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.

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.

Riding Rollercoasters with HCM – Results Presented at AHA Meeting

In May of this year, HCMBeat published this interview with Yale’s Dr. Daniel Jacoby and Dr. Nikolaos Papoutsidakis about their online survey of HCM patients who engage in risk-taking activities.

In this conversation, Drs. Jacoby and Papoutsidakis emphasized that the shared decision making process is an important facet of the patient/physician relationship for HCM patients. Risks should be explained, and decisions made with each patient’s set of values and priorities in mind. The doctors hoped that the results from their study would help to inform the shared decision-making process as applied to activities that involve any amount of patient risk-taking.

In a poster presented at this weekend’s American Heart Association Scientific Sessions in Chicago, Drs. Jacoby and Papousidakis made the results of this survey public.

After analyzing data from 633 patients (282 men and 351 women), 556 patients reported participating in thrill-seeking activities, while 331 continued such participation after their HCM diagnosis.  The doctors found that only 33.6% of the patients who engaged in the thrill-seeking activities experienced such minor adverse events as dizziness, nausea, palpitations or chest pain, while only .02% experienced significant events during or within an hour following the activity.  Only one ICD shock was reported.

Hence, the doctors concluded that the risks associated with such activities appear to be low.

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.

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