Ninerafaxstat, an investigational drug being studied by Imbria Pharmaceuticals, may be the first drug specifically for non-obstructive hypertrophic cardiomyopathy.
Cytokinetics today released positive results from Sequoia-HCM, its Phase 3 clinical trial of the experimental drug aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Patients treated with aficamten showed significantly increased exercise capacity as demonstrated by a 1.74 point increase in peak oxygen uptake (pVO2) measured during cardiopulmonary exercise testing. Improvements were also seen in provoked outflow tract gradients, and most importantly, patients felt better.
The study had enrollment of approximately 300 patients who were followed for 24 weeks.
Aficamten was well-tolerated, adverse events were comparable to those taking a placebo, and importantly, there were no instances of worsening heart failure or treatment interruptions due to low left ventricular ejection fraction (LVEF).
According to an article in Med City News, the drug may have an advantage over the Bristol Myers Squibb drug mavacamten (sold under the brand name Camzyos) because there were no reports of worsening heart failure. In the Phase 3 EXPLORER trial of mavacamten, seven patients in the treatment group experienced reductions to their LVEF.
The use of direct anti-coagulant drugs like Pradexa, Xarelto and Eliquis, which began in 2010, has had a major impact in reducing stroke risk in HCM patients who suffer from Afib. And, there is a low threshold for the initiation of these drugs for HCM patients who experience episodes of atrial fibrillation, even if such episodes are sporadic or infrequent. Also, anti-arrhythmic drugs as well as catheter and surgical ablation procedures can be helpful treatment options which are available to these patients.
There are also behavior modifications which can have a positive impact on Afib since patients who are overweight or who suffer from obstructive sleep apnea have a higher risk for atrial fibrillation.
Featured below are some past articles on HCMBeat about atrial fibrillation:
Tenaya Therapeutics and the Cleveland Clinic today announced that the first patient in Tenaya’s groundbreaking gene therapy clinical trial for hypertrophic cardiomyopathy has been dosed. This trial is testing a groundbreaking therapy intended to treat HCM caused by the MYBPC3 gene which is one of the most common HCM genes.
The Phase 1b trial is looking at the investigational drug TN-201. Preliminary results are expected in 2024.
Viz.ai has received FDA approval for an artificial intelligence algorithm that can spot HCM from a standard electrocardiogram or EKG.
The algorithm automatically reviews EKGs as they are performed, and alerts the cardiology care team if it identifies a patient with suspected HCM. Then, the care team is able to follow up with the patient and conduct further testing, if deemed appropriate.
The Chinese single center study enrolled 47 patients with obstructive hypertrophic cardiomyopathy. Surgeons used a minimally invasive limited anterior thoracotomy using a transapical approach. The surgeries were performed while the hearts were still beating.
The paper describes the minimally invasive nature of the surgery, and stresses the benefit of the surgeon’s ability to assess obstruction in real time, instead of having to put the patient back onto bypass if more tissue removal is necessary.
46 of the 47 patients enrolled in the trial had successful removal of their obstruction, though there was one death and there were two serious complications.
A companion editorial by Dr. Hartzell Schaff of Mayo Clinic points out that while the minimally invasive approach sounds good to patients, more than 30% of the patients who undergo myectomy at Mayo also need contemporaneous procedures in order to address valve issues, atrial fibrillation or coronary artery disease. These other procedures would not be possible using the minimally invasive approach. Also, Dr. Schaff points out that post-operative pain from a minimally invasive approach is not necessarily less than that experienced from the more invasive alternative.
In summary, this approach could prove to be a promising option for some patients, but larger studies are needed. As always, patients should consider surgical volume and consistent results when evaluating whether to undergo any surgery.
Research funded by the British Heart Foundation using novel cardiac imaging techniques was described in a recent article in Circulation. These techniques, such as quantitative perfusion cardiac magnetic resonance imaging and cardiac diffusion tensor imaging, can detect pre-clinical hypertrophic cardiomyopathy (HCM) before the development of any thickening in the heart.
With novel treatments like myosin modulators now available to patients, and with experimental treatments such as gene therapy now on the horizon, these new imaging techniques could allow doctors to intervene at a much earlier stage in order to potentially prevent disease.
You can read more about these imaging techniques here.
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 348,616 devices implanted between October 13, 2017 to June 9, 2023 with the following models being affected:
Visia AF, Visia AF MRI, Evera, Evera MRI, Primo MRI, Mirro MRI ICDs
These devices fail to deliver therapy due to inappropriate activation of the Short Circuit Protection feature. The issue is more likely to occur for devices with a glassed feedthrough that are configured to deliver therapy in the AX>B delivered pathway.
A reduced-energy shock, or no shock at all, may fail to correct a life-threatening arrhythmia, which can lead to cardiac arrest, other serious injury, or death.
There have been 28 incidents, 22 injuries, and no deaths for this issue.
A software update delivered to your device will address the issue. This requires a visit to your health care practitioner for a quick update. I had mine updated in a quick 10 minute visit to my ICD clinic.
To look up your device by product name, model or serial number to see whether it is impacted, click here.
NOTE: You can find the name, model and serial number of your device on the plastic identification card provided to you at the time of your implant.
The box in the upper right corner labeled “Customer Communications 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.
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
Editor’s note: Recently, Cynthia Waldman of HCMBeat had the chance to interview Dr. Laura Robertson of Tenaya Therapeutics . Dr. Robertson is charged with leading the clinical development program for Tenaya’s experimental gene therapy treatment for HCM.
You have probably read about gene therapy and wondered whether it could ever be used to treat hypertrophic cardiomyopathy. HCMBeat has written several stories about the growing field of gene therapy, shining a light on the researchers and companies focused on this effort.
Bristol Myers Squibb’s first-in-class myosin modulator mavacamten (brand name Camzyos) has been approved by the European Commission for the treatment of obstructive hypertrophic cardiomyopathy in all countries which are part of the European Union.