Current & Evolving Understanding in Hypertrophic Cardiomyopathy

Podcast Transcript

Announcer:

Welcome to Cleveland Clinic Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular, and Thoracic Institute at Cleveland Clinic.

Milind Desai, MD, MBA:

We will do some simple math. HCM is thought to have a prevalence of about one in 500, and it is generally thought to be uniform across the world. Some folks say it could be as high as one in 200. If you do the math, there are expected to be almost a million patients in the USA. As of right now, we know about a hundred thousand. That means eighty-five percent patients are not diagnosed, misdiagnosed, or certainly underdiagnosed. If you extrapolate this into the rest of the world, we are talking millions of people where the opportunity to not only diagnose, but to treat exists. This is why there's a lot of excitement in this field, and new therapies always result in new excitement.

Fundamentally, I am still an imager and I will contend multimodality imaging is key to diagnosing hypertrophic cardiomyopathy, not only to establish the diagnosis, develop appropriate phenotype, but also help with differential diagnosis. We have to connect the dots of symptoms with the morphology and what you are seeing. The symptoms could be due to outflow tract obstruction. Outflow tract obstruction could be due to basal septal hypertrophy. The fundamental name, HCM, comes from hypertrophic cardiomyopathy, but I'm going to show you, it's not just about hypertrophy. You could have additional things like mitral valve problems, papillary muscle problems or you could be symptomatic without outflow tract obstruction due to combination of diastolic dysfunction, apical hypertrophy, subendocardial ischemia, arrhythmias, etc.

We have to have an understanding of what the risk of sudden cardiac death is in that given individual. Of course, this is genetically mediated for the large part, so we have to know what the implications are in that front. These are four different patients with HCM, big septum, big apex, concentric LVH, papillary muscle problem. Each one of them is HCM, but they come in very different sizes. Not all HCM is thick walls and not all thick walls are HCM. Two examples, the first one is your standard garden variety, thick wall systolic anterior motion of the mitral valve, outflow tract obstruction, posterior MR, large obstruction. Obviously, this person's treatment is simple. You do a myectomy. This patient was gene negative.

What about this person? There's no hypertrophy. Still, there's a lot of [inaudible 00:03:22]. This patient, we took care of him a few years ago. This is what got our alternate theories of why you could have outflow tract obstruction going. This person was gene positive with the same symptomatology. You cannot do a myectomy in this person. We developed a new procedure. Dr. Smedira was instrumental in doing that, where he manipulated the papillary muscle. This has had a huge impact on our practice, our referral pattern.

It is important to have a tailored approach. You don't want to look like me. You want to look like Dr. Krishnaswamy when it comes to being dressed. Most of us will agree there, Amer's sitting there. Another aspect is recognize this is emerging. The apical hypertrophy is emerging as a major... Now, that we know a lot about the standard HCM, the apical variant HCM is emerging coming into focus. We know now that if you have apical hypertrophy, you have to work hard, look for apical aneurysms. If you don't look, you will not find, and why is that important? Because the risk of sudden cardiac death is threefold compared to if you don't have an aneurysm. When you have an apical HCM patient, always be on the lookout. Expect in your report to say there is or there is no apical aneurysm. If not, if you cannot find, you need to adjust your views and you need to give contrast.

A lot of new stuff is coming in the context of left ventricular strain, I'm just highlighting a couple of papers. This is a paper we did a few years ago on echocardiography, almost 1,110 hundred HCM patients where we have shown that strain provides incremental prognostic value for heart outcomes. This paper was just published last week, I think in JACC Imaging, almost 2,300 patients who underwent cardiac MRI as a part of a multi-center registry where we are now trying to understand using 3D CMR strain, what some of the predictors are. The next step will be whether or not this adds incremental value in terms of prognosis. A lot of stuff is happening in advanced imaging. A lot of stuff is happening in the context of this HCMR registry that we started along with Oxford and University of Virginia a few years ago now, almost 2,800 hundred patients who've been very well characterized, and now we are in the follow-up stage. We will not only have diagnostic utility, but prognostic, whether or not it adds prognostic value or not.

We are entering the era of artificial intelligence, machine learning, et cetera. This is, again, on 2,400 patients who underwent extensive phenotyping as part of the HCMR registry. This was published at the end of last year where we are using different patterns, machine learning to identify which patients may obstruct, which patients may obstruct that stress, what does the role of genotyping play in all this? This field is the field of imaging, machine learning and you put the disease, whatever disease in this context, HCM. This is rapidly evolving, so a lot of stuff is going to emerge in the next few years.

I have chosen to show this paper to highlight some of the potential pitfalls of going gung-ho on artificial intelligence. This is a paper published by another large center, which shows that using artificial intelligence, you can diagnose HCM with a very high degree of accuracy. The problem is ninety-five percent patients were Caucasian and majority were men. Most of us know that HCM has similar race preponderance. In African-American ethnicity, the ECG at baseline could have a lot of abnormalities that could be picked up as abnormalities that are not really abnormalities. Anytime we see a machine learning AI type paper, we have to look at the, you cannot just read the conclusions or the abstract. You've got to go deeper into this.

Some of the additional work we've done in collaboration in terms of machine learning, superior to assess wall thickness. This is something that we worked with the Heart Hospital in London, and this again, this paper was published last year where using just single view on cardiac MR, we can ascertain basically a presence of obstruction. We can understand various aspects of pathophysiology. A lot of exciting new stuff is happening in this context.

Step two, it is absolutely important to elicit outflow tract obstruction. If you don't look, you won't find, and if you can't find, you cannot treat. It is absolutely important. I'm highlighting this case of a young guy who after seeing a couple of psychiatrists was sent to us. The only reason he pursued cardiac evaluation because his mother had standard HCM. He was told that this is nothing going on. You put him on a treadmill. His gradient is more than a hundred, and he had all the symptoms that brought him to the doctors.

Outflow tract obstruction versus no LVOT obstruction is associated with the worst long-term outcomes. It is important that we recognize this and utilize all means to provoke outflow tract gradient. Without provocation, resting gradient is seen in twenty-five percent patients. With provocation you can see it in 70% patients. That statistic alone should be enough for us to elevate our game. Designating somebody as non-obstructive HCM without full extent of testing is not appropriate in 2023. Stress echo can and does provide significant incremental value, not just prognosis, but also diagnosis. It assesses latent symptoms, functional capacity, outflow tract gradient. Again, a few years ago we published this paper, 430 patients who came to the Cleveland Clinic saying they were asymptomatic with HCM. Prove it to us. We put them on a treadmill. Only 18, 1-8 percent patients achieved what was expected off of them. Not all of them were just deconditioned and obese. A lot of them had symptoms that they did not realize. This is important.

Third thing, this is what, essentially, a large part of our practice is, substantial part of our practice, because of our experience with this, recognize not only typical but atypical variants of obstructive HCM. Majority of the patients are going to have the standard thick wall outflow tract obstruction type HCM. But you will see a fair number of patients, especially in the Cleveland Clinic Echo Lab, where you have papillary muscle problems, cordal problems, mitral valve problems, et cetera. It is important to recognize this because management plan is different.

Again, designating somebody as not having HCM because they do not have hypertrophy is not appropriate in 2023. You have to work to rule out other variants. These are three examples that we have seen in our practice over the years. The first one has a very long entomitral leaflet, no basal septal thickness. Everything else looks like HCM on Doppler. Bifid papillary muscles on MRI, no wall thickness. Again, severe outflow tract obstruction, somebody with an abnormal cordial attachment. Again, severe outflow tract obstruction. None of these patients can have a myectomy because there's not much muscle to shave off.

It is important to recognize this. Differential diagnosis is important because there's a lot of things that have thick walls or look like HCM. Using strain on echocardiography, we can ascertain some of the differential diagnosis. The top left is your standard HCM. Top right is somebody who has normal strain except in the apex that is most likely expected to be apical HCM. The flip side is the cherry on top, the apical sparing amyloidosis case that, again, was first described at the Cleveland Clinic. Using multimodality imaging, especially CMR and scar assessment, you can further ascertain, could it be Fabray’s disease? Could it be amyloidosis? Is this athlete's heart? It is important when in doubt to expand your thought process. If there's clues in history, you need to chase that.

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