Signs and Symptoms of oHCM

Anjali Owens, MD: So, Michelle, take us out of pathophysiology a bit and into the clinic. What are the features that you look for? What are the signs on history and physical, how do you approach a patient, and when do you keep hypertrophic cardiomyopathy [HCM] on the differential?

Michelle M. Kittleson, MD, PhD: What a great question. So let’s start with the history. Patients can present generally in 1 of 2 ways. They’re asymptomatic but they present for medical attention, or they actually have symptoms. If they’re asymptomatic, they generally present for 1 of 2 reasons: family screening because it is a genetic condition and there may be cascade testing and subsequent screening, or because someone hears a murmur or their electrocardiogram, done for other reasons, is abnormal. So those are the 2 most common reasons asymptomatic patients present. Otherwise, patients may have the classic symptoms, which are chest discomfort, shortness of breath, presyncope, syncope…. When you think about how patients present, we think about those variations in the history. When you think about the physical exam, there is the classic murmur of obstructive HCM, the harsh systolic murmur that varies in intensity with the different physiologic state. So when you hear that systolic murmur then you do maneuvers to see if it changes in a way that is consistent with an outflow tract obstruction. So the murmur should increase with the Valsalva maneuver. It should decrease with things like squatting or hand grip, and that is how you can differentiate the murmur of obstructive HCM from other systolic murmurs.

Anjali Owens, MD: …So let’s move to further diagnostic evaluation. Jim, maybe you can walk us through. You have a patient in clinic, maybe you do hear that murmur, you’re getting a history of some shortness of breath or dyspnea on exertion, maybe a little lightheadedness. What are your next steps in terms of diagnostic pathway?

James Januzzi, MD: I can’t emphasize enough that a high index of suspicion is critically important to make the diagnosis. I think we all have examples of patients who had a dutifully recorded ECG every year showing progressively more significant LVH [left ventricular hypertrophy] with strain…. It’s important to recognize the features of the diagnosis in order to really maintain a level of suspicion. So you suspect the presence, and the next step—aside from a thorough family history, which I think is critically important here—is to also think about how imaging can be useful to make the diagnosis 2 dimensional. Echocardiography obviously is the first thing we reach for. We can run right down the hall and get an echo immediately on our patients, which can help to confirm the presence of obstructive disease hypertrophy as well. Above and beyond that, of course, and we’ll be talking more about the importance of imaging as a biomarker. I suppose you know cardiac MRI is critically important here in order to establish the diagnosis, help to evaluate for phenocopies or other diagnosis that may be present, and also inform the presence of underlying myocardial fibrosis as reflected by late gadolinium enhancement. Above and beyond that, once we have a case that’s a suspected proband of hypertrophic cardiomyopathy, we may turn to genetic testing. The issue with genetic testing is that it’s useful when it’s positive, but only about 30% of individuals with HCM have an identified mutation, and there are probably a dozen or more genes definitively linked to the diagnosis, but thousands more yet to be conclusively linked to the presence of hypertrophic cardiomyopathy…. There aren’t a lot of other things that we reach for from a biomarker perspective, natriuretic peptides are elevated in proportion to obstruction and fibrosis, but they’re not widely used really at this stage, although it with myosin inhibitors, people are starting to use natural peptides more as we can discuss and the same thing goes… with high sensitivity troponin— elevated, but not specific by any means for hypertrophic cardiomyopathy.

Anjali Owens, MD: Thank you so much. As a heart failure, doctor, I do check NT-proBNP and our patients with HCM and track it over time. I hope that that will become a theme and something that’s useful as we have targeted therapies that really, you know, can affect the underlying pathophysiology.

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