Myocardial Revascularization

From WiserWiki

[edit] Myocardial Revascularization

Eric H. Lieberman

Jaime Burkle

Symptomatic coronary artery disease is present in more than 6 million people in the United States. Despite the availability of effective medical therapy, a significant proportion of patients are candidates for a revascularization procedure because of unacceptable symptoms or potentially life-threatening lesions.^[1] An estimated 300,000 coronary artery bypass operations and 500,000 coronary angioplasty procedures were performed in 1996, a more than tenfold increase over the past decade.

Direct myocardial revascularization began in 1958 with Sones and collaborators at the Cleveland Clinic, when selective coronary angiography was introduced. In January of 1962, Effler was able to repair a severe obstruction of the left main coronary artery by the patch graft technique developed by Senning. Shortly thereafter, Sones demonstrated for the first time that by means of collateral circulation, coronary bypass could ameliorate the myocardial perfusion deficit of the anterolateral wall of the left ventricle due to a severe obstruction of the left anterior descending branch of the left coronary artery.

Although Sabiston and then Garret and DeBakey performed aortosaphenous vein coronary artery bypass in 1962 and 1964, respectively, Favaloro and Effler established this procedure as a reliable and effective treatment for patients with severe coronary atherosclerosis. Since 1969 the coronary artery bypass graft (CABG) operation has become the most completely studied operation in the history of surgery. It is highly effective in the relief of severe angina, and under some circumstances has the capability for considerably prolonging useful life. The CABG operation consists of the construction of new pathways (conduits) between the aorta (or other major arteries) and segments of coronary arteries beyond obstructive lesions for the purpose of bringing blood to myocardium made ischemic by these lesions. Since the early years of the operation, reversed segments of autologous saphenous vein have been used as the conduit. In 1968 Green used the left internal mammary artery to bypass the left anterior descending coronary artery, leading to better and longer graft patency rates. Segments of radial artery, arm veins, allograft arteries, and veins and synthetic tubes are now being used with variable results.^[2]

Coronary angioplasty was first introduced by Gruentzig in 1977 as an alternative form of revascularization and led to a revolution in the management of patients with coronary artery disease.^[3] During the early years of its application, Gruentzig and others used the procedure predominantly to treat patients with discrete, proximal, noncalcified, subtotal occlusive lesions in a single coronary artery. Although the early experience with angioplasty was limited to patients with stable symptoms, normal left ventricular function, and proximal, discrete stenoses, technologic development and operator experience have greatly widened the indications for percutaneous coronary intervention (PCI). In subsequent years the technique has been used successfully in patients with multivessel disease, multiple subtotal stenoses in the same vessel, certain complete occlusions, partial occlusion of saphenous vein or internal mammary artery grafts, or recent total thrombotic occlusions associated with acute myocardial infarction. Acute complications resulting from the angioplasty procedure itself and the occurrence of late restenosis following the procedure have motivated cardiologists to seek alternative methods of improving flow through obstructed arteries. Directional and rotational coronary atherectomy, laser angioplasty, and coronary stenting have improved initial results in certain anatomic situations.

[edit] INDICATIONS FOR MYOCARDIAL REVASCULARIZATION IN CHRONIC ISCHEMIC HEART DISEASE

[edit] Medical vs. Surgical Therapy

When evaluating a patient with chronic stable angina for the best possible therapy to achieve relief of symptoms as well as survival benefit, special consideration should be made of the following factors: left ventricular function (i.e., ejection fraction), number of diseased vessels, location of stenotic lesions, severity of angina, age, sex, presence of peripheral vascular disease, abnormal electrocardiogram (ECG), and hypertension. An effective clinical strategy in managing patients with chronic stable angina should seek to identify patients whose lives would likely be prolonged by CABG. Based on a retrospective analysis of the three largest clinical trials of coronary artery bypass grafting, the Veterans Administration Cooperative Study of coronary artery surgery (VACS),^[4] the European Coronary Surgery Study (ECSS),^[5] and the Coronary Artery Surgery Study (CASS),^[6] the sicker the patient, as gauged by relevant measures of coronary disease and cardiovascular morbidity, the more likely CABG will prolong life. The VACS included 686 male patients younger than 67 years of age, with chronic stable (predominantly class II and III) angina for >6 months, left ventricular dysfunction in more than half of them (ejection fraction [EF] <50%), and at least 6 months since the last acute coronary event. The ECSS randomized 768 male patients younger than 65, with chronic class I to III angina for >3 months but no evidence of left ventricular dysfunction (EF >50% in all patients). Finally the CASS trial included 780 patients (90% male) younger than 65, with no worse than class II angina for at least 2 months (or 3 weeks after acute myocardial infarction), and ejection fractions of at least 35. The patient population underrepresented or excluded certain categories of patients with high incidence of coronary disease, including women, patients over 65 years of age, patients with moderate and severe angina, those with new onset angina or recent myocardial infarction, and patients with severely impaired left ventricular function. In summary, a CABG-related improvement in survival is therefore more likely to occur if there is left ventricular dysfunction, multivessel disease, proximal coronary lesions (more muscle is threatened by such lesions), high-grade lesions as determined by angiography, more severe angina, or low-level inducible ischemia.

Thus, patients are likely to live longer after CABG if they have:

• Left main disease (see Special Considerations)
  
• Three-vessel disease with left ventricular dysfunction (ejection fraction less than 50%); class III or IV angina; provokable ischemia; or disease in the proximal left anterior descending coronary artery
  
• Two-vessel disease with proximal left anterior descending coronary artery involvement
  
• Two-vessel disease with class III or IV angina and either severe left ventricular dysfunction alone or moderate left ventricular dysfunction together with at least one proximal lesion
  

When it is less clear whether to do CABG, the presence of peripheral vascular disease, female sex, baseline electrocardiographic ST-segment and T wave changes, or older age (over 60) should weigh in favor of doing CABG.^[7]

[edit] Surgical vs. Percutaneous Coronary Intervention

Coronary angioplasty and coronary bypass grafting are both intended to improve myocardial blood flow. Both are palliative rather than curative and should be seen as complementary rather than competitive procedures and are associated with potential risks including stroke, myocardial injury, and death. The major advantage of coronary angioplasty is its relative ease of use, making unnecessary general anesthesia, thoracotomy, extracorporeal circulation, mechanical ventilation, and prolonged convalescence. Repeat angioplasty can be performed more easily than repeat bypass surgery and revascularization can be achieved more quickly in emergency situations. The disadvantages of angioplasty are high early restenosis rates (especially in the pre-stent era) and the inability to relieve many stenoses because of the nature and extent of the coronary lesions.

The preferred method of revascularization (i.e., CABG vs. PTCA) remains controversial. Several randomized studies comparing PTCA with CABG have recently been completed. The Randomized Intervention Treatment of Angina trial (RITA), an Argentine trial of PTCA and CABG (ERACI), the German Angioplasty Bypass Surgery Investigation (GABI), the Emory Angioplasty versus Surgery Trial (EAST), the Coronary Angioplasty Bypass Revascularization Investigation (CABRI), and the Bypass Angioplasty Revascularization Investigation (BARI) together enrolled almost 4800 patients. The EAST trial was the first of the randomized trials of angioplasty vs. CABG.^[8] It consisted of 392 patients with multivessel disease; 40% had three-vessel disease and 60% had two-vessel disease. Three-year survival data from the EAST trial demonstrate no significant difference between those patients initially randomized to PTCA or CABG.^[9] The BARI trial, designed to test a primary endpoint of total mortality at 5 years, randomized 1829 patients.^[10] There was no significant difference between the PTCA and CABG groups (86.3% vs. 89.3%, p = 0.19). Patients randomized to an initial strategy of PTCA in both the EAST and the BARI trial had a significantly higher rate of repeat revascularization. It is worth noting that the diabetic subgroup in the BARI trial demonstrated that those randomized to CABG had an 80% 5-year survival compared with 65% for the PTCA group.^[11]

It is important to note that the patients randomized represent only a small proportion of the entire population, and this raises the issue of selection bias. Coronary bypass surgery has the advantages of greater durability (graft patency rates exceeding 90% at 10 years with arterial conduits) and more complete revascularization irrespective of the morphology of the obstructing atherosclerotic lesion. Generally speaking, the greater the extent of coronary atherosclerosis and its diffuseness through the vessel wall, the more compelling the choice of coronary artery bypass surgery, particularly if the left ventricular function is depressed. Patients with lesser extent of disease and localized lesions are good candidates for percutaneous coronary intervention.

[edit] Medical Therapy vs. Percutaneous Coronary Intervention

The development of PTCA led to significant questions about the appropriate treatment of patients with stable angina. The widespread use of PTCA had no impact on the incidence of coronary artery bypass surgery, suggesting that PTCA primarily replaced medical therapy for a large number of patients.^[12] A number of randomized studies of PTCA have been performed in an effort to define the appropriate use of these techniques. The first randomized trial was the Angioplasty Compared to Medicine (ACME) trial.^[13] This study randomized 212 patients with stable angina and one-vessel disease, an abnormal stress test, or a recent myocardial infarction to either PTCA or medical therapy. The primary endpoints were exercise tolerance and symptoms at 6 months. PTCA was associated with better symptom relief and improved performance on an exercise test compared with medical therapy. There was no difference in the frequency of MI or death between the two groups. A follow-up ACME trial involved 101 patients with two-vessel disease, stable angina, and evidence of ischemia on stress testing.^[14] This study failed to show any difference in exercise duration, relief of symptoms, and overall quality of life. RITA-2 randomized 1018 patients with stable angina to either PTCA or medical therapy. This study included patients with multivessel disease and left ventricular dysfunction. The primary endpoint was the combination of all-cause mortality and nonfatal myocardial infarction. Although patients randomized to PTCA had greater reductions in anginal symptoms, the risk of death and nonfatal myocardial infarction was increased to 6.3% of PTCA patients vs. 3.3% of medically treated patients (p = 0.02).^[15] In reviewing these studies, the following conclusions can be made: (1) PTCA affords better relief of angina than medical therapy, especially for those patients with more severe angina, and (2) the improvement in symptomatic relief comes at the expense of increased risk of morbidity and mortality.

[edit] SURGICAL REVASCULARIZATION

There are a variety of risk factors that affect morbidity and mortality in patients undergoing coronary artery surgery. Recent acute myocardial infarction, hemodynamic instability, left ventricular dysfunction, the presence of left main coronary disease, and severe or unstable angina adversely affect surgical outcome. In addition, factors related to the aggressiveness of the atherosclerotic process, as reflected in associated carotid peripheral vascular disease, impact on risk. Biologic factors, including age at operation, diabetes mellitus, and female gender, increase the perioperative risk of surgery. Intraoperative factors that impact on outcome include ischemic damage and type of graft used; use of internal mammary grafts favorably impacts on long-term outcome.^[16][17]

A number of complications can occur in patients undergoing CABG. Perioperative myocardial infarctions are more likely to occur in women and in patients with severe perioperative angina pectoris, severe stenosis of the left main coronary artery, and three-vessel disease. Unstable angina and prolonged cardiopulmonary bypass times are also risk factors for perioperative myocardial infarction. Perioperative myocardial infarction, particularly if it is associated with hemodynamic or dysrhythmic complications or preexisting left ventricular dysfunction, has a major adverse effect on early and late prognosis. The diagnosis of perioperative myocardial infarction is hampered by the lack of specificity of repolarization abnormalities and enzyme changes during the perioperative period.^[18]

Postoperative changes in pulmonary function after CABG are frequent and troublesome, but rarely serious, except in patients with preexisting chronic lung disease or the elderly. Impaired hemostasis and bleeding complications are an inherent risk of coronary bypass surgery. Reoperation for bleeding is required in 2% to 5% of patients.^[19] Cardiopulmonary bypass causes derangements of the intrinsic coagulation and fibrinolytic systems in addition to platelet function. The risk of bleeding is increased with age, a smaller body surface area, reoperation, bilateral internal thoracic artery grafts, and the preoperative use of heparin, aspirin, and thrombolytic agents. Major perioperative wound complications, especially mediastinitis and/or wound dehiscence, occur in approximately 1% of patients. These are associated with markedly increased in-hospital mortality, morbidity, and length of stay. This risk is substantially increased by the use of double internal mammary artery grafts, particularly in diabetic patients.^[20]

The incidence of stroke is 1% to 5% and is age-related. The return of a normal level of consciousness is delayed in approximately 3% of patients; intellectual dysfunction in the early postoperative period, as assessed by a battery of neurocognitive tests, has been noted in approximately 75% of patients. Transient mild visual deficits are common. Fortunately, major long-term sequelae are uncommon. Mild degrees of confusion, agitation, and delusional behavior are frequent and usually transient.^[21]

Atrial fibrillation is one of the most frequent complications of coronary bypass surgery, occurring in up to 40% of patients. Preoperative and postoperative administration of β-blockers has been shown to reduce the risk of postoperative atrial fibrillation.^[22] In the early postoperative period, rapid ventricular rates and loss of atrial transport may compromise systemic hemodynamics and increase the risk of embolization. Administration of β-blockers, calcium antagonists, digoxin, or a combination of these medications is indicated to control the ventricular response. Occasionally rate control alone will facilitate conversion back to normal sinus rhythm (NSR). When restoration of NSR is not achieved within 24 hours, antidysrhythmic therapy (i.e., procainamide, ibutilide, or sotalol) may be instituted. If chemical cardioversion is unsuccessful, then direct current (DC) cardioversion can be attempted in an effort to restore NSR. If conversion to NSR is unsuccessful within 48 to 72 hours, full anticoagulation is indicated to prevent risk of systemic embolization. Chronic requirement of antidysrhythmic therapy for postoperative atrial fibrillation is extremely rare, unless the patient was taking the medication before surgery. Differences of opinion remain as to whether efforts should be made to actively restore NSR in the immediate postoperative period or if anticoagulation should be instituted and cardioversion attempted at a later time if atrial fibrillation does not spontaneously revert to NSR.

The incidence of postoperative bradydysrhythmias requiring permanent pacemaker implantation was 0.8% in a series of 1614 consecutive patients discharged from the hospital after CABG.^[23] Predictive factors were preoperative left bundle branch block, concomitant left ventricular aneurysmectomy, and older age. Patients with coronary disease who develop fascicular conduction disturbances often have diffuse myocardial disease and unfavorable prognosis. The causes of death are ventricular dysrhythmias and cardiac failure.

In-hospital mortality after isolated coronary bypass surgery was characterized by a steady decline from 1967 to the early 1980s. Overall mortality for elective first bypass procedures in the United States from 1980 to 1990 was 2.2% in 58,384 patients in the Society of Thoracic Surgeons database. It was 2.6% in elective patients without internal mammary artery grafts and 1.3% in patients receiving such an implant.^[24] More recently there has been a stabilization or even a slight overall increase in morbidity and mortality, which reflects the changing characteristics toward an older and sicker population of patients undergoing operation.

The CABG operation has a favorable effect on symptoms and useful life expectancy in many patients. However, it does not cure atherosclerotic heart disease, and in most patients, usually many years after operation, clinical evidence of myocardial ischemia returns and is followed by death, which in more than half the patients is related to recurrent myocardial ischemia. Death from any cause is a secure endpoint with which to judge the efficacy of CABG, and to compare it with alternative forms of therapy. In general, about 96.5% of heterogeneous groups of patients survive at least 1 month after the operation, and 95%, 88%, 75%, and 60% respectively, survive 1, 5, 10, or >15 years after the operation.

The evidence, both symptomatic and from graded exercise testing, is complete that the coronary artery bypass operation relieves angina in most patients. However, the return of angina is the most prevalent of the postoperative ischemic events. The return of angina shortly after coronary bypass, typically recognized with resumption of activity, usually is due to incomplete revascularization or early closure of grafts. Angina occurring later usually is a reflection of narrowing or closure of one or more grafts or progression of native vessel disease, or both.

In general, sudden cardiac death is uncommon after CABG. By 10 years after undergoing the operation, 95% of patients are alive, as are about 90% by 15 years. Only 5% to 10% of deaths after CABG occur in patients with the syndrome of chronic heart failure. In part, this is because patients with ischemic heart disease and important chronic heart failure usually have severe left ventricular dysfunction as a result of extensive myocardial scarring, and are not advised to undergo bypass surgery.

It is nearly impossible to quantify an unsatisfactory quality of life after CABG, even though it is one of the most important unfavorable outcome events. This relates in part to the fact that a satisfactory quality of life is a composite of at least freedom from limiting angina or heart failure, the preservation of a reasonable exercise capacity, and reasonable freedom from the need for medication, rehospitalization, and reintervention. Most surviving patients have a satisfactory quality of life early after bypass operation, but the probability of retaining this quality begins gradually to decline after about 5 years. The rate of decline in the quality of life is probably similar to that of the freedom from angina.^[25]

[edit] Conduits

Since the early years of the operation, reversed segments of autologous saphenous vein have been used as the conduit. Greater saphenous vein is expendable, generally available in sufficient length, appropriately sized to match the coronary arteries, capable of reaching beyond the stenoses of all diseased arteries, pliable enough to allow easy suturing, and autologous. When a greater saphenous vein is not available, the lesser saphenous vein can be used. Saphenous veins are used as free grafts, anastomosed proximally to the ascending aorta and distally to one or more coronary arteries.

The time-dependent diminution of patency in saphenous vein bypass grafts has led to the wide use of the left internal mammary artery (LIMA), particularly for revascularization of the left anterior descending (LAD) coronary artery system. The LIMA is left attached to its origin from the left subclavian artery, mobilized from the chest wall, and anastomosed distal to the LAD stenosis. The right internal mammary artery (RIMA) can often be used in a similar fashion. The highest patency rates for coronary bypass grafts are associated with the use of the LIMAs to bypass important proximal stenoses of the LAD coronary artery. These patency rates are approximately 95% at 10 years after operation, and failure to use the mammary arteries in this matter has been demonstrated to be a risk factor for premature late death after the operation.^[26]

The use of LIMA or RIMA as a free graft from the ascending aorta to the LAD provides almost comparable results. Currently available information indicates that the LIMA should be used almost routinely for revascularizing the LAD system in the coronary bypass operation. Use of bilateral internal mammary artery grafting has become popular, but as yet the available evidence does not support the hypothesis that long-term survival is increased by its use, and the risk of sternal wound complications is increased by the double internal mammary artery procedure in obese or diabetic patients. The patency advantage of the internal mammary artery when anastomosed to vessels other than the LAD is uncertain.

When neither the LIMA nor the RIMA can be used, the right gastroepiploic artery, the inferior mesenteric artery, or the inferior epigastric artery may be used, although long-term advantages of these arteries over saphenous vein grafts have not been demonstrated. Segments of radial artery, upper extremity veins, allograft arteries and veins, and synthetic tubes (polytetrafluoroethylene) have been less satisfactory as conduits and should be used only as a last resort.

[edit] Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) Grafting

The morbidity and mortality of CABG is largely attributed to the use of cardiopulmonary bypass, global cardiac arrest, hypothermia, and median sternotomy. A major limitation appears to be a 6.1% incidence of neurologic events observed in retrospective studies. These neurologic events are attributed to plaque emboli that are dislodged by manipulating the ascending aorta and to low perfusion pressure or microemboli due to the extracorporeal circulation. The trend to operate on progressively older patients is expected to exacerbate the problem of adverse cerebral outcome. The “invasive” nature of cardiopulmonary bypass implies that obviating the need for it is likely to be of major benefit to the patient. CABG on the beating heart, however, requires temporary interruption of the coronary flow in the recipient artery and anastomosis site stabilization. If only a LIMA to LAD graft is needed, a limited anterolateral thoracotomy (minithoracotomy) is aesthetically attractive, reduces bleeding, and prevents sternal infection and dehiscence, a rare but serious complication of median sternotomy. The results warrant further exploration of beating-heart coronary surgery.

Recent reports of cumulative experience in MIDCAB in more than 14 different countries have revealed promising results. As expected, the approaches vary and the numbers vary widely. With few exceptions, beating-heart coronary operation is associated with arterial grafting. About 49% of patients had one-vessel disease and 28% and 13% had two-and three-vessel disease, respectively. The average number of anastomoses per patient ranges from one to two. CABG without cardiopulmonary bypass constitutes 1% to 43% of the current bypass procedures performed in specialized centers. CABG on the beating heart may reduce the hospital length of stay from a median of 8 days after conventional CABG to about 4 days, or even less in the case of minithoracotomy LIMA-LAD grafting. Work and social activities may be resumed after 2 to 3 weeks rather than after 2 to 3 months. In selected patients, the costs of coronary revascularization will be reduced substantially. The ultimate value of the currently evolving, less invasive surgical treatment strategies for coronary artery disease remains to be established.^[27]

[edit] PERCUTANEOUS CORONARY INTERVENTION

In general the procedural success rate for PTCA is estimated to be 92% to 98%; 1% to 3% of patients require emergent coronary artery bypass surgery, myocardial infarction occurs in 1% to 3%, and death in less than 1%.^[28] Despite the early success rate, it has been estimated that 25% to 50% of patients require repeat coronary intervention due to restenosis, incomplete revascularization, or disease progression.^[29] Perhaps the greatest limitation of angioplasty has been the threat of restenosis. Depending on a number of factors, restenosis occurs in 10% to 50% of lesions. The mechanisms accounting for restenosis include elastic recoil, accelerated atherosclerosis, and neointimal hyperplasia. This neointimal hyperplasia results from the response to the injury of the intima that is a necessary component of the angioplasty.

A number of situations are associated with increased risk of restenosis. These include coronary spasm, lesion location (left anterior descending greater than right or circumflex artery), serum lipid concentrations, presence of unstable angina, previous angioplasty, and multivessel disease. In addition, saphenous vein grafts have been shown to have the highest rate of restenosis.^[30] A variety of pharmacologic regimens were studied in an effort to alleviate the threat of restenosis. The studies included trials of anticoagulation, antiplatelet agents, steroids, antimitotic agents such as colchicine, vasoactive agents (calcium channel blockers and angiotensin-converting enzyme [ACE] inhibitors), and lipid-lowering agents. None of these trials demonstrated any significant reductions in the risk of restenosis. Due to the disappointing results associated with systemic administration of these pharmacologic agents, interest has developed in the potential of local drug delivery to limit the rate of restenosis. To date there are no studies demonstrating efficacy to this approach. The recent proliferation of stent appears to have had a favorable effect on the incidence of restenosis; however, the problem has not been eliminated. Efforts continue to develop mechanical and biologic solutions to the problem of restenosis.

[edit] Factors Affecting Risk

There are a number of clinical factors that appear to affect the risk of complications occurring with angioplasty. Patients undergoing percutaneous intervention in the setting of an acute ischemic syndrome (unstable angina, myocardial infarction) are at increased risk of abrupt vessel closure and thrombosis.^{[31][32][33][34][35][36]} The development of platelet IIb/IIIa inhibitors has significantly lowered this risk, allowing complication rates similar to those for patients with stable angina.^[37] Older patients also appear to be at increased risk of complications.^[38][39] The higher incidence of calcified lesion and more diffuse disease may account for this increased risk.^[40] In addition patients who have either low (<25 kg/m²) or high (>35 kg/m²) body mass index are at increased risk.^[41]

There are a number of anatomic features that affect the procedural success of angioplasty. A scoring system was codified by the American College of Cardiology and subsequently modified by Ellis that defined the expected success and risk of intervening on a particular lesion. Variables included lesion length and morphology, tortuosity of the vessel, presence or absence of thrombus, and a number of other variables.^[42] This classification system, however, appears to be becoming outdated with the advent of new techniques, pharmacologic agents, and increased operator experience. Certain factors remain important in evaluating a lesion for percutaneous interventions. These factors include the ability to access the lesion, ability to cross the lesion with the interventional device (e.g., balloon, atherectomy catheter, stents), and the characteristics of the lesion. The characteristics of the lesion that affect intervention include the presence and severity of calcification, presence of thrombus, proximity to side branches or bifurcation, and the presence or absence of collateral vessels supplying or being supplied by the target vessel. The presence of significant calcium at the site of intervention interferes with the ability to successfully perform the intervention and often necessitates the use of adjuvant devices (i.e., rotational atherectomy). Branch vessels increase the complexity of the intervention as well as the risk of complications due to the potential of closure of these side branches. If the target vessel is supplied by collateral, the risk of the procedure is diminished. However, if the target vessel supplies collaterals to other vessels, the risk of the procedure is increased.

Operator experience also appears to impact on both procedural success and the treatment of complications associated with PTCA.^[43][44] A number of reports have shown a direct correlation between operator caseload and lower complication rates.^[45] The risk of death in association with angioplasty is related to the amount of myocardium that is jeopardized by an abrupt vessel closure. The risk of death is significantly increased when there is a large amount of ischemic or nonfunctional myocardium. A successful angioplasty procedure is likely to occur if the following factors are present:

• Experienced operator at a high-volume institution
  
• Patient-related factors include younger age, male gender, and no history of diabetes mellitus, prior myocardial infarction, prior bypass surgery, or impaired left ventricular function
  
• Favorable angiographic appearance defined as a discrete (<10 mm length), concentric, readily accessible, nonangulated segment with smooth contour, little or no calcification, less than totally occlusive, not ostial in location, without major side branch involvement, and with absence of thrombus.
  

[edit] Newer Technology

Simpson developed directional coronary atherectomy (DCA), which was first used in the peripheral circulation in 1985, and was subsequently extended to the coronary circulation. DCA was designed to remove atheromatous tissue and improve the angiographic results relative to PTCA. Initially the device was targeted for those lesions that were not effectively treated with balloon angioplasty, including aortoostial lesions, bifurcation lesions, and lesions with a large amount of atheromatous material. The first randomized trial of DCA, the CAVEAT trial, compared the technique with balloon angioplasty in native coronary arteries. In this trial, no significant benefit in terms of restenosis was found, and there was an increase in the risk for non–Q wave myocardial infarction in the DCA group.^[46] One-year follow-up showed an excess mortality in the DCA group. CAVEAT 2 tested DCA in saphenous vein grafts; however, no benefit of DCA compared with balloon angioplasty was found.^[47] The BOAT trial attempted to optimize the use of DCA by more vigorous removal of tissue. The investigators found that by utilizing this technique, incidence of restenosis was 32% in the DCA group compared with 40% in the balloon group.^[48] Nevertheless, DCA has fallen out of favor, especially with the advent and widespread use of stents. Although DCA provides excellent angiographic results when used by experienced operators, no significant improvement in clinical outcome has been demonstrated. Furthermore the technique is more tedious and time-consuming, and fails to achieve the same clinical benefits as stenting.

The transluminal endarterectomy atherectomy catheter (TEC) was designed by Stack to cut and aspirate atheroma. The role of TEC in percutaneous interventions remains controversial; however, it may have a role in degenerating saphenous vein bypass grafts and/or thrombotic lesions. In contrast to DCA and TEC, rotational atherectomy removes plaque by abrading it and dispersing the debris into the distal vessels. The major indication for rotational atherectomy is in calcified lesions. It also appears to have a role in “pretreating” lesions that cannot be crossed with an angioplasty balloon, ostial lesions, bifurcation lesions, and distal lesions.

The rotational atherectomy device (Rotoblator) spins at a speed of 150,000 to 200,000 rpm and ablates tissue. The ablated tissues are sent downstream and removed in the microcirculation. Overly vigorous advancement of the device can result in the generation of larger particles that can lead to obstruction of the microcirculation or to dissection of the vessel. It is targeted for patients with calcific lesions and those who cannot be successfully dilated with balloon angioplasty. The device does not improve the risk of restenosis.

Despite initial enthusiasm, laser angioplasty has been disappointing. The laser ablates tissue by vaporization and shock waves. The ERBAC demonstrated no advantage in terms of restenosis. When compared with the NACI registry, lasers appear to have a higher complication risk. The lesions most suitable for laser therapy include aortoostial lesions, undilatable lesions, total occlusions, calcified lesions, and long lesions. Lesions that are contraindicated for use of the laser include those in tortuous segments, those containing thrombus, and those at the site of bifurcation. Ongoing research efforts with laser angioplasty include investigating its use in stent restenosis and the use of a “laser wire” to cross total chronic occlusions. In addition, lasers may have applicability in treated diffuse stent restenosis.

The greatest advances in percutaneous intervention since the development of balloon angioplasty have come from application of stents. Stents provide a scaffold that is designed to enlarge the lumen and seal dissections associated with coronary angioplasty. Stent design varies considerably and includes meshes, slotted tubes, coils, and rings. They can be made of stainless steel, nitinol, tantalum, or a number of other materials. Newer stent designs included heparin-coated stents and radioactive stents, both designed to further reduce the risk of restenosis. The Belgium Netherlands Stent Trial (BENESTENT) and the Stent Restenosis Trial (STENT) demonstrated that intracoronary stents reduced the incidence of angiographic restenosis in patients undergoing an initial percutaneous coronary intervention.^[49][50] Restenosis rates for those patients treated with stents were lowered from 42% to 32% in STRESS and from 32% to 22% in BENESTENT. The initial limitation to stenting was the risk of stent thrombosis; subsequently efforts were aimed at reducing the risk of thrombosis. Vigorous anticoagulation regimens were developed that led to marked reductions in stent thrombosis; however, there was a significant excess risk of bleeding due to these regimens.

Positive clinical results increased with the improvements in achieving complete stent deployment and the discovery that antiplatelet therapy with ticlopidine and aspirin would effectively prevent subacute thrombosis. The ISAR trial demonstrated that ticlopidine effectively prevented subacute stent thrombosis while reducing the risk of bleeding that was associated with more vigorous anticoagulation regimens that included warfarin.^[51] Aspirin alone was shown to be inadequate in the prevention of stent thrombosis in the STARS trial.^[52] Clopidogel is the subject of a number of ongoing trials; earlier results suggest that it is likely to be a safe alternative (in addition to aspirin) to ticlopidine for patients undergoing revascularization with a stent. These interventions led to reductions in subacute thrombosis, bleeding complications, and hospital length of stay. As a result of these studies, stent deployment is rapidly growing, with many centers utilizing stents in the majority of their percutaneous interventions. Further economic analyses are necessary to determine the cost-effectiveness of stenting relative to balloon angioplasty. The greatest question remains the overall impact of stenting on clinical outcome in patients with multivessel disease relative to surgical revascularization. Two ongoing trials, ARTS and SOS, are evaluating the impact of an initial strategy of multivessel stenting vs. surgical revascularization on death, myocardial infarction, and need for revascularization.

There has been a tremendous proliferation in the design and availability of new stents. Currently over 40 stents are being used worldwide. These newer stents broaden the applicability of the device to other lesions and locations. Despite the enthusiasm for stenting, problems do remain. Although the rate of restenosis is reduced with stenting, stent restenosis is more difficult to treat and less likely to respond to redilation.

[edit] Coronary Revascularization and Acute Coronary Syndromes

The overall success rate for percutaneous intervention for patients with unstable angina is somewhat lower than patients undergoing the procedure for stable angina. Patients with unstable angina have a higher mortality, risk of myocardial infarction, and need for emergency coronary artery bypass surgery. It is thought that the increased risk of complications is due to increased thrombotic milieu that accompanies acute ischemic syndromes. These patients have increased platelet reactivity and vasospasm, putting them at increased risk of acute vessel closure. The risk associated with percutaneous intervention for unstable angina appears to diminish if there is an initial period of “stabilization” prior to the intervention.

New pharmacologic intervention has had an impact on the risk of PCI in the setting of acute ischemic syndromes. Platelet aggregation occurs as a consequence of fibrinogen binding to platelets and allowing for cross bridging of platelets, resulting in a platelet plug. The glycoprotein IIb/IIIa receptor mediates the binding of fibrinogen to the platelet surface. This receptor is expressed once platelets are activated; it is the final common step in platelet activation regardless of the stimulus for platelet activation. The first randomized control trial of a IIb/IIIa receptor inhibitor was the Evaluation of 7E3 in Preventing Acute Ischemic Complications Trial (EPIC).^[53] EPIC studied abciximab, a monoclonal antibody to the IIb/IIIa receptor, in patients with unstable angina or high-risk lesion who were to undergo angioplasty. It demonstrated that this IIb/IIIa receptor blockade results in a clinically and statistically significant reduction in the risk of acute complications. Furthermore, the benefits achieved have been maintained over a 3-year follow-up. In this study, however, patients treated with abciximab had a significantly increased risk of bleeding. Follow-up studies, including EPILOGUE, demonstrated that similar efficacy could be achieved with lower risk of bleeding by adjusting the dose of the heparin that was used concomitantly.²⁰⁰

[edit] EXPERIMENTAL TECHNIQUES

[edit] Transmyocardial Laser Revascularization

Transmyocardial laser revascularization (TMR) has been introduced for the treatment of refractory angina (class IV) in patients who are not candidates for CABG or catheter-based revascularization. Clinical trials of TMR have demonstrated significant improvements in angina class, decreased need for antianginal medications, and fewer hospitalizations for angina. Operative mortality in stable patients with class IV angina has been acceptable. The procedure consists of a standard left anterolateral thoracotomy, and dissection of the pericardium, creating a cradle. Using a laser system with variable output, frequency, and pulse width, transmural channels are made beginning in the area of reversible ischemia on the basis of preoperative thallium studies or coronary artery anatomy and clinical judgment if the patient had not been able to tolerate a preoperative thallium perfusion study. Laser channels are placed about 1 cm apart to provide a distribution of 1 laser channel per cm². A mean of 30 to 40 laser channels is made. Bleeding from the channels is controlled with digital pressure or, rarely, an epicardial suture. After creation of the transmural channels, a pericardial chest tube is placed and standard wound closure is performed.^[54]

[edit] Brachytherapy

The effect of radiation therapy for the prevention of restenosis was tested initially using external beam radiation. Early reports suggested the effectiveness of this treatment in reducing neointimal formation postvascular injury in experimental models, but the findings of accelerated atherosclerosis and vascular injury following radiation therapy for patients undergoing cancer treatment further delayed investigation of radiation as a mode of therapy with potential for vascular applications.

In 1965 Friedman described the potential of endovascular radiation to prevent restenosis in an injured atherosclerotic rabbit aorta that inhibited smooth muscle cell proliferation. Liermann and Schoppol in 1991 started using endovascular radiation to prevent restenosis in the peripheral vascular system. These investigators have recently reported an 80% patency rate at 5-year follow-up using endovascular gamma radiation with 192-iridium.

In 1992, Waksman, Weinberger, and Raizner initiated studies to determine the effectiveness of intracoronary radiation therapy against restenosis following balloon overstretch injury with and without stenting in animal models. These animal models utilized both γ- andgamma;-and β-isotopes, demonstrating nearly complete inhibition of neointimal formation at 2 and 4 weeks following vascular injury. Hehrlein and Fischell began utilizing endovascular brachytherapy using radioactive stents. This concept was tested and found to be effective and safe in animal models. Clinical studies have subsequently been initiated to determine the effectiveness of this therapy in humans. In 1994 the first patient was treated with intracoronary radiation after balloon angioplasty utilizing a wire that hand-delivered 192-iridium into a close-end lumen catheter. The BERT study utilized 90-Sr/Y as a pure β-emitter. The SCRIPPS trial was a randomized double-blind trial that studied 55 patients with restenosis, demonstrating a significant reduction of restenosis rates by angiographic findings, intravascular ultrasound (IVUS), and clinical events. The BETA WRIST trial demonstrated that patients with in-stent restenosis treated with β-radiation utilizing a 90-yttrium source had lower than expected rates of angiographic and clinical restenosis.^[55] Additional trials of brachytherapy are ongoing.

[edit] Growth Factors

Delivering treatment directly to the myocardium and the coronary arteries promises a revolution in the management of serious and life-threatening cardiac diseases. The pericardial sac provides the route for a variety of treatments aimed directly at the subepicardial structures, essentially within the epicardium. This technique utilizes therapeutic agents in concentrations that could not be tolerated systemically, as well as angiogenic factors to increase vascularity in patients with subacute and chronic coronary artery disease who are not good candidates for other types of revascularization. The elevated levels of various angiogenic cytokines in patients with myocardial ischemia indicate a potential role of the pericardium in ischemia-induced angiogenesis. Intrapericardial or epicardial administration of these cytokines appears to result in functionally significant angiogenesis in animal models of chronic myocardial ischemia. In a recent study, Laham and collaborators demonstrated the ability of a single bolus injection of basic-fibroblast growth factor (bFGF) into the pericardial space to induce myocardial angiogenesis and improve regional perfusion, regional left ventricular function, and microvascular reactivity, and to increase angiographically visible collaterals and magnetic resonance-detected collaterals. Thus the pericardial space offers an attractive drug delivery reservoir that might be used to deliver therapeutic substances to the heart.^[56]

[edit] REFERENCES