Carta al editor

Translational medicine in the treatment of hypertrophic cardiomyopathy: Mavacantem "The new promise"

Medicina traslacional en el tratamiento de la miocardiopatía hipertrófica: Mavacantem "La nueva promesa"

Juan Santiago Serna Trejos 1*https://orcid.org/0000-0002-3140-8995

Junior Rene Madroñero Lenis 2 https://orcid.org/0009-0002-1167-3799

Juan Camilo Diaz Beltrán 1https://orcid.org/0009-0002-6304-1718

1 Intensive Care Unit, Clínica Imbanaco, Cali, Colombia.

2 Universidad Libre, Cali, Colombia.

* Author for email: juansantiagosernatrejos@gmail.com

Received: 12/05/2024

Accepted: 06/07/2024

Published: 13/08/2024

Dear Editor

Hypertrophic cardiomyopathy (HCM) is an entity with a high global impact. Within the spectrum of hereditary cardiomyopathies, HCM is the most prevalent, reporting a global prevalence, since it is estimated that, for every 500 people, one case of HCM will be found. It is mainly associated with left ventricular hypertrophy that can be defined with a left ventricular thickness greater than or equal to 15 mm, making the diagnosis by exclusion with other entities that can cause said hypertrophy such as arterial hypertension or aortic stenosis. The presence of HCM is usually associated with clinical spectra such as severe heart failure and sudden cardiac death.(1,2).

Currently, different investigations have been carried out in the face of HCM to identify the origin of the problem, it is proposed that this entity is associated with the aberrant activity of the muscular sarcomere, which is responsible for carrying and executing the contractile machinery of the heart, dysfunctions in this muscular structure have been identified, of which a high incidence of genetic and/or familial mutations in certain genes that encode contractile proteins has been demonstrated, mostly in the MYH7 gene which encodes the human cardiac myosin heavy chain β, mutations have also been seen in the MYBPC3 gene, which encodes the cardiac myosin binding protein C MyBP-C (3).

Mavacamten, also previously known as MYK-461, is a molecule developed by MyoKardia Inc., which was approved by the Food and Drug Administration (FDA) in April 2022 for commercial use in HCM, the axis of its action is focused on the inhibition of the cardiac myosin ATPase. The purpose of a targeted and/or selective regulation of cardiac contractility of myosin induced by Mavacantem, then provides a profile of normalization of myocardial contraction and relaxation. It is the selectivity of Mavacantem's action that makes it a high-value drug in the management of HCM, this selectivity is focused on the action on myosin and all its isoforms, conditioning a myosin in more relaxed states. Other functions related to the use of this innovative drug are related to normalizing the contraction and relaxation phenotypes related to mutations that cause HCM in many sarcomeric proteins concomitantly with the inhibition of myosin function in a reversible manner and protects the heart from other aggressions that cause diseases in HCM. This is explained by the reduction in the power production of the heart muscle by inhibiting the biomechanical properties of myosin.(4,5).

Mavacantem is an innovative discovery, according to the Web of Science database, literature findings are only available since 2017. To date, up to 2023, about 202 articles of any type (Originals, reviews, editorials, letters to the editor, etc.) are described (Table 1). Of these, there has been an annual increase of 79.5% in scientific research growth, with 2023 being the year with the highest literary production (n = 66 articles) (Figure 1). The country with the greatest contribution in research with Mavancem and MCH was the United States. This innovative therapy represents a major advance in translational and precision medicine for the management of HCM. The rising research landscape and the results condition an encouraging future in the management of this entity.

Figure 1. Annual scientific production on Mavacantem and hypertrophic cardiomyopathy in the Web of Science (WOS) database

Description: Prepared by the authors through the execution of a search in the WoS database; with statistical analysis using R and Rstudio; Bibliometrics and Biblioshine. The search strategy used was: (ALL=(Mavacamten)) AND ALL= (Cardiomyopathy, Hypertrophic).

Table 1. Information available on the annual scientific production on Mavacantem and hypertrophic cardiomyopathy in the Web of Science (WOS) database

 Description: Prepared by the authors through the execution of a search in the WoS database; with statistical analysis using R and Rstudio; Bibliometrics and Biblioshine. The search strategy used was: (ALL=(Mavacamten)) AND ALL= (Cardiomyopathy, Hypertrophic).

References

1. Geske JB,Osmmen SR,Gersh BJ.Hypertrophic Cardiomyopathy:Clinical Update.JACC Hear Fail [Internet]. 2018 [cited 2024 Apr 28]; 6(5): [about 12 p.]. Available from: https://pubmed.ncbi.nlm.nih.gov/29655825/

2. Zegkos T, Tziomalos G, Parcharidou D, Ntelios D, Papanastasiou CA, Karagiannidis E, et al. Validation of the new American College of Cardiology/American Heart Association Guidelines for the risk stratification of sudden cardiac death in a large Mediterranean cohort with Hypertrophic Cardiomyopathy. Hell J Cardiol [Internet]. 2022 [cited 2024 Apr 28];63:[about 7 p.]. Available from: https://www.sciencedirect.com/science/article/pii/S1109966621001263

3. Tian Z, Li L, Li X, Wang J, Zhang Q, Li Z, et al. Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: The EXPLORER-CN Randomized Clinical Trial. JAMA Cardiol [Internet]. 2023 [cites 2024 Jun 8]; 8(10): [about 9 p.]. Available from: https://jamanetwork.com/journals/jamacardiology/fullarticle/2809051?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jamacardio.2023.3030

4. Heitner SB, Jacoby D, Lester SJ, Owens A, Wang A, Zhang D, et al. Mavacamten treatment for obstructive hypertrophic cardiomyopathy a clinical trial. Ann Intern Med [Internet]. 2019 [cited 2024 Jun 8]; 170(11): [about 8 p.]. Available from: https://www.acpjournals.org/doi/10.7326/M-183016

5. Saberi S, Cardim N, Yamani M, Schulz-Menger J, Li W, Florea V, et al. Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy: EXPLORER-HCM Cardiac Magnetic Resonance Substudy Analysis. Circulation [Internet]. 2021 [cited 2024 Jun 8];143(6): [about. 3 p.]. Available from: https://www.ahajournals.org/doi/epdf/10.1161/CIRCULATIONAHA.120.052359

Declaration Of Conflict Of Interest

The authors declare not to present conflict of interest in the preparation of the investigation.

Declaration Of Financing

The authors declare not having received funding to carry out this research.

Statement Of Authorship:

Conceptualization: Juan Santiago Serna Trejos, Junior Rene Madroñero Lenis, Juan Camilo Diaz Beltrán.

Investigation: Juan Santiago Serna Trejos, Junior Rene Madroñero Lenis, Juan Camilo Diaz Beltrán.

Validation: Juan Santiago Serna Trejos, Junior Rene Madroñero Lenis, Juan Camilo Diaz Beltrán.

Writing - original draft: Juan Santiago Serna Trejos, Junior Rene Madroñero Lenis, Juan Camilo Diaz Beltrán.

Writing -review and editing: Juan Santiago Serna Trejos, Junior Rene Madroñero Lenis, Juan Camilo Diaz Beltrán.