New Biomarker Detects Aortic Valve Disease

Michael Markl, PhD, vice chair for research in the Department of Radiology and the Lester B. and Frances T. Knight Professor of Cardiac Imaging at Northwestern Medicine, discusses his research published in JACC Cardiovascular Imaging regarding the association of regional wall shear stress and progressive ascending aorta dilation in bicuspid aortic valve patients.
New Biomarker Detects Aortic Valve Disease
Featured Speaker:
Michael Markl, PhD
Dr. Markl is the Vice Chair for Research in the Department of Radiology at Northwestern University Feinberg School of Medicine. He received his PhD in Physics from the University of Freiburg, Germany (2000), and served as a postdoctoral fellow at the Lucas MRI/S Center at Stanford University, Radiology (2001-2004). In 2004, he returned to the University Hospital in Freiburg, Germany as the Director of Cardiovascular MRI. 

Learn more about Michael Markl, PhD
New Biomarker Detects Aortic Valve Disease

Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, we're talking about how a new biomarker detects aortic valve disease.

Joining me is Dr. Michael Markl. He's the Vice Chair for Research in the Department of Radiology and the Lester B. and Frances T. Knight professor of Cardiac Imaging at Northwestern Medicine.

Dr Markl, it is a pleasure to have you with us for this fascinating topic today. And as we get into it, can you first tell us a little bit about the history of imaging modalities to detect cardiovascular anomalies? How has MRI become this important tool for the clinical evaluation of patients with cardiovascular disease?

Dr Michael Markl: Well, thank you very much for having me today. So that's a great question. Of course, there's many competing imaging modalities that we have available today in the clinic for investigating patients with heart valve disease. MRI is actually one of the later ones that became available clinically. It's actually been available since the 1980s and '90s, but there really has been tremendous technical progress over the last couple of decades. And particularly in the early 2000s, there has been almost a paradigm shift in terms of imaging and MRI has then become available really for imaging of many aspects of the heart valves and surrounding vessels. In particular, it's now possible in relatively short time really doing a simple breath hold, make an image of the beating heart or of the flowing blood through the heart. And that really has transformed healthcare in the sense that you can now really get very detailed information about the structural and functional flow of the heart.

Melanie Cole (Host): It's absolutely fascinating. What an exciting time to be in your field. So tell us about your study with the 4D flow MRI as a hemodynamic monitoring tool and cardiopulmonary exercise testing and what 4D flow MRI was used to detect really.

Dr Michael Markl: So let me just talk a little bit about the background. So this was a study in patients with heart valve disease, more specifically aortic valve disease, which is actually a very frequent disease affecting about 2% to 3% of the US population. One important subset or subgroup is patients with bicuspid aortic valve disease. In fact, bicuspid aortic valve disease is the most common heart birth defect of the heart. And it affects 1% to 2% of the population.

In BAV, the three typical leaflets of the aortic valve, two of those are fused and that results in a much more narrow opening of the heart valve when the blood is ejected from the heart into the aorta. Now, if you were born with a bicuspid aortic valve, this is not necessarily cause for action or concern. However, there are severe secondary complications associated with bicuspid aortic valve disease, or can be such as aortic dilatation, aneurysm, dissection or even rupture.

Now, what's really interesting about this disease is that not everybody was born with it develops these complications. Only a subset of patients go on to develop aortic dilatations and aneurysms, whereas others stay normal for the rest of their lives. So the question is or the really interesting question is why? Why do some patients develop complications and other don't?

So there's two schools of thought. One is kind of a genetic defect, so you kind of have a birth defect, so there's the thought that there's a genetic abnormality of the aorta that weakens the aorta and that's partly true. There are some evidence. And the second hypothesis is that it's the flow. Remember that kind of more narrow opening of the bicuspid aortic valve changes the flow that goes through to valve, accelerates it and then it hits the aortic wall. So the thought is that these changes in flow could kind of promote remodeling of the aorta and lead to disease.

Now, 4D flow MRI is a new imaging technique that was for a large part actually developed here at Northwestern that can measure 3D blood flow dynamics in 3D and over time. That's why it's called 4D. And the study we conducted, we looked at 70 patients with bicuspid aortic valve disease and used 4D flow MRI to better understand if we can extract parameter from the flow through the valve that would kind of help us to better understand who is at risk developing these complications.

Melanie Cole (Host): Wow. So what did your findings indicate, Dr. Markl?

Dr Michael Markl: So what's really interesting about this study is it was a longitudinal study. So we included 70 patients at baseline and followed them more than five years later to see who developed complications and who didn't. And then we looked at several kind of imaging biomarkers. And one of those, it turns out, that's called wall shear stress, which kind of quantifies the drag force or the shear force of flowing blood along the wall. It turns out if that wall shear stress is elevated at a baseline, that was predictive for patients developing aortic dilatation. So in other words, if you have higher wall shear stress in the aorta, you're more likely to developing these complications.

Melanie Cole (Host): I'm an exercise physiologist, Dr. Markl, and the implications of these findings are really astounding. So how important is the early detection of disease progression in the development of prevention and mitigation strategies? How do you feel this will help with that? And how will this study translate to patient care?

Dr Michael Markl: That's a great question, obviously. And, you know, in bicuspid aortic heart disease, the health team all struggle with how to plan patient management for actually decades. I mean, again, remember this is a birth defect. You have to plan care for decades of the lives in these patients. And right now, it's more like a regular monitoring to see if the aorta grows. And if the growth is too large, then actually that's an indication for surgery and replacement of the valve. So kind of a very, very big intervention. So with this parameter, hopefully we'll have a new measure, a new biomarker at our disposal, so that early into life, we can really identify those patients with high risk and then really adjust the therapy plan, their management over time. So you can think about, you know, doing this measurement in a patient early in life. And then if your wall shear stress is low, you can say, "Okay, I mean, this patient, we can do a very kind of minimal monitoring scheme. Bring the patient back every five years for an echocardiography." Whereas somebody else who has higher risk, you probably want to have regular visits on an annual basis and really pay more attention to any changes in their cardiovascular system.

Melanie Cole (Host): What an important tool. So tell us about an MD and PhD collaboration, because I find this fascinating as well during the study. What can other professionals learn from this collaboration?

Dr Michael Markl: I think what's really critical to the success of this imaging technique, this study, and generally research in that area is really cross-disciplinary collaboration, and what you've mentioned really tight collaborations between MDs and PhDs. I'm a physicist by training. And it was always important to me and critically important to me, really directly connect to my clinical colleagues in radiology, cardiology and cardiac surgery, really as a team to evaluate the diagnostic value and prognostic value of these new techniques. It's really important to combine that complementary information or that complementary expertise that everybody brings to the table really. And that's what in the end will improve healthcare and therapy management of those patients.

Melanie Cole (Host): So Dr. Markl, do you have any final thoughts for other providers, things that you would like them to know about the 4D flow MRI as that hemodynamic monitoring tool and new biomarker that can detect aortic valve disease?

Dr Michael Markl: One thing to keep in mind that this is one study in a reasonable science cohort. So we still need to do more research to solidify our findings. But I think we do have new promising biomarkers. And the message to the healthcare provider really is to consider cardiac or cardiovascular MRI as an option for their patients, because there are a lot of ongoing development. There are very meaningful images that are generated with that technology that can really help in managing those patients.

Melanie Cole (Host): Well, thank you so much, Dr. Markl. What a fascinating episode this was. To refer your patient or for more information, please visit our website at

And that concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole..