Disease-Based Models of Cardiac Electromechanics
5. Simulation of hypertrophic cardiomyopathy
5.1 Cardiac parameters for hypertrophic cardiomyopathy
Like dilated cardiomyopathy (DCM), idiopathic hypertrophic cardiomyopathy (HCM) is a disease that affects the correct function of the myocardium. However, contrary to DCM, HCM is characterised by a focal or global thickening of the myocardium without enlargement of the cavities and, at a microscopic level, by myocardial fibre disarray and fibrosis.
HCM may be asymptomatic and diagnosed only after a genetic survey performed when a family member of the patient suffers from this disease. When HCM is symptomatic, the main clinical features that characterise it are congestive heart failures and heart rhythm disturbances which may lead to sudden death.
The pathogenesis is unknown but genetic mutations are more and more identified as possible reasons of HCM (Wigle et al., 1995, Maron, 2002). That is why genetic surveys are often realised when a patient is found to suffer from HCM. However, other factors may cause HCM. Indeed, they may be the result of congenital metabolic diseases (mitochondrial disorders) or of overload pathologies like for instance the Pompe disease (a glycogen storage disease) or Friedreich's ataxia (an inherited neuro-muscular disease), both affecting the myocardium. HCM may also be found in syndromes such as the Noonan syndrome, a congenital genetic condition.
There exist various types of HCM, with or without outflow obstruction. Since about 75% of the patients do not have any valvar obstruction (Maron, 2002), we chose to simulate this category of HCM first. Moreover, global HCM without ventricular dilatation is considered here, where the left ventricle is entirely affected by the disease but the right ventricle is healthy. In the following the parameters of the simulation are briefly presented.
Contrary to right-ventricle overload and dilated cardiomyopathy, there is no typical geometry of hypertrophic heart. The only common feature is a focal or global thickening of the myocardium. In this experiment, the normal geometry is modified by thickening the left ventricle myocardium (+28%), without cavity enlargement. The fibre orientations stay normal, i.e. from +90° to -90°, as well as the geometry of the right ventricle.
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Geometrical model of HCM.
Left panel: simulated HCM anatomy. Black lines correspond to the cardiac fibre directions.
Right panel: Comparison between HCM (in transparent red) and normal (in blue) geometry.
The HCM left-ventricular myocardium is thicker than in the normal heart.
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INTERACTIVE 3D MESH |
INTERACTIVE 3D MESH |
As stated in (Wigle et al., 1995), HCM is characterised at a microscopic level by a myocardial fibre disarray and fibrosis. This, along with the increased thickness of the cardiac muscle, leads to a stiffer muscle and an impaired cardiac relaxation affecting the diastolic function. In particular, relaxation rate and volume filling is reduced, which results in a slower myocardium relaxation.
To simulate these observations, the relaxation rate of the 3-D model is decreased (from αr=20 in the normal heart to αr=10) (more information here) and the maximum contraction is reduced from &sigma0 = 0.025 to &sigma0 = 0.022
Only these biomechanical parameters are explicitly modified since:
- stiffness will be implicitly increased owing to the thickening of the myocardium,
- electrical propagation speed will be implicitly reduced because of the enlargement of the myocardium of the left ventricle (the electrical waves must cross more tetrahedra due to the thickening of the cardiac muscle).
Since we aim at simulating hypertrophic cardiomyopathy without valve obstruction and with normal atria, the boundary conditions are kept at their normal values.
Next table summarises the parameters of the HCM heart. Normal values are mentioned for comparisons. The differences are highlighted in blue.
| Hypertrophic cardiomyopathy | Normal heart |
| Geometrical parameters | |
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Degree of the super-ellipsoid: 2.5 RV passive volume: 65 mL LV passive volume: 40 mL RV passive volume / LV passive volume: 1.61 Fibre orientations: +90° to -90° |
Degree of the super-ellipsoid: 2.5 RV passive volume: 65 mL LV passive volume: 72 mL RV passive volume / LV passive volume: 0.90 Fibre orientations: +90° to -90° |
| Biomechanical parameters | |
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Relaxation rate αr: 10 Maximum contraction σ0: 0.022 |
Relaxation rate αr: 20 Maximum contraction σ0: 0.025 |
The other biomechanical parameters stay unchanged (see normal values).
5.2 Results and discussion
Four cardiac cycles have been simulated. The steady state of the system has been reached after the second cycle. We therefore report in the following table only the results of the last simulated cycle.
| Right Ventricle (RV) | Left Ventricle(LV) |
| RV EDV = 77.00 mL | LV EDV = 45.80 mL |
| RV ESV = 42.11 mL | LV ESV = 15.85 mL |
| RV SV = 34.89 mL | LV SV = 29.95 mL |
| RV EF = 45.31 % | LV EF = 65.39 % |
| End Diastole Volume Ratio: 1.68 | |
The scales are aligned for comparison.
The main feature of the simulated volume variations is the slight increase of left-ventricular ejection fraction (from 63.2 % to 65.4 %, that is an increase of 3%), whereas the right-ventricular ejection fraction stays constant. This result can be compared with clinical data of asymptomatic non-obstructive HCM where it has been shown that systolic function in HCM is usually normal or, when abnormal, with high ejection fraction (Wigle et al., 1995).
However, it is worth mentioning that these results are valid in patient suffering from this specific type of HCM only. Indeed, in other cases, HCM may evolve towards ventricular dilatation and wall thinning because of the myocardial fibrosis. The systolic function is then impaired: the ejection fraction is reduced and the end-systolic volume increased.
By analysing the volume variation diagram one can notice that the slope of the volume curves at the filling phase is lower than the one obtained during the simulation of the normal heart. The heart takes more time to relax, the filling is slower. This result is also visible on the video sequence of the simulation where the pathological heart seems to relax slower than the normal organ (see video below). By decreasing the relaxation rate we managed thus to get an anomalous feature consistent with clinical observations (Wigle et al., 1995).
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5.3 Conclusion
This experiment constitutes a simulation of hypertrophic cardiomyopathy. Only asymptomatic non-obstructive HCM with global thickening of the left ventricle was considered. Moreover, no focal variations of electro-mechanical features are implemented though very common in patients suffering from HCM. Finally, only two biomechanical parameter, the maximum contraction and the relaxation rate, have been modified according to clinical observation.
Nevertheless, despite these approximations, the 3-D model managed to capture two main features of this type of HCM: a significant increase of the left-ventricular ejection fraction, and a visible impairment of the diastolic function with slower relaxation speed.
For a personnalized simulation, the implementation of focal variations of the electromechanical model of the heart would be needed to better model HCM. In a second stage, valve movements and obstruction may be modelled to further improve the results.
5.4 References
- Maron, B. J., 2002. Hypertrophic Cardiomyopathy. Circulation, vol. 106, pp. 2419-2421
- Wigle, E. D., Rakowski, H., Kimball, B., Williams, W. G., 1995. Hypertrophic Cardiomyopathy, Clinical Spectrum and Treatment. Circulation, No. 92., pp. 1680-1692.