Section 6 -

Percutaneous Coronary Intervention (PCI) - Angioplasty (PTCA) and Stenting Jagdish Butany John Veinot

Case 5 - Percutaneous coronary intervention (PCI) - angioplasty (PTCA) and stenting This 63-year-old man had congestive heart failure with increasing dyspnea, orthopnea and paroxysmal nocturnal dyspnea. Past history included prior CABG (LITA to LAD), angioplasty (PTCA) of his circumflex artery 2 years ago, PTCA with stenting of his RCA one year ago, myocardial infarct, diabetes mellitus, systemic arterial hypertension, peptic ulcer and heavy smoking. He had worsening chest pain and developed pulmonary edema with respiratory failure requiring intubation. He also developed atrial fibrillation, refractory to therapy. Coronary catheterization showed a patent LITA graft, but with a severe distal LAD stenotic lesion which was angioplastied (PTCA). Following this procedure he developed acute renal failure, probably from the radiographic dye and systemic hypotension. Coagulopathy was noted with a high INR that was difficult to control. He continued to have episodes of pulmonary edema, atrial fibrillation and developed pulmonary hemorrhage. Creatine kinase was noted to be elevated. Shortly thereafter he had a cardiac arrest and died. Findings at complete autopsy: recent and prior angioplasty, CABG Old patchy subendocardial infarct of posterior left ventricle Recent myocardial infarct of anteroseptal and lateral left ventricle Coronary atherosclerosis - severe triple vessel coronary artery disease Prior angioplasty / PTCA effects of circumflex artery with restenosis - disrupted internal elastic lamina with fibrointimal plaque Prior stent RCA - mild restenosis in the stent - fibrointimal plaque in the stent LITA graft patent; mild stenosis at anastomosis Recent angioplasty / PTCA effects in distal LAD - atherosclerotic plaque disruption with cracked plaque Severe pulmonary edema with moderate alveolar hemorrhage Interventional Coronary Artery Pathology The last decades have given rise to an explosion of interventional and surgical devices for the management of atherosclerotic cardiovascular disease. [1] In many cases non-surgical procedures (including vascular angioplasty) are replacing surgical procedures such as bypass grafting. Many interventional cardiac procedures are done in North America each year. Every new technology creates new pathological processes and challenges for pathological examination. Techniques such as balloon angioplasty and stenting are now grouped by Cardiologists under the term Percutanous coronary intervention - PCI. Percutaneous Transluminal Coronary Angioplasty - PTCA - Balloon Angioplasty Angioplasty represents a major advance in the treatment of coronary artery and vascular disease. The procedure is used for individuals with stable and unstable angina (chest pain), congestive heart failure secondary to ischemia, and with myocardial infarction (MI). Balloon dilatation causes a radial expansion force to the artery wall with denudation of the lining/endothelium of the artery, fracture of the atherosclerotic plaque, intramural dissection and stretching of the vessel. The plaque is compressed and redistributed in the artery. This procedure, by its very nature, generates vascular pathology with newly created complex pro-thrombotic blood exposed surfaces. Complications include thrombosis, myocardial infarction, arterial occlusion, thromboembolism, and vascular spasm - all of which may acutely close the vessel. Potent anti-platelet agents are given to prevent this. [2, 3, 4] Acute pathological findings at angioplasty Plaque compression Intimal flaps Plaque rupture Thrombus Plaque cracking Dissection Chronically the artery narrows by a process termed "restenosis". Restenosis occurs in approximately 30-40 % of patients after PTCA. Stents, especially drug eluting types, have significantly decreased the rate of arterial restenosis. Restenosis is a complex vascular healing process with thrombosis, chronic inflammation, myofibroblast migration, proliferation and synthesis of extracellular matrix - processes similar to wound healing in other sites. Early, the injured arterial wall may thrombose. The injured vessel and the adherent thrombus release growth factors causing smooth muscle cell proliferation and migration. The smooth muscle cells of the media layer proliferate and migrate to the neointima (the new intima). Myofibroblast cells from the outside/adventitia of the vessel also contribute to this neointimal plaque. Recent research has suggested that circulating stem cells and endothelial progenitor cells may be important contributors to the neointimal formation process. [5, 6] The restenotic plaque is not atherosclerosis. It contains little lipid and is smooth muscle and extracellular matrix rich. It is the product of vascular wound healing. Restenosis pathology Early (24 hours to 7 days) Recent thrombus Adherent macrophages Intermediate (1 week to 1 month) Organizing thrombus Myofibroblasts Late (weeks - months) Neointima smooth muscle Percutanous Angioplasty and Intervention in Non-coronary Vessels and Grafts Angioplasty may also be used in peripheral vessels, including the carotids. It also may be utilized to treat diseased vein grafts, but not without risk of complications, especially embolization. With the bulky soft atheromatous plaques that vein grafts tend to get, many think this procedure should be avoided and give preference to angioplasty of the native vessels, or re-do operation especially if arterial conduits can be used. [7] If veins are treated then distal embolic protection devices are recommended due to the near certain risk of emboli. Such distal protection devices are also being commonly used after angioplasty of carotid arteries due to the risk of stroke. These protection devices or filters are like windsocks or bags that are inflated or opened before the procedure and then removed when the procedure is finished. When the pathologist examines the filter material retrieved, the captured material is thrombus and plaque components including fibrous fragments, calcium, cholesterol and atheroma with foam cells and plaque core material. [8] Distal embolization post procedure may contribute to a "no reflow" state where despite a patent artery or graft, there is no distal perfusion due to the microemboli, thrombus, endothelial swelling, interstitial myocardial edema, and microvascular spasm and dysfunction. This state of poor perfusion is difficult to treat and is best prevented. The other clinical situation where one can expect the risk of post - PCI distal embolization to be high is primary PCI of a thrombosed artery in acute myocardial infarction. This type of primary intervention is increasing, and is becoming the standard of practice, in centers where the infarct patient can quickly reach the coronary cath lab. Coronary Endarterectomy and Atherectomy Angioplasty with balloon redistributes atherosclerotic plaque but does not remove plaque mass. Processes such as endarterectomy and atherectomy (directional or rotational) actually remove plaque material by excision or ablation. The acute and chronic vascular complications are similar to balloon angioplasty. In coronary endarterectomy the surgeon opens the coronary artery and physically removes the plaque. This is done at the time of bypass grafting so that the bypass graft may be sewn into an adequate arterial lumen with good distal run off. A similar operation is done to open up the carotid arteries in the neck (carotid endarterectomy), or the proximal leg arteries (often at the time of peripheral bypass grafting). The endarterectomy sites may thrombose acutely and also chronically undergo restenosis similar to angioplasty sites. [9] Atherectomy procedures do not require opening the chest. Rather they are closed interventional procedures where the heart is accessed via the peripheral arteries, usually the groin vessels. With rotational atherectomy, a rotational drill breaks up the plaque. There is potential extensive distal vessel embolization of plaque material. Embolic protection devices are utilized to catch the released distal plaque material and prevent embolization. [8] With directional atherectomy, a small cutting blade removes pieces of plaque and stores them in the catheter, where they are later removed. Any layers of the arterial vessel may be removed including the media and adventitia. It is disturbing to see adventitial tissues in the specimen and a phone call to the clinician is warranted. Interestingly these individuals are usually fine clinically. One worries about long term future arterial aneurysms, but these do not seem to be common probably due to fibrous contraction and restenosis of the site. The resected arterial fragments represent a new opportunity to obtain tissues from live patients and study atherosclerosis and vascular pathobiology. Vascular Stents Vascular stents have revolutionized interventional vascular medicine. Programs of "minimally invasive" medicine include surgery procedures and interventional vascular devices. Stents may be used to treat stenotic native arterial plaques or treat post-procedural complications such as PTCA related abrupt closure due to thrombosis, or intimal flaps. Vein grafts may also be stented. [10] These metal stents are placed on the outside of a balloon. Inflation of the balloon opposes and embeds the stents into the vascular wall. The stent provides metal scaffolding and thus creates a large regular lumen supporting the intimal flaps and dissections. Since most stents are stiff metals, they limit vascular recoil, prevent spasm and increase blood flow. This decreases thrombosis and potentially decreases chronic restenosis. Early stent vascular pathology shows damage to the inner endothelial lining, stretching of the blood vessel wall and accumulation of fibrin and white blood cells. These eventually cover with neointimal cells and the wires of the stents become embedded. The neointima cells are myofibroblast - like smooth muscle cells with collagenous and glycosaminoglycan extracellular matrix. Some of the neointimal cells derive from the arterial wall while others probably originate from circulating stem or endothelial progenitor cells. The endothelium eventually grows back and covers the stents, although this takes time. The body recognizes stents as foreign bodies and there is foreign body giant cell type reaction. [10] The inflammation related to the stent struts is now being recognized as an important component of the healing process after this intervention. Coronary stents range in size from 2.5 mm to 6 mm diameter and from 8 to 15 mm in length. Many different stent types and materials have been designed and each has its own distinctive pathology and complications. Recently there is much promise of drug eluting coated stents with pharmaceutical agents designed to prevent smooth muscle migration or proliferation. Anti-growth factor and anti-proliferative agents, such as rapamycin (Sirolimus) and Taxol, have also been tried with variable success. [11, 12] These drug eluting stents have concerns of delayed healing, delayed endothelialization and the potential for late thrombotic events. Future stents may include bioabsorbable and different metals, organic materials, innovative drugs and polymers or antibody coated stents. The use of radiation delivered via an intraluminal catheter in the stent has also been found to be promising in some studies, although others have found extensive scar adjacent to the stent limiting the effectiveness of the procedure. Delayed thrombosis due to delayed endothelialization is a concern. "Blind spots" of poor radiation treatment may also be found to be responsible for post-procedure restenosis. Currently, radiation may have a role in treating "in stent" restenosis. It may be falling out of favor and its role in the era of drug eluting stents remains to be seen. [13] Metal stents require special histological processing to cut them. One may remove the stent struts manually using a dissecting microscope, but this destroys the overall architecture of the vessel. Alternatively, and with more effort, the stents are plastic embedded and ground or cut using a blade; techniques similar to those developed for study of bone disease. [14, 15] With these special histological procedures, stent pathology may be evaluated. This may be important in the evaluation of stented arterial segments that may have occluded shortly after the procedure and caused death. One can determine if the stent is thrombosed or if there is another cause for the bad outcome. It also may be important to know the status of a stent when a patient with a stent is found with apparent sudden death. Other stents (different sizes and types) are used in the esophagus, bile ducts, urethra, ureters, aorta and large veins. Stents with prosthetic graft material are utilized in large vessel pathology including aortic dissections and aneurysms, including abdominal aortic aneurysms. Composite stent grafts with bio-engineered materials are being developed and studied. Stents loaded with cells and polymers containing growth factors will prove to be interesting in the near future. Bio-stents with absorbable components are under investigation. Different polymers for drug elution with variable time and means of delivery are also interesting. Stenting of a Vessel with Plaque Top - The catheter with the stent is advanced into the diseased artery. Middle - The inflated balloon deploys the stent into the vascular wall, compressing the original plaque Bottom - The successfully deployed stent has displaced the plaque and opened the lumen Right - intravascular Ultrasound (IVUS) images Modified from http://www.heartbc.ca/books/ptca/ptca5types.htm References Windecker S, Meier B. Coronary disease: Intervention in coronary artery disease. Heart 2000;83(4): 481-90. Landau C, Lange RA, Hillis LD. Percutaneous Transluminal Coronary Angioplasty. N Engl J Med 1994; 330(14):981-93. Waller BF. "Crackers, breakers, stretchers, drillers, scrapers, shavers, burners, welders and melters"--the future treatment of atherosclerotic coronary artery disease? A clinical-morphologic assessment. JACC 1989;13:969-87. Waller BF. 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