Mickey Renaud – Hypertrophic Cardiomyopathy
In the winter of 2008, Mickey Renaud, a young hockey star that was drafted by the Calgary Flames, collapsed and died in his family home. The loss of such a promising talent left many people devastated but also puzzled: how could a 19 year old athletic die so suddenly from no apparent cause? The answer came months later when an autopsy revealed that Renaud had suffered from a rare genetic disease called Hypertrophic Cardiomyopathy (also called sudden cardiac death). It is a disease of the heart muscle and unfortunately for some, the first symptom of this disorder can be sudden death. Sadly, Renaud’s story is not unique, but recent medical advances and genetic screening approaches have provided new insights into hypertrophic cardiomyopathy causes, and have aided in hypertrophic cardiomyopathy diagnosis and prevention.
What are hypertrophic cardiomyopathy symptoms?
Common hypertrophic cardiomyopathy symptoms include a shortness of breath, chest pain, lightheadedness, fatigue, and fainting. Hypertrophic cardiomyopathy affects people of all ages and racial backgrounds and is more common than originally thought. It affects approximately 1 in 500 people in the general population, making it the most common genetic cardiovascular disorder. It can vary in severity with some individuals being completely asymptomatic and others can suffer from heart failure or even sudden death. Cardiac function is disrupted by the thickening (hypertrophy) of the heart muscle (myocardium) due to the expansion of muscle fibers (Figure 1). The increase in muscle fibers size leads to the abnormal alignment of muscle cells and genes that are responsible for muscle fiber structure and are the genes most commonly mutated in hypertrophic cardiomyopathy.
Most hypertrophic cardiomyopathy patients may lead a normal life, but need to avoid rigorous physical activities and sports that may trigger fatal heart failure. Therefore, the knowledge of genetic predisposition to this disease can be lifesaving.
Figure 1. Hypertrophic cardiomyopathy leads to thickening of the heart muscle (right) when compared to a normal heart (left). Image courtesy of Nucleus Medical Media Inc., (www.aurorahealthcare.org).
What causes Hypertrophic Cardiomyopathy?
Hypertrophic cardiomyopathy can occur sporadically in isolated individuals or can be familial, which is inherited from ones parents.
Hypertrophic Cardiomyopathy Inherited
The method of inheritance for familial hypertrophic cardiomyopathy is autosomal dominant – children of affected individuals carrying hypertrophic cardiomyopathy-causing mutations have a 50% chance of inheriting the disorder. The first gene to be linked to hypertrophic cardiomyopathy was the beta-myosin heavy chain gene involved in muscle fiber formation, and mutations in this gene account for 45% of all mutations that have been associated with the disease. From there, studies identified mutations in other genes that are required for maintaining muscle fiber structure that are mutated in hypertrophic cardiomyopathy including cardiac troponin T, alpha-tropomyosin, myosin-binding protein C, the myosin essential and regulatory light chains, troponin I and troponin C. Today, over 250 mutations within 13 muscle fiber-related genes have been shown to be involved in hypertrophic cardiomyopathy, and many more genes are linked to the disease, but most of them are extremely rare.
Considering the fact that hypertrophic cardiomyopathy can vary in severity, it is clear that different mutations within different genes have varying functional consequences. Furthermore, even within families carrying the same mutation, there are differences in the clinical severity of the disease. This suggests that there are other factors that are likely to be involved in hypertrophic cardiomyopathy including other gene modifiers, gender and environmental factors like diet and exercise.
3 ways to diagnose and treat Hypertrophic Cardiomyopathy
1. Specialized ultrasound imaging technique
The most reliable way to diagnose hypertrophic cardiomyopathy is through a specialized ultrasound imaging technique known as 2D and M-mode transthoracic echocardiography. At the cellular level, hypertrophic cardiomyopathy can be identified by an increase in size of muscle cells, their disorganization, as well as an increase in collagen secretion and fibrosis, but this is typically only observed post-mortem. Other methods that have been used for hypertrophic cardiomyopathy diagnosis include ECG monitoring, exercise testing and genetic testing.
2. Drug Therapies
Hypertrophic cardiomyopathy can be treated through drug therapies including the use of beta-blockers (Propranolol), calcium channel blockers and diuretics, aimed at reducing the incidence of arrythmias, improving diastolic dysfunction and improving heart failure-related symptoms. Implantable cardiac defibrillators have become a powerful tool to protect high-risk individuals from sudden cardiac death.
3. Genetic Testing
The screening of individuals though genetic testing can be particularly useful since it can assist in the early diagnosis of patients which will promote the regular monitoring of symptoms and advise younger patients to avoid strenuous activity and competitive sports. With familial cases of hypertrophic cardiomyopathy, at risk relatives are encouraged to get genetic testing.
Lind, J.M. et al. Expert Rev. Cardiovasc. Ther. 2006. Genetic basis of hypertrophic cardiomyopathy. 4 (6): 927-34
If you would like to learn more about genetic disorders, continue reading this related blog post: “Genetically Inherited Diseases”.