A Primer on HCM, Part 3

Third of three parts

Hypertrophic cardiomyopathy is a complex condition that researchers and clinicians are just beginning to understand. Managed Healthcare Executive® asked Ty Gluckman, M.D., FACC, FAHA, to the explain some of the basics of the condition — the terminology, the incidence, the pathophysiology and the treatment choices. In this segment, Gluckman discusses second-line treatments, including septal myectomy, and mavacamten, a new therapy that is under FDA review for approval. Gluckman is medical director of the Center for Cardiovascular Analytics, Research, and Data Science at the Providence St. Joseph Heart Institute in Portland, Oregon.

On second-line treatment

So for patients with symptomatic, in particular obstructive hypertrophic cardiomyopathy, beta blockers or centrally acting calcium channel blockers, and in some cases, a combination of those two, represent out-of-the-gate, initial pharmacologic approaches. This is all based on a bedrock of avoiding medications that can exacerbate obstruction and avoidance of medications like diuretics or other things, like dehydration, that can make the obstruction worse.

For individuals that have their symptoms well controlled, that are highly functional and aren't limited by symptoms, that may suffice. But there are patients who continue to have limiting symptoms — limiting shortness of breath, chest discomfort — for which other therapies need to be explored. These include other pharmacologic therapy, a medication such as disopyramide, or what's referred to as septal reduction therapy, (which are) ways of, essentially, minimizing the obstruction related to the septum — those muscle fibers between both lower pumping chambers. That can be done either surgically, where a cardiothoracic surgeon actually removes components of those muscle fibers in the septum. That’s referred to as septal myectomy. Or doing what's referred to as alcohol septal ablation: selectively creating a controlled heart attack involving the septum to cause atrophy or dissolution of those muscle fibers so as to not produce obstruction.

On centers of excellence and high-volume

So with septal reduction therapies, whether you're talking about alcohol septal ablation or septal myectomy, there's no question — and there's a good amount of evidence suggesting — that your best outcomes are often in your highest volume centers.

In addition to that there are designations for centers of excellence for hypertrophic cardiomyopathy, and many patients — by no means all but many — receive their care at centers of excellence that often have skilled surgeons and/or interventional cardiologists doing these invasive procedures that constitute septal reduction therapy.

For patients who are pursuing those types of septal reduction therapy approaches, often it's very common for them to seek out institutions, high-volume centers. (The high-volume center) are often destination referral centers for people that may come from across the country, if not around the world.

On mavacamten

All the pharmacologic therapies that we've had to date are not changing the natural history or halting progression of hypertrophic cardiomyopathy. But importantly — and for good reason — they are prescribed to make people feel better and function further.

Mavacamten is a selective inhibitor of cardiac myosin ATPase. It's a more targeted therapy. And it's been studied in a large — relative to (other) hypertrophic cardiomyopathy trials — trial exploring mavacamten's ability to improve the degree of obstruction involving what’s referred to as the left ventricular outflow track, and importantly, (the trial used) subjective and objective ways to assess whether people are feeling better and functioning further.

That trial, called the Explorer HCM trial, sought to evaluate mavacamten on a background of first-line therapy, most commonly with a beta blocker or a centrally acting calcium channel blocker.

It is not yet FDA approved, but I would anticipate mavacamten being an add-on therapy to those individuals who persist in having limiting symptoms that limit their ability to function as much as they'd like to, despite being on maximally tolerated doses of a beta blocker or a centrally acting calcium channel blocker.

It remains to be determined where (mavacamten) fits vis-à-vis drugs like disopyramide. It also remains to be determined where it fits in relative to other interventions like septal reduction therapy.

So I think because it is not FDA approved (and) was not included in the most recent guidelines, time will tell — informed by a lot of different factors, including by patient opinion about what they want — how it gets sequenced …and where it (will sit) in our armamentarium.