Lisa Mielniczuk, MD - phaware® interview 525

Why Pulmonary Hypertension Isn’t Just a Lung Problem
Cardiologist Dr. Lisa Mielniczuk from the Mayo Clinic pulls back the curtain on one of the most common — yet misunderstood — forms of pulmonary hypertension: the kind caused by left heart disease. In this episode, she explains why it’s time we stop thinking of PH as a rare condition.

My name's Lisa Mielniczuk. I'm a cardiologist and I work at the Mayo Clinic in Rochester, Minnesota. I've been working in the field of PH now for almost 20 years. I also work in the field of advanced heart failure and heart transplantation. I've been connected in PH through my activities both inside and outside of the hospital.

I've been involved in research in pulmonary hypertension. I've also been working with some great organizations like the Pulmonary Hypertension Association of Canada and PHA, as well. It's just been an outstanding opportunity for me to learn from other people to contribute to both clinical care and research. 

I'm here today to talk about the most common type of pulmonary hypertension that our patients are getting diagnosed with, and that's pulmonary hypertension, secondary to underlying left heart disease.

Now, for those of you that know, and I think many people do know that are listening, pulmonary hypertension in and of itself is not a diagnosis, it's a classification of different types of diseases. I often tell my patients pulmonary hypertension is caused by high blood pressure in the blood vessels that are connecting the heart to the lungs. There's many, many reasons for that.

As clinicians looking after our patients, it's our job to figure out if patients have pulmonary hypertension, why they have pulmonary hypertension. Because the treatments are very unique to the different causes. One of the most common causes of pulmonary hypertension is that that occurs from underlying what we call left heart disease. The left heart disease refers to the left ventricle.

There are basically four main chambers in the heart. We sort of arbitrarily define them as the left side and the right side. The job of the left side of the heart is to pump all that nice oxygen rich blood into our body. The left side of the heart is often thought of as the workhorse of the heart, because it operates under high pressure and volume. Even when we're just sitting here, you and I right now, we might be pumping five or six liters of blood every minute through that left side of the heart. So it works hard for us all the time. 

Unfortunately, there can be different diseases that affect the functioning of the left side of the heart. When that happens, patients can develop pulmonary hypertension. There are many, many causes of pulmonary hypertension from underlying left heart disease. Those could include problems with your heart valves. It could include problems with too much stiffness in the heart. Or problems with weakness of the heart muscle function. Anytime that happens, the pressure builds up inside the left side of the heart and that pressure buildup is transmitted backwards to the top chamber of the left side of the heart, and then it can be transmitted backwards even further to those blood vessels.

If that pressure is there for a long time, changes in the blood vessels can occur. You can get high blood pressure there, you can get remodeling of those blood vessels and people get pulmonary hypertension. What does that mean for our patients? It means that they feel short of breath and they often feel most short of breath early on when they're starting to exercise or do physical activity.

Because when we start to exercise, work harder, move our heart more, those pressures build up faster and they get into our lungs and we feel short of breath. This is a very common condition. As I said, patients often feel short of breath. They can have some chest discomfort. They can sometimes feel very tired and sometimes develop the signs and symptoms of heart failure.

I always say to folks, heart failure is a terrible term because it doesn't necessarily mean the heart has failed completely, but what it means is the heart is unable to meet the needs of our body, essentially a supply-demand mismatch. When that happens, we feel those symptoms of shortness of breath, tired, sometimes fluid retention, sometimes chest discomfort.

One of the most important things I think to talk about, and one of the most exciting things to talk about is how do we treat pulmonary hypertension that is due to an underlying process that is affecting the left side of the heart? Our understanding of this problem has changed so dramatically over the last 10 or 15 years. You might be surprised to know that 20 years ago, we didn't even have a classification system to really try to understand patients who develop pulmonary hypertension from left heart disease, even though it's been known about for 50, 60, 70 years in people with rheumatic heart disease, et cetera. But we just didn't know how to describe it and we certainly didn't know how to treat it. I'd say there's been some very significant advancements over the last 10 years in this field. 

Historically, we've thought of the treatment of this in really two prongs. The first is, and most importantly, we want to do everything we can to improve that heart function. I'm going to talk in a minute a little bit about what those treatments might be. But in the same token, we have done many clinical trials to look and see if some of the treatments that we use for what we call Group I pulmonary hypertension or pulmonary arterial hypertension might actually work in patients who have what we call Group II pulmonary hypertension or this type we're talking about today, which is pulmonary hypertension due to left heart disease.

Let's talk a little bit about the first part. How do we treat underlying left heart disease? Well, obviously it really depends on the cause, right? If you have a significant valve problem, the treatment is often to fix the valve. If your heart muscle is weak, there are great therapies that can help to improve the function of the heart. In the last couple of years, there's been some really nice developments on that field.

One of those medications that has been shown to have great promise in people with left heart disease is a medication known as a class of medications called SGLT-2 inhibitors. Now, these medications, and you may have heard of them before, have traditionally been used to treat patients with diabetes. Then, over time, it was shown that if patients with diabetes had these medications, you could prevent heart failure.

Then, they move the needle further, and they studied them in patients with heart failure and they found, my goodness, these medications can actually treat heart failure and improve people's outcomes when they're used, even if you don't have diabetes. The way this drug works does a lot of things that could potentially help patients with pulmonary hypertension and left heart disease.

It helps to relax the heart. It helps to get rid of that pressure or fluid buildup inside our body. It helps the kidneys. We also believe that it might actually help to improve both the right side of the heart and the blood vessels that we're talking about today that are connecting the heart to the lungs. This is a really important medication now that is offered to patients who have a diagnosis of heart failure, whether or not they have pulmonary hypertension. That's one exciting development, which is new. 

I think when we think about pulmonary hypertension from left heart disease, one of the most common things that we see very often is that the left side of the heart gets stiff. There are many things that can stiffen up the left side of the heart. It happens more frequently as we get older. It is particularly a condition that happens more often in women than men. It can create substantial exercise intolerance, shortness of breath and fluid retention. There haven't really been a lot of treatments for people who have this sort of stiffness of the left side of their heart. Many people who get this stiffness in the left side of their heart get pulmonary hypertension. 

If you ask me, "How often does that happen?" Interestingly enough, we don't have a good answer because it depends on who we sample and how we define it. But based on clinical studies and registries, this could happen anywhere from 30 to 80 percent of the time, a very, very common condition. Pulmonary hypertension from left heart disease is a common condition. It's not rare. Pulmonary hypertension from left heart disease, from left heart stiffness is a very, very common condition and consequence of people who have this left stiffness of their heart. As I said, we didn't have very good treatments up until a few years ago. But now we know that this class of drugs, these SGLT-2 inhibitors, they work really, really well for patients who have stiffness of the left side of the heart.

We believe now that this is the standard of care for patients who have a diagnosis of heart failure with this, what we call preserved ejection fraction or stiffness in the left side of the heart. Many of these patients will have pulmonary hypertension. But the needle doesn't stop there. There are other classes of medications that are moving forward that can really help patients who have this very common type of pulmonary hypertension.

One thing we've also noticed is that there is a real link or association between obesity, having a higher body weight, and developing this stiffness on the left side of the heart. Obesity and the excess body weight we carry does a lot of things that actually can increase our risk of heart failure. It increases the inflammation and stiffness in our body and creates a lot of downstream consequences. I'm sure many of us have heard of the class of medications called GLP receptor agonists.

They're always being advertised all over the TV and radio. I don't think I can drive a day in my car and not hear about them. But they're very, very exciting medications. Again, these medications were used in people who had issues with weight and diabetes, and they demonstrated significant benefit. Now, there's been two very, very promising what we call landmark trials where these class of medications were used to treat patients who had this stiffness of the heart, so heart failure with preserved ejection fraction, plus they had a BMI over 30. 

So they were obese by our sort of characteristic definitions. What they found is that these medications helped people feel better, their quality of life improved, their exercise tolerance improved, and yes, they did lose weight and it made a substantial impact on their overall well-being. Here's another class of medications that I think is just coming around the corner for our patients with pulmonary hypertension and left heart disease, because the incidence of obesity in this patient population is at least 30 or 40 percent. That's fantastic. 

The third class of medications, which I think are coming right around the corner as well, are medications that people may also be familiar with. You may have heard of drugs like Spironolactone or eplerenone. These drugs belong under an umbrella of a class of medications called mineralocorticoid receptor antagonists. Many people may be on them because they can be used for diuretic properties. They can help us to get rid of the extra water in our body.

But there's also new data now that shows that these drugs can help reduce the risk of us developing worsening heart failure events if we have this heart failure from stiffness of the left side of the heart. So, therein is three brand new classes of medications that have all just come to the forefront in the last, I would say, two to five years. We now have good, good, good solid evidence that this should be the standard of care.

In the span of, I'm going to say 15 years, we've gone from having essentially no treatments for patients with pulmonary hypertension from left heart disease caused by stiffness of the left side of the heart, to three very powerful evidence-based medicines. I think it is a time to be encouraged that we're moving the needle forward.

The last thing I'll say about the treatments, and I've talked a lot about their effect on patients who have a diagnosis of heart failure with preserved ejection fraction. These drugs have not yet been studied specifically in our patients with pulmonary hypertension and left heart disease. But like I said, many, many patients with left-sided heart disease like this will have some degree of pulmonary hypertension.

The postulated mechanisms of these medications is very favorable, that many of the ways that these drugs work would really help our patients with PH and left heart disease. 

So, to summarize, where we are in 2025 is a really exciting place. We have brand new treatments that can be used and should be used for our patients with pulmonary hypertension and left heart disease. I think we very much understand that this is a common condition. It is not rare. The global estimates are that if you're over 65, probably 10% of people have some degree of pulmonary hypertension from left heart disease. That's how common this condition is. And that the most common type of PH in left heart disease we see is that stiffness that we talk about, or heart failure caused by stiffness on the left side of the heart.

We now have treatment recommendations, in addition, to all the other non-treatment, non-pharmacologic recommendations we have about blood pressure control, activities, salt and fluid restriction, and all those really important other things that we can do to help to keep ourselves well. That's where we are in the pharmacology. 

There's one other quick thing I'll say, which is I think it's just an example of how quickly the needle moves forward in medicine, particularly how fast the field is evolving in pulmonary hypertension. In addition to these medication treatments, there are also non-pharmacologic treatments that are coming up around the corner that are showing some promise in patients with pulmonary hypertension and left heart disease. Now, these are not ready for prime time by any means, but in small clinical studies, there's been some really promising evidence to show that things like nerve ablation can help reduce the inside the heart and help people feel better.

And different types of minor procedures that can help to reduce pressures either through stimulating nerves, which relax our heart, or inhibiting nerves, which excite our heart, or even creating small shunts to help offload fluid from one place to another. So, stay tuned because there may very well be a whole discussion about the non-pharmacologic treatments of PH and left heart disease in the next few years. 

My name's Lisa Mielniczuk and I am aware that I'm rare.

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