Ask the Mito Doc – January 2026: Cardiac Mito — Genetics and Clinical Insights to Jumpstart the Year
All answers today are based on personal experience of the participants. As always, please consult your personal physician prior to taking any action.
Topic: Cardiac Mito 2026: Genetics and Clinical Insights to Jumpstart the Year
Moderator:
- Margaret Moore, UMDF Associate Director of Support & Education
Speakers:
- Hilary Vernon, MD, PhD, Johns Hopkins University School of Medicine
- Andreas S. Barth, MD, PhD, FAHA, Johns Hopkins University
- Rebecca McClellan, MGC, CGC, Kennedy Krieger Institute
Q: Have you heard of anyone who has the TTN mutation as well as mitochondrial myopathy at the same time – both documented?
A: Rebecca McClellan, MGC, CGC: We all have changes in our DNA and it is certainly possible to have a mitochondrial genetic condition as well as a TTN gene variant. The risks associated with TTN depend on the specific change and its location in the gene, but some changes can put individuals at risk for cardiomyopathy and arrhythmias. You should discuss your specific variant and its risks with your team and then follow their cardiac screening recommendations.
Q: We know Valproate (Depakote) is contraindicated for the liver in Alpers; are there similar “absolute no-no’s” for cardiac medications in this specific population? Is there anything that people should really avoid and make sure that their doctors know that they should avoid it? Are there any specific gene therapies or small-molecule drugs being discussed for 2026 that aim to stabilize mitochondrial DNA depletion specifically in heart and liver tissue?
A: Andreas Barth, MD: From my perspective there are clearly a lot of medications that are contraindicated in mitochondrial disease in general, and usually when patients are referred by Dr. Vernon to my clinic, patients are very well aware already which medications those are. From a very practical perspective, we see that patients can get into trouble at times with the statins, those are medications that are used to lower the cholesterol. One participant asked whether mitochondrial disease leads to high cholesterol, not necessarily. But we know that high cholesterol is very common in the general population and often patients who have mitochondrial disease also happen to have high cholesterol. And then, it’s usually a well-meaning primary care physician who says, you have high cholesterol, here’s a statin for you. What we typically see is that those patients who have underlying mitochondrial disease can develop this profound muscle ache, or we’ll hear their joints really hurt and they don’t feel well. Often this is attributed to the statins, and once we stop the statins and put them on alternative cholesterol-lowering medications, those patients often do much better.
Q: In primary mitochondrial myopathy, is it common to have bouts of tachycardia and ectopy? Exactly how will calcium channel blockers (Diltiazem) effect skeletal and heart muscles?
A: Andreas Barth, MD: Yes. When you have mitochondrial myopathy, the heart is a different type of muscle than a skeletal muscle, so if your skeletal muscle is affected, it does not automatically mean that your heart muscle is affected, too, but it can be. It’s certainly a risk factor and it requires, as Dr. Vernon mentioned before, very close monitoring. You need to see a cardiologist at least once and then with regular follow up to make sure that there is no progression of the disease. And what we can see is that you can develop a weakening of the heart muscle, but you can also develop abnormal rhythms that can present as tachycardia and it’s important to investigate that further. Is this an arrhythmia that’s coming from the upper chamber of the heart, or from the bottom chamber of the heart. We can see both in patients who have mitochondrial myopathy. We talked a lot about slowing of the electrical activity that can occur in the heart with mitochondrial disease that may require then pacemakers. That is true, but sometimes we see that patients have actually extra wires that build in the heart. We call that WPW (Wolff-Parkinson-White syndrome), and that can give rise to sort of short circuits of electrical activities that can then lead to tachycardia. So that’s something that we can diagnose on the surface with EKG and then we can treat either with medications or with an electrophysiology study that we put a catheter all the way up in the heart through a blood vessel, identify this extra wire and are able to cauterize it and get rid of it. So with tachycardia there can be many reasons for that and it certainly requires more investigation.
Q: Can you explain the issue of having treated hypertension for years but also episodes of low BP w activity during the day?
A: Andreas Barth, MD: If you have labile arterial hypertension, this may be indeed more difficult to treat, as you have both BP readings that are too high and some that are too low. If you have episodes of BP that are too low, you may consider drinking more (if you are dehydrated, the BP lowering effect of antihypertensive medications is more pronounced). If this does not resolve the problem, you may have to talk to your provider to see whether the dose of antihypertensive medications can be reduced.
Q: As some mitochondrial diseases progress, dysautonomia worsens without cardiac structural changes. Does this make it a neurological problem and not cardiac problem even though it is treated with cardiac medications? Do you ever treat dysautonomia with a pacemaker?
A: Andreas Barth, MD: In the rare cases and exceptions we treat dysautonomia with a pacemaker. That should be the exception, it’s not the rule. I think this would be worthy of another seminar, frankly, because dysautonomia is a completely different world.
Q: How often should mito patients have cardiac evaluations and what should they include each time?
A: Hilary Vernon MD, PHD: It’s so important to establish a genetic diagnosis, if you can, because there are specific risks associated with specific mitochondrial variants. I’m very conservative, so regardless of the variant that I find, if it’s a known established primary mitochondrial disease, I send all of my patients for an initial cardiac screening, both kids and adults. And this includes an echocardiogram and an EKG and a referral to a cardiologist if either there’s an abnormality or the risk is high. Then at that point we really have to look at the specific variant and what that risk is. And that’s where we really bring in our cardiology colleagues to ask what next?
My general approach is if there’s a variant that a patient has that has not been established or has been very low likelihood to be established or’ to be associated with cardiac disease, I will still do screening, but I will generally stretch out the amount of screening over time in which a patient needs to be seen. Because we have enough doctor’s visits to go to when you have a mitochondrial disorder, our goal is to keep people safe and healthy, but not too many appointments. I see Rebecca and Andreas nodding so hopefully I’m giving the right information from their perspective as well.
Q: Is a MRI the only way to detect scarring progression?
A: Andreas Barth, MD: Yes, only the cardiac MRI will show the scar. The echo will not show the scar. I typically recommend getting a cardiac MRI at baseline and then every 3-5 years to monitor for progression of scar tissue. In between (in the years you don’t have a cardiac MRI), I recommend annual echo’s. Depending on your heart function, more frequent echo’s may be needed.
Q: What is the difference between LVAD and ICD?
A: Rebecca McClellan, MGC, CGC: An LVAD is used to help support the strength or squeeze of the heart. An ICD is a device that is used to treat a dangerous heart rhythm.
Q: The American Heart Association recently published this Scientific Statement on Mitochondrial Genetics in Cardiovascular Health and Disease. Strikingly, in Table 4 for LHON it states the prognosis as: “In adulthood mortality risk is doubled compared with the general population.” Can you comment, or provide any insight to the LHON community on this topic?
https://www.ahajournals.org/doi/10.1161/CIR.0000000000001393
A: Hilary Vernon, MD PHD: So I can speak to my practice. I’ve thought about cardiac considerations in LHON for quite a long time because for a long time the risk hadn’t been quantified as double the general population, but there were plenty of case reports of cardiac involvement in patients with LHON to make us think that we should be careful. So these are the patients that as soon as we make a diagnosis, if they’re asymptomatic, if they don’t have symptoms that they’re not complaining of things like fainting or heart racing, we’ll have an EKG and an echocardiogram. Generally, when my patients and any of my colleagues, please pipe in if you disagree with me, hit the teen years, if we’ve made the diagnosis early, particularly if it’s a family consideration, if there’s symptoms, I will consider doing a halter, one of those patch halter monitors as well. And then again, if a patient remains asymptomatic and there’s no changes every 3-ish years, I will still ask them to get an echocardiogram and an EKG. I just want to be very, very careful. We still don’t really understand what this risk is, what it’s coming from and who’s exactly at risk with LHON and in my opinion, the echocardiogram and EKG are non-invasive enough that it’s something I usually say, you know, do it over the summer when you’ve got some time, when you have some time off, but just make sure you have it done.
Q: What if you have (supposedly) Sinus Bradycardia? Picked up several times during ER visit, was seen & of concern by Anesthesiologist pre-op.
A: Andreas Barth, MD: When you have sinus bradycardia that means that your heart rhythm is too slow. This electrical system breaks down in the heart, this wiring breaks down, but it means that your own microchip, your biological conductor that we all have in the heart, the biological pacemaker that we all have is too slow. And the first question is if you have sinus bradycardia, that is slow heart rhythm, when it’s at night, when you’re sleeping, you’re asymptomatic, you can ignore that. That is often sort of a byproduct that we see when we monitor your heart rhythm over a couple of days and we see that at night, your heart rate may be 37 or 35 or you may get an alert from your apple watch – You can disregard that. We also ask is there any reversible reason. Are you on any medications that slow your heart rate down? Do you have an under-active thyroid gland that can also lead to a slowing of the heart rate? So there may be some reversible reasons that we look at in that aspect. And if you have sinus bradycardia that is very profound during the day where you say, well, when I exercise, I’m unable to increase my heart rate. What we do in that aspect, and there are no reversible reasons for that, what we do is we definitely consider implantation of a heart, of a pacemaker in those patients.
Q: Do you have any examples/treatment considerations if an individual as an ICD and has dilated cardiomyopathy with a low EF?
A: Hilary Vernon MD PHD: This is actually a good question. So for those of you who may or may not be familiar with Barth syndrome, it’s a mitochondrial disorder with some really significant effects on the heart. A number of our patients have a low ejection fraction (EF) with an ICD in place. It’s lifesaving. And really with the improvement in optimization of medical therapy, we’ve had some patients who really do quite well with the ICD in place with a lower EF without progression. And so continuing to be regularly monitored and following again the pillars of cardiac care and continuing on with your EP specialist and cardiologist to make sure that all those things are in good working order.
A: Andreas Barth, MD: I agree if your ejection fraction is low. One of the things that I want to stress, just going back to the element before, it’s really important that you’re seen by a cardiologist who is familiar with mitochondrial disease. One of the factors that can lead to increased mortality in these patients is that you develop this progressive cardiac conduction disease, that there’s slowing of the electrical activity in the heart. And the indication to place a pacemakers are a little bit different in patients who have underlying mitochondrial disease. We’re a little bit more aggressive. And if you just don’t connect the dots, if you don’t make a connection, oh, cardiac conduction disease and mitochondrial disease in this patient belong together, you may not be as aggressive with implantation of the pacemaker.
And this is why I think it’s important that you’re seen in a specialized mitochondrial clinic by a team of providers who’s very familiar with mitochondrial disease.
When it comes to low EF, the defibrillator and the heart failure treatment, they go sort of hand in hand, but they cover different areas. So the medications that I mentioned is four pillars of heart failure treatment. And as Dr. Vernon mentioned, they’re really quite improved now compared to what they were 10 or 20 years ago. So you really can change the course of the disease quite dramatically. And many patients will, even if they don’t recover completely their heart function, but they will improve and remain stable at a level that is very acceptable and consistent with a good quality of life for many years. Now the defibrillator is something that we do. On top of that, if we see that your ejection fractions below a certain level that we know is associated with an increased risk of arrhythmias, we place that defibrillator and it’s important that the defibrillator doesn’t really make you feel any better. The defibrillator is there as a life insurance if you ever have a dangerous life-threatening arrhythmia that the medication wasn’t able to help because it didn’t strengthen the heart to that extent. It’s like having an electrical accident of the heart, and if that happens, that defibrillator won’t be able to get you out of it.
And usually when we see that the heart function gets weaker or you have you a lot of electrical instability in the heart with lots of arrhythmias, you may need to see one of the cardiomyopathy providers who are able to say, well, now you’re ready for the next step, namely this advanced heart failure therapies where you may need this external pump or where we may need to discuss with you a transplant. So it’s really important that you have all those options available. And it may require more than one cardiologist in the future. It may require an electrical specialist, it may require heart failure specialist. And they need to talk to each other and provide the best care.
Q: Is there any help available to get tested for SANDO familial mitochondrial disease? My brother passed away from it & many family members cannot afford the cost for testing.
A: Bethany Bonner-UMDF Edu/Support: Please consider our No Cost Genetic Testing Program https:// umdf.org/genetictesting/ For questions, contact registry@umdf.org.
Q: Could you speak to the current research landscape for MELAS? Are there any active clinical trials or recent studies that show promise for treatment or management?
A: UMDF EDU/Kara Strittmatter: Our Feb 17 Ask the Mito Doc will focus on MELAS and Dr. Karaa can address this question during that webcast.
You can also view clinical trials and studies at https:// umdf.org/clinical-trials/