Stents, to put or not to put? This is a biomechanical question

As soon as you see the title, you will say: What? Doesn't the doctor have the final say on whether to put in a stent? How is it related to biomechanics?

Don't be anxious, don't be anxious! Stay calm, stay calm! Let me explain it to you slowly.

First, let’s take a look at what the bracket is used for.

1.What is the bracket used for?

I often hear some "fresh meat" in scientific research say in academic papers and reports that "as people's living standards improve, the incidence of cardiovascular diseases is getting higher and higher." This statement feels awkward! How come more and more people are getting sick as living standards improve?

In fact, the high incidence of cardiovascular disease is because people are living longer and longer, and degenerative diseases such as cardiovascular disease are inevitably increasing. Degenerative diseases generally refer to diseases caused by the deterioration of body functions as people age. The most fair thing in the world is that everyone will grow old and die. Therefore, aging and physical decline are the "way" of nature. The older you live, the higher the risk of cardiovascular disease.

So, to use the words of a "veteran" in scientific research, the previous sentence can be said as "As people's life expectancy increases, the incidence of cardiovascular diseases increases."

This is just a small prelude. Now let’s get to the point.

Cardiovascular disease is recognized as the "number one killer" threatening human life and health! Among them, ischemic heart disease is the most dangerous (Figure 1), and this trend is still intensifying and worsening.

Figure 1 Ranking of the top 10 causes of death worldwide

In medicine, ischemic heart disease refers to heart disease caused by coronary atherosclerosis that narrows or blocks the blood vessel lumen, or myocardial ischemia, hypoxia or necrosis due to coronary artery spasm. "Cut the head and take the tail", ischemic heart disease refers to coronary atherosclerotic heart disease, referred to as coronary heart disease.

( 1 ) What is coronary heart disease?

The shape of the heart is like an inverted, slightly flattened cone, or to put it more vividly, the heart is like a peach, about the size of a person's fist. The arteries located on the surface of the heart and almost surrounding the heart are the arteries that supply blood to the heart, and are called coronary arteries. If the heart is regarded as a head, it just fits the saying - "heart head". The coronary artery is like a crown, buckled on the "heart head", which is the origin of its name. The coronary artery originates from the root of the aorta and is divided into two branches, namely the left coronary artery (which is divided into the left coronary circumflex branch and the left anterior descending coronary artery) and the right coronary artery, which run on the surface of the heart (Figure 2).

Figure 2 Schematic diagram of the anatomical structure of the coronary artery

The coronary artery is the artery that provides blood perfusion to the heart, that is, the delivery pipeline for nutrients to the myocardium. The irrigation of the myocardium, a "heart field", requires two blood vessels, the left and right coronary arteries, to deliver nutrients smoothly. The coronary artery is such an important pipeline, but it is a common site for atherosclerosis. For the specific reasons, please refer to my WeChat public account article: "Thirty years in the east, thirty years in the west" and the blood circulation system .

Once coronary heart disease occurs, atherosclerotic plaques will block blood vessels, causing vascular stenosis. As a result, the myocardium perfused through the capillary network downstream of the coronary artery stenosis will not receive enough blood perfusion, causing myocardial ischemia, hypoxia, and necrosis (i.e., myocardial infarction, Figure 3). The corresponding myocardium loses its contraction and relaxation functions, and the heart beats weakly, leading to serious consequences such as heart failure and sudden death!

Figure 3 Myocardial infarction caused by coronary heart disease

This is like drip irrigation in farmland. If the valve at the water inlet is turned down, the water flow will decrease, the irrigation area downstream will be short of water, and the seedlings will wither and die (Figure 4).

Figure 4 Schematic diagram of drip irrigation in farmland

It can be seen that coronary heart disease is really fatal! What is more terrible is that coronary heart disease often occurs quietly; many patients do not feel obvious symptoms, but once a heart attack occurs, they die before they can be sent to the hospital! - I left quietly, just as you came quietly; in the blink of an eye, I left without taking any money...

( 2 ) What is the bracket used for?

When the blood vessels are narrowed, it is like the river bank collapsing and the dam breaking, blocking the river.

What should we do if the river is blocked? In engineering, grid structures are often used to build river bank protection, strengthen the river bank, and keep the river unobstructed (Figure 5).

Figure 5: Riverbank slope protection after river collapse

So can the methods used in engineering be applied to the treatment of vascular stenosis and blockage?

The answer is yes. Vascular stents use engineering technology to reshape narrow blood vessels.

Vascular stent refers to the placement of an internal stent in the stenotic segment of a blood vessel on the basis of luminal balloon dilatation to achieve the purpose of supporting the stenotic and occluded segment of the vessel, reducing vascular elastic retraction and reshaping, and maintaining smooth blood flow in the lumen (Figure 6).

Figure 6 Stent release process

Vascular stent intervention is a minimally invasive surgery. It does not require "opening the stomach" like traditional surgical operations. Instead, a "needle eye" is made in the superficial artery of the skin, and then the stent is sent up along the blood vessel to the site of coronary artery disease. Therefore, it is called percutaneous coronary intervention (PCI). In layman's terms, it means placing a stent .

The human body's blood vessels are the natural channels leading to the heart, and interventional surgery is performed by going "upstream" along the blood vessels into the heart.

The most common puncture sites are the radial artery on the wrist or the femoral artery on the inner thigh (Figure 7). This needle entry site is the only surface wound in this operation.

Figure 7 Femoral artery puncture

After selecting the puncture site, the guide wire, catheter, and sheath are inserted along the puncture needle to expand the blood vessel into a channel. The metal stent is wrapped on the surface of a balloon and is compressed into a very thin shape. Along the channel, the doctor pushes the stent and balloon to the blood vessel at the lesion site; inflates the balloon with a pressure of about 10 times the atmospheric pressure to expand the metal stent; then the balloon is depressurized and withdrawn, leaving the stent in the blood vessel (Figure 8).

Figure 8 Stent intervention

Once placed, this stent will maintain this shape and permanently support the stenosis. Just like the slope protection of a river channel, the vascular stent strengthens the river channel of the blood vessel and expands the vascular cavity to make the blood flow smooth, thereby restoring the blood perfusion of the downstream myocardium. The expansion of the stenotic blood vessel is like the opening of the water inlet valve of the irrigation system in Figure 4, so that the downstream irrigation area is fully irrigated.

In fact, the above process is often a race against time. The patient has already suffered a myocardial infarction and is in a critical condition. He is sent to the emergency room. Whether the blocked blood vessel can be opened as quickly as possible is the key to saving life and health. Stent intervention has saved countless lives from the brink of death .

The advantages of coronary stent intervention are less trauma and faster recovery, and it is suitable for patients with coronary heart disease with relatively simple lesions, as well as emergency treatment for patients with acute myocardial infarction. The disadvantages of coronary stent intervention are high risk of recurrent stenosis, and relatively limited treatment effect for patients with severe coronary heart disease and complex lesions.

In any case, coronary stent intervention has been widely accepted by doctors and patients around the world due to its obvious advantages . The patient with the most stents placed in his body is an American patient, who has a total of 67 stents placed and is known as the "Iron Man" in the field of stent intervention.

Since stent interventional treatment has obvious advantages and is widely popular, why are there always some doubts in various media and rumors? Should we put in a stent or not?

2. Stents, to put them in or not? This is a biomechanical question

Here, we will not analyze subjective factors such as the psychological and cognitive reactions of doctors and patients to this issue. We will only analyze the essential issues behind it from a scientific perspective.

The blood vessels are narrowed. Should a stent be placed?

This question has expert consensus and a standard answer.

Coronary angiography and intravascular ultrasound (IVUS) have always been considered the "gold standard" for diagnosing coronary heart disease, but these two methods can only perform imaging evaluation of the degree of stenosis, and it is unknown whether the stenosis affects distal blood flow (functional evaluation). In other words, using medical imaging to evaluate the severity of vascular stenosis, that is, using the vascular stenosis rate to evaluate coronary stenosis, is a morphological evaluation method . To what extent does the stenosis affect the blood perfusion of the downstream myocardium and how severe the myocardial ischemia is, this is a functional evaluation method .

The degree of vascular stenosis can be observed using angiographic data. Lesions with a diameter stenosis of 50% are usually considered to require vascular reconstruction, that is, stent placement. However, a large number of studies have shown that when the angiographic stenosis rate is 50% to 70%, 1/3 of ischemic patients will be ignored and no stents will be placed, delaying treatment and causing adverse events; when the angiographic stenosis rate is greater than 70%, 1/5 of patients without ischemia will be stented based solely on the angiographic diagnosis results, which is overtreatment and a waste of medical resources. This shows that relying solely on morphological indicators will cause many misdiagnoses .

Why is this so? This is mainly related to the factors that affect myocardial ischemia. Whether the myocardium is ischemic is not only related to the degree of vascular stenosis, but also to many factors such as myocardial remodeling, perfusion area, multiple branches/multiple lesions, myocardial blood flow, etc. For example, if the downstream myocardium of a lesion with a large stenosis rate is not ischemic, it may be because of the existence of collateral circulation, which compensates for the low perfusion of the stenotic lesion (that is, other blood vessels next to the stenotic lesion provide blood perfusion to the myocardium downstream of the stenosis); if the downstream myocardium of a lesion with a small stenosis is ischemic, it may be caused by microcirculation disorders of the myocardial tissue. Therefore, judging only by the morphological indicators of the stenosis rate cannot determine whether to place a stent or not .

Obviously, just from an intuitive point of view, the functional evaluation method should be more objective .

Coronary artery blood flow reserve fraction (FFR) has become a recognized indicator for the functional evaluation of coronary artery stenosis and is currently the " gold standard " for evaluating myocardial ischemia.

( 1 ) What is FFR ?

FFR refers to the ratio of the maximum blood flow Qsmax that can be obtained in the myocardial area supplied by the coronary artery when there is a stenosis lesion in the coronary artery to the maximum blood flow QNmax that can be obtained in the same area under normal circumstances without stenosis: FFR=Qsmax/QNmax.

This definition is rigorous in theory, but it is not feasible in practice. It is impossible for a person's coronary artery to be both diseased and stenotic and normal and non-stenotic, so the two flow rates Qsmax and QNmax cannot be measured at the same time.

In clinical practice, the actual FFR measurement and calculation method used is the ratio of the pressure Pd downstream of the coronary artery stenosis to the pressure Pa upstream of the stenosis: FFR = Pd/Pa. In this way, it is easy to use the pressure guide wire to measure the two pressures upstream and downstream of the stenosis lesion respectively (Figure 9). The FFR value obtained in this way is approximately equal to the FFR value defined above (the specific derivation process refers to Ohm's law in circuit knowledge, which will not be explained here). At the same time, this technology is simple and easy to operate, and has high repeatability. Therefore, it is reliable, objective and accurate.

Figure 9 Pressure guidewire measuring pressure upstream and downstream of stenosis

For coronary arteries without stenotic lesions, the theoretical value of FFR is 1. For coronary arteries with stenotic lesions, all lesions with FFR<0.75 can induce myocardial ischemia; while for lesions with FFR>0.80, more than 90% will not induce myocardial ischemia. Stent intervention for lesions with FFR<0.75 can significantly improve the patient's long-term prognosis; while lesions with FFR≥0.75 cannot benefit from stent intervention. Generally, FFR=0.75~0.8 is selected as the critical value. If FFR is larger than the critical value (>0.8), it indicates that the stenotic lesion here has no practical significance, which is an indication for drug treatment and no stent placement is required; if FFR is smaller than the critical value (<0.75), it indicates that the lesion needs to be treated, and revascularization and stent placement are appropriate; while FFR=0.75~0.8 is a gray area, and doctors can decide whether to perform revascularization based on the patient's clinical condition and the importance of vascular blood supply. This is the expert consensus and "gold standard" of FFR, a functional "myocardial ischemia" evaluation indicator .

If we say that whether to place a stent is a biomechanical issue because FFR is calculated from the ratio of two pressures, that would be too simple!

( 2 ) Should we put in a stent or not? Why is it a biomechanical question?

According to the calculation method of FFR, we further analyze the physical meaning of FFR. As shown in Figure 10, following Ohm's law in circuit knowledge, the calculation of FFR can be expressed as Rm/(Rm+Rs). In this formula, Rm represents the microcirculatory resistance of the perfused myocardium downstream of the stenosis; Rs represents the blood flow resistance of the stenotic part; then Rm+Rs represents the total resistance.

Figure 10 The physical meaning deduction process of FFR

FFR=Rm/(Rm+Rs) is to calculate the proportion of microcirculatory resistance to total resistance; in physical essence, it is to compare the relative size of narrow flow resistance and microcirculatory resistance . These two resistances are related to blood rheology and hemodynamics from a macroscopic perspective; from a microscopic perspective, they are related to convection, diffusion, osmotic pressure, and cell molecular biomechanics . If we go back to the source and trace the origin, it is ultimately related to the "two core issues of biomechanics": constitutive relations and stress-growth relations. I will stop here, and those who are interested can refer to my WeChat public account article **"**Two Core Issues in Biomechanics". It can be seen that FFR is indeed an out-and-out biomechanical problem.

If FFR<0.75, it means that the blood flow resistance Rs in the stenotic part contributes more to downstream myocardial ischemia. At this time, there will be a big difference whether to place a stent to treat the stenosis, so the expert consensus is to "place a stent"; because after placing the stent, the blood flow resistance Rs will be significantly reduced, and thus the FFR can be significantly improved, which means that the condition of myocardial ischemia will be significantly improved.

When FFR=0.8, microcirculation resistance accounts for 80% of the total resistance, stenosis resistance accounts for 20% of the total resistance, and Rs=0.25Rm. In this case, the total resistance Rs+Rm=1.25Rm. If the stenosis diameter expands by 1 time after stent placement, then according to Poisueille's law, the flow resistance is inversely proportional to the fourth power of the tube diameter. At this time, the stenosis resistance is Rs=0.25Rm/16=0.015625Rm. In this case, the total resistance Rs+Rm=1.015625Rm, and the rate of change before and after stent placement is 18.75%.

When FFR=0.6, microcirculation resistance accounts for 60% of the total resistance, stenosis resistance accounts for 40% of the total resistance, and Rs=0.67Rm. In this case, the total resistance Rs+Rm=1.67Rm. If the stenosis diameter expands by 1 time after stent placement, then the stenosis resistance is Rs=0.67Rm/16=0.041875Rm. In this case, the total resistance Rs+Rm=1.041875Rm, and the change rate before and after stent placement is 37.61%. It is about twice the above FFR=0.8, and the improvement effect is obvious.

If FFR>0.8, it means that the blood flow resistance Rs in the stenotic part does not contribute much to downstream myocardial ischemia. At this time, it does not make much difference whether or not to place a stent to treat the stenosis, so the expert consensus is "not to place a stent"; because after the stent is placed, even if the blood flow resistance Rs is significantly reduced, it will not lead to a significant increase in FFR.

Let's explain the reason by comparing the relative size of stenotic flow resistance and microcirculatory resistance. If myocardial ischemia is caused by stenotic flow resistance, then it means that stenotic flow resistance has a greater impact on myocardial ischemia; at this time, stent placement is needed to treat stenosis. If myocardial ischemia is not caused by stenotic flow resistance, but by microcirculatory resistance, then it means that it is irrelevant whether to place a stent, and stent placement will not solve the problem of microcirculatory resistance. In other words, the "key" to unlock the "lock" of myocardial ischemia should be microcirculation rather than stenotic lesions. Otherwise, it would be putting the cart before the horse, trying to catch fish in a tree, treating the symptoms instead of the root cause, and enduring hardships without getting any thanks!

If we use the drip irrigation system in Figure 4 as an example, it will be easier to understand. If the drip irrigation system fails because the valve is not open, then opening the valve will obviously solve the problem; if the problem is in the microcirculation system downstream of the valve, then opening the valve will not help. This is the criterion for whether the valve needs to be further opened (whether to place the bracket).

After all this talk, you should understand why we say “Stent, to put it in or not? This is a biomechanical question.” This is directly related to where the resistance that causes myocardial ischemia comes from.

So, the question immediately arises: Why do many stent intervention surgeries not measure FFR or perform functional evaluation, but still use traditional angiographic morphological evaluation?

Data shows that the global application rate of FFR is about 6% to 8%. In developed countries, FFR is already widely used. The application rate in the UK is 18%, and the application rate in the United States is 30.8%. As of now, the application rate of FFR in China is less than 1%. The application rate of FFR in China is not high. On the one hand, it is because of inadequate market education and high difficulty in operation; on the other hand, the reason is that the FFR pressure guidewire is monopolized by two giant overseas companies and the price is very expensive. The terminal price in hospitals is roughly around 10,000 to 20,000 yuan, which is too expensive! Of course, there are many other complex reasons, including the subjective wishes of doctors and patients, and the emergency rescue time for patients with critical acute myocardial infarction.

3. Summary

Stent placement or not is a biomechanical question. From a theoretical perspective, whether to place a stent requires evaluating the relative size of stenotic flow resistance and microcirculatory resistance. From a clinical perspective, whether to place a stent requires predicting the therapeutic effect after the stent is placed. The basic knowledge of biomechanics and the practical application of clinical medicine complement each other. Our common goal is to provide precise treatment for the benefit of mankind.

For more popular science articles about biomechanics around us, please follow my WeChat public account “Medical Biomechanics” (Medical_biomechanics).

Stents, to put or not to put? This is a biomechanical question