Model-Based decomposition of myocardial strains: activation time and contractility mapping

1. Model-Based decomposition of myocardial strains:activation time and contractility mapping Borut Kirn Department of Biomedical Engineering University of Maastricht The Netherlands In collaboration Institute of Physiology University of Ljubljana Slovenia

2. Detection of cardiac motion MRI-tagging US - speckle tracking

3. Coordinated contraction Circumferential strain (εcc)

4. Discoordinatedcontraction LBBB LBBB + Ischemia Left bundle brench block (LBBB) and Ischemia

5. Clinical problem In cardiac resynchronization therapy patients are selected upon: • QRS duration (LBBB) • Heart failure indices (LV dilatation, low EF) 30% of patients show no benefit + 20% no reduction of LV dilatation Can we improve patients selection and PM positioning using mechanical indices?

6. Normal conduction Short QRS duration R P S Q Time[ms]

7. Conduction during LBBB Prolonged QRS duration R P Q S Time[ms]

8. Ischemia

9. Mechanical indices of asynchrony onset of shortening

10. However, • Onset of shortening time is not activation time • Early activated regions are not detected • Activation time is only one component of dyscoordination

11. Aims • Design of a model to simulate local circumferential shortening (εcc) for different • activation time (Act) • contractility (Con) • Mapping by inverse use of model fit to εcc • map of Act • map of Con

12. CircAdapt model of heart and circulation Modeling of circulation - lumped model in modules: chambers, tubes, valves Dynamic(t)CompliancesInertiasNon-linear Adaptation of modules to load,i.e. wall mass, cavity size Arts T et al. Am J Physiol. 2005;288:H1943-H1954

13. Characteristics of CircAdapt • Modular architecture • Structured parameter data base

14. SarcMech (Act, Con) SarcMech (Act, Con) SarcMech (Actn, Conn) SarcMech (Act, Con) SarcMech (Act, Con) SarcMech (Act, Con) SarcMech (Act, Con) SarcMech (Act, Con) Actn, Conn Act, Con Actn-1, Conn-1 Actn-2, Conn-2 CircAdapt with Multi-segment myofiber C i r c A d a p t Timing CavityMech RepSarc Valves Tubes

15. 1 2 3 n-1 Assumption: Equal stress in all regions of ventricular wall n Sarcomere element: Passive Active

16. Solving inverse problem INPUT PARAMETERS: RESULT: Act1, Act2 … Act160 εcc,1 , εcc,2 …. εcc,160 MODEL Con1, Con2 … Con160 compare MAPS: measured εcc simulated εcc

17. Solution 1: 159 sarc.el. with Act=0; Con=1 1 sarc.el. with Act=?; Con=? Influence of Activation time: Influence of Contractility: Sarcomere length Sarcomere length time time Sarcomere length

18. Solution 2: linear decomposition

19. Reconstruction of maps, using MRI-tagging measurement on a dog model: ischemia induced by ligation 0 anterior Contractility (normalized) septum 1 apex base 2

20. anterior septum apex base Reconstruction of maps, using MRI-tagging measurement on a dog model: ischemia induced by ligation 70 50 Activation time [ms] 30 10

21. Reconstruction of maps, using MRI-tagging measurement on human: LBBB Activation time Contractility

22. Reconstruction of maps, using MRI-tagging measurement on human: LBBB + Ischemic cardiomyopathy Activation time Contractility

23. Reconstruction of maps, using MRI-tagging measurement on human: healthy Activation time Contractility

24. Reconstruction of maps, using MRI-tagging measurement on a dog model: healthy, +ischemia, +LBBB Contractility Activation time healthy +ischemia +LBBB

25. Conclusions • The circumferential strain as a function of time (εcc) in asynchronous contracting left ventricle (LV) was modelled as a long fibre around the LV, consisting of a series of fibre segments, each having its own activation time (Act) and contractility (Con). • Applying the model inversely, the measured maps of regional εcc were converted to maps of activation time and contractility. • Obtained maps were in agreement with clinical diagnosis of LBBB and ischemia in animal experiments and in patients.

26. Colaborators Theo Arts, Joost Lumens, Tammo Delhaas, Wilco Kroon and Frits Prinzen