Understanding hypertrophic cardiomyopathy (HCM)
What is HCM
Hypertrophic cardiomyopathy (HCM) is a disease of the heart muscle characterized by hypertrophy of the left ventricle, in the absence of other cardiac, systemic or metabolic conditions that explain this thickening1. It affects approximately 1 in 500 adults in the general population1, although a proportion of cases remain undiagnosed2. Furthermore, it predominantly affects young people.1being one of the main causes of sudden cardiac death in this population group2. In 60% of patients, a familial genetic component is identified due to mutations in genes that encode cardiac sarcomere proteins3.
Obstructive and non-obstructive
In HCM, the walls of the left ventricle can thicken and become stiff, limiting the amount of blood the heart can pump.4. Depending on the presence or absence of left ventricular outflow tract obstruction (LVOT), the disease is classified as:
• Non-obstructive hypertrophic cardiomyopathy (HNCM): The walls are thickened, but they do not block the flow of blood out of the heart4.
• Hypertrophic obstructive cardiomyopathy (HCM): Hypertrophy, especially in the interventricular septum (the wall that separates the two ventricles), blocks or reduces blood flow from the left ventricle to the aorta4. Approximately 2/3 of patients have MCHO6 and most experience significant symptoms.
In Spain, HCM affects approximately 97,000 people, of which 68,000 would have Hypertrophic Obstructive Cardiomyopathy (HCM).5.
Impact on the patient: mortality and risk of comorbidities
Mortality and sudden cardiac death
HCM is one of the main causes of sudden death in those under 35 years of age, a particularly dramatic event that can occur both in conditions of rest or low physical load, and during high-intensity exercise or sports7.
Mortality of patients with HCM is 3 times higher than in the general population8reaching a rate 4 times higher in young patients (20 to 29 years) and 3 times higher in patients in the age range between 50 and 69 years8. Annually, between 0.22% and 0.4% of patients with HCM die from sudden death9,10, which is equivalent to between 210 and 381 deaths annually in Spain5.
Quality of life and comorbidities
La MCH increases mortality, risk of comorbidities and adverse cardiovascular events8, and its symptoms limit physical, emotional and social activities, deteriorating the quality of life of patients6.
• Symptoms: In 89% of patients with HCM experience dyspnea, fatigue, dizziness or syncope6.
•Comorbidities: Up to 6% of patients with HCM may suffer from stroke or other systemic thromboembolism2. The probability of developing atrial fibrillation (AF) in people with HCM it is 4 to 6 times higher than in the general population14. In these patients, AF is associated with a high risk of heart failure, mortality, stroke, and functional disability, particularly in patients with HCM.14. The estimated prevalence of heart failure in patients with HCM is 22%8.
• Functional impact: Symptomatic patients suffer psychological impacts (anxiety and depression) and physicalwhich limit their social functioning, leading to a deterioration in quality of life6. It is associated with limitations at work and educational level and activities of daily living.11,12,13
Mavacamten, first and only cardiac myosin inhibitor
What is mavacamten
Mavacamten, whose trade name is Camzyos®, is indicated for the treatment of symptomatic hypertrophic obstructive cardiomyopathy (HCM) in adults15. Mavacamten is the first and only cardiac myosin inhibitor approved in the European Union for the treatment of patients with obstructive HCM in NYHA functional class II-III*16.
Mavacamten, financed in Spain since November 1, is the first drug that specifically treats the disease rather than its symptoms16, through specific and reversible inhibition of cardiac myosin14. This is an oral treatment, administered once a day15.
*The NYHA (New York Heart Association) scale is the most used and recommended to estimate the functional capacity (FC) of patients with heart disease.
How it works
Excess myosin-actin cross-bridges and dysfunction of the super-relaxed state of myosin are key features of HCM, responsible for the hypercontractility, poor relaxation and excessive energy consumption. Mavacamten acts by modulating these processes, normalizing contractility, reducing LVOT gradient and improving cardiac filling pressures16.
Mavacamten represents a response to an unmet medical need within the current therapeutic strategies of MCHO20. And it is that no pharmacological agent traditionally used for the treatment of these patients (beta blockers, non-dihydropyridine calcium antagonists and disopyramide) is designed to treat the disease, if not solely provide symptomatic relief20. These treatments may be ineffective or poorly tolerated, and do not address the molecular mechanisms of HCM or modify its natural history20.
In the pivotal EXPLORER-HCM and VALOR-HCM clinical trials, Camzyos® has demonstrated significant benefits:
• Effort capacity: 37% of patients treated with Camzyos® improved maximum oxygen consumption (pVO2) and their NYHA functional class simultaneously (primary combined objective of the EXPLORER-HCM study)18
• Reduction of the LVOT obstructive gradient: Patients treated with Camzyos® presented an average decrease of 47 mmHg in the LVOT obstructive gradient18
• Functional improvement: 65% of patients treated with Camzyos® improved at least one NYHA functional class18
• Avoid invasive procedures: 82% who received Camzyos® were no longer candidates for septal reduction therapies according to the HCM clinical guidelines (primary objective of the VALOR-HCM study)17
Bristol Myers Squibb’s Commitment to Heart Disease
With more than 70 years of leadership in cardiovascular innovation, Bristol Myers Squibb has positioned itself as a pioneer in the transformation of the management of these pathologies. We focus on developing medicines that modify the course of complex diseases, such as thromboembolic diseases, heart failure and inherited cardiomyopathies, offering solutions that were previously unattainable.
We address these challenges with bold science and a clear vision: to create truly innovative therapies that not only treat symptoms, but change the trajectory of diseases. We know that our impact depends not only on innovation, but also on ensuring that our medicines and knowledge reach those who need them most, regardless of their age, gender, ethnicity or socioeconomic situation.
We collaborate closely with organizations that share our vision and sense of urgency. Because our mission is not just to advance science, but to tangibly improve outcomes for millions of people living with cardiovascular disease.
References
1 Marian AJ, et al. Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy. Circ Res. 2017; 121(7): 749–770.
2 Maron, B, Desai, M, Nishimura, R. et al. Diagnosis and Evaluation of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review. JACC. 2022 Feb, 79 (4) 372–389.
3 Elliot et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy. The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). European Heart Journal (2014) 35, 2733–2779.
4 Hypertrophic Cardiomyopathy (HCM). American Heart Association. Available in: https://www.heart.org/en/health-topics/cardiomyopathy/what-iscardiomyopathy-in-adults/hypertrophic-cardiomyopathy. Last access May 2024.
5 Report Cardiomyopathies Matter. Cardiomyopathies matter. 2023. Hiris care, Madrid, Spain.
6 Zaiser E, et al. Patient experiences with hypertrophic cardiomyopathy: a conceptual model of symptoms and impacts on quality of life. J Patient Rep Outcomes. 2020;4(1):102.
7 Castelletti et al., 2022; Brownrigg et al., 2022; Borsari et al., 2022; Esteve et al., 2018; Bagnall et al., 2016; Eckart et al., 2011).
8 Ho CY, et al. Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy Circulation. 2018;138(14):1387-1398.
9 Cardim N, Brito D, Rocha Lopes L, Freitas A, Araújo C, Belo A, Gonçalves L, Mimoso J, Olivotto I, Elliott P, Madeira H; participating centers. (2018). The Portuguese Registry of Hypertrophic Cardiomyopathy: Overall results. Rev Port Cardiol (Engl Ed). Jan;37(1):1-10. English, Portuguese. org/10.1016/j.repc.2017.08.005
10 Cecchi F, Olivotto I, Betocchi S, Rapezzi C, Conte MR, Sinagra G, Zachara E, Gavazzi A, Rordorf R, Carnemolla G, Porcu M, Nistri S, Gruppillo P, Giampaoli S. (2005). The Italian Registry for hypertrophic cardiomyopathy: a nationwide survey. Am Heart J. Nov;150(5):947-54. org/10.1016/j.ahj.2005.01.005.
11 Borsari W, Davis L, Meiers E, Salberg L, Barbara McDonough. (2022). Living with hypertrophic cardiomyopathy: a patient’s perspective. Future Cardiol. Jan;18(1):43-50. org/10.2217/fca-2021-0091.
12 Cardiomyopathy UK. (2017). Emotional wellbeing and mental health. Living with the impact of cardiomyopathy. Disponible en: org/sites/default/files/2021-04/ emotional-wellbeing-and-mentalhealth-october-2017.pdf.
14 Olivotto I, et al. Impact of Atrial Fibrillation on the Clinical Course of Hypertrophic Cardiomyopathy. Circulation 2001;104(21):2517-2524
15 Camzyos® technical sheet (mavacamten)
16 NICE Guidance. Mavacamten for treating symptomatic obstructive hypertrophic cardiomyopathy. Sept2023.
17 Desai MY, et al. Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy. J Am Coll Cardiol. 2022;80(2):95-108.
18 Olivotto I, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyophaty (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, pase 3 trial. Lancet.2020;396 (10253):759-769.
19 Reyes KRL, Bilgili G, Rader F. Mavacamten: A First-in-class Oral Modulator of Cardiac Myosin for the Treatment of Symptomatic Hypertrophic Obstructive Cardiomyopathy. Heart Int. 2022 Oct 5;16(2):91-98. doi: 10.17925/HI.2022.16.2.91. PMID: 36741099; PMCID: PMC9872784.
20 Zhu, M, Reyes, K, Bilgili, G. et al. Medical Therapies to Improve Left Ventricular Outflow Obstruction and Diastolic Function in Hypertrophic Cardiomyopathy. JACC Adv. 2023 Oct, 2 (8).org/10.1016/j.jacadv.2023.100622
Fuente: Cicero Communication
