A Case of Déjà Vu

It's a beautiful spring morning when you and your partner are dispatched on a reported chest pain call. As you approach, you find a 42-year-old male sitting on the front porch of his residence. You observe him to be pale and diaphoretic, actively rubbing his chest and left shoulder.

After introductions, you begin your assessment. Mr. Smith’s chief complaint is sub-sternal chest pain that radiates into his left shoulder. He rates the severity of his pain as a 9out of 10, with an onset of 30 minutes prior to calling EMS. While you question Mr. Smith, your partner is attaching the electrodes to acquire a 12-lead ECG. The patient says he was moving some boxes inside his house when the pain began. He adds that he had two episodes of chest pain yesterday that seemed to only last a few minutes. Your partner hands you the 12-lead ECG as you administer 324 mg of aspirin. After ruling out left bundle branch block and other imitators of STEMI, you observe 4 mm of ST segment elevation in leads V1 through V4, which you interpret as an acute anterior wall myocardial infarction.

You quickly place Mr. Smith into the ambulance and begin transport. You activate a “Code STEMI” at the receiving hospital and continue your history, assessment and treatment as per your protocols. You are greeted at the hospital by the cardiologist and cath lab personnel, who quickly transport Mr. Smith to the cath lab, where he undergoes emergent cardiac catherization. Mr. Smith receives balloon angioplasty to restore flow to his left anterior descending artery and a bare metal stent is placed. He is released the second day with no heart damage.

One week later, you and your partner are dispatched on a reported chest pain call at a local restaurant, where you are amazed to find Mr. Smith sitting at a table, appearing pale and diaphoretic and complaining of chest pain. You place him on the cardiac monitor and acquire a 12-lead, again showing ST segment elevation in the precordial leads V1 through V4. “Code STEMI” activation is given and you transport him to the ED. Upon arrival, Mr. Smith is transported to the cath lab, where a complete blockage of his left anterior descending artery at the site of his recently placed stent is found. The clots are evacuated and flow is reestablished.

Mr. Smith, fact or fiction? Although the name and circumstances have changed, Mr. Smith is a real patient. So what happened? How could Mr. Smith have a stent placed, only to suffer another acute myocardial infarction a few days after being released from the hospital? To answer our question, we must first have a good understanding of how the body responds when a patient undergoes a balloon angioplasty. We also need to understand the differences between bare metal and drug-eluting stents and how the body responds to the type of stent deployed against the arterial wall in an attempt to restore homeostasis.

Effects of Angioplasty

Let’s begin with the body’s natural response to balloon angioplasty. After all, this life-saving intervention in itself is a very traumatizing event. Coronary artery restenosis, or recurrence of the occlusion of blood flow, is a direct response to the injury and inflammatory response of the vascular wall following deployment of a stent or balloon angioplasty. In order to better understand this process, let’s review the structures of the arterial wall.¹

The tunica intima, or intima, is the innermost lining of the artery, consisting of a single layer of very fragile cells that line the arterial wall. These cells, known as endothelial cells, are also found in veins and play a very important protective role in vascular homeostasis. The endothelial cells inhibit thrombosis, release relaxation factors that dilate the vessel and stimulate angiogenesis, a process where new vasculature is formed as a "repair mechanism" for damaged tissues. It is important to understand that with any disruption to endothelial integrity, inflammatory and immune responses are initiated in an attempt to restore homeostasis.^2–5

The tunica media, or media, is the middle layer of the arterial wall which is made up of mostly smooth muscle. The media is directly responsible for constriction and relaxation of the vessel. The ability of the vessel to actively constrict and dilate is a primary means by which the body regulates blood pressure. The tunica adventitia, or adventitia, is the outermost layer of the vessel and is primarily made up of collagen and elastin. The adventitia forms a sheath around the vessel, providing architectural support and anchoring to neighboring tissues.^2,5

In balloon angioplasty, the lesion or clot inside an artery is crossed with a wire and a balloon is inflated, dilating the artery and restoring blood flow to the heart. However, once blood flow has been restored, reocclusion of the artery is always of concern. There are four basic mechanisms that can lead to reocclusion or restenosis of the artery: 1) elastic recoil, 2) negative arterial remodeling, 3) neointimal hyperplasia, and 4) thrombosis. Interestingly, balloon angioplasty itself has a restenosis rate of 40%–50%.^{1, 4, 6–9}

When the balloon is inflated, the arterial wall is stretched in an attempt to permanently deform the media, making the vessel larger in diameter. In the case of elastic recoil, the vessel wall does not remain dilated, but returns to its original diameter. Vascular remodeling is caused by an alteration of the connective tissue within the arterial wall, causing the vessel itself to shrink and further reducing the lumen.^4,7–9

To prevent elastic recoil and vascular remodeling of the artery following balloon angioplasty, a stent is deployed. A stent is commonly described as metallic scaffolding or mesh that provides structure to the inside of the artery, thereby maintaining flow. “Coronary stents have been used for the treatment of atherosclerosis for over 10 years, but the restenosis rate remained high at approximately 25%,” says Dr. David Blick, director of cardiology at St. Mary’s Medical Center in Blue Springs, MO. There are several manufacturers of stents in the marketplace today; however, there are primarily only two types of stents: bare metal and drug-eluting. As the name states, a bare metal stent is simply bare metal. A drug-eluting stent is also constructed of a metallic alloy, but is coated with medication that is slowly released over time once deployed. This medication acts on the intima and smooth muscle cells to decrease the rate of restenosis by inhibiting cell division. According to Blick, the restenosis rate drops to approximately 5% when a drug-eluting stent is deployed.^1,6,10,11

A less common cause of restenosis in the artery as a result of direct balloon angioplasty is neointimal hyperplasia—a process in which the intima, or innermost layer, increases in thickness as a result of the body's inflammatory and immune responses. Neointimal hyperplasia is more commonly the culprit for restenosis when stents are deployed following balloon angioplasty.^7-9,12

Because the stent is a foreign body that has been deployed into the vascular wall, the body’s immune and inflammatory response is accelerated. Inflammatory cells then trigger smooth muscle cells to proliferate and migrate from the media into the intima in an effort to cover the injury site. This continuous proliferation and migration is the culprit of rapid neointimal hyperplasia. The greater the neointimal hyperplasia, the less flow permitted in the lumen of the artery; thus the patient is likely to experience symptoms of ischemia.^7–9,12

The ultimate outcome following stent deployment is a complete repair of the endothelium. The goal is an intact single layer of functioning endothelial cells and an artery with a lumen wide enough to provide adequate flow. This physiological process generally takes around 120 days, but can take significantly longer in some patients. Opportunities for reocclusion primarily from thrombosis or neointimal hyperplasia can be measured in days post-stent deployment. Vascular thrombosis usually occurs at a specific site of injury to the arterial wall. Injury can be from chemicals (smoking), torsion of the vessel (hypertension), or direct mechanical force such as balloon angioplasty and stent placement.^1,3,7-9

During the first 15 days following balloon angioplasty and stent placement, the risks of thrombosis are greatest, due to injury to the arterial wall that activates platelet aggregation and adhesion. To decrease this risk, patients are generally prescribed clopidogrel (Plavix) along with aspirin, which, when taken together, have proven to be an effective antiplatelet therapy. The duration of the antiplatelet therapies is generally governed by the type (bare metal or drug-eluting) of stent placed.

Because drug-eluting stents delay repair of the endothelium, more patients are at risk for late thrombosis. The way to reduce this risk is to lengthen the duration of the dual antiplatelet therapy. “The recommended duration of antiplatelet therapy, aspirin and clopidogrel for bare metal stents is one month,” says Blick, “whereas the duration for drug-eluting stents is one year.” ^1,4,6,13

Smooth muscle proliferation and migration usually peaks around 40 days. Drug-eluting stents secrete anti-inflammatory and anti-proliferative agents that inhibit the proliferation and migration of the smooth muscle cells in the media, thus controlling inflammation and neointimal hyperplasia.^7-9

Around 30 days following stent placement, a protein matrix begins to form on the vessel wall, providing a foundation for a single layer of fully functioning endothelial cells to form. Once this layer of endothelial cells has successfully covered the wall of the vessel, it is considered healed.^1,7–9

Conclusion

So what about Mr. Smith? Was it reocclusion due to thrombosis, neointimal hyperplasia, elastic recoil or vascular remodeling? Mr. Smith admitted he had not been compliant with his daily Plavix and aspirin regimen following hospital discharge. The reocclusion of his left anterior descending artery was due to thrombosis, or a blood clot, at the site of the recently deployed stent.

References

1. Fauci, Braunwald, Kasper, et al. Harrison's Principles of Internal Medicine. Columbus, OH: McGraw-Hill Companies, 2008.

2. Caroline NL. Emergency Care in the Streets, Sixth Edition. Sudbury, MA: Jones and Bartlett, 2008.

3. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease. J Am Coll Cardiol, 2004. Volume 43, Issue 10, 19 May 2004, Pages 1731–1737

4. Kim. Restenosis after successful angioplasty. Journal Watch: General Medicine, 1987.

5. Martini FH, Bartholomew EF, Bledsoe BE. Anatomy and Physiology for Emergency Care. Upper Saddle River, NJ: Pearson Prentice Hall, 2008.

6. Suwaidi JA, Berger PB. Coronary artery stents. JAMA, 2000.

7. Zidar J. Restenosis and Metal Stents: The Hard Data. www.TCTMD.com.

8. Simon. Inflammation: The key element in the biology of restenosis. Inflammation Summit. www.TCTMD.com, 2003.

9. Forrester, et al. Restenosis. J Am Coll Cardiol 17:758–769, 1991.

10. Hermann HC. Stents reduce restenosis in small arteries. Journal Watch: Cardiology, 2001.

11. Herrmann HC. Drug-eluting stents for primary PCI in STEMI. Journal Watch: Cardiology, 2006.

12. Subbotin VM. Analysis of arterial intimal hyperplasia: Review and hypothesis. Theoretical Biology and Medical Modeling, 2007.

13. Fleischmann KE. New guidance on antiplatelet therapy after stenting. Journal Watch: General Medicine, 2007.

Michael L. Wallace, MPA, EMT-P, CCEMT-P, is EMS Division Captain for the Central Jackson County Fire Protection District in Blue Springs, MO.