypertrophy.

J Hypertens 2021 Mar 11. Epub 2021 Mar 11.

School of Biomedical Engineering and Imaging Sciences, Kings College London, London, UK Cardiovascular Ultrasound, GE Vingmed, Oslo, Norway Institute of Biomedical Research August Pi Sunyer (IDIBAPS), Barcelona Catalan Institution for Research and Advanced Studies (ICREA), Barcelona Hospital Clinic de Barcelona Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Sant Joan de Déu, Barcelona, Spain.

Background: Basal septal hypertrophy (BSH) is an asymmetric, localized thickening of the upper interventricular septum and constitutes a marker of an early remodelling in patients with hypertension. This morphological trait has been extensively researched because of its prevalence in hypertension, yet its clinical and prognostic value for individual patients remains undetermined. One of the reasons is the lack of a reliable and reproducible metric to quantify the presence and the extent of BSH. This article proposes the use of the curvature of the left ventricular endocardium as a robust feature for BSH characterization, and as an objective criterion to quantify current subjective 'visual assessment' of the presence of sigmoidal septum. The proposed marker, called average septal curvature, is defined as the inverse of the radius adjacent to each point of the endocardial contour along the basal and mid inferoseptal segments of the left ventricle.

Method: Robustness and reproducibility were assessed on a cohort of 220 patients, including 161 hypertensive patients (32 with BSH) and 59 healthy controls.

Results: The results show that compared with the conventionally used wall thickness metrics, the new marker is more reproducible (relative standard deviation of errors of 7 vs. 13%, and 8 vs. 38% for intra-observer and inter-observer variability, respectively) and better correlates to the functional parameters related to BSH, with main difference (absolute rank correlation 0.417 vs. 0.341) in local deformation changes assessed by longitudinal strain.

Conclusion: Average septal curvature is a more precisely defined and reproducible metric than thickness ratios, it can be fully automated, and better infers the functional remodelling related to hypertension.
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http://dx.doi.org/10.1097/HJH.0000000000002813DOI Listing
March 2021

Integration of artificial intelligence into clinical patient management: focus on cardiac imaging.

Rev Esp Cardiol (Engl Ed) 2021 Jan 17;74(1):72-80. Epub 2020 Aug 17.

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; ICREA, Barcelona, Spain.

Cardiac imaging is a crucial component in the management of patients with heart disease, and as such it influences multiple, inter-related parts of the clinical workflow: physician-patient contact, image acquisition, image pre- and postprocessing, study reporting, diagnostics and outcome predictions, medical interventions, and, finally, knowledge-building through clinical research. With the gradual and ubiquitous infiltration of artificial intelligence into cardiology, it has become clear that, when used appropriately, it will influence and potentially improve-through automation, standardization and data integration-all components of the clinical workflow. This review aims to present a comprehensive view of full integration of artificial intelligence into the standard clinical patient management-with a focus on cardiac imaging, but applicable to all information handling-and to discuss current barriers that remain to be overcome before its widespread implementation and integration.
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http://dx.doi.org/10.1016/j.rec.2020.07.003DOI Listing
January 2021

Distribution of myocardial work in arterial hypertension: insights from non-invasive left ventricular pressure-strain relations.

Int J Cardiovasc Imaging 2021 Jan 12;37(1):145-154. Epub 2020 Aug 12.

Institute of Biomedical Research August Pi Sunyer (IDIBAPS), Carrer del Rosselló, 149, 08036, Barcelona, Spain.

A index of non-invasive myocardial work (MWI) can account for pressure during the assessment of cardiac function, potentially separating the influence of loading conditions from the influence of the underlying tissue remodelling. The aim is to assess LV function accounted for loading and explore hypertensive MWI distribution by comparing healthy individuals to hypertensive patients without and with localized basal septal hypertrophy (BSH). An echocardiogram was performed in 170 hypertensive patients and 20 healthy individuals. BSH was defined by a basal-to-mid septal wall thickness ratio ≥ 1.4. LV speckle-tracking was performed, and the MWI calculated globally and regionally for the apical, mid and basal regions. An apex-to-base gradient, seen in regional strain values, was preserved in the distribution of myocardial work, with the apical region compensating for the impairment of the basal segments. This functional redistribution was further pronounced in patients with localized BSH. In these patients, segmental MWI analysis revealed underlying impairment of regional work unrelated to acute loading conditions. Non-invasive MWI analysis offers the possibility to compare LV function regardless of blood pressure at the time of observation. Changes in MWI distribution can be seen in hypertension unrelated to the load-dependency of strain. Accentuated functional changes affirm the role of BSH as an echocardiographic marker in hypertension.
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http://dx.doi.org/10.1007/s10554-020-01969-4DOI Listing
January 2021

Handling confounding variables in statistical shape analysis - application to cardiac remodelling.

Med Image Anal 2020 10 19;65:101792. Epub 2020 Jul 19.

BCN Medtech, Dept. of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain; ICREA, Barcelona, Spain.

Statistical shape analysis is a powerful tool to assess organ morphologies and find shape changes associated to a particular disease. However, imbalance in confounding factors, such as demographics might invalidate the analysis if not taken into consideration. Despite the methodological advances in the field, providing new methods that are able to capture complex and regional shape differences, the relationship between non-imaging information and shape variability has been overlooked. We present a linear statistical shape analysis framework that finds shape differences unassociated to a controlled set of confounding variables. It includes two confounding correction methods: confounding deflation and adjustment. We applied our framework to a cardiac magnetic resonance imaging dataset, consisting of the cardiac ventricles of 89 triathletes and 77 controls, to identify cardiac remodelling due to the practice of endurance exercise. To test robustness to confounders, subsets of this dataset were generated by randomly removing controls with low body mass index, thus introducing imbalance. The analysis of the whole dataset indicates an increase of ventricular volumes and myocardial mass in athletes, which is consistent with the clinical literature. However, when confounders are not taken into consideration no increase of myocardial mass is found. Using the downsampled datasets, we find that confounder adjustment methods are needed to find the real remodelling patterns in imbalanced datasets.
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http://dx.doi.org/10.1016/j.media.2020.101792DOI Listing
October 2020

Comprehensive data integration-Toward a more personalized assessment of diastolic function.

Echocardiography 2020 11 10;37(11):1926-1935. Epub 2020 Jun 10.

Institute of Biomedical Research August Pi Sunyer (IDIBAPS), Barcelona, Spain.

Background And Aim: The main challenge of assessing diastolic function is the balance between clinical utility, in the sense of usability and time-efficiency, and overall applicability, in the sense of precision for the patient under investigation. In this review, we aim to explore the challenges of integrating data in the assessment of diastolic function and discuss the perspectives of a more comprehensive data integration approach.

Methods: Review of traditional and novel approaches regarding data integration in the assessment of diastolic function.

Results: Comprehensive data integration can lead to improved understanding of disease phenotypes and better relation of these phenotypes to underlying pathophysiological processes-which may help affirm diagnostic reasoning, guide treatment options, and reduce limitations related to previously unaddressed confounders. The optimal assessment of diastolic function should ideally integrate all relevant clinical information with all available structural and functional whole cardiac cycle echocardiographic data-envisioning a personalized approach to patient care, a high-reaching future goal in medicine.

Conclusion: Complete data integration seems to be a long-lasting goal, the way forward in diastology, and machine learning seems to be one of the tools suited for the challenge. With perpetual evidence that traditional approaches to complex problems may not the optimal solution, there is room for a steady and cautious, and inherently very exciting paradigm shift toward novel diagnostic tools and workflows to reach a more personalized, comprehensive, and integrated assessment of cardiac function.
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http://dx.doi.org/10.1111/echo.14749DOI Listing
November 2020

Main Patterns of Fetal Cardiac Remodeling.

Fetal Diagn Ther 2020 26;47(5):337-344. Epub 2020 Mar 26.

Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Institut Clínic de Ginecologia Obstetricia i Neonatologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.

The heart is a central organ in the fetal adaptation to an adverse environment. Fetal cardiac changes may persist postnatally and increase the risk of cardiovascular disease in adulthood. Knowledge about fetal cardiac structural as well as functional remodeling has radically improved over the last few years. As it occurs in postnatal life, the fetal heart remodels - changing its structure and shape - to adapt to an insult. Several conditions have been reported to be associated with fetal cardiac remodeling including intrauterine growth restriction, diabetes, exposure to antiretroviral drugs, conception by assisted reproductive technologies, pulmonary stenosis, and other congenital heart diseases. Here we summarized the main observable patterns of cardiac remodeling, i.e., globular shape, hypertrophy without dilation, and hypertrophy with cardiomegaly. We discuss the potential pathophysiology behind different types of remodeling. Defining precisely the distinct patterns of fetal cardiac remodeling is critical for advancing in the understanding of fetal cardiovascular programming and its consequences on adult health, and potentially for the design of preventive strategies that might have an impact on long-term cardiovascular health.
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http://dx.doi.org/10.1159/000506047DOI Listing
March 2021

Basal Ventricular Septal Hypertrophy in Systemic Hypertension.

Am J Cardiol 2020 05 8;125(9):1339-1346. Epub 2020 Feb 8.

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Cardiovascular Institute, Hospital Clínic and Universitat de Barcelona, Barcelona, Spain; CIBERCV, Instituto de Salud Carlos III (CB16/11/00354), CERCA Programme/Generalitat de Catalunya, Madrid, Spain.

Basal septal hypertrophy (BSH) is commonly seen in patients with systemic hypertension and has been associated with increased afterload. The impact of localized hypertrophy on left ventricular (LV) and left atrial (LA) function is still unclear. Our aim is to investigate if BSH is a marker of a more pronounced impact of hypertension on cardiac function in the early stages of hypertensive heart disease. An echocardiogram was performed in 163 well-controlled hypertensive patients and 22 healthy individuals. BSH was defined by a basal-to-mid septal thickness ratio ≥1.4. LV dimensions and mass were evaluated. LV global and regional deformation was assessed by 2-dimensional (2D) speckle tracking echocardiography, and LV diastolic function by 2D and Doppler imaging. LA function was evaluated with phasic volume indices calculated from 2D and 3-dimensional volumes, as well as speckle tracking echocardiography. The population was 54% men, mean age 57 (53 to 60) years. BSH was seen in 20% (n = 32) of the hypertensive cohort. Patients with BSH showed decreased regional LV systolic deformation, impaired LV relaxation with a higher proportion of indeterminate LV diastolic function, and LA functional impairment defined by a reduction of reservoir strain and a change in LA functional dynamics. In conclusion, in well-controlled hypertension impairment of LV and LA function is present in patients with early LV remodeling and localized hypertrophy. BSH might be useful as an early marker of the burden of hypertensive heart disease.
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http://dx.doi.org/10.1016/j.amjcard.2020.01.045DOI Listing
May 2020

Machine Learning in Fetal Cardiology: What to Expect.

Fetal Diagn Ther 2020 7;47(5):363-372. Epub 2020 Jan 7.

Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.

In fetal cardiology, imaging (especially echocardiography) has demonstrated to help in the diagnosis and monitoring of fetuses with a compromised cardiovascular system potentially associated with several fetal conditions. Different ultrasound approaches are currently used to evaluate fetal cardiac structure and function, including conventional 2-D imaging and M-mode and tissue Doppler imaging among others. However, assessment of the fetal heart is still challenging mainly due to involuntary movements of the fetus, the small size of the heart, and the lack of expertise in fetal echocardiography of some sonographers. Therefore, the use of new technologies to improve the primary acquired images, to help extract measurements, or to aid in the diagnosis of cardiac abnormalities is of great importance for optimal assessment of the fetal heart. Machine leaning (ML) is a computer science discipline focused on teaching a computer to perform tasks with specific goals without explicitly programming the rules on how to perform this task. In this review we provide a brief overview on the potential of ML techniques to improve the evaluation of fetal cardiac function by optimizing image acquisition and quantification/segmentation, as well as aid in improving the prenatal diagnoses of fetal cardiac remodeling and abnormalities.
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http://dx.doi.org/10.1159/000505021DOI Listing
March 2021

Pulmonary transit of contrast during exercise is related to improved cardio-pulmonary performance in highly trained endurance athletes.

Eur J Prev Cardiol 2020 09 4;27(14):1504-1514. Epub 2019 Dec 4.

Cardiovascular Institute, Hospital Clínic, Barcelona, Spain.

Background: The mechanisms underlying the high interindividual variability demonstrated for right-ventricular (RV) adaptation to exercise have not yet been identified, but different pulmonary vascular adaptations among individuals could be involved. Pulmonary transit of agitated saline (PTAS) during exercise has been demonstrated to be a good estimator of vascular reserve.

Aim: The aim of this study was to evaluate the presence of PTAS among endurance athletes (EAs) of both sexes and its influence on RV adaptation to exercise.

Methods: A total of 100 highly trained EAs performed a maximal cardiopulmonary exercise test. Bi-ventricular functional and structural characteristics as well as PTAS were evaluated at baseline and at peak exercise. Athletes were distributed between two groups based on the amount of PTAS during exercise as high (HTPAS; >12 bubbles) and low (LPTAS; ≤12 bubbles).

Results: Overall, 11 EAs exhibited an intra-cardiac shunt at rest and 1 met the criteria for chronic pulmonary disease and were excluded from the study. Among the remaining 88 EAs (51% women), 47 (53%) athletes were classified as HPTAS and 41 (47%) as LPTAS. HPTAS capability was associated with significantly larger RV contractile reserve, larger pulmonary vascular reserve and an enhanced maximal exercise capacity. On multivariate analysis, females were the only independent correlate of the HPTAS capability.

Conclusion: In highly trained endurance athletes, a HPTAS capability during exercise corresponded to an increase in pulmonary vascular and RV contractile reserves as well as an enhanced maximal exercise capacity. The long-term clinical or performance implications of the absence or presence of pulmonary shunting, and the subsequent RV afterload increase while performing exercise, remains to be determined.
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http://dx.doi.org/10.1177/2047487319891779DOI Listing
September 2020

Analysis of nonstandardized stress echocardiography sequences using multiview dimensionality reduction.

Med Image Anal 2020 02 6;60:101594. Epub 2019 Nov 6.

SIMBIOsys, ETIC, Universitat Pompeu Fabra, Barcelona, Spain.

Alternative stress echocardiography protocols such as handgrip exercise are potentially more favorable towards large-scale screening scenarios than those currently adopted in clinical practice. However, these are still underexplored because the maximal exercise levels are not easily quantified and regulated, requiring the analysis of the complete data sequences (thousands of images), which represents a challenging task for the clinician. We propose a framework for the analysis of these complex datasets, and illustrate it on a handgrip exercise dataset including complete acquisitions of 10 healthy controls and 5 ANT1 mutation patients (1377 cardiac cycles). The framework is based on an unsupervised formulation of multiple kernel learning, which is used to integrate information coming from myocardial velocity traces and heart rate to obtain a lower-dimensional representation of the data. Such simplified representation is then explored to discriminate groups of response and understand the underlying pathophysiological mechanisms. The analysis pipeline involves the reconstruction of population-specific signatures using multiscale kernel regression, and the clustering of subjects based on the trajectories defined by their projected sequences. The results confirm that the proposed framework is able to detect distinctive clusters of response and to provide insight regarding the underlying pathophysiology.
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http://dx.doi.org/10.1016/j.media.2019.101594DOI Listing
February 2020

Author Correction: Comprehensive Analysis of Animal Models of Cardiovascular Disease using Multiscale X-Ray Phase Contrast Tomography.

Sci Rep 2019 Nov 29;9(1):18278. Epub 2019 Nov 29.

Paul Scherrer Institut, Villigen PSI, Switzerland.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-019-54945-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884576PMC
November 2019

Variability in the Assessment of Myocardial Strain Patterns: Implications for Adequate Interpretation.

Ultrasound Med Biol 2020 Feb 26;46(2):244-254. Epub 2019 Nov 26.

Universitat Pompeu Fabra, Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain; Katholieke Universiteit Leuven, Leuven, Belgium.

Variability in global and regional peak strain has been thoroughly studied, but variability in spatiotemporal myocardial strain patterns has not been studied as well. This study reports on such variability and its implications for adequate disease interpretation. Forty in-training operators, distributed on 20 workstations, analyzed six cases with representative deformation patterns with commercial speckle tracking. Inter-operator differences were quantified through the variability in myocardial delineations, spatiotemporal longitudinal strain patterns and peak longitudinal strain. Intra-operator differences were assessed similarly using 10 repeated measurements from a single clinician expert. Delineations varied mainly along the lateral wall and at the valve level. Peak longitudinal strain variability was low to moderate. The spatiotemporal strain patterns were consistent despite high variability at the apex and near the valve. The results indicate that relevant pattern assessment is possible despite heterogeneous experience with speckle tracking and that careful interpretation of pattern abnormalities should be recommended before a more systematic quantitative analysis.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2019.10.013DOI Listing
February 2020

Structural coronary artery remodelling in the rabbit fetus as a result of intrauterine growth restriction.

PLoS One 2019 21;14(6):e0218192. Epub 2019 Jun 21.

Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain.

Intrauterine growth restriction (IUGR) is a fetal condition that affects up to 10% of all pregnancies and is associated with cardiovascular structural and functional remodelling that persists postnatally. Some studies have reported an increase in myocardial coronary blood flow in severe IUGR fetuses which has been directly associated to the dilatation of the coronary arteries. However, a direct measurement of the coronaries' lumen diameter in IUGR has not been reported before. The aim of this paper is to perform, for the first time, a quantitative analysis of the effects of IUGR in cardiac geometry and coronary vessel size in a well-known rabbit model of IUGR using synchrotron-based X-ray Phase Contrast Tomography Imaging (X-PCI). Eight rabbit fetal hearts were imaged non-destructively with X-PCI. 3D reconstructions of the coronary arterial tree were obtained after semi-automatic image segmentation. Different morphometric features including vessel lumen diameter of the three main coronaries were automatically quantified. IUGR fetuses had more globular hearts and dilated coronary arteries as compared to controls. We have quantitatively shown that IUGR leads to structural coronary vascular tree remodelling and enlargement as an adaptation mechanism in response to an adverse environment of restricted oxygen and nutrients and increased perfusion pressure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218192PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588274PMC
February 2020

Breaking the state of the heart: meshless model for cardiac mechanics.

Biomech Model Mechanobiol 2019 Dec 3;18(6):1549-1561. Epub 2019 Jun 3.

Medisys, Philips Research, Suresnes, France.

Cardiac modeling has recently emerged as a promising tool to study pathophysiology mechanisms and to predict treatment outcomes for personalized clinical decision support. Nevertheless, achieving convergence under large deformation and defining a robust meshing for realistic heart geometries remain challenging, especially when maintaining the computational cost reasonable. Smoothed particle hydrodynamics (SPH) appears to be a promising alternative to the finite element method (FEM) since it removes the burden of mesh generation. A point cloud is used where each point (particle) contains all the physical properties that are updated throughout the simulation. SPH was evaluated for solid mechanics applications in the last decade but its capacity to address the challenge of simulating the mechanics of the heart has never been evaluated. In this paper, a total Lagrangian formulation of a corrected SPH was used to solve three solid mechanics problems designed to test important features that a cardiac mechanics solver should have. SPH results, in terms of ventricle displacements and strains, were compared to results obtained with 11 different FEM-based solvers, by using synthetic cardiac data from a benchmark study. In particular, passive dilation and active contraction were simulated in an ellipsoidal left ventricle with the exponential anisotropic constitutive law of Guccione following the direction of fibers. The proposed meshless method is able to reproduce the results of three benchmark problems for cardiac mechanics. Hyperelastic material with fiber orientation and high Poisson ratio allows wall thickening/thinning when large deformation is present.
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http://dx.doi.org/10.1007/s10237-019-01175-9DOI Listing
December 2019

Should the septum be included in the assessment of right ventricular longitudinal strain? An ultrasound two-dimensional speckle-tracking stress study.

Int J Cardiovasc Imaging 2019 Oct 25;35(10):1853-1860. Epub 2019 May 25.

Cardiovascular Institute, Hospital Clínic, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomèdica en Red Enfermedades Cardiovasculares (CIBERCV), Villarroel 170, 08036, Barcelona, Spain.

Right ventricular longitudinal strain (RVLS) by 2D speckle-tracking echocardiography (2D-STE) is a useful parameter for assessing systolic function. However, the exact method to perform it is not well defined as some authors evaluate only free wall (FW) segments while others include all six RV segments. To compare the assessment of RVLS at rest and during exercise by these two approaches. Echocardiography was performed on 80 healthy subjects at rest and during exercise. The analysis consisted of standard and 2D-STE assessment of RV global and segmental strain tracing only RVFW and also tracing all six RV segments. At rest, RVLS could be assessed in 78 (feasibility 97.5%) subjects by both methods. However, during exercise, RVLS by RVFW method was feasible in 67 (83.8%) as compared to 74 (92.5%) by RV6S approach. Both at rest and during exercise, RVLS values by the two methods showed excellent correlation (r =  > 0.90). However, RVLS values assessed by RV6S were lower (absolute values) than those by RVFW approach (RV6S vs. RVFW; rest: - 27.0 ± 3.9 vs. - 9.5 ± 3.9, p < 0.001 and exercise: - 30.7 ± 5.2 vs. - 33.3 ± 5.1, p < 0.001). Furthermore, basal strain was higher and apical strain lower (absolute values) by RV6S approach. At rest, reproducibility for RVLS was excellent and similar for the two methods. However, during exercise, reproducibility for RVFW method was poorer, especially at the apex. The two currently described methods for RVLS assessment by 2D-STE demonstrated excellent agreement. However, the RV6S approach seemed to be more feasible and reproducible, particularly during exercise. Moreover, global and segmental strain values are different with both methods and should not be interchanged.
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http://dx.doi.org/10.1007/s10554-019-01633-6DOI Listing
October 2019

Comprehensive Analysis of Animal Models of Cardiovascular Disease using Multiscale X-Ray Phase Contrast Tomography.

Sci Rep 2019 05 6;9(1):6996. Epub 2019 May 6.

Paul Scherrer Institut, Villigen PSI, Switzerland.

Cardiovascular diseases (CVDs) affect the myocardium and vasculature, inducing remodelling of the heart from cellular to whole organ level. To assess their impact at micro and macroscopic level, multi-resolution imaging techniques that provide high quality images without sample alteration and in 3D are necessary: requirements not fulfilled by most of current methods. In this paper, we take advantage of the non-destructive time-efficient 3D multiscale capabilities of synchrotron Propagation-based X-Ray Phase Contrast Imaging (PB-X-PCI) to study a wide range of cardiac tissue characteristics in one healthy and three different diseased rat models. With a dedicated image processing pipeline, PB-X-PCI images are analysed in order to show its capability to assess different cardiac tissue components at both macroscopic and microscopic levels. The presented technique evaluates in detail the overall cardiac morphology, myocyte aggregate orientation, vasculature changes, fibrosis formation and nearly single cell arrangement. Our results agree with conventional histology and literature. This study demonstrates that synchrotron PB-X-PCI, combined with image processing tools, is a powerful technique for multi-resolution structural investigation of the heart ex-vivo. Therefore, the proposed approach can improve the understanding of the multiscale remodelling processes occurring in CVDs, and the comprehensive and fast assessment of future interventional approaches.
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http://dx.doi.org/10.1038/s41598-019-43407-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502928PMC
May 2019

Cardiac performance after an endurance open water swimming race.

Eur J Appl Physiol 2019 Apr 18;119(4):961-970. Epub 2019 Feb 18.

Cardiovascular Institute, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.

Purpose: Endurance exercise competitions have shown a transient negative effect on global right ventricular (RV) performance. Most published studies are based on terrestrial sports. The aim of our study was to evaluate the cardiac effects after an open water swimming race.

Methods: We evaluated 33 healthy swimmers (mean age 40.9 ± 7.2) participating in a 9.5 km open water swimming race. All subjects underwent a standard transthoracic echocardiography including an evaluation of dimensions and myocardial ventricular deformation. Echocardiography was performed 24 h before and within the first hour of arrival at the finish line. Cardiac troponin I (cTn I), NT-ProBNP and leukocytes were also evaluated.

Results: No changes in left ventricle (LV) ejection fraction or LV global longitudinal strain were observed. A significant increase in RV end-diastolic area (RVEDA) was noted after the race (RVEDA at baseline 15.12 ± 1.86; RVEDA after race 16.06 ± 2.27, p < 0.05), but no changes were seen in RV fractional area change or RV global longitudinal strain. Cardiac biomarkers and leukocytes significantly increased. No association was detected between the increase in cTn I or NT-proBNP and the RV acute dilatation or LV performance. A significant association was observed between cTn I and leukocytes (r = 0.375, p < 0.05).

Conclusions: An acute RV dilatation but without an impairment in RV deformation was observed after participating in an endurance swimming race. The correlation between the increase in cTn I and leukocytes, but not with ventricular performance, may support the hypothesis of an exercise-induced increase in myocardial sarcolemmal permeability due to an inflammatory response rather than myocardial injury.
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http://dx.doi.org/10.1007/s00421-019-04085-xDOI Listing
April 2019

MicroCT imaging reveals differential 3D micro-scale remodelling of the murine aorta in ageing and Marfan syndrome.

Theranostics 2018 15;8(21):6038-6052. Epub 2018 Nov 15.

Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.

Aortic wall remodelling is a key feature of both ageing and genetic connective tissue diseases, which are associated with vasculopathies such as Marfan syndrome (MFS). Although the aorta is a 3D structure, little attention has been paid to volumetric assessment, primarily due to the limitations of conventional imaging techniques. Phase-contrast microCT is an emerging imaging technique, which is able to resolve the 3D micro-scale structure of large samples without the need for staining or sectioning. Here, we have used synchrotron-based phase-contrast microCT to image aortae of wild type (WT) and MFS mice aged 3, 6 and 9 months old (n=5). We have also developed a new computational approach to automatically measure key histological parameters. This analysis revealed that WT mice undergo age-dependent aortic remodelling characterised by increases in ascending aorta diameter, tunica media thickness and cross-sectional area. The MFS aortic wall was subject to comparable remodelling, but the magnitudes of the changes were significantly exacerbated, particularly in 9 month-old MFS mice with ascending aorta wall dilations. Moreover, this morphological remodelling in MFS aorta included internal elastic lamina surface breaks that extended throughout the MFS ascending aorta and were already evident in animals who had not yet developed aneurysms. Our 3D microCT study of the sub-micron wall structure of whole, intact aorta reveals that histological remodelling of the tunica media in MFS could be viewed as an accelerated ageing process, and that phase-contrast microCT combined with computational image analysis allows the visualisation and quantification of 3D morphological remodelling in large volumes of unstained vascular tissues.
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http://dx.doi.org/10.7150/thno.26598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299435PMC
September 2019

Added value of cardiac deformation imaging in differential diagnosis of left ventricular hypertrophy.

Glob Cardiol Sci Pract 2018 Aug 12;2018(3):21. Epub 2018 Aug 12.

Cardiovascular Institute, Hospital Clínic, University of Barcelona & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer).

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http://dx.doi.org/10.21542/gcsp.2018.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209440PMC
August 2018

Complex Congenital Heart Disease Associated With Disordered Myocardial Architecture in a Midtrimester Human Fetus.

Circ Cardiovasc Imaging 2018 10;11(10):e007753

Institute of Cardiovascular Science (P.G.-C., A.C.C.), University College London, United Kingdom.

Background: In the era of increasingly successful corrective interventions in patients with congenital heart disease (CHD), global and regional myocardial remodeling are emerging as important sources of long-term morbidity/mortality. Changes in organization of the myocardium in CHD, and in its mechanical properties, conduction, and blood supply, result in altered myocardial function both before and after surgery. To gain a better understanding and develop appropriate and individualized treatment strategies, the microscopic organization of cardiomyocytes, and their integration at a macroscopic level, needs to be completely understood. The aim of this study is to describe, for the first time, in 3 dimensions and nondestructively the detailed remodeling of cardiac microstructure present in a human fetal heart with complex CHD.

Methods And Results: Synchrotron X-ray phase-contrast imaging was used to image an archival midgestation formalin-fixed fetal heart with right isomerism and complex CHD and compare with a control fetal heart. Analysis of myocyte aggregates, at detail not accessible with other techniques, was performed. Macroanatomic and conduction system changes specific to the disease were clearly observable, together with disordered myocyte organization in the morphologically right ventricle myocardium. Electrical activation simulations suggested altered synchronicity of the morphologically right ventricle.

Conclusions: We have shown the potential of X-ray phase-contrast imaging for studying cardiac microstructure in the developing human fetal heart at high resolution providing novel insight while preserving valuable archival material for future study. This is the first study to show myocardial alterations occur in complex CHD as early as midgestation.
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http://dx.doi.org/10.1161/CIRCIMAGING.118.007753DOI Listing
October 2018

Machine learning-based phenogrouping in heart failure to identify responders to cardiac resynchronization therapy.

Eur J Heart Fail 2019 01 17;21(1):74-85. Epub 2018 Oct 17.

Department of Information and Communication Technologies, University Pompeu Fabra, Barcelona, Spain.

Aims: We tested the hypothesis that a machine learning (ML) algorithm utilizing both complex echocardiographic data and clinical parameters could be used to phenogroup a heart failure (HF) cohort and identify patients with beneficial response to cardiac resynchronization therapy (CRT).

Methods And Results: We studied 1106 HF patients from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) (left ventricular ejection fraction ≤ 30%, QRS ≥ 130 ms, New York Heart Association class ≤ II) randomized to CRT with a defibrillator (CRT-D, n = 677) or an implantable cardioverter defibrillator (ICD, n = 429). An unsupervised ML algorithm (Multiple Kernel Learning and K-means clustering) was used to categorize subjects by similarities in clinical parameters, and left ventricular volume and deformation traces at baseline into mutually exclusive groups. The treatment effect of CRT-D on the primary outcome (all-cause death or HF event) and on volume response was compared among these groups. Our analysis identified four phenogroups, significantly different in the majority of baseline clinical characteristics, biomarker values, measures of left and right ventricular structure and function and the primary outcome occurrence. Two phenogroups included a higher proportion of known clinical characteristics predictive of CRT response, and were associated with a substantially better treatment effect of CRT-D on the primary outcome [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.19-0.64; P = 0.0005 and HR 0.36; 95% CI 0.19-0.68; P = 0.001] than observed in the other groups (interaction P = 0.02).

Conclusions: Our results serve as a proof-of-concept that, by integrating clinical parameters and full heart cycle imaging data, unsupervised ML can provide a clinically meaningful classification of a phenotypically heterogeneous HF cohort and might aid in optimizing the rate of responders to specific therapies.
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http://dx.doi.org/10.1002/ejhf.1333DOI Listing
January 2019

Quantification of the detailed cardiac left ventricular trabecular morphogenesis in the mouse embryo.

Med Image Anal 2018 10 2;49:89-104. Epub 2018 Aug 2.

Department of Information and Communication Technologies, Universitat Pompeu Fabra, c. Roc Boronat 138, Barcelona 08018, Spain.

During embryogenesis, a mammalian heart develops from a simple tubular shape into a complex 4-chamber organ, going through four distinct phases: early primitive tubular heart, emergence of trabeculations, trabecular remodeling and development of the compact myocardium. In this paper we propose a framework for standardized and subject-independent 3D regional myocardial complexity analysis, applied to analysis of the development of the mouse left ventricle. We propose a standardized subdivision of the myocardium into 3D overlapping regions (in our case 361) and a novel visualization of myocardial complexity, whereupon we: 1) extend the fractal dimension, commonly applied to image slices, to 3D and 2) use volume occupied by the trabeculations in each region together with their surface area, in order to quantify myocardial complexity. The latter provides an intuitive characterization of the complexity, given that compact myocardium will tend to occupy a larger volume with little surface area while high surface area with low volume will correspond to highly trabeculated areas. Using 50 mouse embryo images at 5 different gestational ages (10 subjects per gestational age), we demonstrate how the proposed representation and complexity measures describe the development of LV myocardial complexity. The mouse embryo data was acquired using high resolution episcopic microscopy. The complexity analysis per region was carried out using: 3D fractal dimension, myocardial volume, myocardial surface area and ratio between the two. The analysis of gestational ages was performed on embryos of 14.5, 15.5, 16.5, 17.5 and 18.5 embryonic days, and demonstrated that the regional complexity of the trabeculations increases longitudinally from the base to the apex, with a maximum around the middle. The overall complexity decreases with gestational age, being most complex at 14.5. Circumferentially, at ages 14.5, 15.5 and 16.5, the trabeculations show similar complexity everywhere except for the anteroseptal and inferolateral area of the wall, where it is smaller. At 17.5 days, the regions of high complexity become more localized towards the inferoseptal and anterolateral parts of the wall. At 18.5 days, the high complexity area exhibits further localization at the inferoseptal and anterior part of the wall.
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http://dx.doi.org/10.1016/j.media.2018.08.001DOI Listing
October 2018

Quantification of Right Ventricular Electromechanical Dyssynchrony in Relation to Right Ventricular Function and Clinical Outcomes in Children with Repaired Tetralogy of Fallot.

J Am Soc Echocardiogr 2018 07;31(7):822-830

The Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: Electromechanical dyssynchrony occurs ubiquitously following tetralogy of Fallot (TOF) repair, manifesting electrically as a wide QRS duration and mechanically as a right-sided septal/apical flash. Early septal activation and prestretch of the right ventricular (RV) basal lateral wall followed by its postsystolic shortening contributes to inefficient RV mechanics. However, a right-sided septal flash is a dichotomous finding, and the severity of RV dyssynchrony as a continuous spectrum in relationship to RV dysfunction and clinical outcomes in patients with repaired TOF has not been studied. The aim of this study was to quantify the severity of electromechanical dyssynchrony in relation to RV remodeling and clinical outcomes in a pediatric cohort following TOF repair.

Methods: A retrospective analysis was performed in 81 children with RV volume loading after TOF repair, aged 13.6 ± 2.9 years, and compared with 50 matched control subjects.

Results: Patients had higher RV basal-lateral prestretch and postsystolic strain amplitude and duration, RV mechanical dispersion, and basal lateral-septal wall delay compared with control subjects (P < .001 for all). All intra-RV dyssynchrony timing parameters were associated with reduced cardiac magnetic resonance-derived RV ejection fraction and/or echocardiography-derived RV longitudinal strain. Prestretch duration as a percentage of total shortening time and RV basal lateral-to-midseptal delay were independently associated with RV dysfunction. Postsystolic strain amplitude was higher in patients with ventricular arrhythmias compared with arrhythmia-free patients (7.8% [4.2%-13%] vs 2.0% [0%-12.5%], P = .03).

Conclusion: RV prestretch duration, postsystolic strain, and RV lateral-septal delay quantify RV electromechanical dyssynchrony severity and reflect the underlying pathophysiology. The prestretch duration percentage and RV basal lateral-to-midseptal delay were independently associated with RV dysfunction, potentially providing a clinical tool to quantify RV electromechanical dyssynchrony.
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http://dx.doi.org/10.1016/j.echo.2018.03.012DOI Listing
July 2018

Machine learning from fetal flow waveforms to predict adverse perinatal outcomes: a study protocol.

Gates Open Res 2018 Feb 12;2. Epub 2018 Feb 12.

Cardiology Care for Children, Lancaster, PA, 17601, USA.

In Pakistan, stillbirth rates and early neonatal mortality rates are amongst the highest in the world. The aim of this study is to provide proof of concept for using a computational model of fetal haemodynamics, combined with machine learning. This model will be based on Doppler patterns of the fetal cardiovascular, cerebral and placental flows with the goal to identify those fetuses at increased risk of adverse perinatal outcomes such as stillbirth, perinatal mortality and other neonatal morbidities. This will be prospective one group cohort study which will be conducted in Ibrahim Hyderi, a peri-urban settlement in south east of Karachi. The eligibility criteria include pregnant women between 22-34 weeks who reside in the study area. Once enrolled, in addition to the performing fetal ultrasound to obtain Dopplers, data on socio-demographic, maternal anthropometry, haemoglobin and cardiotocography will be obtained on the pregnant women. The machine learning approach for predicting adverse perinatal outcomes obtained from the current study will be validated in a larger population at the next stage. The data will allow for early interventions to improve perinatal outcomes.
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http://dx.doi.org/10.12688/gatesopenres.12796.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974597PMC
February 2018

Machine Learning Analysis of Left Ventricular Function to Characterize Heart Failure With Preserved Ejection Fraction.

Circ Cardiovasc Imaging 2018 04;11(4):e007138

Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain (S.S.-M., G.P., B.H.B.); Asclepios Research Group, Université Côte d'Azur, Inria, Sophia Antipolis, France (N.D.); Wales Heart Research Institute, Cardiff University, United Kingdom (T.E., A.G.F.); Department of Cardiology, Oslo University Hospital, Norway (G.K., S.A.); Department of Circulation and Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway (S.A.); Clinic of Cardiology, St. Olav Hospital, Trondheim, Norway (S.A.); Department of Cardiology, University of Eastern Piedmont, Novara, Italy (A.D., P.M.); Division of Cardiology, University Hospital "S.Maria della Misericordia", Perugia, Italy (E.C.); and Catalan Institution for Research and Advanced Studies, Barcelona, Spain (B.H.B.).

Background: Current diagnosis of heart failure with preserved ejection fraction (HFpEF) is suboptimal. We tested the hypothesis that comprehensive machine learning (ML) of left ventricular function at rest and exercise objectively captures differences between HFpEF and healthy subjects.

Methods And Results: One hundred fifty-six subjects aged >60 years (72 HFpEF+33 healthy for the initial analyses; 24 hypertensive+27 breathless for independent evaluation) underwent stress echocardiography, in the MEDIA study (Metabolic Road to Diastolic Heart Failure). Left ventricular long-axis myocardial velocity patterns were analyzed using an unsupervised ML algorithm that orders subjects according to their similarity, allowing exploration of the main trends in velocity patterns. ML identified a continuum from health to disease, including a transition zone associated to an uncertain diagnosis. Clinical validation was performed (1) to characterize the main trends in the patterns for each zone, which corresponded to known characteristics and new features of HFpEF; the ML-diagnostic zones differed for age, body mass index, 6-minute walk distance, B-type natriuretic peptide, and left ventricular mass index (<0.05) and (2) to evaluate the consistency of the proposed groupings against diagnosis by current clinical criteria; correlation with diagnosis was good (κ, 72.6%; 95% confidence interval, 58.1-87.0); ML identified 6% of healthy controls as HFpEF. Blinded reinterpretation of imaging from subjects with discordant clinical and ML diagnoses revealed abnormalities not included in diagnostic criteria. The algorithm was applied independently to another 51 subjects, classifying 33% of hypertensive and 67% of breathless controls as mild-HFpEF.

Conclusions: The analysis of left ventricular long-axis function on exercise by interpretable ML may improve the diagnosis and understanding of HFpEF.
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http://dx.doi.org/10.1161/CIRCIMAGING.117.007138DOI Listing
April 2018

Remodeling of the cardiovascular circulation in fetuses of mothers with diabetes: A fetal computational model analysis.

Placenta 2018 03 4;63:1-6. Epub 2018 Jan 4.

Physense, DTIC, Universitat Pompeu Fabra, Barcelona, Spain; ICREA, Barcelona, Spain.

Aims: Myocardial structural and functional abnormalities are known to occur in fetuses of mothers with diabetes mellitus (FMDM). The main aim of this investigation was to explore the cardiovascular circulatory patterns in FMDM using a validated lumped computational model of the cardiovascular system.

Methods: This was a multi-institutional study involving FMDM compared to fetuses of maternal controls (FC). Fetal echocardiographic Doppler data from left and right ventricular outflow tracts, aortic isthmus, middle cerebral and umbilical arteries were fitted into a validated fetal circulation computational model to estimate patient-specific placental and vascular properties. Non-parametric comparisons were made between resistances, compliances and flows in the brain and placenta in FMDM and FC.

Results: Data from 23 FMDM and 31 FC were fitted into the model. In FMDM, compared to FC, placental relative resistance was lower (0.59 ± 0.50 versus 0.91 ± 0.41; p < .05) with higher brain relative resistance (2.36 ± 1.65 versus 1.60 ± 0.85; p < .05). Middle cerebral artery flow was lower in FMDM than FC (0.12 ± 0.14 vs. 0.27 ± 0.21 ml/min; p 0.04) with a lower cerebral-placental flow ratio. Combined stroke volume was lower in FMDM (3.65 ± 2.05 ml) than FC (4.97 ± 2.45 ml) (p 0.04).

Conclusions: Blood flow is redistributed in FMDM to the placenta, away from the brain. This alteration may play a role in the postnatal health of these fetuses.
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http://dx.doi.org/10.1016/j.placenta.2017.12.020DOI Listing
March 2018

Quantitative Analysis of Electro-Anatomical Maps: Application to an Experimental Model of Left Bundle Branch Block/Cardiac Resynchronization Therapy.

IEEE J Transl Eng Health Med 2017 16;5:1900215. Epub 2016 Dec 16.

PhySense, Information and Communication Technologies DepartmentUniversitat Pompeu Fabra.

Electro-anatomical maps (EAMs) are commonly acquired in clinical routine for guiding ablation therapies. They provide voltage and activation time information on a 3-D anatomical mesh representation, making them useful for analyzing the electrical activation patterns in specific pathologies. However, the variability between the different acquisitions and anatomies hampers the comparison between different maps. This paper presents two contributions for the analysis of electrical patterns in EAM data from biventricular surfaces of cardiac chambers. The first contribution is an integrated automatic 2-D disk representation (2-D bull's eye plot) of the left ventricle (LV) and right ventricle (RV) obtained with a quasi-conformal mapping from the 3-D EAM meshes, that allows an analysis of cardiac resynchronization therapy (CRT) lead positioning, interpretation of global (total activation time), and local indices (local activation time (LAT), surrogates of conduction velocity, inter-ventricular, and transmural delays) that characterize changes in the electrical activation pattern. The second contribution is a set of indices derived from the electrical activation: speed maps, computed from LAT values, to study the electrical wave propagation, and histograms of isochrones to analyze regional electrical heterogeneities in the ventricles. We have applied the proposed methods to look for the underlying physiological mechanisms of left bundle branch block (LBBB) and CRT, with the goal of optimizing the therapy by improving CRT response. To better illustrate the benefits of the proposed tools, we created a set of synthetically generated and fully controlled activation patterns, where the proposed representation and indices were validated. Then, the proposed analysis tools are used to analyze EAM data from an experimental swine model of induced LBBB with an implanted CRT device. We have analyzed and compared the electrical activation patterns at baseline, LBBB, and CRT stages in four animals: two without any structural disease and two with an induced infarction. By relating the CRT lead location with electrical dyssynchrony, we evaluated current hypotheses about lead placement in CRT and showed that optimal pacing sites should target the RV lead close to the apex and the LV one distant from it.
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http://dx.doi.org/10.1109/JTEHM.2016.2634006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477765PMC
December 2016

Heart rate reduction improves biventricular function and interactions in experimental pulmonary hypertension.

Am J Physiol Heart Circ Physiol 2018 03 4;314(3):H542-H551. Epub 2017 Dec 4.

The Labatt Family Heart Center, Division of Cardiology and Cardiovascular Surgery, Hospital for Sick Children and University of Toronto , Toronto, Ontario , Canada.

The objective of the present study was to investigate mechanisms of heart rate (HR) reduction on biventricular function and interactions in experimental pulmonary arterial hypertension (PAH). We compared cardiac cycle mechanics and interventricular interactions in 15 sham, 8 monocrotaline-PAH, 9 PAH + carvedilol, and 8 PAH + ivabradine rats. We used echocardiography to assess biventricular function, timing of cardiac cycle events, and septal position in PAH rats and related HR reduction effects on biventricular function measured by echocardiography and conductance catheter. HR was 302 beats/min in PAH + carvedilol rats and 303 beats/min in PAH + ivabradine rats versus 359 beats/min in PAH rats ( P < 0.01). Sham rats showed temporal alignment between right ventricular (RV) and left ventricular (LV) events, whereas PAH rats showed increased biventricular isovolumic contraction times (ICTs), delayed RV peak radial motion, and impaired early relaxation. Temporal malalignment was associated with decreased tricuspid and mitral diastolic annular peak velocities (3.7 vs. 6.4 and 3.4 vs. 5.3 cm/s, respectively, P < 0.001), delayed and shortened biventricular filling, and reduced early diastolic LV filling velocity (0.56 vs. 0.81 cm/s, P < 0.01). LV eccentricity index was increased at systole (2.0 vs. 1.2, P < 0.001), early diastole (2.1 vs. 1.1, P < 0.001), and end diastole (1.6 vs. 1.1, P < 0.001) in PAH versus sham rats. HR reduction with carvedilol and ivabradine shortened biventricular ICTs and the time to biventricular peak radial motion, improved RV relaxation, and increased early diastolic LV filling through reduced interventricular interaction and improved timing. These improvements corresponded with enhanced hemodynamics (increased cardiac output, RV contractility, and diastolic relaxation). In conclusion, HR reduction by carvedilol and ivabradine improves biventricular filling and hemodynamics in experimental PAH through realignment of RV-LV cardiac cycle events and improved interventricular interactions. NEW & NOTEWORTHY Carvedilol improves biventricular function in experimental pulmonary arterial hypertension, but the mechanisms of heart rate reduction versus β-blocker effect are inadequately defined. Here, we demonstrate that reducing heart rate using either carvedilol or ivabradine (hyperpolarization-activated current inhibitor without β-blocker effect) improves right ventricular filling and biventricular hemodynamics through the realignment of right ventricular-left ventricular cardiac cycle events and improved interventricular interactions.
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http://dx.doi.org/10.1152/ajpheart.00493.2017DOI Listing
March 2018