Thank you very much, thanks Dr. Marin for the introduction. AFib is a really common adverse complication within HCM, occurring with symptomatic episodes occurring in about 20% of patients. In fact, this sustained arrhythmia is the most common sustained arrhythmia in this disease, about four times more common than ventricular arrhythmias leading to sudden death events. It's the second most common adverse pathway within HCM, second to symptomatic heart failure, secondary to obstruction. If you include asymptomatic episodes that are seen fortuitously on long-term monitoring, an additional 20 to 25% of patients may have asymptomatic atrial fibrillation, making it potentially the most common adverse pathway in the disease. However, there really remains limited data in terms of asymptomatic atrial fibrillation, certainly an area that needs more studying in the future. I'm really going to be focusing on my talk about symptomatic atrial fibrillation. AFib prevalence-wise increases with age, similar to AFib in the general population. Average age of AFib in HCM is in the mid-50s. However, importantly, it can also occur at younger ages. About 5% of initial episodes occur in individuals with HCM under the age of 30, and 30% occur in HCM patients in their 30s and 40s, so can occur in your younger HCM population patients. AFib occurs at rates 4 to 6 times higher in HCM than age- and gender-matched populations. In the past, AFib was really felt to be a major adverse complication in this disease, a key determinant of HCM-related mortality, and a major turning point in HCM that decisively influenced long-term outcomes. And this perception is based on data in the past. This is a study from patients from Minneapolis and Florence, 100 HCM patients with AFib. Patients with HCM and AFib, compared to patients without AFib, had three times higher mortality risk, with that excess mortality predominantly due to stroke and heart failure-related deaths. In part, that was because of the therapeutic options available in the past. Really, anticoagulation limited to Warfarin, with about 50% of HCM patients in that study not on anticoagulation, either declining or not offered. Many young patients who didn't want to be on Coumadin because difficulty to manage. Antirhythmetics, a significant concern in the past about safety, and really limited to amiodarone for rhythm control. And that really raises the question as to whether or not the prognosis of AFib and HCM in the modern treatment era is the same. And we took the opportunity to examine 300 patients consecutively with AFib at Tufts Medical Center for long-term outcomes, followed for five years on average from initial AFib episode. And the first important point that we found is that AFib is not always progressive in this disease. In 2001, at the end of follow-up, about 60% of patients developed chronic atrial fibrillation. In sharp contrast, at the end of our follow-up, 26% of patients had permanent or long-standing persistent atrial fibrillation. In large part, the reason for that is because of management. AFib leads to worsening heart failure symptoms in most HCM patients. These symptoms are reversible when sinus rhythm is restored. And therefore, we're really aggressive in terms of rhythm control in our symptomatic patients, with the majority of these patients either on antiarrhythmetics or undergoing an ablation procedure. Antiarrhythmetics really can be safe in HCM, and it's not just amiodarone and disoperamide. This is data from Mark Link and Chase Miller, looking at other antiarrhythmetics and safety in HCM, with Sotolol and dofetilize selectively safe in your HCM patients. And at Tufts, Sotolol really, for the majority of our patients with AFib, is our first-line therapy. How about AFib ablation? If you look at radiofrequency ablation or catheter ablation, it can be effective in HCM. But both data from our study, where one-year freedom from AFib is about 40% after catheter ablation, it's certainly less effective than in the general population. The majority of these patients requiring addition of antiarrhythmetics or repeat ablation to maintain sinus rhythm. In contrast is May's procedure at the time of myectomy. Our surgeon routinely performs Cox May's 4 procedure in symptomatic patients undergoing myectomy to reverse obstruction. Dr. Rasagar has a one-year freedom from AFib of about 75% after this combined procedure. And in part, that's really for two reasons. One is much more extensive ablation by atrial with the Cox May's 4. But also, you're relieving, you have hemodynamic improvements with the myectomy, relieving obstruction, decreasing mitral regurgitation, both probably contributing to the superior one-year freedom from AFib after May's plus myectomy. Who's at risk for stroke with HCM? And who should be anticoagulated? There's a multicenter study from Europe, large study looking at Chad's VASC score in HCM and really showing that despite low Chad's VASC score, your patients with HCM remain at risk for embolic events. And therefore, at Tufts, we really consider all HCM patients for anticoagulation after their first episode of symptomatic AFib. How does that do in preventing stroke? So in 2001, over 20% of HCM patients with AFib had embolic strokes. Down to 6% in our cohort, but that really doesn't tell the whole story. We had 18 embolic events. Of those, 14 declined anticoagulation, or during the first episode of atrial fibrillation. We just had four strokes while on anticoagulation. Event rate on anticoagulation is just .3% per year. All those strokes had mild or no residual deficits. And the only two stroke deaths that we had were in patients not on anticoagulation. We also found no evidence that AFib is the turning point for end-stage heart failure in this disease. At the end of follow-up, 90% of our patients with AFib, or in NYHA class I or II, really benefiting for the same interventions for symptomatic obstruction with myectomy or selectively alcohol septal ablation. Just about 10% of our patients had NYHA class III or IV symptoms at the end of follow-up. And just about 5% developed true end-stage disease requiring consideration for transplant. So with treatment in our cohort, HCM mortality with AFib was low, .7% per year, and not different from HCM patients without atrial fibrillation. So with treatment, you're really looking at a completely different natural history in the modern era. If you look at that cohort from 2001, NYHA class symptoms at the end of follow-up, over 50% of patients had advanced heart failure symptoms, as compared to just about 10% in our current cohort. Embolic events can be really low with anticoagulation in HCM. And importantly, HCM-related mortality. In 2001, over 33% of HCM patients with AFib died at the end of follow-up from complications from the disease. In contrast, just 3% of our cohort died from HCM-related complications. So I think with treatment, AFib in HCM really is not inevitably progressive. You can have low disease-related mortality with treatment. It is rarely the primary cause of death in HCM. You should really have a low threshold for anticoagulation. After first episode, with child's VASc score not reliable. AFib really is different in this disease, but treatable in HCM. Thank you. Okay, we have five minutes for questions from the audience. Here's one right here. Do you have any experience with AV node ablation? AV node ablation. Most of these patients would have dual-chamber ICD. Or perhaps even His bundle pacing and AV node ablation. Yeah. We obviously consider AV node ablation last line for these patients. Young patient population. In our cohort, from that paper I just cited, about 10 patients ended up with AV node ablation. Again, we consider that last line. We have limited experience or no experience with His pacing to date. I have a question regarding the anticoagulation in AF and HCM. Which one is better? The novel anticoagulation or the anti-vitamin K? We predominantly use novel anticoagulants in our young patients at this stage. And it's really from a patient preference standpoint. Young patient population, they tolerate it. And as I said, really low event rates with that. Okay, thank you. Prakash, New Jersey. Prakash, New Jersey. At your center and in your experience, what's your experience on the mechanism of AFib? One, in your mapping data, non-PV triggers, substrates. I think that's very important in this ablation thing. And on the same note, incidence of atypical flatters. So what's the difference with atrial arrhythmias? Both with regards to mechanism and the type of atrial arrhythmias in this population versus non-HCM population. Well, there are clear risk factors for AFib and HCM. Age, left atrial size. But if you're asking my opinion, I also personally think that there's probably an underlying left atrial myopathy in this disease. Which drives the high burden of atrial fibrillation. And that's really supported by left atrial size in some patients. Which are out of proportion to their other disease features. The fact that AFib can actually happen despite normal left atrial size. There are studies looking at left atrial fibrosis in HCM. And showing that it occurs at high rates. Higher than would be expected in general AFib patients. So my opinion, even though not really proven, is that there is an underlying left atrial myopathy that drives AFib. And to be specific, so what you're saying is the PVs are not as important in the HCM population. And the sort of PV isolation may not be the first line of ablation strategy. Yeah, I mean, our first line is anti-arrhythmetics. And then if they fail, we'll do PV isolation. But as I showed, success of isolation alone is much lower than in the general population. In terms of the anti-arrhythmic therapy, do you have different ways that you're following these patients than the normal population? And like dofetilide, sotolol, traditionally we would avoid. Yeah, so similar. Obviously inpatient admission, making sure QT is good for sotolol. Dofetilide, our experiences were a little more cautious. The Cleveland Clinic, I know has good data out there as well with dofetilide. Obviously, risk stratification is key because of the concern of sudden death risk as well in these patients. So if there are risk factors, we would not start these anti-arrhythmetics without an ICD. But without risk factors, as I said, we have good safety even without device placement. Okay, very briefly, I have a minute. What about the management of asymptomatic, clinically occult atrial fibrillation, which is so common in this disease? Okay. So asymptomatic AFib seen on implantable devices or long-term monitoring, really not great data out there in terms of knowing what to do. We really look at AFib burden and duration to help make decisions. Clear decision if the AFib is over 24 hours in terms of anticoagulation. In general, if it's a short duration, a few minutes, we will not anticoagulate those patients but with close follow-up. And then really a personalized decision when it's a few hours in length for AFib. Okay, thank you very much. Thank you.

Atrial fibrillation

Hypertrophic cardiomyopathy

Arrhythmia

Rhythm control

Anticoagulation