Burt Humburg posted Entry 2560 on September 3, 2006 07:30 AM.
Trackback URL: http://www.pandasthumb.org/cgi-bin/mt/mt-tb.fcgi/2554

We here at the Thumb are taking advantage of the long weekend to rest and recuperate: please don’t expect another review to be posted before Tuesday.

In the meantime, I’ve posted a review of modern cardiological techniques today. The backstory is that a few of the contributors to the Panda’s Thumb have, in their time, suffered chest pain or heart attacks. A question was recently asked about the difference between ballooning and stenting and, in an email of response, I ended up summarizing the history of invasive cardiology and thrombolytics in a brief essay. Below the fold, I post a version of that essay with hyperlinks to web resources where you can learn more about cardiology.

Best wishes for a great weekend from The Panda’s Thumb crew!

In the late-70’s, the pathophysiology of heart attacks was elucidated. Previously, it was thought that the vessels supplying the heart with oxygen, the coronary vessels, became progressively narrowed by fat deposition, a term known as atherosclerosis. This is a fairly straightforward conclusion, since autopsies of people with heart disease and angina (defined later in this paragraph) often show fatty buildup on the walls of arteries; it makes sense that as such buildups accumulate, the flow through the lumen of the vessel would reduce. Eventually, the amount of oxygen that the heart would need to function would become more than the amount of oxygen the blood flowing through that narrowed lumen could provide. On these occasions, victims would note chest pain, especially upon exertion. Such chest pain is known as angina.

This model or understanding of heart disease worked decently well for typical angina, but it did not explain nor did it predict those who died suddenly of coronary disease. In medical school, I heard an anecdote of a patient who was seen by a cardiologist due to a strong family history of coronary disease. For some reason, he underwent cardiac catheterization, in which contrast is injected into the coronary arteries, mapping any narrowing within the artery. During this procedure, he was found to have essentially full flow. Soon after his procedure, within a week or two, he suffered a fatal heart attack. Upon autopsy, the luman had completely occluded.

What was interesting about these kinds of cases, though, was that the lumens of these coronary vessels weren’t occluded by fat depostion from the walls of the arteries. Rather, they were occluded by clot. Unlike the old model, in which fat buildup on the walls of the vessels slowly but progressively built up until the lumen was occluded and flow was reduced, this was a situation in which a complete, flow-limiting clot formed within a very short period of time, probably within minutes to hours.

For this reason, cardiologists abandoned the “progressive fat deposition” model of acute coronary syndromes (in distinction to typical angina) and have replaced it with a new model of coronary artery disease. This new model or understanding involves the sudden buildup of clot in the coronary artery, which blocks flow downstream in that artery. This new model became the dominant explanation for sudden onset of chest pain. This model is explained at the Plavix website, under the section of Heart-Related Chest Pain, Heart Attack, Stroke and Poor Leg Circulation. But here’s the gist of it:

People who smoke or have strong family histories of cardiac disease or have diabetes or high cholesterol (see the American Heart Association’s website for a full list of known cardiac risk factors) tend to accumulate fat depositions on the walls of not just the coronary arteries, but all arteries in the body. (It is for this reason that the number one cause of death in people undergoing an operation for carotid disease is heart attack: carotids are arteries and if you’ve got disease in them, you’ll almost always have disease in the vessels of your heart.) These depositions of fat do not merely remain depositions of fat, but change over time (due to reasons that this article won’t review, but interested readers could review at Pathogenesis of Lesion Initiation). This changed fat is extremely thrombogenic - which is to say that a clot forms when normal blood is exposed to it. Thankfully, under normal circumstances, the endothelium of the vessel - the absolutely innermost layer of cells within a vessel - prevents this clot from forming. However, as the lumen of the vessel narrows, the turbulence in the flow increases. Eventually a portion of the endothelialized fat chips off, leaving the highly-thrombogenic changed lipids underneath. A clot forms, which reduces the flow of blood downstream in a very short time period; the patient feels sudden chest pain and the other effects of reduced coronary artery flow, including possibly life-threatening dysrhythmias or death.

From a historical perspective, this change in understanding of the pathophysiology of heart attacks caused a sea change in the way heart attacks were managed. Streptokinase had been known and well described since the 1930s - and lovers of history of science should not miss this biography of William Smith Tillett, who in addition to streptokinase also described C-reactive protein. Streptokinase is a drug that dissolves recently-formed clots, but few if any people used it for heart attacks. (Why would they if coronary disease was solely the result of lipid deposition?) But in the late 70’s, history saw a surge of articles identifying agents that dissolve these coronary clots - thrombolytics - with improved outcomes. Today, there are agents that break up clots that aren’t purified from bacteria and interested readers are invited to Google the search term “Tissue Plasminogen Activator” to learn more about them.

So that covers thrombolytics as a treatment for heart attacks, but most heart attacks today are treated with cardiac catheterization, at least if there’s a hospital nearby that performs them. Therefore, let’s back up a bit and talk about the advent of catheterizations. Even as of the late 70s, cardiac catheterizations were being attempted. It was already possible to snake a sterile catheter with a balloon at the end of it into a coronary artery, dilate the balloon to several atmospheres of pressure, and deflating the balloon which restored coronary flow. This procedure today is known as POBA, or “plain old balloon angioplasty.” (Seriously.)

However, POBA wasn’t all that successful. In many, perhaps even most, of the cases, the clot would return once again, sometimes within minutes. Keep in mind that most cardiologists were working off the model of progressive stenosis; thus, the intention was to develop techniques to keep the walls apart and stents were developed. A stent, pictured here, is a device that is threaded into a catheter with a balloon inside of it; when expanded or “deployed” by the dilation of the balloon, it becomes rigid and keeps the walls of the vessel held apart. This procedure is more than just angioplasty; such patients have now been “stented.”

But under the new model of heart disease described above, the reasons for that rapid reduction in flow are clear: by dilating the artery, the balloon can also disrupt the vessel wall, further exposing the blood to the thrombogenic fats and membranes underneath. In the course of time, it also became clear, as data from autopsies for people who lived for years with stents became available, that the endothelium that protected the thrombogenic intima from the blood eventually grew through the stent walls. This was a mixed blessing. On the one hand, the “endothelialization” of a stent makes it so that the stent, and especially the disrupted vessel wall under it, was no longer thrombogenic. However, in growing through the stent, the vessel lumen was once again narrowed, requiring procedures like a re-stenting to treat. Sometimes this growth was exuberant, such that restenting was needed within months.

A balance was needed whereby a stent could be deployed, clots that arise from the disruption of the artery wall in question could be prevented, and restenosis of the vessel could be delayed as long as possible. Many techniques were tried, such as using radiation to kill the endothelial cells nearest the clot. Nowadays, the stents cardiologists use are drug-eluting stents. In other words, the metal is encoated with medicines that poison the ability of the endothelium to grow through the stent. People who have such stents are given medicines like Plavix or aspirin in order to prevent clots for longer than they would need for simple bare-metal stents. Despite the use of drug eluting stents, endothelialization eventually takes place and even patients with drug-eluting stents only have to stay on medicines like Plavix or aspirin for at most a few months. (If there are other reasons to continue the medicine, they will remain on them longer, of course.)

With these and other advances, patients who suffer heart attacks do much better, especially if they do not hesitate to call 9-11 if they experience any of the warning symptoms. It remains only to say that most patients who die from heart attacks before they reach the hospital die because of fatal malignant dysrhythmias, like ventricular tachycardia or ventricular fibrillation. The treatment for these catastrophic complications is to defibrillate the heart (the thing you see on medical dramas where they all yell “Clear”). Nowadays, devices known as AEDs are available, which analyze the heart rhythms and administer a shock if it is needed.

I would encourage anyone, whether a reader of a pro-science website or a creationist website - to obtain CPR training.

Commenters are responsible for the content of comments. The opinions expressed in articles, linked materials, and comments are not necessarily those of PandasThumb.org. See our full disclaimer.

Comment #125641

Posted by Tom Moore on September 3, 2006 8:57 AM (e)

This review seems to omit the role of plaque cracking and inflamation in producing infarction. Perhaps you can come back to that at some point?

Comment #125649

Posted by qetzal on September 3, 2006 9:12 AM (e)

Refreshing change of pace; thanks!

I haven’t seen the term ‘POBA’ before. Instead, I’ve seen PCBA: PerCutaneous Balloon Angioplasty. Is that somehow different that POBA?

Comment #125652

Posted by Burt Humburg on September 3, 2006 9:49 AM (e)

Tom Moore wrote:
>>This review seems to omit the role of plaque cracking and inflamation in producing infarction. Perhaps you can come back to that at some point?

Well, it’s sort of implicit in the paragraph that begins, “People who smoke…” But, yes, plaque cracking is an important aspect of the pathophysiology of heart attacks.

Qetzal wrote:
>>I haven’t seen the term ‘POBA’ before. Instead, I’ve seen PCBA: PerCutaneous Balloon Angioplasty. Is that somehow different that POBA?

http://www.nlm.nih.gov/medlineplus/ency/article/002953.htm

PCBA, and the acronym I know PTCA, both refer to the idea of using a balloon to dilate a blockage. However, neither term (I don’t think) refers to ballooning only. The stent is introduced around the balloon - when it dilates, it does not contract again, though the balloon is deflated and withdrawn. Thus, angioplasty (ballooning) can refer to simply plain old angioplasty or angioplasty involving the deployment of a stent.

POBA, on the other hand, refers specifically and literally only to ballooning.

BCH

Comment #125659

Posted by Todd on September 3, 2006 10:45 AM (e)

There are a few more details that people may find interesting.

Several techniques were tried besides angiolplasty to remove the plaque. These included cutting and grinding it off with various tiny power tools or burning it off with a laser. In light of the thrombogenic properties of the plaque, it should be obvious these techinques were unsuccessful.

Here are the rates of restenosis (plaque buildup re-forming) after various techniques as given in my quantitative physiology course:

Balloon angioplasty: 50%
cutting, grinding, laser plaque removable: 50% (more acute events than balloon angiolplasty)
Bare-Metal Stent: 25%
Beta-raditation Stent: 12.5%
Drug-eluting stent: 5-10%

Another issue is that if restonosis is going to happen, it happens within the first year. Therefore, the stents are set up to work only during this period.

The drugs in the stents don’t actually supress epithelial groth, the problem is actually smooth muscle growth (the muscle that lines the walls of arteris) so they actually supress the growth of it. The drug-eluting stents are also not bare metal, they have polymer coatings.

Stenting is also not always used. There is also cardiac arterial bypass grafting, which is where they cut an artery out of one part of the body and stitch it to the coronary artery that is affected in order to bypass the blockage). It is an extremely invasive procedure, involving stopping the heart and being placed on a heart-lung machine then cutting opening the chest. There is a death rate of about 2-3% per year, which is far better than if the people didn’t get the procedure since it is mostly done in extreme cases. Also, the heart-lung machine often causes a condition called “pump head”, which is a measurable (although generally not notiscable) decrease in intelligence. Once again, it is still better than dieing. Stenting only requires a tiny incision, usually in an artery on the inside thigh near the groin, or the same artery on both sides if two endoscopes are used (for instance one for injecting dye so an x-ray can see the blockage and another for actually placing the stent).

CABG is generally used instead of stenting in the following conditions:
-Three-vessel disease
-Left main coronary artery disease
-Two-vessel disease with a history of diabetes
-Significant or critical lesion(s) that are in locations not suitable to stenting

This may change thanks to the success of drug-eluting stents. Currently about half as many CABG’s are done each year in the US (500,000) as compared to interventional catheterizations (1,000,000).

Stents are also used in the carotid artery, which also suffers from stenosis that can lead to strokes. However, it requires a balloon to be opened downstream of the stent to catch debri, since even small debri can cause micro-strokes that can destroy very specific brain functions (specific memories, ability to talk, ability to detect motion in a given direction, etc). Removing the plaque physically is easier here since the artery is in the neck. Here the complication rate is only 5-10%, similar to the restonosis rate I assume.

There are also giant stents that are used to stop abdominal aortic aneurysms. In this case the aorta, the main artery coming out of the left side of the heart, somehow weaks and begins to expands. When it gets larger than 5.5 cm in diameter, it becomes very likely that it will rupture. This is 100% lethal, since all the blood coming out of the left side of the heart and going to the rest of the body must pass through the aorta, so the person will have massive internal hemmorhaging. The giant stent basically acts as a serios of huge, uninflatable tubes that take the pressure off the aorta walls and prevent failure of the aorta. However, it does reduce cardiac efficiency a little since the aorta’s ability to inflate is important to its function. It is still better than certain death, however.

Comment #125661

Posted by Karen Spivey on September 3, 2006 10:55 AM (e)

This is informative and interesting– thanks so much.

Comment #125717

Posted by J-Dog on September 3, 2006 3:18 PM (e)

Thanks - I just went to the hospital last weekend for chest pains, but I feel like the boy that cried wolf, as they failed to find anything wrong. While in ER they did normal tests, like EKG, did a CAT scan, and there was no sign of anything abnormal. Then, right before I was going to be released, my blood pressure dropped, and I almost passed out. They admitted me to cardiac ward ASAP, but stress test was all good, still nothing wrong is visable, so I am released, just in time to get Medical Students Syndrome when reading your excellent article!

I will take 2 aspirin, and call in the morning if shortness of breath persists!

Thanks again.

Comment #125816

Posted by Mike Elzinga on September 3, 2006 10:55 PM (e)

Very interesting and timely for me. Two years ago I was experiencing pounding sensations and skipping beats in my chest as though I were wired from too much coffee (which I don’t drink). I checked my blood pressure (245/113) and immediately went to emergency. After a number of tests, a cardiac catheterization found one coronary artery 100% occluded, one 90%, and the other two 80%. I ended up with a quadruple bypass and fortunately no heart damage from a heart attack.

What is interesting is that I had never had any symptoms and had previously passed a cardiolyte stress test. I walked 2 to 5 miles per day (still do), climbed 84 stairs nearly every day, ate properly, and was not overweight. Apparently the main reason I didn’t have symptoms was because I had grown collateral arteries around the blockages as a result of my regular exercise.

I have since learned that heredity has a lot to do with what happens in the arteries. But another factor is infection. I am not sure how many people are aware of the dangers of infections that can get to the heart muscle and arteries by way of the gums in the mouth. Stress also can lead to inflammation which in turn can cause the turbulence that can precipitate plaque buildup. So the entire process is a bit more complicated, but it is gradually being sorted out.

By the way, during recovery, I had developed some pleurisy which mimics nearly all the symptoms of a heart attack. The big clue to discovering it was pleurisy and not a heart problem was that it didn’t get worse with exercise. You have to be a little careful with that test because the deeper breathing which occurs when you exercise makes the pain worse. Briefly holding one’s breath with the lungs not fully inflated helps to sort this out.

Comment #125920

Posted by whheydt on September 4, 2006 10:45 AM (e)

Tood wrote:
There is also cardiac arterial bypass grafting, which is where they cut an artery out of one part of the body and stitch it to the coronary artery that is affected in order to bypass the blockage). It is an extremely invasive procedure, involving stopping the heart and being placed on a heart-lung machine then cutting opening the chest. There is a death rate of about 2-3% per year, which is far better than if the people didn’t get the procedure since it is mostly done in extreme cases.

In my case, about 6.5 years ago, the surgeon used a technique he called “off pump” where the heart is *not* stopped while doing bypass surgery.

And that leads to the joke about the auto mechanic complaining to the heart surgeon about how come he gets paid so much more than the mechanic for doing the same things, like replacing valves. The surgeon replies, “Try doing it while the engine is running.”

Comment #125953

Posted by Andrew McClure on September 4, 2006 2:47 PM (e)

This is really interesting, thanks.

I kind of have to admit one of the main reasons I follow Panda’s Thumb is because one incidentally gets so much random fascinating science information from it.

I keep wondering if there are other blogs or sites which I could also read if I were looking for random science news and information, hopefully with a focus on disciplines other than biology since there’s already so much good biology information at the Panda’s Thumb. (I do already read Good Math, Bad Math.) I keep meaning to start following scienceblogs or sciencedaily but I never get around to it.

Comment #131672

Posted by jonny on September 19, 2006 8:16 PM (e)

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