- Email: [email protected]
Primetime for clinical and research application of intra-cardiac 4D-flow CMR?
IJCA-25424; No of Pages 2 International Journal of Cardiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Primetime for clinical and research application of intra-cardiac 4D-flow CMR? Pier Giorgio Masci Centre for Cardiac MR (CRMC), Cardiology Unit, Heart & Vessels Department, Lausanne University Hospital-CHUV, BH-09-792, Rue de Bugnon 46, CH-1011 Lausanne, Vaud, Switzerland
a r t i c l e
i n f o
Article history: Received 9 August 2017 Accepted 6 September 2017 Available online xxxx
Heart failure carries a mortality of ~50% at 5 years and its incidence and prevalence are expanding rapidly around the globe portending tremendous medical and social burdens [1]. To counteract this pandemic and worrisome condition a thoughtful understanding of the processes leading to ventricular remodeling is urgently needed in order to foster novel and efficient prognosticators and therapeutics [2]. The process of left ventricular remodeling extends to and affects importantly the biology of myocyte and non-myocyte components of the myocardium leading to architectural and functional abnormalities of the ventricle which are eventually associated with increased cardiovascular morbidity and mortality [3]. Cardiovascular magnetic resonance (CMR) is a non-invasive ionizing-radiation free multi-parametric modality which allows to comprehensively and quantitatively investigating the diverse aspects of ventricular remodeling (Table 1). In the evolving field of CMR, novel sequences are continuously developed to render the technique fast, robust and complete. The recently proposed 4D-flow CMR is framed in this direction. This technique is 3D phase-contrast imaging resolved by time which is then segmented on cine images yielding information by flow in multiple directions. When this technique is applied intra-cardiac, it provides key information on velocity vectors, flow velocity, vortex formation, hemodynamic forces as well as components constituting the stroke volume of the ventricles. All these parameters may be altered in ventricular remodeling giving an informative and privileged insight into the relationship between the architectural and functional ventricular and intra-cardiac flow abnormalities. As an example in a dilated and dysfunctional left ventricle the contribution of direct flow, that one which enters and leaves the ventricle in the single heartbeat, to overall stroke volume is significantly reduced as compared to healthy subjects resulting in a relative increase of indirect flows (residual, retained and delayed ejection ones) [4]. The assessment of vortex formation by 4D flow may provide the pathophysiological framework
E-mail address: [email protected]
for thrombus formation in heart chambers [5]. This technique is also capable to give a measure of ventricular kinetic energy profile which is directly based on direct 4D-flow parameters and not depending on complex computational analysist [6]. As an example in normal physiologic condition, the two ventricles equal the stroke volume but differ largely on kinetic energy as result of the diversity in shape, geometry and physiology. Kinetic energy is higher in the right than the left ventricle during the systole and the opposite occurs in diastole [7]. This difference is even exaggerated during the exercise underpinning the diverse working pattern of the two ventricles through these distinct cardiac phases. Kinetic energy pattern has also been investigated in small clinical studies assessing the changes in patients undergoing mitral valve repair [8]. Furthermore, intra-cardiac 4D-flow is capable to simultaneously track cardiac valves circumventing any problem related through-plane motion and, thereby, allowing reliable multi-valvular flow assessment and quantification in the same cardiac cycle [9]. Crandon S. and co-workers made an excellent review of intracardiac 4D-flow CMR incorporating 44 full papers out of 1680 records. They gathered the results based on which heart chambers or valves was investigated by 4D-flow resulting in a careful synthesis of the current literature. Due to the considerable methodological heterogeneity throughout papers, the authors limited their analysis to a narrative review of the literature without performing meta-analysis. Moreover the modified Critical Skills Appraisal Program (CASP) tool is prone to a certain subjectivity which cannot be easily addressed. According to this system of evaluation as many as 27 (62%) and 9 (20%) were found to be highly and potentially clinically applicable, respectively. Although these studies provided promising insights into intra-cardiac 4-flow clinical applications, the vast majority were single-center mechanistic reports. Likely the most promising clinical applications of intra-cardiac 4D-flow appear to be valve tracking and velocity/kinetic energy. However, it has to be acknowledged that, although researchers and industry concurred in improving the applicability of 4D-flow by ameliorating hardware and software components, this technique is still in its ‘formative years’. For comprehensive intra-cardiac 4D-flow assessment, a retrospective (i.e., covering the entire cardiac cycle) acquisition with sufficient time (40–50 ms) and spatial resolution (i.e., 2–3 mm isotropic) has to be timely incorporated into a clinical protocol in combination with a readily and efficient post-processing software. Currently, retrospective 4D-flow is offered only by some specific vendors and the acquisition lasts about 10 min with a rather complex and time-consuming post-processing analysis. These hurdles can be surmounted by the conjunct effort of researchers and industry, and the magnetic resonance
http://dx.doi.org/10.1016/j.ijcard.2017.09.016 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: P.G. Masci, Primetime for clinical and research application of intra-cardiac 4D-flow CMR?, Int J Cardiol (2017), http:// dx.doi.org/10.1016/j.ijcard.2017.09.016
2
Letter to the Editor
Table 1 The cardiovascular pathophysiological correlates of comprehensive CMR. CMR technique Cine imaging
Mapping-techniques
a. T1-mapping technique b. T2-mapping c. T2*-mapping
Phase-contrast (2D and 4D-flow)
a. Intra-cardiac application b. Great vessels Tagging/tissue tracking
Perfusion Late gadolinium enhancement
Pathophysiological correlate a. Geometry and architecture of the ventricles; ventricular volumes, mass and function b. Diastolic function (e.g., peak-filling rate) Comprehensive myocardial tissue characterization
a. Extracellular matrix remodeling/ interstitial fibrosis & infiltrative disease of myocardium b. Myocardial Edema c. Intra-myocardial hemorrhage a. Visualization and quantification of valvular regurgitation and 4D-futurible applications (as reported in the editorial) b. Cardiac output; ventricular-arterial coupling Myocardial deformation analysis (e.g., strain, strain rate, intraventricular asynchrony) Myocardial perfusion Replacement/reparative fibrosis (scar)
vendors and software companies are moving in this sense. After this early development phase, further research is warranted for establishing the diagnostic value of this technique in diverse clinical scenario and its capability of tracking the changes of cardiac disorders over time or in response to treatment. Moreover the standardization of the sequence,
acquisition protocol and post-processing, and the development of normal value (by category of ages and gender) are needed before launching multicenter trials testing the additive prognostic value of this technique beyond the standard-of-care in cost-effective manner [10]. References [1] P.A. Heidenreich, J.G. Trogdon, O.A. Khavjou, J. Butler, K. Dracup, M.D. Ezekowitz, E.A. Finkelstein, Y. Hong, S.C. Johnston, A. Khera, D.M. Lloyd-Jones, S.A. Nelson, G. Nichol, D. Orenstein, P.W. Wilson, Y.J. Woo, Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association, Circulation 123 (2011) 933–944. [2] J.A. Hill, E.N. Olson, Cardiac plasticity, N. Engl. J. Med. 358 (2008) 1370–1380. [3] D.L. Mann, M.R. Bristow, Mechanisms and models in heart failure: the biomechanical model and beyond, Circulation 111 (2005) 2837–2849. [4] J. Eriksson, A.F. Bolger, T. Ebbers, C.J. Carlhäll, Four-dimensional blood flow-specific markers of LV dysfunction in dilated cardiomyopathy, Eur. Heart J. Cardiovasc. Imaging 14 (2013) 417–424. [5] A. Fyrenius, L. Wigstrom, T. Ebbers, M. Carlsson, J. Engvall, A. Bolger, Three dimensional flow in the human left atrium, Heart 86 (2001) 448–455. [6] M. Kanski, P.M. Arvidsson, J. Töger, R. Borgquist, E. Heiberg, M. Carlsson, H. Arheden, Left ventricular fluid kinetic energy time curves in heart failure from cardiovascular magnetic resonance 4D flow data, J. Cardiovasc. Magn. Reson. 17 (2015) 111. [7] M.I. Carlsson, E. Heiberg, J. Toger, H. Arheden, Quantification of left and right ventricular kinetic energy using four-dimensional intracardiac magnetic resonance imaging flow measurements, Am. J. Physiol. Heart Circ. Physiol. (2012) 302 H893–900. [8] N. Al-Wakeel, J.F. Fernandes, A. Amiri, H. Siniawski, L. Goubergrits, F. Berger, T. Kuehne, Hemodynamic and energetic aspects of the left ventricle in patients with mitral regurgitation before and after mitral valve surgery, J. Magn. Reson. Imaging 42 (2015) 1705–1712. [9] J.J. Westenberg, S.D. Roes, N. Ajmone Marsan, N.M. Binnendijk, J. Doornbos, J.J. Bax, J.H. Reiber, A. de Roos, R.J. van der Geest, Mitral valve and tricuspid valve blood flow: accurate quantification with 3D velocity-encoded MR imaging with retrospective valve tracking, Radiology 249 (2008) 792–800. [10] L.J. Shaw, J.K. Min, R. Hachamovitch, E.D. Peterson, R.C. Hendel, P.K. Woodard, D.S. Berman, P.S. Douglas, Cardiovascular imaging research at the crossroads, JACC Cardiovasc. Imaging 3 (2010) 316–324.
Please cite this article as: P.G. Masci, Primetime for clinical and research application of intra-cardiac 4D-flow CMR?, Int J Cardiol (2017), http:// dx.doi.org/10.1016/j.ijcard.2017.09.016
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Primetime for clinical and research application of intra-cardiac 4D-flow CMR? Pier Giorgio Masci Centre for Cardiac MR (CRMC), Cardiology Unit, Heart & Vessels Department, Lausanne University Hospital-CHUV, BH-09-792, Rue de Bugnon 46, CH-1011 Lausanne, Vaud, Switzerland
a r t i c l e
i n f o
Article history: Received 9 August 2017 Accepted 6 September 2017 Available online xxxx
Heart failure carries a mortality of ~50% at 5 years and its incidence and prevalence are expanding rapidly around the globe portending tremendous medical and social burdens [1]. To counteract this pandemic and worrisome condition a thoughtful understanding of the processes leading to ventricular remodeling is urgently needed in order to foster novel and efficient prognosticators and therapeutics [2]. The process of left ventricular remodeling extends to and affects importantly the biology of myocyte and non-myocyte components of the myocardium leading to architectural and functional abnormalities of the ventricle which are eventually associated with increased cardiovascular morbidity and mortality [3]. Cardiovascular magnetic resonance (CMR) is a non-invasive ionizing-radiation free multi-parametric modality which allows to comprehensively and quantitatively investigating the diverse aspects of ventricular remodeling (Table 1). In the evolving field of CMR, novel sequences are continuously developed to render the technique fast, robust and complete. The recently proposed 4D-flow CMR is framed in this direction. This technique is 3D phase-contrast imaging resolved by time which is then segmented on cine images yielding information by flow in multiple directions. When this technique is applied intra-cardiac, it provides key information on velocity vectors, flow velocity, vortex formation, hemodynamic forces as well as components constituting the stroke volume of the ventricles. All these parameters may be altered in ventricular remodeling giving an informative and privileged insight into the relationship between the architectural and functional ventricular and intra-cardiac flow abnormalities. As an example in a dilated and dysfunctional left ventricle the contribution of direct flow, that one which enters and leaves the ventricle in the single heartbeat, to overall stroke volume is significantly reduced as compared to healthy subjects resulting in a relative increase of indirect flows (residual, retained and delayed ejection ones) [4]. The assessment of vortex formation by 4D flow may provide the pathophysiological framework
E-mail address: [email protected]
for thrombus formation in heart chambers [5]. This technique is also capable to give a measure of ventricular kinetic energy profile which is directly based on direct 4D-flow parameters and not depending on complex computational analysist [6]. As an example in normal physiologic condition, the two ventricles equal the stroke volume but differ largely on kinetic energy as result of the diversity in shape, geometry and physiology. Kinetic energy is higher in the right than the left ventricle during the systole and the opposite occurs in diastole [7]. This difference is even exaggerated during the exercise underpinning the diverse working pattern of the two ventricles through these distinct cardiac phases. Kinetic energy pattern has also been investigated in small clinical studies assessing the changes in patients undergoing mitral valve repair [8]. Furthermore, intra-cardiac 4D-flow is capable to simultaneously track cardiac valves circumventing any problem related through-plane motion and, thereby, allowing reliable multi-valvular flow assessment and quantification in the same cardiac cycle [9]. Crandon S. and co-workers made an excellent review of intracardiac 4D-flow CMR incorporating 44 full papers out of 1680 records. They gathered the results based on which heart chambers or valves was investigated by 4D-flow resulting in a careful synthesis of the current literature. Due to the considerable methodological heterogeneity throughout papers, the authors limited their analysis to a narrative review of the literature without performing meta-analysis. Moreover the modified Critical Skills Appraisal Program (CASP) tool is prone to a certain subjectivity which cannot be easily addressed. According to this system of evaluation as many as 27 (62%) and 9 (20%) were found to be highly and potentially clinically applicable, respectively. Although these studies provided promising insights into intra-cardiac 4-flow clinical applications, the vast majority were single-center mechanistic reports. Likely the most promising clinical applications of intra-cardiac 4D-flow appear to be valve tracking and velocity/kinetic energy. However, it has to be acknowledged that, although researchers and industry concurred in improving the applicability of 4D-flow by ameliorating hardware and software components, this technique is still in its ‘formative years’. For comprehensive intra-cardiac 4D-flow assessment, a retrospective (i.e., covering the entire cardiac cycle) acquisition with sufficient time (40–50 ms) and spatial resolution (i.e., 2–3 mm isotropic) has to be timely incorporated into a clinical protocol in combination with a readily and efficient post-processing software. Currently, retrospective 4D-flow is offered only by some specific vendors and the acquisition lasts about 10 min with a rather complex and time-consuming post-processing analysis. These hurdles can be surmounted by the conjunct effort of researchers and industry, and the magnetic resonance
http://dx.doi.org/10.1016/j.ijcard.2017.09.016 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: P.G. Masci, Primetime for clinical and research application of intra-cardiac 4D-flow CMR?, Int J Cardiol (2017), http:// dx.doi.org/10.1016/j.ijcard.2017.09.016
2
Letter to the Editor
Table 1 The cardiovascular pathophysiological correlates of comprehensive CMR. CMR technique Cine imaging
Mapping-techniques
a. T1-mapping technique b. T2-mapping c. T2*-mapping
Phase-contrast (2D and 4D-flow)
a. Intra-cardiac application b. Great vessels Tagging/tissue tracking
Perfusion Late gadolinium enhancement
Pathophysiological correlate a. Geometry and architecture of the ventricles; ventricular volumes, mass and function b. Diastolic function (e.g., peak-filling rate) Comprehensive myocardial tissue characterization
a. Extracellular matrix remodeling/ interstitial fibrosis & infiltrative disease of myocardium b. Myocardial Edema c. Intra-myocardial hemorrhage a. Visualization and quantification of valvular regurgitation and 4D-futurible applications (as reported in the editorial) b. Cardiac output; ventricular-arterial coupling Myocardial deformation analysis (e.g., strain, strain rate, intraventricular asynchrony) Myocardial perfusion Replacement/reparative fibrosis (scar)
vendors and software companies are moving in this sense. After this early development phase, further research is warranted for establishing the diagnostic value of this technique in diverse clinical scenario and its capability of tracking the changes of cardiac disorders over time or in response to treatment. Moreover the standardization of the sequence,
acquisition protocol and post-processing, and the development of normal value (by category of ages and gender) are needed before launching multicenter trials testing the additive prognostic value of this technique beyond the standard-of-care in cost-effective manner [10]. References [1] P.A. Heidenreich, J.G. Trogdon, O.A. Khavjou, J. Butler, K. Dracup, M.D. Ezekowitz, E.A. Finkelstein, Y. Hong, S.C. Johnston, A. Khera, D.M. Lloyd-Jones, S.A. Nelson, G. Nichol, D. Orenstein, P.W. Wilson, Y.J. Woo, Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association, Circulation 123 (2011) 933–944. [2] J.A. Hill, E.N. Olson, Cardiac plasticity, N. Engl. J. Med. 358 (2008) 1370–1380. [3] D.L. Mann, M.R. Bristow, Mechanisms and models in heart failure: the biomechanical model and beyond, Circulation 111 (2005) 2837–2849. [4] J. Eriksson, A.F. Bolger, T. Ebbers, C.J. Carlhäll, Four-dimensional blood flow-specific markers of LV dysfunction in dilated cardiomyopathy, Eur. Heart J. Cardiovasc. Imaging 14 (2013) 417–424. [5] A. Fyrenius, L. Wigstrom, T. Ebbers, M. Carlsson, J. Engvall, A. Bolger, Three dimensional flow in the human left atrium, Heart 86 (2001) 448–455. [6] M. Kanski, P.M. Arvidsson, J. Töger, R. Borgquist, E. Heiberg, M. Carlsson, H. Arheden, Left ventricular fluid kinetic energy time curves in heart failure from cardiovascular magnetic resonance 4D flow data, J. Cardiovasc. Magn. Reson. 17 (2015) 111. [7] M.I. Carlsson, E. Heiberg, J. Toger, H. Arheden, Quantification of left and right ventricular kinetic energy using four-dimensional intracardiac magnetic resonance imaging flow measurements, Am. J. Physiol. Heart Circ. Physiol. (2012) 302 H893–900. [8] N. Al-Wakeel, J.F. Fernandes, A. Amiri, H. Siniawski, L. Goubergrits, F. Berger, T. Kuehne, Hemodynamic and energetic aspects of the left ventricle in patients with mitral regurgitation before and after mitral valve surgery, J. Magn. Reson. Imaging 42 (2015) 1705–1712. [9] J.J. Westenberg, S.D. Roes, N. Ajmone Marsan, N.M. Binnendijk, J. Doornbos, J.J. Bax, J.H. Reiber, A. de Roos, R.J. van der Geest, Mitral valve and tricuspid valve blood flow: accurate quantification with 3D velocity-encoded MR imaging with retrospective valve tracking, Radiology 249 (2008) 792–800. [10] L.J. Shaw, J.K. Min, R. Hachamovitch, E.D. Peterson, R.C. Hendel, P.K. Woodard, D.S. Berman, P.S. Douglas, Cardiovascular imaging research at the crossroads, JACC Cardiovasc. Imaging 3 (2010) 316–324.
Please cite this article as: P.G. Masci, Primetime for clinical and research application of intra-cardiac 4D-flow CMR?, Int J Cardiol (2017), http:// dx.doi.org/10.1016/j.ijcard.2017.09.016