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.

 

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.

CNN Chief Jeff Zucker Set for HCM Surgery

According to several news reports, CNN chief and former NBCUniversal head Jeff Zucker is taking six weeks off to undergo elective surgery to treat his hypertrophic cardiomyopathy.  Specific details about the surgery were not revealed.  New York Magazine reported that in 2010 he visited Minneapolis Heart Institute where he was told he needed an implantable defibrillator.

The most common surgery for the treatment of HCM symptoms is a septal myectomy.

See these stories for more info:

Wall Street Journal

Atlanta Journal Constitution

Los Angeles Times

Deadline

Variety

Hollywood Reporter

HCMBeat wishes Mr. Zucker the best of luck during his surgery and recovery.

Here is a link to some resources we have collected for patients who are going through myectomy:  Resources for Patients About Myectomy

The Business of HCM

This article in Cardiovascular Business discusses the financial benefit to a hospital that adds a center for the treatment of HCM.  In particular, hospitals can expect to see higher volumes in the areas of echocardiograms, cardiac MRI, and electrophysiology.

Do HCM Family Screening Protocols Need Adjustment?

A recent editorial published in Circulation: Genomic and Precision Medicine suggests that current HCM screening protocols may need adjustment to account for recent findings by a study by researchers in the Netherlands.  The Dutch study, published in the same journal, found that of 620 relatives of HCM patients who underwent genetic testing, 43% were found to be genetically positive for HCM, while 30% were diagnosed with HCM at the initial screening. 16% more went on to develop HCM during 7 years of repeated cardiac evaluation.

On the other hand, the 57% of relatives found to be genotype-negative were released from clinical HCM follow-up.

The Australian authors of the editorial, Semsarian and Ingles, note that current screening protocols would have failed to identify the 6 children (15%) who were diagnosed under the age of 12, half of which had a particularly malignant family history.

Additionally, few teens were diagnosed with HCM, which stands in contrast to current opinion that HCM is most likely to develop during adolescence. Indeed, most newly diagnosed family members were older than the age of 36, with 44% being over the age of 50.

Lastly, Semsarian and Ingles note their concern with general utilization of the Dutch practice of releasing a gene negative family member from serial follow up since the impact of all genes which have a role in causing HCM is not yet known while new genes which may cause HCM are still being identified. 

Semsarian and Ingles also note that the Dutch patient sample differs from more typical patient populations found in the U.S. and Australia where causes of HCM are more diverse and cannot be easily tied to a specific gene.

Does the Heart Transplant Allocation Process Discriminate Against HCM Patients?

A recent article by doctors from the University of Utah Health Sciences Center found that patients with HCM who are in need of heart transplantation may wait longer for a new heart than patients with other cardiomyopathies.  Additionally, HCM patients may experience stroke or other adverse consequences while awaiting transplant.

The discrepancy is attributable, in part, to the fact that HCM patients are not often candidates for LVADs (left ventricular assist devices) and other types of mechanical circulatory support devices which are used to bridge patients awaiting transplant.

Hence, the article argues, United Network for Organ Sharing (UNOS -the organization responsible for the allocation of donor organs in the U.S.) should take these factors into consideration as it revises its system of heart allocation for patients awaiting transplant.

On a positive note, the article points out that long-term survival in HCM patients has improved over time, and HCM patients now do as well or better following transplant  than patients who have been transplanted for other types of cardiomyopathy.

Continuing Genetic Counseling Helpful for Silent HCM Gene Carriers

An article entitled Psychosocial Impact of a Positive Gene Result for Asymptomatic Relatives at Risk of Hypertrophic Cardiomyopathy was published in this week’s Journal for Genetic Counseling.

The article focuses on the motivation for and the impact of HCM genetic testing on family members.  The 32 participants in the study all encouraged family members to undergo genetic testing with the hope that the knowledge gained would benefit family members down the line.  However, the study found that the psychological impact of a positive result, in the absence of overt disease, was highly variable. Some gene positive individuals perceived that they had an absolute risk of developing HCM, with substantial detriment to their lifestyle choices, while others were not at all affected by the result and made no lifestyle changes.

Continue reading “Continuing Genetic Counseling Helpful for Silent HCM Gene Carriers”

Australian Summary of Standards for HCM Diagnosis and Management

A summary of current standards for the proper diagnosis and management of patients with hypertrophic cardiomyopathy was recently published by Australian HCM doctor Chris Semsarian in the journal Heart, Lung and Circulation.