Mary Norine Walsh, MD, MACC, is the Medical Director of Heart Failure and Cardiac Transplantation and Medical Director of the St. Vincent Cardiovascular Research Institute, a board member on Women’s Heart, and a past president of the American College of Cardiology. Mary was elected by her peers for inclusion in the best doctors in America annually since 2005 and has published over 150 peer-reviewed papers. She recently spoke with ViVitro Labs Application Manager, Rob Fraser, about her work, unserved markets, ventricular assisted devices (VADs), the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy), and advice for young investigators.
Rob Fraser: Your clinical research for our audience centers around heart failure and cardiology. Could you speak about that work?
Mary Walsh: The focus of our heart failure research really encompasses all different types of research. One of them is medical therapies for patients with both heart failure with reduced ejection fraction, as well as heart failure with preserved ejection fraction. There are a lot of therapies being trialed, including medical therapies, device therapies, as well as major device therapies like left ventricular assist devices. We’ve been involved in a lot of different types of trials from all the way back in the early days of the development of Carvedilol before it was on the market. More recently our group, along with our surgical colleagues, has been involved in randomized trials of the various left ventricular assist devices.
Most recently, we were a leading enroller in the Momentum 3 Trial that demonstrated the superiority of the HeartMate 3 left ventricular assist device. One of the areas of research that’s really underserved in not just the United States, but in the world, is research techniques around heart failure with preserved or normal ejection fraction. Although there are fewer trials enrolling, I tend to try to make sure that we’re involved in enrolling patients in those trials because this is a very underserved population that is generally older than the population of patients who have heart failure with reduced ejection fraction, more commonly women than men. This is an area of investigation that interests me. That’s a broad overview of our work.
Rob Fraser: Why are these an unserved market? Why is no one else looking at these patients?
Mary Walsh: People are looking. It’s well known by pharmaceutical companies, as well as device companies, that 50 percent of people who have heart failure have normal ejection fraction. To some extent, it’s a little bit of an artificial construct that our therapies have always been directed at a given ejection fraction. We’re learning more and more that the phenotype of heart failure matters and that we need to apply our therapies depending on what that phenotype is. I would also say it’s been the lower hanging fruit for decades to look at patients that have a defined disease; their ejection fraction is not normal, it is too low. We will go after that disease with our medications and device therapies.
It’s harder to define heart failure when there is not a gold standard number. A lot of people have normal left ventricular ejection fraction, they’re short of breath, but by other biomarker assessments, they don’t have heart failure. There are a lot of reasons people get shortness of breath. Part of it has been not being able to well define the physiology of heart failure with preserved ejection fraction in the everyday practice of cardiology, both outpatient or inpatient. It results in a heavy focus on the former group, those with reduced ejection fraction.
Rob Fraser: On the device front, ventricular assisted devices (VADs) have come a long way in recent years. You mentioned the Momentum 3 trial. Where do you see the technology today and where do you see the VADs heading in the future?
Mary Walsh: Some patients are very satisfied with their devices and satisfied with their lifestyle. If you were to ask a VAD patient today, a lot of them end up saying, “I really want to get rid of this, I’d rather have a heart transplant if I’m eligible”. The device has complications, including bleeding, thrombosis, and infection. The patients have to carry their power supply with them at all times. They are unable to bathe in a bathtub, unable to swim, unable to get into saunas, that sort of thing.
The technology moving forward that will interest the patients as well as the investigators are smaller devices that better replicate the physiology of humans to decrease the complication rate and much smaller generators. I often tell patients when we have a generator or battery that’s small enough, that is the size of your defibrillator battery, then everything will be inside and that will decrease our infection rate significantly. VADs will be smaller, more physiologically compatible with the human cardiovascular system, and have smaller peripherals. The engineers in all companies are certainly working on this and the surgeons are excited about all the innovations as they come along.
Rob Fraser: Physiology is where a lot of our customers end up using products to help understand those things better. The VADs have gone from steady flow to pulsatile flow and they’re trying to reduce hemolysis. What have you seen that’s promising in terms of making these a little bit more physiological?
Mary Walsh: The HeartMate 3 and adding back pulsatility was a game-changer. That, and the resulting lack of thrombosis necessitating pump exchange was really what drove the primary endpoint of the trial. That was really revolutionary. I am not an engineer, so I’m not going to tell you exactly where they’re going next, but every VAD cardiologist or VAD center would tell you that the numbers of patients we see every day admitted to the hospital with complications include those who have bled either into the GI tract or sadly sometimes into the cerebral hemispheres or infections. These are chronic problems that people live with, and if those are lessened with the next generation of devices, the patient satisfaction will rise and so will the clinician satisfaction.
Rob Fraser: One of the symptoms of heart failure can be a dilated ventricle, which results in functional mitral or tricuspid regurgitation. There’s a host of repair devices out there now trying to treat this, hoping that leads to ventricular remodeling. What are your thoughts?
Mary Walsh: We participated in the COAPT trial and it’s a landmark trial. The most important thing about that trial was for the first time in a valve trial, heart failure cardiologists were partnered with their interventional colleagues and surgical colleagues inpatient identification and enrollment. And the patients had to be well treated with guideline directed medical therapy before they qualified. Once they were treated, they had to be reassessed to see if they qualified.
The sad part about the trial is there wasn’t a registry in place where every patient who saw a heart failure cardiologist was tracked because there were some patients who never were eligible for the trial because their symptoms improved and so did their mitral regurgitation (MR) after adequate medical therapy. The group that was randomized really were truly, treated patients. On top of the best guideline directed medical therapy, mitral clip was demonstrated to be a proven therapy. Had the trial not been conducted that way, we wouldn’t know whom to put the clip in. So it is one of the things that’s in our armamentarium. Myself, along with my senior fellow investigator and colleague, James Hermiller, are involved in several trials involving clipping the tricuspid valve. That is something that’s very needed. We have many patients with right ventricular failure and functional tricuspid regurgitation who are very hard to treat with our current medical therapies, which is primarily diuretics. So that’s a really exciting vista in valve therapy also.
Rob Fraser: It’s tough, we only have so many tools in our toolbox and there aren’t necessarily devices that treat the heart failure yet. To me, we’re treating the symptoms and not necessarily getting at the root cause of the disease.
Mary Walsh: Just as an example, I can describe one patient we all discussed this morning, in order to put a TAVR valve transcatheter aortic valve replacement (TAVR) valve in the aortic position, you have to have enough calcification to seat the valve. The untreated population of patients with aortic insufficiency will also have significant left ventricular dysfunction is a population in need of treatment options. This is a patient population where we ask “should the surgeon operate? Should we do a combined operation with aLVAD) and fix the aortic valve?” That’s another frontier of trying to figure out how to fix aortic regurgitation (AR) for the patient without a calcified valve.
Rob Fraser: You’ve accomplished so much in your career already. What’s next for you?
Mary Walsh: I love a lot of what I’m doing right now. I have a busy clinical practice which I love and don’t intend to leave any time soon. I also enjoy editorial work greatly and I am a deputy or associate editor for a couple of journals which occupies my time and I enjoy that. I’m always looking for a new challenge, I think the COVID pandemic has affected us so greatly. I’m interested in new paradigms of care for our patients and treating them with not just remote monitoring, but in the virtual environment. That’s another area I’m really interested in exploring. And honestly, I sure hope we all get to travel one of these days!
Rob Fraser: Yes, I’m sure there’s a pent-up urge for a bunch of people!
Mary Walsh: All the meetings are not zoom meetings and all the fun parts kind of dropped away.
Rob Fraser: No, I agree! There are not the libations with colleagues after a long day of presentations, it’s just presentations and then loneliness.
Mary Walsh: Yeah, that’s right…and the chatbox.
Mary Walsh: I just gave a talk on this yesterday morning. The ACC (American College of Cardiology) has a clinical trials research boot camp. I am a co-chair of that and one of my responsibilities yesterday was to give a talk to that cohort of young investigators about the workings of multicenter clinical trials. One of the things that I stressed was if you’re going to do research, you have to interleaf clinical research into clinical practice. You have to interleaf patient recruitment into your everyday life. It’s just not separate. For instance, “on a Wednesday afternoon, I’ll do research”. That type of scheduling just doesn’t work. If you’re a clinical researcher, patient screening and enrollment really has to be integrated into your everyday practice. Whether that’s in the office, the clinic, the imaging lab, or the hospital, wherever the patient is. Finding time for research happens if you like doing research. And you find time to do the writing later on at night and on the weekends. Actual clinical research is fully integrated into our practices because that’s where the patients are.
Rob Fraser: That’s good advice. Clinical research is not separate. It has to become part of your whole existence.
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