Chinese Study Links Depression to Worse HCM Outcomes

A recent Chinese study found that patients with hypertrophic cardiomyopathy who also suffered from clinical depression had a higher risk of sudden cardiac death and/or heart failure. 

The researchers behind this study hypothesize that psychological treatment for depression could improve clinical outcomes in these patients and they suggest that further research is warranted.

Medtronic ICD Recall

The FDA has announced a Class I recall of certain models of Medtronic implantable defibrillators and cardiac resynchronization therapy defibrillators.  The statement from the FDA can be found here.

The recall impacts Medtronic’s Evera and Visia brands of ICDs as well as its Viva, Brava, Claria, Amplia and Compia brands of cardiac resynchronization therapy defibrillators (CRT-Ds) implanted from August 31, 2012 to May 9, 2018. The problem is described as “an unexpected and rapid decrease in battery life” caused by a short circuit. The defect may cause devices to go from recommended replacement time (when your alarm sounds to notify you that it is time to schedule a replacement surgery) to full battery depletion in just one day.  Normally, you would have approximately 3 months from the time that the alarm first sounds to schedule a procedure to implant a replacement.

According to this article, there have been 444 complaints and 264 medical device reports about this issue which impacts 239,171 devices.

To look up your device by product name, model or serial number to see whether it is impacted, click here.

The box in the upper right corner labeled “Advisories For This Model” will tell you if there are any advisories for your device.  If this particular recall affects your device, you will see the same advisory which is circled in red in the photo below.

Medtronic recall 1

Patients are advised to continue routine follow ups and use the Care Link Monitoring System.

And, as always, you can call Medtronic Patient Services with any questions at: (800) 551-5544

(M – F, 8am – 5pm Central).

Risk Assessment in HCM Children

A recent study published in the European Journal of Preventative Cardiology found that a 12-lead electrocardiogram (EKG) was not useful as a screening tool to determine which children were at increased risk of sudden death and therefore, a candidate to receive an implantable defibrillator. 

The full article can be found here.

Kids with HCM

A recent study published in the European Heart Journal using data collected from the SHaRe Registry found that while childhood onset HCM (15% of all HCM) is far less common than adult onset HCM, it is often more serious.

Children with HCM are more likely to have sarcomere mutations, have a higher risk of ventricular arrhythmias, and are twice as likely as adults to require advanced interventions like ventricular assist devices, heart transplant or other advanced heart failure therapies. 

Experts Put Mavacamten in Perspective

An article published today in Circulation by HCM experts Dr. Steve Ommen of Mayo Clinic and Dr. Martin Maron of Tufts Medical Center, discusses the prospective use of mavacamten as a treatment for obstructive hypertrophic cardiomyopathy. The doctors conclude that while mavacamten (assuming that it is FDA approved in early 2022) will have its place in the HCM tool kit, it should not replace septal reduction therapy for severe HOCM.

In particular, the article points out that the EXPLORER-HCM study showed modest improvements in symptoms and functional capacity (peak V02), comparable to those seen in the RESET-HCM study, which highlighted the ability of regular exercise to improve functional status in HCM.  

The article notes that there has not yet been a study directly comparing mavacamten with septal reduction therapies such as septal myectomy and alcohol septal reduction. The VALOR-HCM study, which is currently recruiting, will look at these therapies compared head-to-head.  It is noteworthy that the majority of patients in the EXPLORER trial had Class II heart failure and were not the more severely compromised Class III and IV patients most likely to benefit from myectomy or alcohol septal ablation.

This article compared historical myectomy data against the findings from EXPLORER, concluding that septal myectomy produces a better result for patients, with gradients abolished in more than 95% of patients compared to only 50% of patients with mavacamten.  And, the article points out that 25% of the patients in the EXPLORER trial continued to have left ventricular outflow tract gradients greater than or equal to 50mmHg, which still qualified them for septal reduction therapy.

Maron and Ommen’s take-home message is that mavacamten will be a welcome addition to the arsenal of HCM drugs and is potentially suitable for patients who do not have severe symptoms, who do not have access to septal reduction at a HCM specialty center, or who wish to avoid more invasive therapies.  It also may be used in the same way as disopyramide, to defer surgery by improving symptoms to a tolerable level.

Lastly, this article points out that there is a need for longer term follow up to study the effects of cardiac remodeling caused by mavacamten.

While it is wonderful to have options, it is important that patients and their medical team consider all available information, including potential benefit and risk, before moving forward with medical therapy. 

Mavacamten Approaches Finish Line

The United States Food and Drug Administration (FDA) is expected to complete its review of mavacamten and release its decision on whether to approve the drug for sale in the U.S. by January 28, 2022.

This week, Bristol Myers Squibb submitted its New Drug Application for mavacamten to the FDA. Mavacamten is the first drug specifically designed to treat obstructive hypertrophic cardiomyopathy. The application was based on the recent positive results of the Phase 3  EXPLORER-HCM trial

In October of last year, Bristol Myers Squibb paid $13.1 billion to purchase MyoKardia, the San Francisco based biotech company which developed mavacamten as a novel cardiac myosin modulator for the treatment of of HCM.

The FDA has assigned a Prescription Drug User Fee Act goal date of January 28, 2022 to the drug, which means that the FDA is expected to complete its review of mavacamten by January 28, 2022.

 

 

 

 

 

 

DISCLOSURES:  CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVED AS A PATIENT ADVISOR ON THE STEERING COMMITTEE OF MYOKARDIA’S EXPLORER TRIAL AND IS AN AUTHOR OF THE STUDY AS PUBLISHED IN THE LANCET.  CYNTHIA ALSO SERVES ON MYOKARDIA’S PATIENT ADVISORY BOARD.

 

Identical Twins Show Impact of Behavior and Environment on HCM

A recent study of identical twins with HCM found significant variation in the expression of hypertrophic cardiomyopathy, even between twins carrying the same HCM-causing genetic mutation. 

This paper concludes that epigenetics (things which influence expression of DNA like behavioral and environmental factors) greatly influence the expression of HCM genetic mutations. 

The researchers studied 11 pairs of twins with HCM. 9 of the twin pairs had known HCM sarcomere mutations while 2 of the pairs had HCM of unknown cause. The siblings were followed for a time frame of between 5 to 14 years.

Researchers compared left ventricular wall thickness, left atrial size and left ventricular ejection fraction. Differences were found in the left ventricular wall thickness of all 11 pairs of twins, while left atrial size was similar in 3 of the 9 twin pairs who carried HCM mutations. Left ventricular ejection fraction was different in 4 of 7 twin pairs. 

The researchers theorize that similarities in left atrial size may be due to impaired ventricular relaxation directly tied to sarcomere dysfunction. In contrast, environmental factors yield more influence over ventricular function.

HCM epigenetics is a field ripe for research. As HCM patients, we hope that it will yield actionable data in the near future.

Class 1 Recall Issued for Boston Scientific S-ICD Lead

Patients with a Boston Scientific S-ICD should be aware of a Class I recall of the 3501 Emblem subcutaneous electrode.  This model was manufactured from March 2016 through November 2020.
 
 
This same issue was the subject of a product advisory issued in December of 2020, but due to 26 serious injuries and one death associated with the device, the advisory was upgraded to a recall.   
 
 
Boston Scientific has a product lookup tool (www.BostonScientific.com/lookup) where you can look up your device and see if your specific lead is affected.  You can find your serial numbers on your registration card.
 
 
You can read the HCMBeat’s previous entry on this issue here. 
 

HCM Drug Shows Improvement to Heart Structure

The results from the Myokardia EXPLORER- MRI sub-study are in, and there is more positive news for mavacamten (formerly known as MYK-461). According to the results of this small 35 patient study, patients who took mavacamten showed reduction of left ventricular size and wall thickness on MRI. These patients also had a reduction in their left atrial volume. All three of these measurements are predictors of poor outcome for HCM patients Additionally, this study found a reduction in certain biomarkers such as NT-proBNP, which indicate heart stress and injury.

MyoKardia (which was recently acquired by Bristol Myers Squibb) hopes that this drug will be approved by the FDA and available to American HCM patients by the end of this year.

For more on the progress of mavacamten, read these previous entries on HCMBeat:

Positive Results for MyoKardia Drug Mavacamten

MyoKardia Announces Positive Result for Mavacamten for Treatment of HOCM

MyoKardia Announces Positive Results from EXPLORER Trial

More Positive Results for MyoKardia Drug

MyoKardia’s EXPLORER Trial Big Success

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

HCM Genetics Discovery by British Researchers

A recent discovery by British researchers sheds light on how a type of common genetic mutation – a so called “common variant” – influences the expression of hypertrophic cardiomyopathy caused by mutation(s) in the cardiac sarcomere. 

How do Common Variants Impact Sarcomere Mutations?

This research, funded by the British Heart Foundation and spearheaded by Dr. Hugh Watkins of the University of Oxford, explains why some individuals with a particular sarcomere mutation develop a severe case of HCM, while their family members with the same mutation may develop only mild HCM symptoms or show no signs of the disease at all.  It also may explain why people who lack sarcomere mutations develop the disease.

The researchers compared the DNA of 2,780 people with HCM and 47,486 people without HCM and found that common variants acting in concert with rare sarcomere mutations determine whether a person will develop HCM. 

Common Variant HCM Not Hereditable

In addition, the researchers found that HCM attributable to common variants alone is unlikely to be passed on to future generations. This is good news for the children of HCM patients caused by common variants.

Watch your Blood Pressure

Lastly, this paper found that high diastolic blood pressure was associated with the development of  HCM caused by common variants. Hence, keeping blood pressure under control is something that patients can do to minimize their risk of developing HCM in the future.

A link to the study in Nature Genetics can be found here;
You can access a thorough summary by the British Heart Foundation here;
and you can find a short summary at Medical Xpress here.