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!
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.
An article by doctors at the Cleveland Clinic recently published in the Journal of the American Heart Association advocates for earlier surgical intervention for patients with obstructive hypertrophic cardiomyopathy (HCM).
According to this article, obstructed HCM patients who undergo myectomy earlier have better long term survival. Therefore, these doctors take the position that patients should not wait until they become severely symptomatic and/or have run out of medical options to undergo myectomy surgery.
Meanwhile, an accompanying editorial by Dr. Mark Sherrid of NYU Langone Health is to the contrary. Dr. Sherrid argues that medications like disopyramide (Norpace) are effective in reducing symptoms and that the inherent risks from open heart surgery are not outweighed by a theoretical improvement in longevity.
Regardless of the timing of surgery, Dr. Sherrid points out that with multiple companies now developing novel treatments for HCM, visibility of the disease will increase which will ultimately result in better patient outcomes for all with HCM.
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.
According to the press release, preliminary results show substantial reductions in left ventricular outflow tract gradients (LVOT), with only modest decreases in left ventricular ejection fraction. (LVEF).
Based on this early positive data, the study will continue and will enroll a second group of approximately 18 patients.
Cytokinetics hopes to have results from REDWOOD-HCM in the middle of 2021, and hopes to begin a Phase 3 trial for CK-274 by the end of 2021.
For detailed information about this trial see ClinicalTrials.gov.