Cardiac

Introduction


Background

Cardiovascular disease is one of the leading causes of death in the Western World. In the Netherlands 20.000 people die each year of an acute myocardial infarction or stroke. Two-dimensional ultrasound has been the most widely available imaging modality to evaluate cardiovascular structure and function. Improvements in two-dimensional ultrasound image resolution have led to more detailed imaging of the myocardium, heart valves, vessel walls, and atherosclerotic plaques. Doppler techniques are readily available to estimate the blood flow and pressure gradients across heart valves and vascular stenoses. However, two-dimensional B-mode images have a limited reproducibility in three-dimensional structures and do not (yet) allow for detailed tissue characterization.

Specifically, in cardiac function analysis, the standard volumetric biplane measurement of ‘ejection fraction’ to determine systolic function has an inter-rater and longitudinal variability of 5-10%, due to apical foreshortening, suboptimal endocardial contouring and changes in pre- and afterload. Furthermore, it is a rather late marker of systolic dysfunction, knowing that the complex orientation of cardiac muscle fibers allows for compensation of ejection fraction when certain fibers become dysfunctional.

What has been done

In cardiac ultrasound, two-dimensional myocardial deformation (strain) imaging, by means of tissue doppler imaging and now speckle tracking, has found its way into the clinic. Global longitudinal strain (i.e. shortening of the total muscle length in longitudinal direction) has been shown to aid in the prediction of cardiac events and mortality in various cardiac diseases (heart failure, valve disease, postoperative), especially when ejection fraction is still preserved. Furthermore, it is possible to assess regional wall motion abnormalities (lower strain, pre-stretch, post-systolic strain) in more detail than with the naked eye, provided that there are no image artefacts in these regions. Guidelines in adult cardio-oncology have adopted a reduced global longitudinal strain as an early sign of cardiotoxicity and specific strain patterns point to specific myocardial diseases (e.g. apical sparing in cardiac amyloidosis). It furthermore has high potential to aid in the indication for cardic resynchronization therapy by assessment of dyssynchronous patterns. However, the inclusion of myocardial strain analyses in systolic function quantification guidelines has been hampered by the lack of uniform lower limits of normal. These still depend on the software vendor, and furthermore on the myocardial layer in which strain is assessed and the timing of events. Attempts to resolve these problems are undertaken by a dedicated standardization task force.


Our research aim

For cardiac imaging, our current research aims to identify additional clinical applications of deformation imaging and deeper analysis of its current applications. The fields of research include pediatric cardio-oncology and congenital heart disease.


Methods

In the past, we have focussed on the development of strain estimation techniques in two-dimensional and three-dimensional echocardiography data. Currently, we provide an infrastructure with different software packages and technical support to clinicians and clinical studies that involve two-dimensional myocardial strain imaging. Cohort and case-control studies are hosted that compare the hearts of childhood cancer survivors to controls and that assess the hearts of patients with Ebstein anomaly in further detail. Furthermore, we undertake continuous efforts to provide lab- and vendor specific normative strain values.

MUSIC tomtec.png
example of regional (coloured) and average (white) longitudinal strain curves in an apical 4-chamber view in a childhood cancer survivor, obtained in commercially available, vendor-independent strain software.

Results

We have developed 2D and 3D strain estimation and segmentation strategies to improve improve accuracy with respect to commercially available techniques. These strategies are based on analysis of the raw ultrasound (rf) signals: rf-based strain estimation demonstrated to be more accurate than B-mode based commercial techniques (Lopata et al 2009, Lopata et al 2009a, Lopata et al 2009b) and these techniques were extended from 2D to biplane strain imaging (Lopata et al 2010) and full 3D (Lopata et al 2011). Automated segementation based on echo statistics (Nillesen et al 2008)) and decorrelation (Nillesen et al 2009) were developed and validated in vivo (Nillesen et al 2009a) and finally evaluated in children with congenital heart disease (Nillesen et al 2011).

Furthermore, clinical application of strain and strain rate with tissue Doppler (Kapusta et al., 2000a, 2000, 2001,) and speckle tracking in childhood cancer survivors (Mavinkurve-Groothuis et al., 2010, 2012; Pourier et al., 2020; Merkx et al., 2021a, 2021b) ) has advanced this field of subclincial detection of cardiac dysfunction.

Most recently, we described our 15-year experience with measuring myocardial strain in the surveillance of childhood cancer survivors and its potential value over LVEF predicting 10-year cardiac events (Pourier et al., 2022).

Funding

  • Detection of chronic heart failure in children with congenital heart disease with innovative ultrasound techniques (Dutch Technology Foundation STW and Philips Medical Systems, finished)
  • Early recognition of cardiovascular disease (Dutch Heart Foundation CVON 2015-021, finished)


Our people

PhD candidates


Also visiting clinical PhD candidates: Lianne Geerdink, Milanthy Pourier.

Scientific staff



Associated clinicians



Our key publications

  • M. Pourier, R. Merkx, J. Loonen, A. van Cleef, C. de Korte, L. Bellersen, L. Kapusta and A. Mavinkurve-Groothuis. "Cardiac Events in Childhood Cancer Survivors Treated with Anthracyclines: The Value of Previous Myocardial Strain Measurement.", 2022. Abstract/PDF DOI PMID

  • R. Merkx, J. Leerink, E. de Baat, E. Feijen, W. Kok, A. Mavinkurve-Groothuis, J. Loonen, H. van der Pal, L. Bellersen, C. de Korte, L. Kremer, E. van Dalen and L. Kapusta. "Asymptomatic systolic dysfunction on contemporary echocardiography in anthracycline-treated long-term childhood cancer survivors: a systematic review.", 2021. Abstract/PDF DOI PMID

  • R. Merkx, J. Leerink, E. Feijen, L. Kremer, E. de Baat, L. Bellersen, E. van Dalen, E. van Dulmen-den Broeder, M. van der der Heiden-van Loo, M. van den Heuvel-Eibrink, C. Korte, J. Loonen, M. Louwerens, A. Maas, Y. Pinto, C. Ronckers, A. Teske, W. Tissing, A. de Vries, A. Mavinkurve-Groothuis, H. van der Pal, G. Weijers, W. Kok, L. Kapusta and D. Group. "Echocardiography protocol for early detection of cardiac dysfunction in childhood cancer survivors in the multicenter DCCSS LATER 2 CARD study: Design, feasibility, and reproducibility.", 2021. Abstract/PDF DOI PMID

  • M. Pourier, A. Mavinkurve-Groothuis, M. Dull, G. Weijers, J. Loonen, L. Bellersen, C. de Korte and L. Kapusta. "Myocardial 2D Strain During Long-Term (>5 Years) Follow-Up of Childhood Survivors of Acute Lymphoblastic Leukemia Treated With Anthracyclines.", 2020. Abstract/PDF DOI PMID

  • A. Mavinkurve-Groothuis, K. Marcus, M. Pourier, J. Loonen, T. Feuth, P. Hoogerbrugge, C. de Korte and L. Kapusta. "Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study", 2013. Abstract DOI PMID

  • R. Lopata, M. Nillesen, J. Thijssen, L. Kapusta and C. de Korte. "Three-dimensional cardiac strain imaging in healthy children using RF-data", 2011. Abstract/PDF DOI PMID

  • A. Mavinkurve-Groothuis, J. Groot-Loonen, K. Marcus, L. Bellersen, T. Feuth, J. Bökkerink, P. Hoogerbrugge, C. de Korte and L. Kapusta. "Myocardial strain and strain rate in monitoring subclinical heart failure in asymptomatic long-term survivors of childhood cancer", 2010. Abstract/PDF DOI PMID

  • R. Lopata, M. Nillesen, C. Verrijp, S. Singh, M. Lammens, J. van der Laak, H. van Wetten, J. Thijssen, L. Kapusta and C. de Korte. "Cardiac biplane strain imaging: initial in vivo experience", 2010. Abstract/PDF DOI PMID

  • R. Lopata, H. Hansen, M. Nillesen, J. Thijssen and C. De Korte. "Comparison of one-dimensional and two-dimensional least-squares strain estimators for phased array displacement data", 2009. Abstract PMID

  • R. Lopata, M. Nillesen, H. Hansen, I. Gerrits, J. Thijssen and C. de Korte. "Performance of two dimensional displacement and strain estimation techniques using a phased array transducer", 2009. Abstract/PDF DOI PMID

  • R. Lopata, M. Nillesen, H. Hansen, I. Gerrits, J. Thijssen and C. de Korte. "Performance evaluation of methods for two-dimensional displacement and strain estimation using ultrasound radio frequency data", 2009. Abstract/PDF DOI PMID

  • M. Nillesen, R. Lopata, I. Gerrits, L. Kapusta, J. Thijssen and C. de Korte. "Modeling envelope statistics of blood and myocardium for segmentation of echocardiographic images", 2008. Abstract/PDF DOI PMID

  • L. Kapusta, J. Thijssen, J. Groot-Loonen, J. van Druten and O. Daniëls. "Discriminative ability of conventional echocardiography and tissue Doppler imaging techniques for the detection of subclinical cardiotoxic effects of treatment with anthracyclines", 2001. Abstract PMID

  • L. Kapusta, J. Thijssen, M. Cuypers, P. Peer and O. Daniëls. "Assessment of myocardial velocities in healthy children using tissue Doppler imaging", 2000. Abstract PMID

  • L. Kapusta, J. Thijssen, J. Groot-Loonen, T. Antonius, J. Mulder and O. Daniëls. "Tissue Doppler imaging in detection of myocardial dysfunction in survivors of childhood cancer treated with anthracyclines", 2000. Abstract PMID