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 decide which children were at increased risk of sudden death.
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.
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.
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.
For more on the progress of mavacamten, read these previous entries on HCMBeat:
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
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.
A retrospective analysis recently published in JACC: Cardiovascular Interventions suggests that that the risks of septal reduction therapy may differ for men and women.
In particular, the study found that the need for a pacemaker following septal alcohol ablation was almost 3 times more likely for a female than for a male.
The authors suggested that the reason for this difference may have been more advanced disease among female patients, and a higher instance of myocardial fibrosis and calcification.
Whatever the reason, this is another factor for patients to consider before deciding which method of septal reduction is best for them.
This week Cytokinetics announced that the first patient in Cohort 2 of their REDWOOD-HCM trial has been dosed.
Cytokinetics is testing the safety and tolerability of the cardiac myosin inhibitor CK-274 for the potential treatment of hypertrophic cardiomyopathy. The trial already enrolled completed enrollment of 18 patients in the first cohort. Sites are located across North America and Europe and results are expected in the middle of this year.
Separately, Cytokinetics announced that CK-274 has been granted an orphan drug designation by the FDA. This designation confers certain benefits and financial incentives for drugs intended to treat conditions affecting fewer than 200,000 people in the U.S.
In this study just published in the Heart Rhythm journal of the Heart Rhythm Society, doctors demonstrated that an Apple iPhone 12 (which is built with more magnets than previous iPhone models due to the Mag Safe charging technology) can disable the ability of an implantable defibrillator to deliver therapy.
So, this is a reminder for ICD patients that according to all device manufacturers, in order to avoid a problem, keep your phone at least 6 inches away from your device, and remember that you should NEVER PUT YOUR PHONE (ANY PHONE, NOT JUST AN IPHONE 12) IN YOUR SHIRT POCKET!
Just about everyone involved with HCM has heard the name Dr. Barry J. Maron. Dr. Maron has devoted his entire career to hypertrophic cardiomyopathy and has been perhaps the physician most associated with HCM, having gotten his start in the 1970s at the National Heart Institute.
In a brand new autobiographical essay by Dr. Maron, he retells his recent experience being diagnosed and treated for heart failure.
When Dr. Maron experienced edema, difficulty lying flat, and trouble breathing, he rationalized it all away until he experienced a terrifying and life threatening episode, and even then, he decided to call an Uber to take him to the hospital instead of an ambulance!
Once hospitalized, doctors were able to get to the root of his problem and treat Dr. Maron appropriately. Having received the proper care, he is now feeling much better.
Dr. Maron’s article concludes with three main takeaways:
- Physicians should not diagnose themselves;
- Heart failure is treatable; and
- Listen to your cardiologist and live a healthy lifestyle!
According to a recently published study by doctors in Copenhagen, Denmark, myocardial crypts (clefts, cracks or fissures in the myocardium) are found in the general population. Therefore, this article concludes that crypts seen on scans of the heart are not necessarily an indicator of HCM and do not warrant further investigation.
This paper is a departure from a 2012 paper by doctors at Tufts, which concluded that myocardial crypts were associated with HCM, and that they were often found in relatives of HCM patients found to be gene positive for HCM, but lacking the hallmark thickening of the ventricle.
Here is an example of what the crypts look like on MRI.