ViVitro’s Lab Manager, Rob Fraser (RF), recently spoke with Dr. Amini about his research.
RF: Please tell us about your current work in the research laboratory.
RA: We are conducting experiments and building models to study tricuspid valves, which are located between the right ventricle and the right atrium on the pulmonary side of the heart. This is probably the most understudied of the four cardiovascular valves. Some clinicians call it the “forgotten” valve because of how much work has been conducted on the other three valves.
We are trying to understand how the biomechanics of the valve affect its physiology and pathophysiology. We are hoping to study the influence of different surgical procedures on the valve and look at the changes the surgical procedure causes on the biomechanics of the leaflets at the tissue and sub-tissue levels.
RF: How is the work going?
RA: So far, good. We just published a paper on some of the work we did on mechanical testing of the valves and another paper on the ex vivo beating heart setup where we used the ViVitro SuperPump. In the latter study we have been looking at the deformation of the leaflets when the right ventricle of the heart is passively beating. It is pressurized using the ViVitro pump.
RF: How is the right heart model working for you?
RA: Clearly I saw some major limitations of the model because the muscles are not actively working as they do in vivo. But if you look at most of the work studying the mechanics of valves, specifically the studies where the leaflet strains and deformations have been measured experimentally, most of the times researchers remove the entire valve and mount it on a rigid annulus. Then they put the valve that has been mounted on the rigid annulus on to some sort of simulator that simulates the pressure environments of the ventricle whether it is on the right or left side, mitral or aortic or tricuspid valve doesn’t matter.
That is what’s done a lot. In recent years the whole idea of using an entire intact heart and actually pressurizing the ventricles and letting the annulus deform as the valve opens and closes has been shown to be important. The reason it is important in my opinion is that if you use surgical annuloplasty rings and put them on the valves and technically eliminate that motion, you find different strain on the valve in the in vivo set-up. So by fixing the annulus of the valve you are removing a major contribution of the surrounding tissues that let the valves deform more freely. I think the ex vivo beating heart is one step closer to the in vivo case. A lot of the ethical issues that come with in vivo studies don’t exist with ex vivo studies. We can use hearts we get from slaughter houses. Or if later on you want to use human tissues we can get cadaver hearts and use them in studies on surgical procedures and models without ethical issues. Also, some of the in vivo study hearts are too far away to get into the clinical set-up. It has to be first verified in the ex vivo setup.
I used to think the lack of contraction of the heart was a limitation, but it could actually be beneficial in certain cases, say where you want to develop a computational model of the valve and the muscular tissue around it. The advantage of having the actual ex vivo heart is that it allows us to better define the actual boundary conditions on our model and lets us have a slightly more simplified computational model and validate the computational model from something where all the mechanical forces are generated primarily by this pressure change not by the internal stresses from the muscle contraction. That is an important step for verification and validation of the computational model, also a very important task of the computational work which is another aspect of our research lab. We are trying to use this for validating our computational model.
RF: That’s an interesting point. I too see that having the ventricle walls not contracting has limitations, but had not considered the advantages of defining boundary condition, and then validating CFD code. That’s an interesting advantage.
RF: You were the first group that used our ex vivo simulator. How was the experience?
RA: Overall, it’s fantastic. We’re very happy. My former assistant spent a lot of time trying to play around with things. You guys were very helpful and we are very appreciative. Another thing I want to thank you for is when I was submitting the paper I needed a reference for the waveform we were using over a holiday and I got a response back from you in a short period of time.
RF: Glad we could help. Earlier you mentioned the tricuspid is a forgotten valve for research. That’s also true for product development. Many of the technologies that came to market were for the aortic valve. Now they’re switching to the mitral valve and it seems people are going after all four valves of the heart. What do you think has caused this increase in study and then treatment for all the valves of the heart?
RA: There are a lot of new, interesting hypotheses developing in the minds of the surgical and clinical community. For the longest time there was a lot of effort on just removing the valve and replacing it with a prosthetic valve. Nowadays, a repair procedure is preferable to a total valve replacement. The patient doesn’t have to take a lot of medications. The success of repair procedures has been improved by the work of surgeons. Most of this work has been done on the mitral and aortic valves. Now that the success of the systemic side of the heart is being improved, more and more attention is going to the pulmonary side. Other diseases that cause secondary regurgitation to the tricuspid valve such as pulmonary hypertension, which is another disease we know little about, affects the biomechanics of the tricuspid valve and leads to regurgitation of the tricuspid valve. So a combination of improvements on the mitral and aortic side has led to more investigation on tricuspids.
RF: What are your future plans and goals with this work?
RA: We are currently working on a couple of interesting studies. One is looking at the biomechanics of the normal leaflet. We are measuring the deformation of the valve in response to the normal pressure. Then we plan on repeating the same study by increasing the pressure and seeing how the biomechanic changes in a “pulmonary hypertension” environment. We’re very excited because we believe having this sort of information will help people doing studies on the cellular level of the valve. They try to understand how much the mechanical environment of the valve actually changes when you expose them to a higher level of pressure. Then hopefully they can answer why changes in pressure lead to changes in the valve that lead to regurgitation.
The other thing we are doing is building a computational model of the right side of the heart. We are trying to use the same type of data that we get from an ex vivo beating heart to validate our model. We are also interested in looking at a mitral surgical procedure that is currently being conducting and first understand how they affect the biomechanics of the leaflet, and what we can do to maintain the “normal” physiological deformation of the leaflet of the heart using this surgical procedure. Hypothetically if we do a procedure that is going to deviate the stresses and strains on the leaflet, from its normal physiological response, then in the long term we should expect that it’s going to affect the quality of the valve surgical procedure. So what can we do? Can we use a different annuloplasty ring shape? Can we use a more flexible annuloplasty ring? Or maybe the sizing should change or something like that? How about percutaneous procedures? That’s the other advantage. We can use the connectors that we used to send our endoscopic camera to perform percutaneous procedures on the valve to see how that affects the stresses and strains on the leaflets and the general quality of the valve repair.
RF: It sounds like there is more than enough to keep you busy for years to come. Do you have any advice for academics and people doing similar work?
RA: My piece of advice to people in the research realm is to be persistent and if they think they have a good idea and when they face hard times, there comes a point where all of the hard work will be fruitful. For us the whole idea of using the ex vivo beating heart and combining it with some other tools such as sonomicrometry using piezoelectric transducers was really challenging initially. But we didn’t give up and were excited to make these things happen. I think in this case we were very excited when we managed to collect our first set of data. If you refer to the Journal of Biomechanical Engineering paper you can see we got a pretty consistent data set with a good level of variability even though these are pig hearts and we didn’t have any specific criteria to select the hearts form a specific group of animals. We collected them from a local slaughterhouse. For our lab, we have received funding from the American Heart Association and we are really grateful that we can continue our work. As we talked, I mentioned 4-5 different research ideas and we hope to have more funding to be able to continue these studies.
Read more interviews with Cardiovascular Pioneers.
Research by Dr. Rouzbeh Amini using ViVitro equipment or services includes: