A Primer on HCM, Part 1

First 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 and the pathophysiology. 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 terminology and definitions

Hypertrophic cardiomyopathy, or HCM, is the preferred terminology. It has had lots of different names or labels previously.

Hypertrophic cardiomyopathy is an inherited condition, where there's thickening of the walls of the heart, particularly the left lower pumping changer, the left ventricle, not due to another cause. It is an inherited condition.

Previously terms like hypertrophic obstructive cardiomyopathy were used but not all of our patients have obstruction of blood flow out of the left lower pumping chamber.

Ultimately there are a lot of different manifestations of the disease itself … these include symptoms related to inadequate blood flow getting out of the heart, and, in addition to that, an increased risk for arrhythmias that can portend life-threatening arrhythmias, that can portend a risk of sudden cardiac death.

On incidence, genotype and the phenotype

From a genetic standpoint about 1 out of 500 individuals can have the genotype. That being said, it's been estimated that as few as one out of six, maybe even one out of seven, people with hypertrophic cardiomyopathy have actually been identified as having that condition.

This gets complex pretty quickly, because simply having the genetic abnormality doesn't mean that you will demonstrate clinical evidence of disease. And so there may be individuals who have been inherited a genetic abnormality that puts them at risk, but they ultimately don't develop the disease and may never manifest symptoms at all.

The interplay between our environment and our genetics is obviously true for a lot of inherited conditions. It's not completely clear why some individuals with one genotype in a family will develop more severe manifestations of a disease and others will not. So there are perhaps environmental factors that may influence that.

There are also multiple different genetic abnormalities — or genotypes — that underlie the phenotype or the characteristic finding of thickening of the walls of the heart that often will manifest with symptoms that are related to limited blood flow getting out of the heart.

So hypertrophic cardiomyopathy is a broad umbrella term for which there are varying genetic abnormalities that underlie it. (Making it even) more complex is the fact that two individuals with the same genotype may have different clinical presentations and individuals across genotypes may have different presentations.

On the pathophysiology

So, by definition, there is thickening of the walls of the heart most commonly or most evidence involving in the left lower pumping chamber, the left ventricle.

Classically, we talk about thickening involving the septum, or the muscle bundle fibers that sit between the left lower and the right lower chambers of the heart.

That being said, there are people who will have manifestations of hypertrophic cardiomyopathy that only involve the apex, or the tip of the heart.

There are individuals that can have thickening that extends across all of the walls of the heart.

The reason we talk about the septum — or those muscle fibers that sit between the left and right lower chambers of the heart, is that those individuals — particularly with a more pronounced thickening of that wall, can have impairment of blood getting out of the heart that can manifest with symptoms of shortness of breath, chest discomfort, lightheadedness, particularly with activity where there may be an increased demand for blood flow but there's a dynamic outflow- tract obstruction or a dynamic limitation of blood getting out of the heart.