A Primer on HCM, Part 2

Second 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 explain some of the basics of the disease. In this segment he discusses diagnosis and treatment. 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 symptoms

So importantly hypertrophic cardiomyopathy has two clinical manifestations, and when we're evaluating people and figuring out how best to treat them, we look at these in parallel — not in sequence but in parallel.

So one thing is that hypertrophic cardiomyopathy, an underpinning of it, is that there is what's often referred to as myocardial disarray. The heart muscle cells are not laid down in a normal, organized fashion, and there is a susceptibility of individuals with hypertrophic cardiomyopathy for arrhythmias — abnormal heart rhythms — some of which can be life threatening.

So for some individuals, the initial manifestation of hypertrophic cardiomyopathy, very tragically could be sudden death. And for some people, if they're able to survive, we obviously have a very clear direction on what we do and approaching that.

In parallel with that — so at the exact same time that we are trying to assess their risk for sudden death and initiate therapies to mitigate that — we also are evaluating are they having symptoms that are often unrelated to arrhythmias. Are they (experiencing) shortness of breath? Are they fatigued? Do they have chest discomfort? Do they have lightheadedness? And those symptoms are often related to what we refer to as dynamic — because it's not a fixed — obstruction of blood coming out of the heart.

To make things even a little bit more confusing, there are people who have hypertrophic cardiomyopathy who don't have obstruction of blood flow, but still can have shortness of breath, still can have some of these other symptoms.

So importantly, when we're eliciting or trying to tease out symptoms for individuals — do they have any signs or symptoms that may suggest an arrhythmia? — that may guide you down that path. And, similarly, do they have symptoms that may be suggestive of impairment of blood getting out of the heart?

Our treatments are targeted distinctly — they may overlap — but distinctly. How do we alleviate symptoms that most commonly are related to obstruction of blood out of the heart? And how do we, similarly, mitigate the risk of having a life-threatening (abnormal) heart rhythm or, if they're at high risk for it, how do we intervene to prevent them from experiencing sudden death.

On hypertrophic cardiomyopathy and other heart conditions

Unequivocally hypertrophic cardiomyopathy is an underdiagnosed condition.

That being said, cardiovascular disease is one of the most common forms of disease for mankind and most individuals that have a arrhythmias, such as atrial fibrillation, the most common sustained arrhythmia, don't have hypertrophic cardiomyopathy. Most patients with heart failure don't have hypertrophic cardiomyopathy. Most patients with ischemic heart disease or coronary artery disease don't have hypertrophic cardiomyopathy.

That being said, individuals who have heart failure, individuals with coronary disease, individuals with hypertrophic cardiomyopathy with atrial fibrillation, the presence of hypertrophic cardiomyopathy will inform decision making about how we may approach those other conditions if they happen to have coexistent hypertrophic cardiomyopathy.

On early onset

I would say there are clearly individuals that can manifest symptoms before adulthood. That being said, there can be decades of latency where individuals born with that genetic abnormality (for hypertrophic abnormality) that don't manifest until the third, fourth, fifth, sixth or even later decades of life.

We don't fully understand why — and this speaks to the interplay between genetics and environment — about why some individuals with the genotype will go an entire lifetime without having symptoms, others will manifest severe manifestations very early in their lifetime. This may depend upon the underlying genetic type or abnormality that someone has. Even within a family where they share a common genetic abnormality, there's a lack of clarity about why someone may present at age 25, and another one may manifest at age 55.

So I think the field with increased recognition of the heterogeneity of the condition, both from a genetic and from a phenotypic perspective, (it emphasizes) the importance of taking a detailed family history, even going back three generations, if possible, to try and elicit whether or not there's a greater or lesser likelihood of there being hypertrophic cardiomyopathy in one's differential diagnosis.

On first-line treatment

The guidelines by the American College of Cardiology and the American Heart Association were just updated in 2020, and they were the first guideline updates in a quite a long period of time.

So the mainstay, traditionally, for hypertrophic cardiomyopathy (when) the priority for us as clinicians is to try and alleviate symptoms most commonly due to dynamic obstruction is to give medications that slow the heart rate and prolong the filling time of the heart to limit that obstruction. And these include drugs like beta blockers and what are referred to as centrally acting calcium channel blockers. Again, these medications slow the heart rate, prolong the diastole, or filling phase of the heart, and will mitigate — help to decrease — the amount of obstruction.

On the type of beta blockers and calcium channel blockers used to treat hypertrophic cardiomyopathy

So importantly, when looking for a beta blocker, you want a non-vasodilating beta blocker. But in terms of the calcium channel blocker, they're referred to as dihydropyridine and nondihydropyridine calcium channel blockers. We generally are using nondihydropyridine calcium channel blockers. They are centrally acting and work to slow heart rate by a different, but analogous, mechanism to how beta blockers work to prolong that filling phase of the heart.