My encounter with hypertrophic obstructive cardiomyopathy

Blog 4 Apr 28, 2024
Hypertrophic Obstructive Cardiomyopathy

How could the thickening (and stiffening) of the cardiac muscle possibly lead to the life-changing symptoms of HOCM? The link between HCM and the symptoms is the reduction of the heart’s ability to pump blood. The blood as it flows from the left ventricle to the aorta through the left ventricular outflow tract (LVOT) experiences added resistance or obstruction. HCM with this obstruction is called hypertrophic obstructive cardiomyopathy (HOCM). This link between HCM and the obstruction to blood flow is the topic of this article.

About 70% [1] of the people suffering from HCM at some point or another suffer from HOCM. This obstruction is thought to be a natural progression of the disease.

There are many mechanisms that cause the blood flow obstruction. These include the following three, which we will discuss in somewhat detail: (i) the reduction in the left ventricular volume, (ii) the increased resistance to the flow because of the narrowing of the LVOT, and (iii) an interference of the mitral valve leaflet with the blood flowing through the LVOT to the aorta. Of these, the interference of the mitral valve leaflet is an instance of fluid-structure interaction and the most potent in obstructing the flow.

If you or a loved one is suffering from HOCM, understanding the origin of the blood flow obstruction is central to managing and treating this disease. The obstruction is at the root of diagnosis, medical treatment, surgical intervention, lifestyle changes and psychological effects. Therefore, it is worthwhile to spend some time to study the cause of the blood flow obstruction – this article is longer than others for that reason.

4.1 Recap from Mar 31, 2024

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)
Figure 4.1: Anatomy of (a) a healthy human heart and (b) one suffering from HOCM, reproduced from Fig. 2.1. (a) Labels: 1. Superior vena cava, 2. pulmonary artery, 3. pulmonary vein, 4. mitral valve, 5. aortic valve, 6. left ventricle, 7. right ventricle, 8. left atrium, 9. right atrium, 10. aorta, 11. pulmonary valve, 12. tricuspid valve, 13. inferior vena cava, 14. septum, 15 left ventricular outflow tract, 16. chordae tendinae. (b) The walls of the left ventricle including the septum thicken due to HOCM, which reduces the volume of the left ventricle. Any non-uniform thickening of the septum also possibly decreases the width of the left ventricular outflow tract. (Image credit: wikimedia. Contribution made by numerous artists.)

Ensure that you remember the left ventricle, the mitral valve, the septum, the left ventricular outflow tract (LVOT), the aorta and the aortic valve. Also revisit, the post from Apr 07, 2024 for an introduction to HCM.

Now let us turn to the three causes of blood flow obstruction.

4.2 Left ventricular volume

The thickening of the left ventricular wall caused by HCM reduces the volume available for the blood in the left ventricle. This is important especially during diastole because the chamber can at most pump during systole the volume of blood it contains immediately after diastole. In other words, if the chamber does not have space for the blood the fill when it expands, then only a small amount of blood can be pumped in each cardiac cycle. This reduces the cardiac stroke volume, i.e. the amount of blood the left ventricle pumps in one cardiac cycle.

The stiffening of the cardiac muscle plays a central role here. Remember that during diastole, the inflated arteries drain there blood to the heart chambers (see 2.2 for a reminder). Because the heart muscles are now stiffer, they do not expand so easily to let the blood fill the chamber, especially the left ventricle. This further reduces the amount of blood available for the stroke volume.

(When we discuss medical treatment, we will see how certain drugs try to improve the diastolic filling of the left ventricle.)

My story

My case exhibited a septum thickened to about 20 mm. The average healthy septum thickness is 6-10 mm. The outer wall of the left ventricle was also thickened, but not as much. This had caused the reduction in the capacity to hold fluid in this chamber. At the end of systole, when the left ventricle contracts, the septum actually touched the outer wall.

Also, I am embarrased to admit that in the beginning I thought the thickening of the heart walls (hypertrophy) made the heart stronger and more capable of pumping blood. I live and learn.

4.3 Narrowing of the LVOT

The LVOT shape can be affected, especially narrowed, depending on the exact shape of the thickened septum. In this case, the blood has to squeeze through a narrower space between the mitral valve and the septum to the aorta. The narrowed space thus causes an increase in resistance to the flow of blood from the left ventricle to the aorta. The obstruction to the blood flow in the LVOT is termed as left ventricular outflow tract obstruction (LVOTO). The LVOTO is quantitatively defined as the maximum pressure difference between the left ventricle and the aorta during a cardiac cycle. This pressure is usually reported in terms of milimeters of mercury, or mm-Hg, just as blood pressure is reported in these units.

Technical details[Uncaptioned image]

Although this is a pressure difference, in medical terminology it is called as the “LVOT gradient”. Strictly, it can only be measured by inserting probes into the two location, perhaps during a surgery or using a catheter. However, a proxy for it is estimated using the echocardiograph, which provides an approximate blood flow speed in the LVOT.

The echocardiograph can be used in the doppler mode to measure the speed of blood flow in different regions of the heart. Suppose the echocardiogram measures a blood flow speed of V1 in the narrowest part of LVOT. (The narrowest part will be where the largest V1 is measured.) Then the estimate of the LVOT gradient is made using the expression

Δ⁢pLVOT=12⁢ρ⁢V12, (4.1)

where ρ is the density of blood. Using the value in SI units ρ=1060 kg/m3, measuring V1 in m/s, and converting the result to mm-Hg yields the working expression

Δ⁢pLVOT⁢(in mm-Hg)=4⁢V12(where V1 is in m/s). (4.2)

(Students of dimensional analysis will note this non-standard practice of committing to a system of units in a mathematical expression. This equation violates dimensional consistency, but such is the clinical practice. Such is life.)

Now consider the assumptions that underlie (4.1). It is based on the Bernoulli equation, so an inviscid flow approximation is inherent. The Reynolds number for the flow is in the 100-1000 range, so this is not such a bad assumption. The flow in the left ventricle leading upto the LVOT must be laminar, again not a bad assumption. The unsteady inertial term is assumed to be negligible. This is also not such a bad assumption because at the peak flow during the cardiac cycle, the rate of change of velocity is nearly zero. Finally, the velocity in the left ventricle (say V0 at the location where the left ventricle label 6 is located) is assumed to be negligible compared to V1. If it were not negligible, the right hand side of (4.1) would be of the form

12⁢ρ⁢(V12−V02), (4.3)

but because V0 is negligible, the second term can be neglected compared to V12. This approximation gets better in the case of a narrow LVOT, in which case, due to conservation of mass, V1 increases relative to V0.

The final point is that, while the LVOT gradient is defined between the left ventricle and the aorta, the proxy uses the narrowest part of the LVOT for its estimate. The thought behind doing so is that the boundary layer of the blood flow near the septum must separate at the narrowest LVOT point and thus the pressure does not recover even when the outflow tract widens. This too is not unreasonable, especially if used in conjunction with the symptoms the patient report. Other signatures of boundary layer separation, e.g. turbulence in the flow, may also help evaluate this possibility.

In this manner, it is remarkable that the pressure difference in such a complex flow situation can be approximated by such a simple expression.

The LVOT gradient also changes with exercise, because the heart pumps harder during exercise. Therefore, two values of the LVOT gradient are used clinically – the resting LVOT gradient and the provoked (by exercise) LVOT gradient. In the healthy case, the resting LVOT gradient is less than 10 mm-Hg, so the corresponding LVOT speed V1 is less than about 1.6 m/s. Either a resting LVOT gradient a 30 mm-Hg or a provoked value of 50 mm-Hg is clinically considered to be the threshold for HOCM. A resting LVOT gradient of 50 mm-Hg is considered severe.

My story

In my case, echocardiography showed a resting LVOT gradient of 64 mm-Hg in Oct 2022. By Nov 2023, the disease had progressed so much that my resting LVOT gradient was 123 mm-Hg. This would correspond to a flow speed in the LVOT of 6.5 m/s, if the simple picture described in the technical box above holds. However, the picture is complicated by the interference from the mitral valve leaflet. This is technically the most interesting part of this disease for fluid dynamicists. Yes, such a large obstruction to blood flow through the LVOT is dangerous, but I was thrilled by the mechanics.

For a moment, let us ignore the influence of the leaflet. Then a blood flow speed of 6.5 m/s (compared to a healthy estimate of 1.6 m/s) implies a 4-fold narrowing of LVOT. If the healthy LVOT is 1-2 cm in width, then the above simple picture would imply that in my case the width is reduced to 2-5 mm. Such was the level of the obstruction.

4.4 Interference of the mitral valve leaflet

The short version of the story is that the anterior mitral valve leaflet (see Fig. 4.2), which is open at the end of diastole, is too close to the LVOT. As the systolic phase begins, it fails to move towards closure of the mitral valve, and lingers in the LVOT area, thereby increasing the resistance to the blood flow towards the aorta. Below is a more detailed explanation, which I hope is accessible to everyone.

It is first crucial to understand some of the anatomy of the left ventricle. The elements that interest us are shown in Fig. 4.2. Keep in mind that this is an incomplete description because a complete one will be too long. The mitral valve is the central element here; it separates the left atrium and the left ventricle. The valve leaflets are devoid of any muscles themselves and is made of thin, pliable, elastic tissue. The leaflet region is generally divided into two: the anterior leaflet (label 17) and the posterior leaflet (label 18), as shown in Fig. 4.2. The website by Mt Sinai Hospital on mitral valve leaflets shows a three-dimensional reconstruction that some may find helpful to understand the anatomy.

Next, it is important to understand the relative position of the mitral valve, the aortic opening and the septum. The aortic opening, where the aortic valve is situated, is located between the anterior leaflet of the mitral valve and the septum. Therefore, when the mitral valve is open (e.g. at the end of diastole, when the aortic valve is closed), the anterior leaflet is close to the LVOT, if not inside it.

Figure 4.2: Details of the left half of the heart, especially the mitral valve. (a) Healthy heart at the end of diastole, when the left ventricle is done being filled with blood. The mitral valve at this instance is open. (b) Healthy heart at the middle of systole, i.e. when the left ventricle is pumping blood to the aorta. At this instance, the leaflets of the mitral valve are closed preventing any blood to flow back to the left atrium. (c) Heart with a hypertrophic septum at the end of diastole. The anterior mitral valve leaflet now overlaps with the LVOT. As the left ventricle enters systole, the blood will be pushed to flow, and in this case the anterior leaflet of the mitral valve will be pushed further into the LVOT. Labels are same as in Figs. 2.1 and 3.1 as follows: 4. mitral valve, 5. aortic valve, 6. left ventricle, 8. left atrium, 10. aorta, 15. left ventricular outflow tract (LVOT), 16.chordae tendineae, 17. anterior mitral valve leaflet, 18. posterior mitral valve leaflet, 19. papillary muscles.

In a healthy heart, the mitral valve starts to close and the aortic valve begins to open as systole begin. Let us imagine what happens at that moment. As the left ventricle starts contraction, the blood flows towards the aortic opening and the mitral valve. The mitral valve leaflets are so light and floppy that they simply move with the flow (at least until the chordae tendineae tense up by the action of papillary muscles). In a healthy heart, the blood around the anterior leaflet moves towards the mitral valve. The blood in the LVOT stays lear of the mitral valve leaflet and moves towards the aortic valve. This causes the two leaflets of the mitral valve to converge and the mitral valve to close, while the aortic valve opens. When that happens, the tension in the papillary muscles and the chordae tendineae builds up and the mitral valve leaflets start resisting the flow. This resistance causes the blood flow pattern to change in the left ventricle, and blood starts flowing only towards the aorta. This is the mechanism of a healthy systole.

In HOCM, the thickened septum implies less space between the septum, the aortic opening and the anterior mitral valve leaflet. The anterior leaflet is also longer compared to a healthy heart. At begin systole, as the blood starts to be pushed out of the left ventricle, at least a part of the anterior leaflet is pushed into the LVOT and perhaps towards the aortic valve. This part of the leaflet blocks the path of blood towards the aorta. Consequently, the resistance to blood flow towards the aorta increases (but hopefully some blood flow is sustained, which continues to tug on the anterior leaflet keeping it near the aortic opening). This mechanism is called the Systolic Anterior Movement (SAM) of the mitral valve leaflet. The failure of the mitral leaflets to close causes the blood in the left ventricle to regurgitate (i.e. flow back) into the left atrium. This process is called mitral regurgitation (MR). With exercise (i.e. provocation), the symptoms get worse because the mechanism underlying SAM becomes more and more effective. SAM of the mitral valve is usually associated with symptoms such as shortness of breath, dizziness and lightness of head, mainly because the blood flow to the body is much reduced. When the body detects reduced blood flow, it directs the heart to beat faster, which can cause heartache.

One consequence of mitral regurgitation is that the left atrium is subject to the much higher systolic pressures. In a healthy heart, the mitral valve closes and isolates the left atrium from the high pressures in the ventricle that build during systole. But if SAM causes the mitral valve to remain open during systole, then not only does the blood flow back to the left atrium, but the high pressure also causes the left atrium to inflate like a baloon. This pressurization of the left atrium causes its size to gradually grow, and lead to a condition called left atrial dilation, or left atrial enlargement. To the extent I understand, left atrial enlargement is nothing to worry by itself but is a symptom of somethign else wrong with the heart (in this case, HOCM and SAM of the miltral leaflet).

My story

In my case, SAM of the mitral valve leaflet and mitral regurgitation was detected early using echocardiography. SAM is a better explanation for my aggravated LVOT gradient of 123 mm-Hg. My left atrium was dilated to a diameter of 60 mm. The average size of the left atrium in men is expected to be about 40 mm. Left atrial dimaeters in the range 41-46 mm are considered mildly dilated, 47-51 mm are moderlately dilated and any size above 51 mm is severely dilated. (Women’s left atrial diameter is on average smaller than men’s.)

Technical details[Uncaptioned image]

The mechanism behind SAM currently accepted was presented by Jiang et al in 1987 [2]. Prior to 1987, the prevalent theory for SAM invoked the flow in the narrowed LVOT towards the aorta. Because of the Venturi effect, the fluid pressure in this narrow region is expected to be low, and therefore pull the leaflet towards the septum. Intellectually, the Venturi-effect-based mechanism has a certain seductive appeal to the fluid dynamical mind. But it is best to avoid this temptation in favour of facts. There were many holes in this Venturi-effect-based-hypothesis, mainly that the beginning of SAM was observed way before any pressure difference had a chance to build up at begin systole. This mechanism was questioned by Jiang et al, who proposed a drag based mechanism, which is in its essence presented above. Jiang et al instead argued that it is not the Venturi effect but fluid dynamical drag forces that causes the mitral valve leaflet to move as it does during SAM.

The critical factor to keep in mind is that the mitral valve leaflet is light and floppy. Therefore, mechanically, like a flag it does not have the strength to resist the flow to bending (but it can resist extension). The leaflet can neither resist drag nor lift. Thus, the leaflet must simply follow the flow, unless the chordae tendineae tense up and provide some strength to the leaflet. (In an unrelated paper, I had made a similar argument for fish fins, which are also thin, light and floppy.) In other words, the valve leaflet operates in a regime of such weak elasticity that its velocity is slaved to the velocity of the surrounding fluid. If it were not so then the fluid dynamic forces (whether lift or drag) could not be balanced by any elastic forces within the leaflet. In this manner, the direction of the flow of the blood surrounding the leaflet determines the leaflet motion.

In a healthy left ventricle, the flow that is set up at the beginning of systole is such that the anterioir leaflet moves posteriorly, the posterior leaflet moves anteriorly, and this drives the valve to closure. In HOCM, some of the blood surrounding the anterior leaflet moves towards the aorta and drags the leaflet anteriorly towards the aorta. The leaflet stabilizes if it collides with the septum, the aortic opening, or the chordae tendineae tense to provide some resistance. The floppy nature of the leaflet changes when it is stretched by the papillary muscles through the chordae tendineae. When this happens, the leaflet starts behaving like the surface of a trampoline instead of flapping flag. The surface of the leaflet can then act as a boundary of the LVOT. It is at this instance that the Venturi effect can also come into play, and pull the outstretched leaflet towards the septum. In this way (and in my educated opinion), the Venturi theory should not be completely discarded but applied in the correct circumstance.

4.5 Conclusion

HOCM is much more complicated than I can do justice in this simple presentation. In this chapter, we saw three different mechanisms for reduction in the ability of a heart suffering from HOCM to pump blood. The first is the reduced volume of the left ventricle. The second is the reduced width of the left ventricular outflow tract, or LVOT, to the aorta. And the third is the interference of the mitral valve leaflet, especially it’s SAM, with the blood flow in the LVOT. Mitral regurgitation and dilated left atrium are hallmarks of SAM.