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.

The SHaRe Registry centers that participated in the study are:

  • Brigham and Women’s Hospital, Boston
  • University of Michigan Medical Center
  • Stanford University Medical Center
  • Boston Children’s Hospital
  • Yale-New Haven Hospital
  • Careggi University Hospital, Florence, Italy
  • Erasmus University Medical Center, Netherlands
  • Laboratory of Genetics and Molecular Cardiology, Sao Paulo, Brazil

Working together, these centers, led by Dr. Carolyn Ho, M.D. of Boston’s Brigham and Women’s Hospital, made some significant findings.

Patients with HCM Genetic Mutations Fare Worse HCM patients with a known genetic mutation were diagnosed with clinical disease at a younger age (37.5 years, compared to 51.1 years for patients without a mutation) and were more than twice as likely to experience HCM-related complications and early death than HCM patients who had a non-genetic form of HCM.  Patients with more than one mutation and those who carried a MYH7 mutation were found to have a higher risk of HCM related complications than those with single mutations or those with a MYBPC3 mutation.

HCM Burden Increases Over Time:  The burden of disease and complications increased progressively over time for HCM patients, with most HCM-related complications occurring later in life between the ages of 50-70 years.  In particular, the researchers found that patients who were less than 40 years old at diagnosis had a 77% chance of having an adverse incident such as a cardiac arrest, heart failure, atrial fibrillation, stroke, or death by the time they reached age 60. The most common complications were heart failure and atrial fibrillation.  In contrast, patients diagnosed with HCM after the age of 60 years of age had only a 32% cumulative incidence of such complications by age 70 years.

HCM Mortality is Significant:  Mortality among HCM patients was found to be significantly higher than that of the general U.S. Population. In fact, among young HCM patients ages 20 – 29, mortality was found to be four times higher than that of their healthy counterparts.

The lead author of the paper, Dr. Ho, suggests two major takeaways from this research:

1. A young age of diagnosis and the presence (or absence) of sarcomere mutation(s) should be taken into consideration when forming treatment plans.

2.  Given that the majority of HCM complications occur later in life, there is need for long-term care and follow-up of HCM patients, as well as for the development of new therapies that prevent long term complications such as heart failure and atrial fibrillation.

 

Are HCM Kids With MYH7 Gene at Increased Risk?

A recent Canadian study found that children with HCM who carry a single mutation in the MYH7 gene or who have multiple HCM-causative genetic mutations are at increased risk of major adverse cardiac events when compared to children who carry a single mutation in another gene.

Of the 98 gene positive children in this study, those with a MYH7 mutation or those with multiple mutations were more likely to need a myectomy or an ICD or to experience a sudden cardiac arrest or a heart transplant when compared to children with other HCM causative mutations.

The article also suggests that current screening protocols which recommend clinical and genetic screening for HCM beginning at age 12 may be insufficient.

Unwitting Geneticist Discovers Her Own Cardiomyopathy Gene: Heidi Rehm’s Story

Dr. Heidi Rehm is a human geneticist and clinical laboratory director at Harvard Medical School who has spent much of her career studying the genetics of cardiomyopathy.

Imagine her surprise when she found out that she, her mother and her daughter all have a mutation in the MYH7 gene which has been associated with dilated cardiomyopathy!

The unexpected revelation came as an indirect result of a visit to her daughter’s orthodontist.  When one of her daughter’s teeth was delayed coming in, the orthodontist suggested that there might be a genetic cause for the late tooth.  This provided the idea behind her high school daughter’s summer biology research project: 2 weeks in her mom’s lab sequencing her exome, looking for a genetic cause for her delayed tooth.

Though the mouth genetics turned out to be normal and the tooth eventually arrived, an totally unexpected incidental finding turned up instead:  a variation in the MYH7 gene which has been associated with dilated cardiomyopathy.

Continue reading “Unwitting Geneticist Discovers Her Own Cardiomyopathy Gene: Heidi Rehm’s Story”

HCM May Develop Later in Life

A recent study followed 14 patients carrying one of two known genes associated with HCM (MYBPC3 and MYH7) over a 10+ year period .  At the time  of gene identification, none of the patients shown clinical evidence of hypertrophy.  Over the time span of the study, 3 patients, who were then adults, had developed signs of HCM.  Hence, the study suggests that periodic screenings are necessary for gene positive individuals throughout adulthood.

According to Cardiomyopathy U.K., the researchers undertook this project due to the lack of information and guidelines available to patients who are gene positive but have no outward signs of the disease.