In this blog:
Let us start with a revision of the anatomy of the heart and the path of blood flow through it. Verify that you are familiar with the anatomy Fig. 3.1 (which is a reproduction from Fig. 2.1). If needed revisit §2.1 for revision.
| (a) | (b) |
Ensure that you remember the left ventricle, the mitral valve, the septum, the left ventricular outflow tract (LVOT), the aorta and the aortic valve.
Now we are ready to discuss HCM. Literally, HCM means excess thickening or growth of the cardiac muscle. Here hyper- implies excess, -trophy is growth, cardio- refers to the heart, -myo- means muscles, and -pathy mean abnormality.
I do not completely understand the biochemistry of HCM, but here is what I understand – take it with a good pinch full of salt. (Maybe another dedicated post can be made on this topic.) HCM is caused by mutations in genes that encode for the structure of the -myosin protein, which is part of the cardiac muscle. Remember, myosin is that motor protein, which plays the part of people in the tug-of-war analogy of the sarcomere. A consequence of these mutations is an increase in the fraction of myosin molecules that remain attached in the muscle sarcomere. (In the above analogy, the tired people do not let go of the rope so quickly after the pull and/or there is more space for people to hold the rope.)
Consequently, the cardiac muscle responds in two ways:
The natural growth mechanisms of the muscle in response to the increased load of pumping blood causes the muscle to thicken.
The increased number of attached myosin motors, and their longer duration remaining attached, makes the muscle stiffer, i.e. more rubbery.
Most of the muscular thickening in HCM is seen in walls of the left ventricle. This thickening is shown schematically in Figure 3.1(b). In many cases, the septum thickens more than the outer wall of the left ventricle in a condition termed as asymmetric hypertrophic cardiomyopathy. A healthy septum is somewhere betwen 6 mm and 10 mm in thickness, and septum thickness greater than 15 mm is classified as HCM.
In addition to the thickening of the cardiac muscles, one salient change that can occur in the HCM heart is the lengthening of the mitral valve leaflets. The biochemical origin of this lengthening is not well understood.
In a later blog post, we will link the physical changes in the heart caused by HCM to the obstruction to the blood flow and then to the symptoms of HCM (a signpost will be added then). The spatial arrangement of the sarcomeres in the muscle also becomes more disorganised. Whether this disorganization has any connection with the symptoms is unclear to me.
Estimates of how many people suffer from HCM vary and are still under investigation [1]. Studies that used echocardiography to observe the thickening of the cardiac muscles report the prevalance in the population to be 1:500. While studies that look for genetic markers of the disease report a higher prevalence of about 1:200. HCM is found on every continent and affects both genders equally. We will discuss methods of diagnosing HCM in a later post (and a signpost will be included here then).
In my opinion, the prevalence of this disease is important for HCM patients to understand, especially combined with the diversity in its form. For example, the Cambridgeshire UK, where I live, the population of the county is about 653,000 people (in 2019), out of which, 1 in 500 implies about 1300 people will suffer from HCM at some point in their life. Also given that symptoms can develop at any age between 10 and 80 years of age, not all 1300 people will be turn symptomatic in a given calendar year. Let us say that 1300 divided by 40, so about 32, will be diagnosed per year. These 32 get distributed between the various medical teams in the county (mostly GPs). This simple example shows that HCM is prevalent enough that quite a few people suffer from it, but not so prevalent that all GPs will have ample experience with it. This situation is exacerbated by the fact that the symptoms of HCM (fainting, breathlessness, dizziness) are shared by many other diseases. The specific numbers in the above examples may vary from region to region, but the general conclusion still holds. Therefore, it is critical that HCM be identified as a possible cause early and treated by a team of cardiac specialist who have experience with the disease.
Even though there is no known cure for HCM, the good news is as follows. A majority of the genetic carriers of this disease are not phenotypic, i.e. they carry the genetic mutation but not the muscular hypertrophy. Many of those who are phenotypic are asymptomatic, i.e. they live a normal life without any severe symptoms. For those who are symptomatic, even with severe symptoms, the outlook is quite good. With suitable treatment, we get to live a normal lifespan, and perhaps even with our symptoms relieved.
As mentioned earlier, HCM is genetic in origin and, therefore, it could be hereditary. Apparently, there are both familial and nonfamilial forms of HCM – the familial form is inherited and the nonfamilial form is not. The familial form could be inherited from either parent. Because the heriditary nature of HCM and its influence on the left ventricular septum, various modifiers may be attached to the disease name, e.g. Familial asymmetric septal hypertrophy, hereditary ventricular hypertrophy, or heritable hypertrophic cardiomyopathy. According to MedlinePlus, the symptoms of familial form of HCM are more severe than those of the nonfamilial form.
The significance of the genetic nature of HCM for a patient is that their family members are also susceptible to it, and may be undiagnosed. Once HCM is diagnosed in a person, it is prudent to screen their siblings, parents and children (older than 14 yrs of age) for HCM.
My story
As far as I know, HCM has not been detected in my family (both my parents have had cardiac examinations at various times), yet I am diagnosed with HCM and am symptomatic. My case contradicts the MedlinePlus article about nonfamilial HCM being asymptomatic, which has confused me about whether HCM genes will be propagated to my children. To be clear, in my case, no genetic testing was performed. I must investigate this more. Perhaps the connection between inheritance and symptoms is not absolute – stay tuned.
So far, we saw that HCM could be asymptomatic, or could be accompanied by heart ache, breathlessness, fatigue, near-fainting or fainting. However, these symptoms are associated with many heart diseases, so the symptoms cannot be used to diagnose HCM. In the case of HCM, the cause is the thickening of the cardiac muscle in the left ventricle, especially the septum. In the next post, we will discuss the origin of obstruction to the blood flow due to HCM, which is the link between the thickened heart muscle and the symptoms. It is going to be a long post with lots of technical details, because it is getting to the crux of the HCM matter. So stay tuned. And remember, HCM patients can have relief from their symptoms with suitable treatment and get to live a normal lifespan.
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