The Future of HCM Care

Dr. Stephen Heitner, together with his colleagues at Oregon Health & Sciences University, published an article last week in the European Journal of Heart Failure which gives a glimpse into the treatment of hypertrophic cardiomyopathy (HCM) in the future.  Although recent publications have stated that the majority of HCM patients today have a favorable prognosis when receiving appropriate treatment, a heavy disease burden continues to be placed upon patients.  Hence, better and more effective treatments for HCM are still needed in order to lessen this burden.

The article provides a very thorough overview of both current and future HCM therapies and divides them into a few different categories listed below.

Drugs:

  • Potential for New Drugs:  No drugs have been specifically approved for the treatment of HCM by the Federal Drug Administration. Up until now, all drugs used to treat HCM patients (with the limited exception of propanolol) have been off-label uses.  However, this is likely to soon change. Current trials of myosin modulators like MyoKardia’s mavacamten and Cytokinetic’s CK-274 have so far yielded promising results and have the potential to change the treatment paradigm for HCM.

 

Arrhythmia Management:

 

  • Subcutaneous ICDs (S-ICDs) are sometimes a reasonable choice for preventing sudden cardiac death in HCM patients when pacing is not required. This allows the patient to avoid risks associated with lead malfunction.

Septal Reduction Therapy:

 

Gene Editing and Silencing:

  • Pre-implantation Genetic Diagnosis (PGD):  Current medical technology allows patients with known HCM gene(s) to use pre-implantation genetic diagnosis of embryos together with in-vitro fertilization in order to avoid passing along the HCM gene to the embryo.  The future may soon see these methods being used in tandem with gene repair, using CRISPR/Cas9 in order to edit out the errant gene and replace it with a normal one.

 

  • Gene Silencing:  Allele specific gene silencing may also prove to be a technique used in the future for preventing HCM. This technique involves the introduction of an adenovirus containing a short RNA segment designed to turn off the HCM gene.

 

In conclusion, this paper highlights the many things that HCM patients have to be optimistic about going forward.  Perhaps one day soon one of these methods will lead to the ultimate goal – a cure!

Atrial Fibrillation? Try Giving Up Alcohol

A recent study published in the New England Journal of Medicine found that drinkers suffering from atrial fibrillation who stopped drinking for the period of the study significantly reduced episodes of atrial fibrillation. 

According to doctors, alcohol consumption appears to be a significant risk factor and trigger for atrial fibrillation, while teetotaling appears to have a profound impact.

Dr. John Osborne, an American Heart Association spokesperson, said the benefit from giving up drinking was similar to results seen from drugs used to treat atrial fibrillation.  Even if patients are not able to completely abstain from alcohol, Osborne advised cutting back significantly. “It costs nothing and led to a substantial reduction in hospital rates. People in the abstinence group also lost an average of 3.8 kilograms [8.4 pounds] in six months,” he said.

Not everyone thinks that teetotaling is a workable treatment for afib, however. Critics say that encouraging abstinence is unrealistic and is not a permanent solution to the problem.  In fact, a planned follow-up study had to be shortened due the difficulty of finding participants willing to abstain from drinking for a whole year.

 

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Cytokinetics Announces its Phase 2 Clinical Trial – “Redwood-HCM”

Cytokinetics today announced that its Phase 2 double-blind study of its experimental drug CK-274 entitled “REDWOOD-HCM” (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM (hypertrophic cardiomyopathy) has begun enrollment.  The trial will enroll patients with symptomatic, obstructive HCM.

CK-274 is a next-generation cardiac myosin inhibitor which the company hopes will prove to be beneficial for the treatment of hypertrophic cardiomyopathy (HCM).

There are currently two companies in clinical trials for HCM:  Cytokinetics and MyoKardia. You can read more about their efforts here and here.

 

Racial Differences in HCM

A recent study  found that African-American patients with HCM tend to be younger and more symptomatic than their white counterparts. Additionally, these patients are less likely to undergo septal reduction therapies or have genetic testing.

The implications, according to Dr. Neal Lakdawala of Brigham and Women’s Hospital who is an author of the study, is that doctors should always consider the possibility of hypertrophic cardiomyopathy in patients with left ventricular hypertrophy.  If diagnosed with HCM, these patients should be referred to specialists with experience in treating HCM.  This could potentially help these patients avoid the two most devastating complications of HCM:  sudden death and stroke.

 

More HCM Research is Needed

A recent study in Europe found that HCM patients’ risk of death continues to exceed the risk in the general population.

This study looked at 4893 patients with hypertrophic cardiomyopathy treated at 7 different European HCM centers between 1980 and 2013. Although the statistics improved for those who were treated more recently, this study makes it clear that there is still much room for improvement in risk stratification and treatment for patients with HCM.

Overweight HCM Patients Fare Worse

This week, researchers from the eight HCM centers comprising the Sarcomeric Human Cardiomyopathy Registry [SHARE Registry] published a paper that every HCM patient should take to heart.

The sobering findings are that overweight HCM patients have a higher incidence of obstruction, heart failure and atrial fibrillation than their normal weight counterparts. As a result of this study, the researchers suggest heightened attention to weight management and exercise in order to prevent disease-related progression and complications.

Continue reading “Overweight HCM Patients Fare Worse”

Data From HCM Registry to Inform Personalized HCM Treatment in Future

Several years ago, researchers from the University of Virginia (UVA) and the University of Oxford announced a joint project involving a large international registry of hypertrophic cardiomyopathy (HCM) patients to facilitate research into HCM. Backed with funding from the National Heart Lung and Blood Institute, this project, known as the HCM Registry, includes data from 2,750 patients with HCM at 44 sites in six countries. 

This week, researchers from UVA announced their first findings from this registry which suggest that HCM patients can be separated into two basic groups:

  1.  Patients with a known genetic mutation who are not obstructed but have scarring of the heart muscle;
  2. Patients who do not have a known genetic mutation and do not exhibit scarring, but who do have a significant amount of obstruction to blood flow.

According to Dr. Christopher Kramer of UVA, this information should provide doctors with information that allows them to better assess the degree of risk to any particular patient, and to help inform a treatment strategy for each patient based on his or her unique profile.

Sudden Death in HCM Less Common than Thought

A recent study by Canadian researchers published in the American Heart Association journal Circulation found a much lower incidence of  HCM related sudden death than expected.  The study included deaths in individuals that occurred between the ages of 10 and 45 in the Canadian province of Ontario between 2005 and 2016.  According to lead author Dr. Paul Dorian of the University of Toronto, the expectation was that 1 incident of sudden cardiac death would be identified in every 100 to 200 people who had HCM.  Instead, researchers found that the likelihood of sudden death of HCM patients was instead only about 1 in 3,000 people/year.

The study also found that found 7 in 10 HCM-related sudden deaths occurred in people not previously diagnosed with the condition.  Men had more than 5 times the risk of sudden cardiac death than women, and most deaths occurred during rest or light activity: only about 17% happened during or immediately after exercise. 

As a result of the study, according to Dr. Dorian, “our findings allow us to lower the temperature on our degree of worry about the condition.”

Another clinical take away from the study, according to the researchers, is that current exercise guidelines for HCM patients may be too restrictive.

HCM Clinical Trials – the Latest News

NEWS FROM MYOKARDIA

MyoKardia recently announced a new clinical trial of its drug, mavacamten (formerly known as MYK-461) which will compare the clinical results of mavacamten with septal reduction therapies currently used in clinical practice, i.e. the open heart surgical procedure known as septal myectomy and the catheter based procedure known as alcohol septal ablation.

The study will be run by the Cleveland Clinic with Dr. Milind Desai serving as principal investigator.  MyoKardia expect to begin enrolling patients in early 2020.

Read the press release here.

 

NEWS FROM CYTOKINETICS:

Cytokinetics released positive data from its Phase 1 study of the drug currently known as CK-274 in a poster session at the HFSA 23rd Annual Scientific Meeting in Philadelphia.  The study found that CK-274 was safe and well tolerated, while no serious adverse events or negative changes to vital signs, ECGs or laboratory tests were observed.

The company will now be moving into a Phase 2 clinical trial of CK-274 in patients with obstructive hypertrophic cardiomyopathy, expected to begin in late 2019.

Read their press release here.

 

 

DISCLOSURES:  HCMBEAT HAS RECEIVED PAST 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.

2 Companies Testing Drugs for HCM

Two San Francisco based companies are now conducting clinical trials for three drugs specifically targeting HCM.

Continue reading “2 Companies Testing Drugs for HCM”