New podcast episode ranges from genetics insights to patient selection for tafamidis
Should everyone with dilated cardiomyopathy undergo a genetic profile? That’s a question without a clear answer pending results from an ongoing multicenter study, but it’s also one of many compelling issues raised in a new episode of Cleveland Clinic’s “Cardiac Consult” podcast.
Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy
In the 13-minute episode, podcast host Steven Nissen, MD, Chief Academic Officer of Cleveland Clinic’s Heart & Vascular Institute, interviews Wilson Tang, MD, about what’s new and notable in cardiomyopathy genetics and medical care.
Dr. Tang brings to bear his dual roles as a translational researcher in cardiovascular genomics and as Research Director of Cleveland Clinic’s Section of Heart Failure and Cardiac Transplantation Medicine to address topics in cardiomyopathy including:
Click on the player below to listen to the podcast now, or read on below for an edited excerpt of the discussion that’s in store — specifically the portion on recent advances on the genetics front.
Dr. Nissen: One of your areas of expertise is genetics, so please bring us up to speed on the genetics of cardiomyopathy.
Dr. Tang: Technological advances over the past five or 10 years have brought significant advances in our understanding. In fact, the number of genes identified as being implicated in some form of cardiomyopathy has almost doubled in that time. So now we estimate that about 30% up to 50% of patients with cardiomyopathy have some genetic abnormality.
Dr. Nissen: We used to call those cases idiopathic and unfortunately not look any further.
Dr. Tang: Yes, too often that used to be the case, particularly in terms of the patient’s family members. No one would ask whether anyone in the family had had sudden cardiac death or heart failure when they were young.
Dr. Nissen: And sometimes it would turn out that there was a whole lineage of people in the family with events suggesting cardiomyopathy.
Dr. Tang: Exactly. Even now it’s easy to miss such events because it often takes multiple rounds of asking family members before such events are remembered or discovered. For instance, I have patient who has a genetic variant. Every time he sees me he brings the family tree and gives me three or four new people that they have identified as having heart problems.
Dr. Nissen: So should everybody with a dilated cardiomyoptahy have a genetic profile?
Dr. Tang: That is a very timely question. In fact, the National Institutes of Health is sponsoring a study that specifically asks that question. It’s called the DCM Precision Medicine Study [NCT03037632] and is a nearly 30-center study being conducted across the U.S. Cleveland Clinic is one of the top-enrolling study sites. It’s asking the question: “How often do we identify unrecognized genetic abnormalities?” So far the answer looks to be about 1 in 5 cases.
Dr. Nissen: Let me play devil’s advocate. Why do it? What do you learn from the genetic profile that might actually benefit the patient? I understand that it’s intellectually satisfying to identify a cause, but how is it actionable?
Dr. Tang: There are three reasons why we do it. The first is that different types of abnormalities identified from the genetic profile could actually identify potential differences in natural history. Some genetic abnormalities are much more severe and progress more rapidly over time. In fact, we have patients who we have seen progress rapidly within a short time of having been identified with these abnormalities.
Dr. Nissen: So do you then triage them to earlier transplant?
Dr. Tang: Yes. We watch them very carefully. These are the individuals who really need centers of excellence and highly experienced clinicians — not just one or two doctors, but teams of doctors. In addition to heart failure specialists, they need electrophysiologists and cardiovascular imaging specialists — a whole team to characterize their disease, follow them and prepare for the next step if they should get worse.
A second and even more important reason is the patient’s family. Once you identify the pathologic variant in a patient, you are able to identify their relatives who are at risk. Those relatives can then be watched very carefully, even if they don’t have any manifestation or symptoms. In fact, we often provide clinical screening for those at-risk relatives and follow them over time. Sometimes we uncover things that clarify uncertainties around a previous diagnosis they had received, where they were told they had one problem and it turns out it was something else. We see that quite often.
The third reason to obtain a genetic profile is because there are many new drugs in late-stage development — and some that are already FDA-approved, like tafamidis — that are specifically targeted to these mutations and can perhaps be offered to patients.
The relationship between MTHFR variants and thrombosis risk is a complex issue, but current evidence points to no association between the most common variants and an elevated risk
One-time infusion of adenovirus-based therapy is designed to restore heart muscle function
Studying gender-specific health factors promises new insight into diagnosis, prognosis, treatment
Consortium is uncovering risk factors that spur disease development in an understudied group
Cleveland Clinic researchers receive $2 million grant from the National Institutes of Health
New Cleveland Clinic fellowship fosters expertise in the genetics of epilepsy
Renal genetic testing confirms diagnosis, guides management
Integrates genetic and clinical data to distinguish from GEFS+ and milder epilepsies