Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy

Observed genes

Polygenic score

Influential genes: SMARCB1

In the context of HCM, the SMARCB1 gene has been implicated as a contributing factor.

Overview

Hypertrophic cardiomyopathy (HCM) is a disease of the heart muscle (myocardium). It is characterized by myocardial thickening (hypertrophy) without the presence of left ventricular dilatation or other pathologies that could explain the myocardial hypertrophy (e.g. arterial hypertension, aortic valve stenosis or ischaemic heart disease).(3) It is most often caused by abnormal genes that cause the walls of the chamber (ventricle) to get thicker and stiffer, which then limits the amount of blood taken in and pumped out to the circulation with every heartbeat.

It is one of the most common types of cardiomyopathy with a frequency of 1:500 and also one of the most frequent causes of sudden death in young individuals and athletes. (3)

Fig. 1: Hypertrophic cardiomyopathy | Mayo Clinic

  

There are two types of HCM

  1. Obstructive type - more common (60-70%), the underlying problem is the enlarged septum, which prevents the blood flowing out of the heart
  2. Non-obstructive type - the walls of the ventricle grow thicker, but they do not obstruct the blood flow

Several abnormalities and complications of the hypertrophic heart can develop over time:

Prevalence & Risk factors

The prevalence of  hypertrophic cardiomyopathy is estimated to be at least 1:500 of the adult population. (4) Although no data  exist in this area, based on the prevalence it is very likely that many patients with HCM remain undiagnosed during their life. (8) 

Hypertrophic cardiomyopathy is the most frequently inherited heart disease and it affects males and females of all ages and ethnic backgrounds. Although most patients with HCM present with no symptoms, it is important to remember that HCM is also associated with dangerous complications such as sudden cardiac death (SCD). 

Most often, patients with HCM are stratified and treated by the risk of SCD. The risk is influenced by several factors: (8)

  • Family history
  • Adolescence and early adulthood (< 35 years)
  • Unexplained fainting (syncope) in past
  • Nonsustained ventricular tachycardia
  • Severe left ventricular hypertrophy
  • Abnormal systolic blood pressure response to exercise
  • Left ventricular outflow tract obstruction
  • Atrial fibrillation

Genetics

Hypertrophic cardiomyopathy is a clinically diverse disease caused by a variety of gene mutations associated with hypertrophy of the left (and occasionally the right) ventricle. In up to 60% to 70% of adolescents and adults with HCM, the disease is caused by mutations in cardiac sarcomere protein genes, which encode parts of the contractile system and is transmitted as an autosomal dominant trait with variable penetrance (some individuals who carry the pathogenic variant express the associated trait while others do not). (1, 4, 5) Mutations in these genes can be found in approximately 60% of patients, and MYBPC3 and MYH7 mutations account for the majority of cases. (8) Nonetheless, several hundred mutations on more than 27 genes have been identified to date. (11) 

In infants and children, HCM is very often associated with specific syndromes (for example Noonan’s syndrome, LEOPARD syndrome) and metabolic diseases (such as the glycogen storage diseases etc.). (8)

Signs & Symptoms

HCM is characterized by left ventricular hypertrophy (LVH) of different morphology. It is associated with variable clinical courses and hemodynamic abnormalities. Although many patients with HCM are asymptomatic, others can develope one or more of the following symptoms (6):

  • fatigue
  • shortness of breath and exertion 
  • chest pain
  • lightheadedness, dizziness
  • palpitations
  • fainting (syncope) and near-fainting (presyncope), especially during or immediately following exertion
  • swelling of the legs and feet

Depending on the severity of disease, patients may also develop the following complications:

  • arrhythmias - both atrial and ventricular
  • heart failure
  • stroke
  • sudden cardiac death

HCM is also well-known for cases of young athletes, who had been asymptomatic all their lives and had died of sudden cardiac death, however the incidence is small (the annual SCD rate is <1%). Those recurring incidents are caused mainly by ventricular arrhythmias (primarily the ventricular fibrillation) and if diagnosed correctly in time, they can be effectively treated by implantable cardioverter defibrillators (ICDs). (8)

Diagnosis

A variety of tests are used in the diagnostics of HCM. It is always very important to exclude other conditions that could cause similar symptoms. The most frequently used tests are:

  • Echocardiogram
  • ECG and arrhythmia evaluation
  • Holter and event monitors
  • Cardiac magnetic resonance
  • Exercise testing
  • Cardiac catheterization
  • Evaluation of first-degree relatives

Therapy

The aim of the therapy is to alleviate the symptoms and prevent sudden cardiac death in high risk patients. The specific treatment depends on the severity of the patient's condition.


Prevention

Since it is a hereditary disease, hypertrophic cardiomyopathy cannot be prevented. However, early diagnosis is crucial to prevent serious complications and facilitate treatment. It is important to realize that most people with HCM do not develop symptoms or require any treatment. To lower the risk of developing cardiac complications, patients with HCM are advised to:

  • Avoid dehydration
  • Avoid strenuous exercise and competitive sports - always discuss physical activity with a physician
  • Maintain optimal weight
  • Quit smoking
  • Lower the alcohol intake
  • Heart-healthy diet
  • Manage stress

Prognosis

Due to the relatively high prevalence and the low overall incidence of complications, the prognosis of patients with HCM is generally good. It is estimated that at least two-thirds of HCM patients have a normal life expectancy. A review of HCM mortality published in 2017 describes a 0.7%/year mortality rate related to HCM and a 1.1%/year mortality rate from non-HCM-related causes. (9)

Recommendations

  • If you are diagnosed with HCM and you experience dizziness, chest pain, palpitations or fainting, always consult it with your doctor
  • Avoid strenuous exercise and competitive sports 

Lower the risk of complications by following a heart-healthy lifestyle:

  • Don’t smoke
  • Limit alcohol to the minimum
  • Stay hydrated
  • Healthy diet - high in plant-based foods, fruits and vegetables, healthy fats from e.g. olive oil and low in saturated fats
  • If you are overweight, lose weight

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Recommendations

  • If you are diagnosed with HCM and you experience dizziness, chest pain, palpitations or fainting, always consult it with your doctor
  • Avoid strenuous exercise and competitive sports 

Lower the risk of complications by following a heart-healthy lifestyle:

  • Don’t smoke
  • Limit alcohol to the minimum
  • Stay hydrated
  • Healthy diet - high in plant-based foods, fruits and vegetables, healthy fats from e.g. olive oil and low in saturated fats
  • If you are overweight, lose weight

Sources

  1. Cecchi, F., Charron, P., Alain Hagege, A., Lafont, A., Limongelli, G., Mahrholdt, H., McKenna, W. J., Mogensen, J., Nihoyannopoulos, P., Nistri, S., & Pieper, P. G. (n.d.). ESC GUIDELINES 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). https://doi.org/10.1093/eurheartj/ehu284
  2. American Heart Association. (2021). What is Hypertrophic Cardiomyopathy? https://www.heart.org/-/media/Files/Health-Topics/Answers-by-Heart/What-is-HCM.pdf Accessed: 2022-04-05
  3. MANN, Douglas L, et al. Braunwald´s Heart Disease : A Textbook of Cardiovascular Medicine. 10th Edition, 2015. ISBN 978-0-323-29429-4.
  4. Definition and classification of the cardiomyopathies - UpToDate. (n.d.). Retrieved April 10, 2022, from https://www-uptodate-com.ezproxy.is.cuni.cz/contents/definition-and-classification-of-the-cardiomyopathies?search=Definition%20and%20classification%20of%20the%20cardiomyopathies&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
  5. Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing - UpToDate. (n.d.). Retrieved April 10, 2022, from https://www-uptodate-com.ezproxy.is.cuni.cz/contents/hypertrophic-cardiomyopathy-gene-mutations-and-clinical-genetic-testing?search=Definition%20and%20classification%20of%20the%20cardiomyopathies&topicRef=4943&source=see_link
  6. Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation - UpToDate. (n.d.). Retrieved April 10, 2022, from https://www-uptodate-com.ezproxy.is.cuni.cz/contents/hypertrophic-cardiomyopathy-clinical-manifestations-diagnosis-and-evaluation?search=Definition%20and%20classification%20of%20the%20cardiomyopathies&topicRef=4926&source=see_link#H274566
  7. Raphael, C. E., Cooper, R., Parker, K. H., Collinson, J., Vassiliou, V., Pennell, D. J., de Silva, R., Hsu, L. Y., Greve, A. M., Nijjer, S., Broyd, C., Ali, A., Keegan, J., Francis, D. P., Davies, J. E., Hughes, A. D., Arai, A., Frenneaux, M., Stables, R. H., … Prasad, S. K. (2016). Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy: Insights From Wave Intensity Analysis and Magnetic Resonance. Journal of the American College of Cardiology, 68(15), 1651. https://doi.org/10.1016/J.JACC.2016.07.751
  8. O’Mahony, C., Elliott, P., & McKenna, W. (2013). Sudden cardiac death in hypertrophic cardiomyopathy. Circulation: Arrhythmia and Electrophysiology, 6(2), 443–451. https://doi.org/10.1161/CIRCEP.111.962043
  9. Dominguez, F., Sanz-Sánchez, J., García-Pavía, P., & Zorio, E. (2018). Follow-up and prognosis of HCM. Global Cardiology Science & Practice, 2018(3). https://doi.org/10.21542/GCSP.2018.33
  10. Jacoby, D. L., DePasquale, E. C., & McKenna, W. J. (2013). Hypertrophic cardiomyopathy: Diagnosis, risk stratification and treatment. CMAJ, 185(2), 127–134. https://doi.org/10.1503/CMAJ.120138/-/DC1
  11. Prinz, C., Farr, M., Hering, D., Horstkotte, D., & Faber, L. (2011). The Diagnosis and Treatment of Hypertrophic Cardiomyopathy. Deutsches Ärzteblatt International, 108(13), 209. https://doi.org/10.3238/ARZTEBL.2011.0209
  12. MANN, Douglas L, et al. Braunwald´s Heart Disease : A Textbook of Cardiovascular Medicine. 10th Edition, 2015. ISBN 978-0-323-29429-4.
  13. American Heart Association. (2021). What is Hypertrophic Cardiomyopathy? https://www.heart.org/-/media/Files/Health-Topics/Answers-by-Heart/What-is-HCM.pdf Accessed: 2022-04-05
  14. Cecchi, F., Charron, P., Alain Hagege, A., Lafont, A., Limongelli, G., Mahrholdt, H., McKenna, W. J., Mogensen, J., Nihoyannopoulos, P., Nistri, S., & Pieper, P. G. (n.d.). ESC GUIDELINES 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). https://doi.org/10.1093/eurheartj/ehu284
  15. O’Mahony, C., Elliott, P., & McKenna, W. (2013). Sudden cardiac death in hypertrophic cardiomyopathy. Circulation: Arrhythmia and Electrophysiology, 6(2), 443–451. https://doi.org/10.1161/CIRCEP.111.962043

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