HCM Treatment: The View from OHSU

If you are looking for a good survey of current practices in the treatment of HCM, a recent article published in the journal Structural Heart by Dr. Ahmad Masri and the team at Oregon Health and Sciences University (OHSU) provides an informative overview of thirty controversies and considerations in the treatment of HCM. This article explains in some detail how the doctors at this HCM Center approach these situations. 

This article, along with the brand new 2020 AHA/ACC HCM Guidelines, will tell you everything there is to know about the contemporary treatment of HCM.  For a short summary of all things HCM, you can also visit the page on this website entitled “Hypertrophic Cardiomyopathy-HCM for Short.”

The issues and concepts discussed in this article are as follows:

SCREENING OF HCM FAMILY MEMBERS:

  • How often should HCM family members be screened? 
  • Do children under 12 need to be screened?
  • What are the clinical implications of obstruction?
  • Are deformation imaging and strain analysis meaningful on echocardiogram?
  • How often should cardiac MRI be repeated?
  • What is the utility of cardiopulmonary exercise testing?
  • What are the implications of HCM genotype?
  • Do gene negative relatives need further screening?

QUESTIONS ABOUT DRUGS USED IN HCM TREATMENT:

  • Can disopyramide (Norpace) be started on outpatient basis?
  • Is ranolazine (Ranexa) useful in HCM?
  • Are anticoagulants needed in HCM patients with apical aneurysm?
  • Are anti-arrhythmics drugs useful in the treatment of HCM?

RISK STRATIFICATION (OR WHO NEEDS AN ICD?):

ELECTROPHYSIOLOGY ISSUES IN HCM

  • Is rhythm control better than rate control for atrial fibrillation?
  • Is catheter ablation preferable to anti-arrhythmic drugs in atrial fibrillation?
  • Is the S-ICD a good option for HCM patients?
  • Should patients at lower risk of sudden death with A-V block get a pacemaker or ICD?
  • Is there a role for the CHA2DS2-VASc score for HCM patients with atrial fibrillation?
  • What is the role of ventricular tachycardia ablation in HCM?

MANAGEMENT OF PATIENTS WHO DON’T RESPOND TO MEDICATION:

  • Which is preferable, myectomy or alcohol septal ablation?
  • Should additional surgical procedures be used to reduce outflow tract obstruction and systolic anterior motion of the mitral valve?
  • Are there any consequences resulting from left branch bundle block after myectomy?
  • Should transapical myectomy be a treatment option?
  • What is the role of the mitral valve repair via MitraClip in HCM?

Click here to access the article.

2020 AHA/ACC HCM Diagnosis & Treatment Guidelines Released

The highly anticipated 2020 American Heart Association/American College of Cardiology Guidelines for the Diagnosis and Treatment of Patients with Hypertrophic Cardiomyopathy have been released.

This document, drafted with reference to published HCM literature, and with input from a committee of HCM experts with broad expertise, updates the prior version published in 2011.  It contains clinical practice guidelines for the broad spectrum of issues which may confront medical professionals as they approach the diagnosis and treatment of patients and families affected by hypertrophic cardiomyopathy.

Some key highlights and updates to the 2011 guidelines include:

  •  Shared Decision Making:  The 2020 guidelines emphasize the process of shared decision-making between patients and medical providers.  Medical providers should provide an overview of all testing and treatment options, and engage the patient in a complete discussion of all risks and benefits.  Most importantly, the patient is encouraged to share their own goals, values, and concerns which should inform the final decision.
  • Exercise is Beneficial:  These guidelines reflect a shift in thinking about exercise in HCM patients.  Prior guidelines suggested caution with regard to exercise.  Current research reflects the cardiovascular benefit to moderate exercise.  The guidelines also encourage the avoidance of dehydration, particularly in those patients who are obstructed, and to avoid exercise in extreme heat and humidity.  Participation in rigorous and physically demanding exercise is a topic for shared decision making and risk assessment between patient and medical professional, as in the first bullet-point above.
  • Referral to HCM Specialty Centers Encouraged:  Referral to specialized HCM Centers with expertise in treatment of the disease is important.  Expert advice is especially important where the treatment path is not clearly defined, or if invasive septal reduction procedures are under consideration.
  • Reconfirmation of Genetic Testing Results:  Genetic testing results should be performed by a cardiac genetic counselor with results being reconfirmed in follow-up visits every 2 – 3 years.  New genetic variants are constantly being identified, while older mutations are sometimes later found to be harmless.
  • Atrial Fibrillation:  HCM patients with atrial fibrillation, whether it is persistent or sporadic, have a heightened risk of stroke. Therefore, all HCM patients with AFib should receive anti-coagulant drugs without regard to traditional stroke risk scoring systems, i.e. the CHADS-VASc score.
  • Updated Risk Factor Calculation:  Risk factors for sudden cardiac death continue to be refined.  New markers, such as apical aneurysm, gadolinium enhancement on MRI and decreased left ventricular systolic function have been identified, while an older risk factor – abnormal blood pressure response during exercise – is no longer considered to be a risk factor.
  • Heart Failure Treatment:  Traditional heart failure treatments should be used in patients with an ejection fraction reduced below 50%, without obstruction (which should always be addressed first with septal reduction methods). These treatments include HF medical therapy, cardiac resynchronization therapy, left ventricular assist device or even heart transplantation.

The top ten take home messages can be found here.

And you can find the entire 2020 HCM Guidelines here.

MyoKardia Acquired by Bristol Myers Squibb – UPDATED

This morning MyoKardia announced that it was being acquired by drug company Bristol Myers Squibb (BMS) for $13.1 billion. BMS plans to continue MyoKardia’s development of mavacamten as the first drug specifically intended to treat hypertrophic cardiomyopathy. The deal is expected to close before the end of 2020.

Last month, MyoKardia published positive results from its Stage 3 EXPLORER trial for obstructive HCM. Earlier this year, the FDA granted mavacamten breakthrough therapy designation which could shorten the FDA approval process by about 4 months. If all goes well, the drug could be available to HCM patients by the end of 2021.

The merger strengthens BMS’ cardiac offerings. Mavacamten will join Eliquis, a blood thinner that will go generic in 2026.

This is not MyoKardia’s first tie to Big Pharma. The French pharmaceutical company Sanofi invested $230 million into MyoKardia in 2014 but after their agreement expired in 2018, MyoKardia bought back the U.S. rights to its drugs for $80 million.

You can read a press release about the merger from MyoKardia here or a press release from BMS here. You can also read about it in the Wall Street Journal here.

DISCLOSURES:  HCMBEAT HAS RECEIVED UNRESTRICTED EDUCATIONAL GRANTS FROM MYOKARDIA.  ADDITIONALLY, CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVED AS A PATIENT ADVISOR ON THE STEERING COMMITTEE OF MYOKARDIA’S EXPLORER TRIAL AND IS CREDITED AS AN AUTHOR OF THE STUDY AS PUBLISHED IN THE LANCET.  CYNTHIA ALSO SERVES ON MYOKARDIA’S PATIENT ADVISORY BOARD.

Atrial Fibrillation May Cause Negative Outcomes in HCM

 

A recent study published in Clinical Research in Cardiology  found that atrial fibrillation is a frequent complication of HCM and can be an important predictor of negative outcomes.

These findings suggest that practitioners should aggressively screen for and treat atrial fibrillation in HCM patients to improve long term outcomes.

ESC Issues New Exercise Guidelines Including Guidance for HCM Patients


The European Society of Cardiology recently published new guidelines for exercise for patients with HCM.

These guidelines offer more flexibility for HCM patients that past guidelines, stating that exercise may be permissible for HCM patients, but that it depends on individual situations. The focus should be on the shared decision process between patient and doctor to determine whether exercise may be appropriate for each individual patient.  Additionally, annual follow up for adults, with more frequent follow up for adolescents and young adults is also recommended.

Section 5.5.1 of the guidelines focuses on Hypertrophic Cardiomyopathy. These guidelines state:

  • The risk of sudden cardiac death or arrest (SCD or SCA) during exercise is likely lower than previously thought and therefore, a total ban on exercise is not warranted.
  • Exercise for physical and psychological well-being should be encouraged, following a careful baseline assessment of patients with HCM which should include:
    • Personal and family history
    • Risk Factors for SCD/SCA
    • EKG at rest and during exercise
    • Echocardiogram/Degree of Obstruction
    • Degree of late gadolinium enhancement indicative of cardiac fibrosis as seen on cardiac MRI
    • Exercise testing and blood pressure response to exercise
    • ESC Score of HCM Risk

 

MyoKardia’s EXPLORER Trial Big Success

The results of MyoKardia’s Stage 3 EXPLORER study for its experimental drug mavacamten were presented on Saturday at the European Society of Cardiology’s virtual annual meeting and contemporaneously published in The Lancet

The findings from the study showed that mavacamten improved exercise capacity, reduced left ventricular outflow tract gradient (responsible for the obstruction in HCM) and improved New York Heart Association functional class, correlating with a reduction in symptoms and an improvement in quality of life in patients with obstructive hypertrophic cardiomyopathy. 

This was the largest placebo controlled randomized trial ever conducted in HCM. Additionally, mavacamten is the first drug specifically developed for the treatment of hypertrophic cardiomyopathy. All drugs previously used for HCM symptoms were developed to treat other conditions and were used “off label” to treat HCM.

According to Florence, Italy’s Dr. Iacopo Olivotto, who presented the results to ESC’s virtual audience, mavacamten was generally well tolerated and did not appear to have serious side effects.

MyoKardia said the Explorer-HCM data will form the basis of its submission to the FDA which is planned for the first quarter of 2021.  Last month, the company announced that the drug was awarded “Breakthrough Drug” designation by the FDA which it hopes will streamline the approval process.

Also, a new trial comparing mavacamten to septal myectomy and septal alcohol ablation entitled VALOR-HCM for patients with symptomatic, obstructive HCM and who are New York Heart Association Class III – IV who meet the criteria for septal reduction therapy and have been referred for such a procedure has just gotten underway with the first patient enrolled earlier this month.

DISCLOSURES:  HCMBEAT HAS RECEIVED UNRESTRICTED EDUCATIONAL GRANTS FROM MYOKARDIA.  ADDITIONALLY, CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVED AS A PATIENT ADVISOR ON THE STEERING COMMITTEE OF MYOKARDIA’S EXPLORER TRIAL and is credited as an author of the study as published in the lancet.  cynthia also serves on myokardia’s patient advisory board.

Sudden Death Risk Factors Differ for Children with HCM

According to a recent paper published in Circulation, children’s risk for sudden death should be evaluated using different risk factors than those used for adults.

Two main differences seen between factors influencing the risk of sudden death of children and adults were that:

  • for children, family history of sudden death was not a risk factor;
  • a left ventricular outflow tract gradient in a child suggested a lower risk of sudden death.

The authors of this study propose that the risk assessment factors highlighted in this study (and not the various risk assessment tools that have been developed for adults) should be used by clinicians to evaluate the need for implantable defibrillators in children.

 

 

MyoKardia Announces Positive Results from EXPLORER Trial

MyoKardia today announced positive topline results for its experimental drug mavacamten from its recent Stage 3 EXPLORER trial for patients with obstructive hypertrophic cardiomyopathy or HCM.

According to the press release, the drug met all primary and secondary endpoints, while relieving outflow tract obstruction, improving symptoms and enhancing quality of life for the patients enrolled in the trial.  Furthermore, the drug was well tolerated and appeared to be free of significant side effects.

MyoKardia plans to seek FDA approval for mavacamten, the first drug specifically targeting the underlying biological mechanism of HCM, in the first quarter of 2021.

Full results of the EXPLORER study will be presented at a scientific meeting later this year.

 

DISCLOSURES:  CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVES AS PATIENT ADVISOR ON THE STEERING COMMITTEE OF MYOKARDIA’S EXPLORER TRIAL AND AS A MEMBER OF MYOKARDIA’S PATIENT ADVISORY BOARD.

 

 

COVID-19: Advice from HCM Doctors

The following guidelines have been developed by HCM specialists at the following hospitals:  Brigham and Women’s Hospital in Boston, Careggi University in Florence, Italy, Stanford University, the University of Michigan and the University of Pennsylvania.

At the bottom of this page you will find the document as a pdf file which should allow you access to the links contained in the document.

Continue reading “COVID-19: Advice from HCM Doctors”

Share Registry Study Focuses on So-Called “End Stage” HCM

Researchers from the Sarcomere Human Cardiomyopathy Registry (or the acronym “SHaRe” for short) have again joined forces to look at a subset of hypertrophic cardiomyopathy (HCM) patients who have what is known as “end stage” HCM.  This term, which is a bit of a misnomer, is used to describe patients who experience left ventricular systolic dysfunction (LVSD) which occurs when the left ventricular ejection fraction (LVEF) is less than 50%.

According to the study published last week in the journal Circulation, of a total of 6,793 HCM patients included in the study, 553 or 8% fell into this category.   The paper goes on to highlight some important observations about patients that fall into this category which are highlighted below.

Continue reading “Share Registry Study Focuses on So-Called “End Stage” HCM”