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The university of Florida College of Medicine is accredited by the accreditation council for continuing medical education. ACCME to provide continuing medical education for physicians, the university of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA category one credit physician should claim only the credit commensurate with the extent of their participation in this activity.

Melanie Cole (Host): Welcome to UF Health Med EdCast with UF Health Shands hospital. I'm Melanie Cole and joining me today is Dr. Calvin Choi. He's an associate professor of medicine in the UF division of cardiovascular medicine at the University of Florida College of Medicine. He specializes in interventional cardiology and he practices at UF Health Shands Hospital. And Dr. Mohammad Al-Ani,, he's an assistant professor in the division of cardiovascular medicine at the University of Florida College of Medicine. He specializes in heart failure, transplant and cardiac imaging, and he practices at UF Health Shands Hospital.

They're here to offer an update in hypertrophic cardiomyopathy. Doctors, thank you so much for joining us, Dr. Al-Ani, I'd like to start with you as we speak about the heritable heart diseases that involve structural changes in heart muscle. Can you tell us a little bit about hypertrophic cardiomyopathy, the prevalence, the scope of the issue we're discussing today and what you see in the trends?

Dr Mohammad Al-Ani: Yeah, sure. Hi, and, thank you so much for having us. So hypertrophy cardiomyopathy, involves really abnormal hypertrophy and, this array of MyCardial fibers, that gives rise to abnormal heart function. So, hallmarks are mycardial stiffness and hyperdynamic function. And there are also, associated structural change represented by hypertrophy of the muscle, in different patterns, so there are different phenotypes, the most common, phenotype recognizes, thickening of the septum, in particular. But, all other areas of the ventrical can become thickened and even the right ventricle can become thickened as well.

The chamber size, the ventricle chamber size may get small, and many patients have obstruction to blood flow. in ventricle, and there are also, some features of abnormal perfusion to the heart, abnormal micro circulation and abnormal function of the ventricle valve. So, each individual, with hypertrophic cardiomyopathy, they have their own combination of these, features, but the hallmark of the disease, all of these patients they have in common, abnormal hypertrophy and disarray of the, myocardial fibers. Most cases. occurred due to a gene mutation that we know of.

So about 60 to 70%, of patients, if they get tested, we're able to identify the mutation that's causing the hypertrophy, but, in the remaining cases we don't, detect a mutation. However, we think that there is probably a mutation under there that, is yet to be discovered. it runs in families for sure. And that's why genetic testing and counseling is important. From a diagnostic standpoint, we start thinking about hypertrophic cardiomyopathy when the left ventricular wall thickness is more than 15 millimeters.

And most individuals with modern therapies, they carry normal life expectancy and a common question that comes up is actually a confusion with athletes, heart. So athletes, can train their heart to become very efficient. And, with that sometimes comes thickening of the heart. So that can sometimes be confused with hypertrophic cardiomyopathy and we have ways to, tell apart if the person has, an athlete's heart that's healthy or is it an abnormal hypertrophy heart muscle.

Melanie Cole (Host): I'm glad you made that point, because that is an important distinction. And as we're talking about distinctions, Dr. Al-Ani. I'd like you to kind of tell us how these other things fit under the umbrella of hypertrophic cardiomyopathy, and speak about hypertrophic, obstructive cardiomyopathy, and left ventricular outflow tracted obstruction, and kind of how these all go together?

Dr Mohammad Al-Ani: So obstruction to blood flow occurs in about 75% of hypertrophic cardiomyopathy cases. It occurs in one or two places, it can occur either at the outlet of the left ventrical, where the mitral valve anatomy and motion, are abnormal. Leading to, abnormal movement or pulling of that anterior leaflet of the mitral valve into the left ventricular outflow. And that can cause various degrees of, obstruction to blood flow out of the left ventricle and various degrees of associated, mitral regurgitation.

And another common type that can also happen is obstruction of blood flow in the middle of the ventricle. So the chamber is a small, the chamber is hyperdynamic and so it can sort of close in the middle, of the ventricle when it's contracting, at maximum degree, you know, in mid and late [inaudible] and. that can cause, obstruction as well. Now obstruction can be provoked, so some patients have obstruction at rest, but others have, no obstruction of flow at rest, but they do obstruct. under certain circumstances. So if the left ventricle is underfilled, for example, the patient is performing valsalva bearing down.

The patient is dehydrated, or standing quickly, If the heart is stimulated to be, hyperdynamic such as with exercise, with fast heart rates, or when the patient has, low blood pressure, for example. and these are conditions that we try to bring when we test these patients in the echo lab, or in clinic, to identify that obstruction.

Melanie Cole (Host): Dr. Al-Ani sticking with you for just a minute here. I'd like you to speak about evaluation and how you diagnose these. When is genetic testing indicated? When do these show themselves and how have advances in some of the imaging enabled you in your diagnostic and therapeutic capabilities for these? Please speak about all of these things and evaluation symptom, risk stratification, tie that all together for us?

Dr Mohammad Al-Ani: Most individuals are really asymptomatic. So, some of them, they come to us because there is a family member who's affected and they like to be screened. And that's how we find out that they have hypertrophic cardiomyopathy. And some patients they do have, an array of symptoms, heart murmur is a common one. shortness of breath, dizziness, Passing out, syncope, somebody who has had an ECG that is very abnormal. So those are the common ways that, patients get diagnosed or, suspected to have hypertrophic cardiomyopathy and get referred to our clinic.

Now, in terms of diagnosis, the first thing we'll have to do is we'll have to establish that the heart structure. And so you would wanna do your normal cardiology evaluation with history and normal cardiac exam and an ECG. And usually with an ECG, you would often see, signs of hypertrophy left ventricle with very high voltage, QRS, and bizarre polarization pattern. And then, with cardiac imaging, starting with an echo, you would see a thickness of the left ventricle, as we mentioned, more than 15 millimeters, hyperdynamic function.

And, you would see, in most patients, obstruction to the LV, blood flow. And if we don't see that obstruction addressed, as we mentioned, we would do provocations, starting with Volvalvum. And if there is no obstruction with Volvalvum, then we may even exercise them with an echo, to bring out that obstruction. And if the above is concerning at least, of hypertrophic cardiomyopathy, then we will have to confirm the diagnosis by, obtaining either an MRI or a CT of the heart, to basically accurately and precisely measure that wall thickness.

Define where is this thickening happening and MRI also helps us detect fibrosis, that is very commonly associated with hypertrophic cardiomyopathy. And that ties into, risk stratification for arrhythmia that Dr. Choi, will tell us about later. and it also helps us, detect, the mechanism of any obstruction. Where is it happening and what's causing it because that can help us, relieve that obstruction later. And genetic testing, comes into, the picture in two ways.

In cases of borderline, testing where some signs indicate maybe hypertrophic cardiomyopathy, but others don't quite fit. Then genetic testing can help, break the tie. But more importantly, perhaps, and more commonly, if we diagnose a patient with hypertrophic cardiomyopathy, then first degree relatives of that person need to be screened and genetic testing help us because if we identify the gene in that person, you would test the first degree relative.

Then if they do have the gene, they need lifelong periodic screening and engagement with a cardiologist. If they don't have the gene, then they are screened out and they can pursue normal medical care without worrying about it.

Melanie Cole (Host): Wow. That was so comprehensive. So Dr. Choi, we did not forget about you. And so I would like you to speak a little bit more, expand on risk stratification, and what's also involved. I'd like you to start into medical management. When you're talking about starting with nonsurgical, some of the new medications available, please tell us what's going on as far as management?

Dr Calvin Choi: So in terms of risk stratification, we start with a thorough history and physical examination. As Dr. Alani mentioned with that information, we are able to streamline what is, effective and, most, efficient way to identify patients at risk. So some of the tests we've mentioned, echo cardiac CT, MRI, stress tests, ambulatory monitor are main stage of risk stratification. So in terms of risk stratification, we are interested in preventing sudden cardiac death in patients with hypertrophic cardiomyopathy.

Again, this is not something that affects vast majority of patients with hypertrophic cardiomyopathy, but very small subset of the patients are at risk for sudden cardiac death. The way to prevent that is, the placement of defibrillator. Class one indication includes sudden cardiac death, ventricular arrhythmia. Class two, many indications include family history of sudden cardiac death, lifted ventricular hypertrophy with septal thickness greater than 30 millimeters, unexplained syncope, APIC aneurysm. The ventricular,ejection fraction, less than 50% abnormal exercise, blood pressure response.

Either less than 20 millimeters of mercury increase or greater than 20 millimeters of mercury decrease in blood pressure during exercise. Class 2B indications include, non-sustained VT. And extensive late gadolinium enhancement and cardiac MRI where the scar or rather late gadolinium enhancement, exceeds 15% of the total myocardium. Moving on to the medical management. There are several options. Now, typically, first. strategy is to avoid vasodilators, which can precipitate hypertension and hence worsen outflow obstruction.

Now the dehydration and use of diuretics, are common, issues that we, advise patients to keep an eye out for. We advise patients to remain hydrated and avoid diuretics if possible. Some of the medications like digoxin can potentially worsen an outflow tract obstruction, due to positive inotropic effect. So digoxin is certainly a medication that we encourage patients to avoid. Other inotropic agents ca, precipitate outflow stroke obstructions as well. So these are the things that, first line recommendations to avoid precipitation of LV outflow obstruction.

In terms of treatment, we recommend controlling heart rate, hence improving the left ventricular filling and reduced LVOT obstruction. Typically beta blocker is used Veropamil, which is a non bioperine calcium channel blocker can be used. Dysoperamide, which is an anti arythmic agent with negative anti Tropic properties can be used as well. However, this is a second line agent. As mentioned before defibrillator is used to prevent sudden cardiac death in patients, who are at increased risk for certain cardiac death.

The novel agent, mavacanton is a new kid on the block. This is a recently approved by FDA for patients with hypertrophic obstructive cardiomyopathy. This is a first in class elective, cardiac myocin ATPA inhibitor. It reduces actin myocin crossbridge formation reduces contractility, improved cardiac efficiency, and studies have, supported its use in patients with hypertrophic cardiomyopathy with obstruction. Moving on to the invasive treatment. We have, septal reduction therapy.

There are two, options for sepal reduction therapy. One is myectomy and the other one is alcohol septal ablation. Myectomy is a surgical procedure where surgeons, under direct vision removed part of the, basal septal wall. Alcohol septal ablation is a chemical means of reducing the basal septal, with infusion of alcohol into a specific, septal perforator. So with respect to sepal reduction therapy, we are talking about myectomy and alcohol septal ablation. Now who, benefits from myectomy or alcohol septal ablation, is the question we often get asked.

So this is treatment options offered to patients with refractory symptoms, despite medical therapy. It does not correlate with, mortality benefit. However, it does improve patient's quality of life. Myectomy is a surgical procedure. It requires sternotomy and cardiopulmonary bypass, and resection of myocardium from the left ventricular basal septum. Alcohol septal ablation is a catheter based procedure and it requires suitable, coronary anatomy, where we inject alcohol into parts of the thick and hard muscle, to scar the tissue and hence, reduce the thickness of mycardium.

There's several differences between myectomy and alcohol septal ablation. As mentioned, myectomy is an open heart surgery that requires cardiopulmonary bypass and sternotomy. This alcohol septal ablation is a catheter based procedure does not require bypass does not require sternotomy. Myectomy is often considered a definitive therapy. Whereas alcohol septal ablation is often considered as a secondary therapy for patients who are at high risk or perhaps even an inoperable candidate due to other comorbidities.

The main, discussion I have with patients when we're talking about myectomy versus alcohol septal ablation is need for permanent pacemaker. With myectomy need for permanent pacemaker is approximately 5%. Whereas alcohol septal ablation, the risk is higher. We generally say it's in the ranges of 10 to 15%. So that is an important factor to consider because once you require permanent pacemaker, Either from myectomy or alcohol septal ablation, this is a permanent commitment. You cannot remove the pacemaker because you are dependent on pacemaker.

So it's not a temporary treatment, but a permanent treatment. Another difference between myectomy and alcohol septal ablation is the recovery period. Myectomy typically takes six to eight weeks of recovery. Whereas alcohol septal ablation typically patients are able to return to their normal activities within a week.

Melanie Cole (Host): This is such an interesting topic doctors, and as an exercise physiologist, I have seen this and it's just so important. What you're really imparting your expertise for other providers. And I'd like to give you each a chance for a final thought and Dr. Al-Ani, to start with you, please tell us about the UF HCM program. Tell us a little bit about the importance of the multidisciplinary approach and why that's so important for these patients and the unique areas that set you apart and why it's important to refer to the specialists at UF Health Shands Hospital?

Dr Mohammad Al-Ani: So, the program that we have, we're really proud of, at UF. We approach this, as a team. So we have a team from interventional cardiology, Dr. Choi, myself from heart failure and imaging. We also have, other, cardiologists, who specialize in electrophysiology, and imagin, interventional cardiology. We have a geneticist and we have cardiac surgery with us. And we try to, give attention to each patient to define their, particular phenotype and risk stratify, them for complications such as arrhythmias. Identify how much, quality of life, impairment they have due to hypertrophic cardiomyopathy and accordingly, would they need a defibrillator or not for protection? And what is the best way to improve cardiac function and blood flow so they can have a, good quality of life?

And so you cannot really refer a patient to us too early. If, hypertrophic cardiomyopathy is suspected in a patient, we are always happy, to see those patients, and arrange an evaluation for them as soon as possible. And we meet monthly in a multidisciplinary way, to review cases who are suspected to have, hypertrophic cardiomyopathy after we complete the initial workup, If you notice that I have, for providers who don't commonly see hypertrophic cardiomyopathy, that comes up a lot.

The first thing that comes up a lot is that, Dr. Choi Mentioned that, vasodilators, need to be avoided. Dehydration definitely can cause those symptoms to bring up. Now this is a hundred percent true. and we all are cautious about these medicines. However, that does not mean that we treat their blood pressure. If the patient is hypertensive, you would still treat the blood pressure. You have just to be cognizant that this is a hypertrophic cardiomyopathy patient, especially if they're obstructive hypertrophic cardiomyopathy and be very cautious about getting that blood pressure on the lower range.

But at the same time, if they need a blood pressure medicine that we can still use blood pressure medicines. And as Dr. Choi mentioned, we would normally start with a beta blocker or calcium channel blocker as our first choice. So that's one point. The other point is that young patients, we are always happy to see them sooner than later, because we all, know, as we have more, data come, on hypertrophy cardiomyopathy that if it starts early in life, then it progresses faster. And so, we're always happy to see those patients sooner than later.

The last thing I would say is a comment on Mavacampton. So we have in our program, started several patients on Mavacampton, and we have had great success with it. We have a streamlined way of, signing up patients to therapy and there is a very structured and FDA mandated follow up, to make sure that, we are dosing the medication, safely and make sure that, we monitor patients for side effects. And the main side effect that we all watch for is causing Ejection fraction or cardiac systolic function to drop too low.

So we want to relieve that hyperdynamic function to a normal function, but we don't want to reduce it below normal. And this is something we have a, streamlined way to systematically monitor and adjusted dose, to make sure that, we achieved that sweet spot.

Melanie Cole (Host): Thank you so much for that. Dr. Al-Ani and Dr. Choi last word to you. I'd like you to speak to other providers about anything exciting or the most exciting advances in inherited cardiac disease. Follow up what you really want. The key takeaways from this podcast today to be about.

Dr Calvin Choi: Dr. Alania has mentioned at US Health, hypertrophic cardiomyopathy. We provide a comprehensive evaluation. And complete treatment options for the patients. These include leading edge imaging studies, as well as, the latest pharmacotherapy, including Mapacampton. Each patient is evaluated and discussed amongst our interdisciplinary team, which consists of interventional cardiology, electrophysiology, heart failure, imaging, cardiac surgeons, as well as genetic counseling.

Now because hypertrophic Cardiomyopathy tends to be associated with a autosomal dominant genetic defect. Genetic counseling is a critical component of the evaluation and treatment, for hypertrophic cardiomyopathy and the patients who are, related to, hypertrophic cardiomyopathy patients.

Melanie Cole (Host): Thank you both so much for joining us today and sharing your incredible expertise to refer your patient or for more information, please visit UFhealth.org/hcm or to listen to more podcasts from our experts, you can visit UFhealth.org/medmatters. That concludes today's episode of UF Health Med EdCast with UF Health Shands Hospital, for updates on the latest medical advancements, breakthroughs and research, follow us on your social channels. I'm Melanie Cole.