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.

 

• Old Drug-New Use:  In addition, the calcium channel blocker diltiazem (commonly used to treat high blood pressure and angina) has been shown to improve cardiac fibrosis, myocyte disarray, and reduce hypertrophy in mice. Diltiazem may prove to be a more useful drug in HCM in the future.

Arrhythmia Management:

• Cardiac MRI Helps ICD Risk Assessment  In the last several years, information gained through the use of cardiac MRI has provided additional information which informs risk assessment for ICD implantation.

 

• 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:

• Myectomy:  Improvements have been made to the traditional myectomy procedure allowing the surgeon to address valve and papillary muscle issues.  Transapical myectomy, which addresses thickness in the bottom and side of the left ventricle and allows the ventricular cavity to fill more fully, has proven to be successful at one center.

 

• Potential New Tools for Septal Reduction:  There are a few new modalities for septal reduction which could see more use in the future. These include the use of the Mitra -Clip to treat systolic anterior motion of the mitral valve, radiofrequency ablation and the use of high-intensity focused ultrasound.

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!