The Pathophysiology of Obstructive Hypertrophic Cardiomyopathy (oHCM)

Anjali Owens, MD: Hello, and welcome to this HCPLive® Peer Exchange titled “Expert Guidance on Novel Treatment Approaches and Obstructive Hypertrophic Cardiomyopathy.” I’m Anjali Owens, a heart failure cardiologist and associate professor of medicine at the University of Pennsylvania where I direct our center for inherited cardiovascular disease. Joining me today for this panel discussion are 4 of my esteemed colleagues.

Andrew Wang, MD: Thanks, Anjali, I’m Andrew Wang. I’m a professor of medicine at the Duke University School of Medicine, where I also direct our hypertrophic cardiomyopathy [HCM] program.

Anjali Owens, MD: Jim?

James Januzzi, MD: Hi. Thanks for having me. I’m Jim Januzzi from the Massachusetts General Hospital Heart Center and Baim Institute for Clinical Research in Boston.

Michelle M. Kittleson, MD, PhD: Hi, I’m Michelle Kittleson. I’m a professor of medicine and director of education in heart failure and transplantation at Cedars-Sinai in Los Angeles, California. I was also a member of the writing committee for the 2020 HCM guidelines.

Anjali Owens, MD: Milind?

Milind Desai, MD, MBA: Thank you for having me. I’m Milind Desai. I’m a professor of medicine at the Cleveland Clinic Lerner College of Medicine. I now am also the vice chair of education for the vascular and thoracic institute, and I direct the HCM center along with a couple of other things at the Cleveland Clinic.

Anjali Owens, MD: Our discussion will focus on obstructive hypertrophic cardiomyopathy. We’re going to start by reviewing strategies to facilitate a prompt and accurate diagnosis and optimization of the use of current first-line treatments. We’ll also discuss the development of novel cardiac myosin inhibitors and ways that we’re implementing them into the treatment plans for our patients. So welcome everyone. I’m looking forward to a lively discussion and we’ll get started. Andrew, I’ll start with you: Tell us a little bit about the background epidemiology of hypertrophic cardiomyopathy.

Andrew Wang, MD: Thanks. Hypertrophic cardiomyopathy is one of the most common genetic cardiovascular diseases. Even though we think of it as a rare disease from echocardiographic surveillance studies, they’ve identified evidence of hypertrophic cardiomyopathy in 1 in 500 persons, regardless of sex, age, geographic distribution, ethnic groups. But the prevalence is actually much higher by genotype studies, where approximately 1 in 200 persons is a carrier of a genetic variant. However, only about 1 in 7 patients with hypertrophic cardiomyopathy is actually diagnosed, based on medical claims data. So there really is a gap in identification of patients who have hypertrophic cardiomyopathy.

Anjali Owens, MD: What an important point, that most of our patients with this disease are currently undiagnosed. We’ll get into…how we are going to identify those patients. Before we get there, Milind, can you tell us a little bit about the etiology of hypertrophic cardiac? We know that there are a lot of conditions that can make your heart thick or give you left ventricular [LV] hypertrophy. But what are the underpinnings of hypertrophic cardiomyopathy?

Milind Desai, MD, MBA: …We know of mutations in myosin, troponin, actin. Fundamentally, what they end up doing is creating structural abnormalities at the myofibril level. Basically, there’s hypertrophy, there’s disarray, there’s increased fibrosis or interstitial fibrosis, there’s coronary arterial dysplasia. All these fundamentally direct the pathophysiology of HCM…. The other fundamental problems that these patients have are underlying diastolic dysfunction, [adherence] problems, and suboptimal utilization of energy despite having hypercontractility and hyper normal LV ejection fraction. But I will also say that not everything that has thick walls is HCM and not all cases of HCM have thick walls….

Anjali Owens, MD: Absolutely. We’re truly entering an era where we need to understand the molecular diagnosis so that we can target therapies.

Transcript is AI-generated and edited for clarity and readability.