Are Your Genetic Test Results Valid?

A recent study by several HCM genetics researchers around the globe, led by Australia’s Dr. Jodie Inglesfound that 2/3 of genetic mutations previously reported to patients as HCM causative may actually NOT trigger HCM.

Dr. Ingles and the researchers looked at 33 genes frequently reported to patients as causative for HCM in commercial genetic tests.  Surprisingly, of the 33 genes tested, only 8 were found to be definitively associated with HCM, 3 had moderate evidence to support their association with HCM and a whopping 22 or 66% of these genes were found to have limited or no association with HCM.

Mutations Definitive for HCM

MYBPC3           TPM1

MYH7               ACTC1

TNNT2              MYL2

TNNI3               MYL3

Mutations with Moderate Evidence for HCM

CSRP3

TNNC1

JPH2

These results should raise a red flag for consumers about genetic testing.  Results of genetic tests require careful and informed interpretation. For accurate results, HCM patients should undergo genetic testing under the supervision of a genetic counselor with experience in HCM.

Not all genetic counselors are alike!

The High Hanging Fruit: Treatment for Non-Obstructive HCM – Commentary by Dr. Sharlene Day

A recent study conducted in the U.K. evaluated whether the anti-anginal drug trimetazidine would improve symptoms and exercise capacity for those patients with non-obstructive hypertrophic cardiomyopathy. 

Unfortunately, this study which was conducted by Dr. Perry Elliott and his colleagues at University College London, found that trimetatazidine did not improve exercise capacity in these patients. Following the results of this study, trimetazidine will now join ranolazine and spironolactone in the compost heap of drugs which tried and failed to improve HCM symptoms.  While a third drug, perhexiline, was found to improve symptoms for non-obstructive HCM, its limitations, including potentially serious side effects, stand in the way of its common usage.

In a companion editorial to this study entitled “Non-Obstructive Hypertrophic Cardiomyopathy-the High Hanging Fruit,” Dr. Sharlene Day of the University of Michigan’s HCM Center discusses the difficulties seen in drug trials related to non-obstructive HCM.

Though seemingly a more benign form of the disease, in fact, patients with non-obstructive HCM share a similar risk of sudden death and heart failure with their obstructed counterparts.  Because treatments available to treat non-obstructive disease have been largely limited to beta blockers, calcium channel blockers and diuretics, there is a great need for new medications directed at this problem.

The problem with setting up HCM Drug trials is complicated by several factors:

  1. Different Types of HCM:  There appear to be multiple kinds of HCM. Some are genetic and some are not. We are now at a place where treatments for HCM should become more individualized.
  2. Difficulty in Recruitment:   It is difficult to recruit enough patients to take part in these trials. Patients often travel considerable distances for care at dedicated HCM Centers. Multi-center trials provide a potential way to get around this issue.
  3. Duration of HCM:  HCM is a disease process which takes place over decades which is not easily studied in a clinical trial of limited duration.
  4. The Unknown:  Timing of interventions may be critical, and it is hard to know the proper window of time to target. The bottom line is that there is still so much that is unknown, HCM researchers much continually adapt as knowledge of the disease process unfolds.

In conclusion, Dr. Day suggests that while medical researchers continue to test new drugs and push forward studies of HCM, physicians should counsel their patients that in addition to medication, lifestyle choices like proper nutrition and exercise will improve their clinical course and the overall outlook for HCM patients.

Visiting Mayo Clinic

I had open heart surgery (a septal myectomy) to treat my hypertrophic cardiomyopathy in 2006.  I went back to Mayo twice for the two years following the surgery, but after that I hadn’t felt the need to return since I was regularly following up with my local cardiologist.  In April of 2018, it had been almost ten years since I had been back to Rochester.  So, I decided it was time to take a trip and make sure that all was in order.

Continue reading “Visiting Mayo Clinic”

The Evolution of HCM: A Historical Perspective

This article, by Drs. Julio Panza and Srihari Naidu of New York’s Westchester Medical Center, describes early efforts to diagnose, categorize and treat hypertrophic cardiomyopathy, while explaining how these methods have evolved over time.  A very interesting and informative read.

MyoKardia and 23andMe Create Online HCM Community

MyoKardia is collaborating with 23andMe, a genetic testing company which provides ancestry and health information directly to consumers, to create an online patient community intended to advance research efforts related to hypertrophic cardiomyopathy. The companies plan to allow 23andMe customers access to the latest information about HCM, as well as the opportunity to participate in research.

The companies will use a custom designed survey to collect baseline and follow-up data from HCM patients. They are hopeful that this collaboration will yield unique insights into HCM.

Research findings gained through the collaboration will be shared with HCM patients through the 23andMe platform.  Currently more than 6,000 HCM patients are customers of 23andMe

More details of the collaboration can be found:

Press release from MyoKardia and 23andMe

P&T Community

Genomeweb

 

 

 

 

DISCLOSURES:  HCMBeat has received unrestricted educational grants from MyoKardia.  Additionally, Cynthia Burstein Waldman of HCMBeat serves as a Patient Advisor on the Steering Committee for MyoKardia’s Explorer trial.

Spotlight on Virginia HCM Specialist

MD Magazine has a nice feature about Dr. Robert Battle of the University of Virginia’s HCM Center. Read it here.

HCM Researchers Put their Heads Together to Improve Lives of HCM Patients

A recent paper published in the journal Circulation looked at the clinical course of approximately 4,600 HCM patients over the course of more than 24,000 clinical years, which the paper describes as the largest comprehensive cohort of HCM patients ever studied.

This study examined patients from eight high volume HCM centers which aggregated their institutional data into a database known as the Sarcomere Human Cardiomyopathy Registry (or the acronym the “SHaRe” for short). The results of the study showed that, in general, HCM patients are at substantially elevated risk for atrial fibrillation and heart failure, and have significantly higher mortality rates than that of the general U.S. population.

Continue reading “HCM Researchers Put their Heads Together to Improve Lives of HCM Patients”

Broad Survey of HCM by Dr. Barry J. Maron

The August 16, 2018 online version of the New England Journal of Medicine contains an broad overview of the current state of clinical knowledge and treatment of HCM written by HCM expert Dr. Barry Maron.  It is entitled “Clinical Course and Management of Hypertrophic Cardiomyopathy.” 

Dr. Maron discusses the many advances that have been made in the diagnosis and treatment of hypertrophic cardiomyopathy since it was first described 55 years ago, noting that life expectancy and qualify of life have dramatically improved in this period of time.  According to Dr. Maron, the contemporary management paradigm for HCM have reduced “the risk of adverse cardiovascular events and death to levels below the levels among patients with other cardiac or non-cardiac disorders.”

 

SCD Risk Assessment Guidelines in HCM: Impact of Myectomy & AFib

A recent study by doctors at the Cleveland Clinic found that current guidelines used to assess risk of sudden cardiac death (SCD) in HCM fall short when applied to the population of patients with the obstructive form of HCM (HOCM).

The study looked at both the European Society of Cardiology (ESC) and American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, and found that both sets of guidelines came up short in predicting SCD.  In particular, the study found that patients who had previously undergone myectomy had a reduced risk of SCD that is not accounted for in existing risk models.

Conversely, the study found that patients with atrial fibrillation had a higher risk of SCD, which is also not reflected in the existing risk models.

A companion editorial by Dr. Harzell Schaff of the Mayo Clinic explains the likely reasons for the myectomy findings, while a second accompanying editorial by Dr. John Jefferies of Cincinnatti Children’s Hospital (who has recently accepted an appointment at the U. of Tennessee Health Science Center in Memphis) maintains that the ESC and ACC/AHA guidelines should be changed to reflect the lower SCD risk following myectomy.

Click here for previous coverage of the ESC and ACC/AHA guidelines.  If you would like to try out the ESC Risk Calculator for yourself, click here.

 

 

Is Whole Genome Sequencing a Better Method for HCM Genetic Testing?

According to this study published recently in the Journal of the American College of Cardiology, whole genome testing may sometimes be used to identify the gene(s) responsible for HCM when targeted genetic testing (the type used in the clinical setting) has been inconclusive.

In particular, the study found the responsible gene(s) in 9 of 26 families (20%) in whom targeted testing had previously been inconclusive.

When used as the initial form of genetic testing, whole genome sequencing identified the responsible HCM gene in 5 of 12 families, or 42%.

According to this article in Wired U.K., a whole genome sequencing test costs about $600 and takes just a few weeks to complete.  On the other had, the cost of data storage necessary to store such a large amount of collective data is, according to this article, prohibitively high.

If not for everyone, perhaps whole genome sequencing could be used in families where traditional genetic testing has proven inconclusive.  Time will tell.