EDITORIAL
European Journal of Cardio-Thoracic Surgery 49 (2016) 365–368
doi:10.1093/ejcts/ezv368 Advance Access publication 21 October 2015
Multiscale modelling of single-ventricle hearts for clinical decision
support: a Leducq Transatlantic Network of Excellence
Tain-Yen Hsiaa,* and Richard Figliolab on behalf of the Modeling of Congenital Hearts
Alliance (MOCHA) Investigators
a
b
Department of Cardiothoracic Surgery, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
Department of Mechanical and Bioengineering, Clemson University, Clemson, NC, USA
* Corresponding author. Cardiac Unit 7th Floor, Nurses Home, Great Ormond Street Hospital for Children, NHS Foundation Trust, London WC1N 3JH, UK.
Tel: +44-207-8138159; e-mail: [email protected] (T.-Y. Hsia).
Keywords: Congenital heart surgery • Modelling • Haemodynamics
Developed in the 1930s and 1940s to study hydraulic problems,
computational fluid dynamics (CFD) has become a practical modelling tool to solve and analyse physical phenomena that involve
fluid flows. In fact, the Food and Drug Administration is now integrating computational modelling into the evaluation and testing
processes with increasing frequency and mandate [1]. In congenital cardiac surgery, where the objective of the operative reconstruction is to reshape the blood flow within the heart and great
vessels to achieve the best dynamics and tissue oxygen delivery,
CFD is a natural tool to uncover suboptimal circulations and
improve surgical techniques. However, a lack of a common language and mutual understanding of each other’s expertise have
often stymied this logical collaboration between cardiac surgeons
and engineers. The breakthrough came in 1996 when Marc de
Leval at Great Ormond Street Hospital in London and his colleagues at Milan’s Politecnico collaborated to show that CFD modelling can be used to improve surgical procedures in the total
cavopulmonary connection (TCPC) [2]. Advances in computational
methods have led to numerous contributions in the field of congenital heart diseases and surgery, including assist device development, studying of valvular and aortic pathologies, modifications to
the Fontan operation and the continuing efforts to understand the
modified physiologies in single ventricular circulations [3–8].
While these advances have shed light into some of the altered
flow dynamic phenomena that are unique in congenital heart
surgery, there has been an increased recognition that modelling
approaches that only focus on the local or the surgical domain will
miss or underrepresent the overall effects on the entire cardiovascular and pulmonary physiology. For example, an isolated flow
model of the TCPC intended to estimate power loss cannot
predict the Fontan pressure, nor could an isolated model of a
3.5-mm modified Blalock–Taussig (mBT) shunt used to calculate
shear stress reveal the systemic oxygen delivery. In effect, the
haemodynamics of the operative reconstruction site are dynamically coupled to the rest of the cardiovascular system. New multiscale modelling methods have been developed to provide a
computationally efficient approach to correctly model both local
and systems-level behaviour. Without going into the mathematical
background, a multiscale model of the cardiovascular system
combines the detailed 3D, anatomically accurate CFD model of
the desired surgical reconstruction with a zero-dimensional (0D)
hydraulic lumped-parameter network (LPN) representation of the
rest of the cardiovascular circulation system. Computationally, the
flow and pressure output values from the 3D CFD model become
the input pressure and flow values to the 0D LPN and, in turn,
these same outputs from the LPN model become the input values
to the CFD model of the surgical domain. This multiscale approach, such as shown for a TCPC model (Fig. 1), allows for
closed-loop circulatory modelling. The initiating conditions set by
the user put into motion a set of calculations that iteratively arrive
at flow and pressure solutions anywhere in the circulation. In a
multiscale TCPC model, not only would shear stress and power
loss within the TCPC be calculated, but also would a host of clinically relevant physiological variables, such as Fontan pressures,
pressure–volume relationship of the single ventricle and cerebral
perfusion. And when combined with fundamental oxygen equations, systemic and end organ, such as cerebral and myocardial,
oxygen delivery can be assessed. Further adjustments to these
models allow for simulations under exercise and growth effects.
In 2010, Fondation Leducq, a private foundation in France,
awarded a 5-year Transatlantic Network of Excellence grant to our
group to continue collaborations that began in 1996. Comprising
four American and three European clinical and engineering institutions, the Modeling of Congenital Heart Alliance (MOCHA)
investigators were tasked to apply the state of the art in computational and engineering to all three stages of the surgical palliative
pathway of single-ventricle physiology to provide a novel clinical
decision support system. Our aim is to establish a new investigative
paradigm in which patient-specific anatomy and physiology are
used in an engineering model to predict surgical outcomes and
supplement patient management, as shown in our research cycle
(Fig. 2). Such a process involves virtual surgery and computational/experimental simulations using clinical data acquired from
echocardiography, computed tomography, magnetic resonance
© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
EDITORIAL
Cite this article as: Hsia T-Y, Figliola R. Multiscale modelling of single-ventricle hearts for clinical decision support: a Leducq Transatlantic Network of Excellence.
Eur J Cardiothorac Surg 2016;49:365–8.
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T.-Y. Hsia and R. Figliola / European Journal of Cardio-Thoracic Surgery
Figure 1: Multiscale model coupling a patient-specific, realistic 3D extracardiac conduit total cavopulmonary connection with the 0D hydraulic lumped parameter
network of entire cardiovascular system, including a single-ventricle heart and pulmonary circulation.
imaging and cardiac catheterization. Multiscale models were constructed to assess the surgically altered flow dynamics, as well as
the overall physiological effect in a clinically relevant manner.
RATIONALE FOR A COLLABORATIVE GROUP
International partnerships are increasingly indispensable in addressing many critical cardiovascular problems. While it would be
difficult for a single institution to assemble expertise in paediatric
cardiology, surgery, imaging, engineering and computer science,
the formation of a transatlantic network leverages the combined
strengths of the different investigators and institutions in a collaborative manner. Firstly, the MOCHA Network integrates the clinical resources of three well-respected, high-volume congenital
cardiac centres (University of Michigan, Great Ormond Street and
Medical University of South Carolina) to provide a shared clinical
database and clinical expertise. Secondly, MOCHA can catalyse
the collaborations among the four engineering centres (Politecnico
di Milano, Institut National de Recherche en Informatique et en
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Figure 2: MOCHA research cycle that begins and continues with patient care.
Automatique, University of California San Diego and Clemson
University) to coalesce complementary strengths and commitments
in mathematics and modelling in a coordinated manner to enhance
modelling advances. Thirdly, the Network promotes multidisciplinary, transatlantic dialogue, allowing shared resources, data and
exchange of ideas. From initial conceptualization to effective
modelling validation, the Network has mandated critical clinical
feedback of the mathematical simulations, and active engineering
guidance on the strengths and limitations of the modelling results.
And lastly, the Network facilitates a robust exchange for American
and European trainees and early-career researchers that not only
engenders a new partnership in biomedical engineering and clinical management, but also prepares and stimulates them for
future participation in international collaborative investigations.
Over the last 5 years, the MOCHA investigators have published
over 60 peer-reviewed manuscripts in both clinical and biomedical engineering journals, been awarded additional research
grants and presented at numerous national and international
conferences. Some of the transformative efforts have led to the
development of important novel concepts and methodologies
that enhance the application of engineering in cardiovascular
physiology. These include a new method that computes residence time in flow simulations that can be linked to risks of
thrombosis or competitive flow, and the derivation of wave intensity analysis from magnetic resonance imaging to assess ventricular–arterial coupling [9, 10]. In addition to having successfully
developed and performed multiscale simulations for all three
stages of single-ventricle palliation, we have also completed corresponding in vitro mock circulatory multiscale models to assess
ventricular work relationship to aortic arch obstruction in Stage 1
Norwood circulation and to examine the benefit of valve implantation in Fontan circulation to impede retrograde flows into
the hepatic and inferior caval veins [11, 12]. Our continuing commitment to innovation includes active investigations quantifying
the inherent uncertainties in modelling predictions, deriving of a
simulated exercise protocol in the Fontan circulation and advancing novel mathematical/numerical approaches in haemodynamic modelling [13–16].
However, the main thrust of the Network has been to translate
advanced mathematical and engineering methods to provide
insights into the unique physiology of single-ventricle circulations
and to answer questions that are clinically relevant. From multiscale modelling, we were able to demonstrate that augmenting a
stenotic right ventricular to pulmonary artery (Sano) shunt in
Stage 1 with an additional mBT shunt is undesirable, and the
hybrid approach to Stage 1 palliation leads to poorer cerebral and
systemic oxygen delivery when compared with a surgical Norwood
palliation [4, 17]. Two separate studies adopting patient-specific
modelling to examine haemodynamic and physiological differences between Glenn and hemi-Fontan in superior cavopulmonary connection, and extracardiac conduit and Y-graft in the TCPC
are near completion. Wave intensity analysis techniques have
correlated poorer ventricular–arterial coupling and reduced arterial distensibility to worse ventricular mechanics in patients with
hypoplastic left heart syndrome [3, 18]. Using multiscale modelling
as a platform to conceptually test the feasibility of a new surgical
technique when no acceptable animal model exists and immediate human application is unethical, simulations suggested that a
novel Stage 1 palliation with a Glenn circulation ‘assisted’ by a systemic shunt to produce an ejector pump effect can achieve adequate pulmonary blood flow without important superior venous
hypertension [19, 20]. While there are other active investigations, a
major effort that pools all the capabilities and resources of the
MOCHA investigators is the development and design of a simulation tool that can predict the postoperative haemodynamics and
physiology, based on patient-specific clinical data, for all three
stages of single-ventricle palliations. Interventions such as pulmonary vascular dilatation and closing collaterals and fenestrations can be simulated, as well as physiological changes such as
exercise and ventricular dysfunction. Following intensive clinical
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T.-Y. Hsia and R. Figliola / European Journal of Cardio-Thoracic Surgery
validation, we are hoping to make this simulation tool available
through the web and as a mobile-device app.
In summary, continuing engineering and mathematical
advances have led to a new paradigm in the application of modelling in congenital heart surgery. Applying to the single-ventricle
circulations, multiscale modelling not only allows for detailed
understanding of the fluid dynamic influence of the surgical palliation, but also insights into the clinical relevant physiological consequences. As modelling can never account for all the biological
processes of the human cardiovascular system, it cannot predict
clinical outcomes or dictate bedside decisions. However, used
with a clear understanding and appreciation of its limitations and
capabilities, computational modelling and advanced engineering
methods can shed light into some of the unique flow mechanics
and physiological features of congenial heart defects and their
surgical treatments. It is with this hope and responsibility that the
MOCHA investigators are continuing the endeavours that began
in 1996.
ACKNOWLEDGEMENTS
MOCHA Investigators: Edward Bove and Adam Dorfman (University
of Michigan, USA); Andrew Taylor, Alessandro Giardini, Sachin
Khambadkone, Silvia Schievano and Tain-Yen Hsia (University
College London, UK); G. Hamilton Baker and Anthony Hlavacek
(Medical University of South Carolina, USA); Francesco Migliavacca,
Giancarlo Pennati, and Gabriele Dubini (Politecnico di Milano,
Italy); Richard Figliola and John McGregor (Clemson University,
USA); Alison Marsden (University of California, San Diego, USA);
Irene Vignon-Clementel (National Institute of Research in
Informatics and Automation, France).
Funding
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
This study was supported by a grant from the Fondation Leducq,
Paris, France.
[16]
Conflict of interest: none declared.
[17]
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