Left main coronary artery disease: importance, diagnosis, assessment, and management.

Left Main Coronary Artery Disease: Importance, Diagnosis, Assessment, and Management Michael Ragosta, MD Abstract: Left main coronary disease is seen in 4%-6% of patients undergoing coronary angiography for an ischemic evaluation and is a potentially fatal condition if not promptly identified and treated. Recent studies have increased our understanding of the complexity of left main coronary artery disease. This lesion subset offers numerous challenges in diagnosis and management. Fractional flow reserve and intravascular ultrasound are important adjuncts to angiography to determine the significance of ambiguous lesions of the left main coronary artery. Surgery is associated with much better outcomes than medical therapy and is considered by many to be the standard of care in patients who are surgical candidates. Recent studies comparing surgery with percutaneous coronary intervention (PCI) have defined subgroups with lesser extent of disease burden that may do just as well with PCI. Challenges remain in the management of bifurcation disease, and the interventional community anxiously awaits the results of the large-scale randomized trials comparing PCI with surgery. (Curr Probl Cardiol 2015;40:93–126.) ithin the vast extent of our arterial vascular tree, there are few, if any, arterial segments as important as the left main stem coronary artery. Acute occlusion of this short, arterial segment is more likely to kill us than an occlusion of any other arterial segment in the body. Atherosclerosis not uncommonly involves the left main stem and significant narrowing may prove fatal if unrecognized and untreated.

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The author has no conflicts of interest to disclose. Curr Probl Cardiol 2015;40:93–126. 0146-2806/$ – see front matter http://dx.doi.org/10.1016/j.cpcardiol.2014.11.003

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Importantly, there are many unique aspects of left main stem disease that challenge the clinician. The disease may be present in asymptomatic patients with coronary disease or may manifest as stable angina, an acute coronary syndrome, or a heart failure syndrome. Diagnosis, using both invasive and noninvasive techniques, can be surprisingly challenging, and it is very important for the clinician to understand the limitations of diagnostic testing as well as the role of adjunctive methods such as fractional flow reserve (FFR) and intravascular ultrasound (IVUS). Treatment of left main coronary artery disease is similarly nuanced. Although coronary bypass surgery has clear benefits over medical therapy for this entity and has become a time-honored, mainstay of therapy, contemporary studies comparing percutaneous coronary intervention with surgery are beginning to challenge this paradigm.

Historical Overview Atherosclerotic involvement of the left main stem was first described more than 100 years ago by Herrick.1 With the adoption of coronary angiography as a routine diagnostic tool during the 1960s, left main stem disease became increasingly recognized and patients with this condition were soon identified as a “high-risk” group.2 In fact, during this early era, performing coronary angiography in patients with left main stem disease was considered dangerous with a mortality as high as 10%-15% by some reports.3,4 This was primarily owing to the large-bore catheters used during that era with the greater potential for injuring the left main stem and disrupting plaque. During the early 1970s, coronary bypass surgery was applied to left main coronary artery disease. The survival benefit with surgery over the natural history of this fatal disease was soon appreciated.5,6 By the late 1970s, several randomized trials demonstrated a survival advantage of bypass surgery over medical therapy for left main coronary artery disease and established surgery as the treatment of choice. Meanwhile, Andreas Gruentzig performed the first successful balloon angioplasty in 1977, and it was not long before he tried this approach on left main stem disease.7,8 However, despite this initial enthusiasm for a percutaneous approach to this disease, the early published experiences of balloon angioplasty for left main coronary artery disease were associated with a high procedural mortality and very poor long-term survival,9 leading to abandonment of this practice for left main coronary artery disease. The advent of coronary stents in the early 1990s reawakened interest in percutaneous coronary intervention for left main stem disease; however, the high restenosis rates with bare-metal stents led to unsatisfactory results, and stenting was used primarily for patients without surgical option. In the current era, the dramatic reduction in restenosis 94


rates associated with drug-eluting stents again changed the therapeutic landscape and again stimulated interest in percutaneous left main intervention. Furthermore, recent studies have increased our understanding of the complexity of this disease including the important role that disease burden plays in determining outcomes as well as the importance of bifurcation disease. At present, numerous contemporary studies using both first- and secondgeneration drug-eluting stents are beginning to challenge the reign of surgery for left main stem disease.

Importance of Left Main Coronary Artery Disease Roughly 1% of the population lacks a left main stem segment and, instead, has separate origins of the left anterior descending (LAD) artery and left circumflex (LCX) artery from the aorta.10 For the rest, the left main stem artery averages 10-20 mm in length and 3-5 mm in diameter. This short segment carries great importance primarily because it accounts for most of the circulation to the left ventricle. In a right dominant circulation, present in approximately 70% of the population, the left main stem supplies blood to 75% of the left ventricular myocardium; in the 20% of individuals with a left dominant circulation, it supplies all of it. Atherosclerotic involvement of the left main stem is seen in 4%-6% of patients undergoing coronary angiography.11,12 Rarely, the left main stem may appear narrowed on angiography owing to vasospasm, either spontaneous or catheter induced. The left main ostium may also become involved with diseases of the aorta. This might occur in patients with calcific aortic stenosis, large vessel vasculitis, or as a consequence of prior chest irradiation used for malignancy. Dissection of the proximal aorta may rarely involve the left main stem. Interestingly, isolated atherosclerotic left main coronary artery disease is uncommon. Several studies have shown that coronary disease confined solely to the left main stem exists in only approximately 9% of patients with left main coronary artery disease.11,13 In the rest, the coexisting disease in other vessels is typically widespread with approximately 70%80% of patients demonstrating multivessel coronary disease. The atherosclerotic disease that is present at other locations in patients with left main coronary artery disease is often complex with a relatively high frequency of chronic total occlusion and extensive calcification.11 Left main stem disease has several angiographic patterns. Stenosis may be limited to the ostium, the midshaft, the distal bifurcation, or some combination of these. It is estimated that bifurcation disease is present in at least 50% of patients with left main stem disease. These patterns of disease are obviously Curr Probl Cardiol, March 2015

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more important when percutaneous intervention is entertained and less important when surgery is planned. Ostial and midshaft disease are easier to manage by percutaneous methods than disease of the distal bifurcation. David Shavelle: The anatomical location of the disease within the left main artery has important implications for planning a percutaneous treatment approach; ostial lesions are usually straightforward to treat; by contrast, disease involving the distal left main and the origins of the left anterior descending and left circumflex arteries (distal bifurcation lesions) are commonly challenging to treat percutaneously.

The clinical manifestations of left main stem disease are numerous and similar to those caused by atherosclerosis at other locations in the coronary tree. Narrowing of the left main coronary artery commonly presents as a chest pain syndrome, as stable angina, unstable angina, or as a non-ST segment elevation acute myocardial infarction (MI). It is not uncommon for the “culprit” lesion, responsible for the clinical presentation, to be from a severe stenosis in another, epicardial coronary vessel and for a significant left main lesion to be incidentally associated. Significant left main coronary artery disease is present in 4%-7% of patients with acute MI.14 Acute occlusion of the left main coronary artery is usually fatal; thus estimates of its prevalence are difficult to determine. Among patients presenting alive with ST segment elevation MI (STEMI), acute occlusion of the left main is observed in approximately 1% of patients with STEMI.15,16 This is classically manifested as ST segment elevation in lead aVR but also may cause ST elevation in the anterolateral leads or even diffuse ST segment depression with elevation in aVR. Significant left main stenosis may also be encountered in asymptomatic patients or may result in a heart failure syndrome, as a cause of severe left ventricular dysfunction or may cause vague symptoms such as syncope, profound fatigue, or unexplained dyspnea.

Diagnosis of Left Main Coronary Artery Disease: Noninvasive Testing The goals of noninvasive testing include both the diagnosis of the presence of coronary artery disease and the determination of prognosis by identifying patients in danger of an adverse cardiac event. The high-risk nature of left main coronary artery disease certainly qualifies as a subset that should be readily recognized by noninvasive tests. 96


Several features observed on exercise and pharmacologic stress tests have been traditionally associated with the presence of left main coronary disease (Table 1). Unfortunately, these findings are neither very sensitive nor specific for identifying left main coronary artery disease. These abnormalities are also seen in patients with multivessel coronary disease and left ventricular dysfunction. Perhaps more concerning, however, is that stress imaging often underestimates the extent of coronary disease and thus, noninvasive tests may “miss” left main coronary artery disease. One study found that 40% of patients with 450% stenosis of the left main coronary artery had low-risk findings,17 and another study found that more than half of patients with severe 3-vessel or left main coronary artery disease had either no perfusion defect or a single-vessel disease pattern.18 An explanation for the observed lack of sensitivity for identifying left main coronary artery disease is that traditional scintigraphic methods are based on the concept of relative flow reserve. If there is left main coronary artery disease plus a very severe stenosis in one artery, the scan will likely show a relative defect in the more severely stenosed territory. Also, the perfusion images may not show a defect or scintigraphic evidence of ischemia if blood flow to the entire heart is reduced in a balanced fashion (so-called “balanced ischemia”). Newer perfusion imaging techniques may overcome these limitations.19 Additionally, the clinician should not rely on just the imaging. Patients with left main coronary artery disease may have less than impressive features on nuclear scintigraphy but are likely to show other characteristics during exercise testing that are clues to high-risk anatomy. These include very low exercise tolerance, angina at a very low workload, TABLE1. High-risk findings on noninvasive testing associated with left main coronary artery disease Exercise test and exercise ECG variables ST depression 42 mm ST depression at low workload ST depression persisting more than 5 min into recovery Abnormal systolic blood pressure response to exercise (fall 410 mm Hg systolic) Achievement of o4 METS Exercise-induced ventricular ectopy Myocardial perfusion variables Multizone ischemia Increased lung uptake (thallium 201) Transient ischemic dilatation Left main coronary artery disease pattern: defects in septal and posterolateral zones ECG, electrocardiography; METS, metabolic equivalents.


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or the presence of deep and persisting ST segment depressions beginning early in exercise. Coronary computed tomography angiography (CTA) is a noninvasive coronary artery imaging modality with an excellent (99%) negative predictive value for identifying coronary artery disease.20 Therefore, this modality is likely to be very useful for excluding left main coronary artery disease. One study focusing on this subset found a 100% sensitivity and 96.3% specificity for detecting 450% left main stenosis.21 The major limitation of this method is that coronary CTA tends to overestimate disease severity.22 In the United States, coronary CTA is currently not commonly used for the diagnosis of coronary artery disease and thus has somewhat limited application. David Shavelle: Another significant advantage of coronary CT angiography is the ability to accurately assess the extent and distribution of coronary calcium within a left main lesion.

Coronary Angiography and Adjunctive Invasive Imaging Coronary angiography has been the gold standard for diagnosing left main coronary disease for more than 50 years, yet the left main stem is surprisingly difficult to image by this technique. The left main coronary artery is a short segment, and lesions may be obscured by overlapping vessels or from reflux of contrast around the catheter in the aortic sinus. Foreshortening artifact may lead to overestimation of lesion severity, particularly in the left anterior oblique projection with cranial angulation. The catheter used to engage the vessel may tether the artery or cause spasms and thus create artifacts. Similar to other segments, the significance of eccentric lesions may be unclear as the disease may appear to be severely narrowed in one view and minimally narrowed in others. The presence of diffuse disease usually leads to underestimating disease severity as there is not a clearly defined reference segment. Both the ostium of the left main coronary artery and the distal bifurcation can be very difficult to see clearly, resulting in missed diagnosis or an underestimation of disease severity. Calcification is common and also leads to difficulty in interpretation. For these reasons, it is no surprise that the left main stem is subject to the greatest degree of observer variability than any other coronary arterial segment.23 In a study comparing visual estimation of left main stem disease severity with IVUS, approximately one-third of lesions with less than 30% stenosis by angiography were found to have significant luminal narrowing by IVUS whereas approximately 40% of lesions classified as showing 450% 98


stenosis by angiography did not have significant obstruction by IVUS.24 This is disturbing, as the consequences of a missed diagnosis may be fatal and the over diagnosis of left main coronary artery disease severity may lead to unnecessary surgery and grafts that may not remain patent.25 David Shavelle: Although coronary angiography remains the “gold standard” for excluding significant obstructive coronary artery disease, lesions within the left main can be difficult to accurately assess. Investigators from the coronary artery surgery study (CASS) appreciated this during the early years of coronary angiography as consensus between 2 independent angiographers in assessing the severity of a left main lesion was less than 50%.

Most clinicians consider a left main coronary artery lesion with diameter stenosis of 450% to be “significant” by angiographic criteria. This determination is often not measured and is, thus, a highly subjective assessment. The best views for the diagnosis of left main coronary artery disease depend on the disease location. Lesions in the midshaft and distal bifurcation are best seen in the right anterior oblique projection with caudal angulation (Fig 1) or a left anterior oblique projection with caudal angulation. Lesion of the ostium can be challenging to image but the anteroposterior projection, the right anterior oblique projection with cranial angulation, and the left anterior oblique projection with cranial angulation may be useful (Fig 2). For ostial lesions, careful attention should be paid to the appearance of the catheter pressure waveform. Damping or ventricularization of the coronary catheter pressure wave is sometimes the only clue to the presence of significant left main stem disease (Figs 3 and 4). Both FFR and IVUS are adjuncts to coronary angiography and are essential tools for the optimal diagnosis of left main coronary disease, particularly when the angiogram is ambiguous. Both the techniques have been well studied in this disease process and have valuable roles as well as important limitations. David Shavelle: In the appropriate clinical setting (ie, high-risk noninvasive stress test) when the severity of lesions within the left main cannot be adequately assessed by coronary angiography, additional imaging and diagnostic methods such as fractional flow reserve or intravascular ultrasound or both should be considered.

FFR is an invasive method of determining lesion significance, and is defined as the ratio of pressure distal to the stenosis to proximal pressure in the aorta (Pd/Pa) during maximal hyperemia induced by adenosine.26,27 Curr Probl Cardiol, March 2015

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FIG 1. Two examples of severe distal left main coronary artery disease involving the bifurcation. Both angiograms are in the right anterior oblique projection with caudal angulation.

A cutoff o0.75 has been correlated with ischemia but a “gray zone” exists between 0.75 and 0.80 and thus, an FFR o 0.80 is generally accepted as representing a “hemodynamically” significant lesion. 100


FIG 2. An example of severe narrowing of the ostium of the left main stem seen in the left anterior oblique projection with cranial angulation.

The FFR technique has been applied specifically to patients with left main stem disease. An early study by Bech et al28 used FFR in 51 patients with angiographically equivocal left main coronary artery disease and found that deferral of surgery in those with FFR Z 0.75 was associated with the same, favorable outcome as patients with an FFR o 0.75 who underwent surgery. Additional studies in larger cohorts of patients with intermediate or ambiguous left main lesions have confirmed this observation and established that FFR is a useful adjunct to angiography.29-31 In the largest of these studies, the investigators found that the angiogram misclassified the severity of left main coronary artery disease in onethird of patients. Among the misclassified patients, 80% had an FFR o 0.80 despite an angiographic stenosis of o50% by quantitative angiography and the remaining 20% had an FFR Z 0.80 with an angiographic stenosis 450%.30 These data again reinforce the unreliability of angiography for decision making and the important role for adjunctive techniques such as FFR. It is important to note that FFR does have limitations in this population. As noted earlier, left main coronary artery disease is often associated with disease in other vessels. The presence of “downstream” stenosis in the LAD artery or in the LCX artery introduces the complex issue of the ability of FFR to accurately determine the significance of an individual stenosis in Curr Probl Cardiol, March 2015

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FIG 3. This patient has narrowing of the ostium of the left main stem of unclear significance. The tapering of the left main stem at the ostium with minimal reflux of contrast agent into the aortic sinus can be noted. (Color version of figure is available online.)

the presence of tandem stenosis. For example, if there is both an ambiguous lesion of the left main stem and another stenosis in the LAD artery, if the pressure wire is placed distal to both lesions, the FFR reflects

FIG 4. Aortic pressure waveform of the patient shown in Figure 3. When the coronary catheter was engaged in the left main coronary artery, significant damping and ventricularization of the catheter pressure was observed. With removal of the catheter, a normal waveform was restored. (Color version of figure is available online.)

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the effect of both lesions on coronary hemodynamics and it is not correct to then pull back the pressure wire across the distal most stenosis and measure the FFR across the left main stem lesion alone. In this case, the downstream lesions might prevent maximal hyperemia across the left main lesion and this might falsely elevate the FFR and thus, the severity of the stenosis might be underestimated.32 However, experimental models have suggested that FFR can still be accurately measured in the presence of mild to moderate disease in the LAD or LCX as long as the pressure wire is placed in the uninvolved artery.33,34 In the presence of severe disease in the LAD or LCX, FFR is simply not very useful for assessment of left main coronary artery disease and, in such cases, IVUS is an excellent alternative. Finally, ostial left main coronary artery disease may further complicate the measurement of FFR. If there is any damping or ventricularization of the catheter pressure waveform because of ostial disease, the FFR might be falsely elevated (Fig 4). Thus, it is important for the operator to look carefully for this finding and back out the catheter from the left main stem if present. David Shavelle: It is important to remember in the initial clinical study evaluating the diagnostic accuracy of fractional flow reserve in assessing indeterminant coronary lesions in 1996 by Pijls, Nh et al (Engl J Med. 1996;334:1703-8) only 2 patients of the 45 included in the study had left main disease. However, subsequent prospective clinical trials have documented the utility of FFR in this patient subset. The use of intravenous, as opposed to intracoronary, adenosine is thought to provide maximal vasodilation and is preferred when fractional flow reserve is performed for a left main lesion.

IVUS is another adjunct to coronary angiography useful for determining the presence of a significant stenosis of the left main coronary artery. IVUS is anatomically based and thus, the main challenge with using this method is defining the appropriate “cutoff” value for a significant lesion. The minimal luminal area (MLA) is the most accepted variable measured by IVUS to define a significant lesion. Approximately, 16.25 mm2 is the average luminal area of a normal left main stem.35 Based on the distribution of values in patients with angiographically normal left main coronary arteries, a group defined the cutoff value defining a significant stenosis using the formula (average MLA 2 standard deviations); this was determined to be 7.5 mm2 for the population studied.35 This value was then applied to a population of patients with indeterminate left main lesions, and patients were treated with bypass surgery if MLA o 7.5 mm2, Curr Probl Cardiol, March 2015

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TABLE 2. Intravascular ultrasound in assessment of angiographically ambiguous left main lesions Minimal luminal area (mm2) o7.5 o5.9 o4.8 o6.0 o4.5

n

Validation

214 55 55 351 112

Outcomes with deferral Correlated with FFR o 0.75 Correlated with FFR o 0.80 Outcomes with deferral Correlated with FFR o 0.80

References 35 29 36 24 37

and surgery was deferred if MLA Z 7.5 mm2. The outcomes were found to be excellent in patients with MLA 4 7.5 mm2 treated medically.35 Additional studies have validated IVUS with FFR or with outcomes with deferral (Table 2).24,29,36,37 Although there remains some debate, a MLA of o6.0 mm2 is generally accepted as the optimal “cutoff” value indicative of a significant lesion by IVUS and this is the value that has been used in current clinical trials involving left main stem disease. However, several studies involving Asian cohorts have suggested that the MLA associated with a “significant” left main stem lesion is smaller than this with cutoff values of 4.8 and 4.5 mm2 recently reported.36,37 It should be noted that these smaller values in Asian cohorts might reflect the relatively smaller hearts and arteries seen in this population. Figure 5 is an example of an ambiguous lesion of the left main stem evaluated by IVUS. David Shavelle: Multiple studies have confirmed the use of intravascular ultrasound assessment of the left main coronary artery. The minimal luminal area (MLA) is thought to be the single best anatomical measurement to assess the severity of a left main lesion. Recent studies suggest that an MLA of o6.0 mm2 identifies a hemodynamically significant left main lesion.

Treatment There are 3 options for treating left main coronary artery disease: optimal medical therapy, percutaneous revascularization, or surgical revascularization. For patients with all 3 options available, surgical revascularization has traditionally been and currently remains the preferred choice of therapy. However, recent clinical trials are beginning to erode this entrenched practice and suggest that some patients with left main coronary artery disease may fare just as well with less invasive, percutaneous approaches. David Shavelle: Although both percutaneous or surgical revascularization can be considered as treatment options for left main disease, all patients require 104


optimal medical therapy to prevent disease progression and reduce future cardiovascular events.

It is interesting to critically review the now ancient trials of surgery vs medical therapy for left main stem disease to understand both where our current practice guidelines came from and the limitations of these studies in

FIG 5. This is an example of an ambiguous left main stenosis. (A) The left anterior oblique projection with cranial angulation. (B) The right anterior oblique projection with caudal angulation. The left main stem segment is of unclear significance. (C) An intravascular ultrasound image of the left main stem in this patient. The minimal luminal area measured 3.7 mm2 and thus was a significant lesion. Curr Probl Cardiol, March 2015

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the light of the sweeping medical advances of the past 40 years. Further, it is important to understand our current early and late outcomes with coronary bypass surgery for this specific entity, as any challenge to this established treatment has to perform at least as good as surgery. Three historic trials compared the outcomes of coronary bypass surgery with medical therapy for left main stem coronary disease: the VA Cooperative Study, the European Coronary Surgery Study Group, and the Collaborative Study in Coronary Artery Surgery (CASS).38-42 Each trial enrolled patients in the early 1970s and there were important differences between them in terms of enrollment criteria. For all the 3 trials, left main coronary artery disease was defined by coronary angiography as 450% stenosis. The VA Cooperative Study38 and the European Coronary Surgery Study Group39 randomized patients with left main coronary artery disease to surgery or medical therapy. In both these trials, the subset of patients with left main coronary artery disease that were randomized was quite small, with 91 and 59 patients randomized in the VA study and European study, respectively. The CASS trial40,41 did not randomize patients with left main coronary artery disease 470% and thus, most of the data regarding surgery vs medical therapy for this subset from the CASS trial comes from the much larger, CASS registry of nonrandomized patients consisting of 1492 patients with left main coronary artery disease (309 treated medically and 1183 treated surgically). The principal results of these trials are shown in Figure 6 and established the paradigm that surgery saves lives over medical therapy for patients with 450% left main stem disease. Additional analysis of the CASS Registry data also suggests that asymptomatic patients with 450% narrowing of the left main coronary artery also benefit from surgery.42 There are several important limitations of these studies. The randomized trials (VA Cooperative and European study) were very small, and the largest data series came from the CASS study and is a nonrandomized registry data and, thus, subject to selection bias. The entry criteria for these studies were based solely on an angiographic definition of significant left main coronary artery disease, with all of the serious limitations noted earlier, particularly with lesions between 50% and 70% in severity. Importantly, in the early 1970s, medical therapy was pathetic. No patients were on statin therapy, and only 18% were on aspirin and 66% on βblocker. Additionally, surgery was suboptimal. During that era, there was less adequate cardiopreservation methods, longer cardiopulmonary support times, and infrequent (10%) use of the internal mammary artery. David Shavelle: At the time of these 3 historic trials of coronary bypass surgery compared with medical therapy, FFR, and IVUS had not yet been developed. 106


Assessment of the severity of coronary lesions, including the left main coronary artery, was based upon visual estimation and occasionally quantitative coronary angiography.

What is the current status of bypass surgery for left main stem disease? Compared with the early days, contemporary bypass surgery has been greatly refined. Cardiopreservation techniques have improved and nearly all patients with left main coronary artery disease receive an internal mammary artery graft. In addition, patients undergoing surgery are more aggressively treated medically. The outcomes are excellent. Several publications describe the expected outcomes of bypass surgery in large cohorts of patients with left main stem disease in the current era. An analysis of more than 10,000 patients with left main stem disease operated

FIG 6. Principal results of the trials of medical therapy vs bypass surgery for left main stem disease. (A) The results of the VA Cooperative study that randomized patients with angina and left main coronary artery disease 450% to medical therapy (n ¼ 43) or surgery (n ¼ 48). (Adapted with permission from Takaro et al.38) (B) The results from the European Cooperative Surgery Study Group that randomized patients with angina and 450% left main stenosis to medical therapy (n ¼ 31) or surgery (n ¼ 28). (Adapted with permission from Lancet.39) (C) The nonrandomized patients who underwent either medical therapy (n ¼ 309) or surgery (n ¼ 1183) from the CASS Registry (Adapted with permission from Chaitman et al.40). Curr Probl Cardiol, March 2015

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on between 1970 and 2003 found a hospital mortality rate of 2.8%.43 Another trial of 3803 patients with left main coronary artery disease from the Cleveland Clinic operated on between 1971 and 1998 found the 5- and 10-year survival rates to be 83% and 64%, respectively.44 Freedom from revascularization in this cohort was 89% and 76% at 5 and 10 years, respectively. These data are important to understand as they serve as benchmarks to compare and critically evaluate the less invasive treatments, challenging the supremacy of surgery. Certainly the treatment with coronary stents must perform at least as well as surgery in terms of these outcomes. A percutaneous approach to revascularizing left main coronary artery disease has both attractive and undesirable features. Surgery has substantial morbidity and a prolonged recovery period. Numerous postsurgical complications or adverse events are not specifically accounted for in published reviews of outcomes with surgery but certainly have a significant effect on the patient's quality of life and sense of well-being. These include postsurgical atrial fibrillation, pleural effusions, infections, delayed wound healing, anemia from blood loss, and depression. A percutaneous approach is clearly more palatable to patients than surgery. For the physician, the left main stem is a large and easily accessible vessel and would be readily amenable to most modern coronary interventional techniques. However, the large vascular territory subtended by the left main coronary artery might lead to cardiovascular collapse with ischemia during balloon inflation. Abrupt vessel closure or stent thrombosis involving the left main stem might be a fatal event. Disease involving the distal bifurcation could be challenging to treat well. All of these factors must be taken into account and their effect clearly understood when comparing the 2 revascularization methods. PCI for treatment of the unprotected left main coronary artery disease has passed through several phases. Balloon angioplasty was a dismal failure with a 9.1% procedural mortality and a 36% 3-year survival rate.9 Coronary stents improved the safety of percutaneous coronary intervention and reduced the occurrence of abrupt vessel closure and restenosis. Naturally, these techniques were tried for the left main lesion subset. There are numerous publications describing the outcomes of nonrandomized cohorts and registries of patients with left main coronary artery disease treated with bare-metal stents. These publications consisted of highly selected populations (emergency vs elective and good vs poor surgical candidates) and demonstrated highly variable outcomes depending on the population studied. Obviously, worse outcomes were observed for patients with left main coronary artery disease undergoing stenting who were in 108


cardiogenic shock and who were not surgical candidates, whereas good outcomes were seen with elective patients that were good surgical candidates. The bare-metal stent era was characterized by high restenosis and repeat revascularization rates, particularly with bifurcation stenoses. Alarmingly, restenosis of left main stents sometimes presented as sudden cardiac death. Drug-eluting stents promised a reduction in restenosis and renewed enthusiasm in percutaneous intervention for left main coronary artery disease. Nonrandomized series and registries have observed better outcomes, but again, they were limited by selection bias regarding the anatomy and patient characteristics.45 Finally, properly designed, largescale randomized controlled trials comparing percutaneous intervention with drug-eluting stents to coronary bypass surgery are beginning to emerge and are providing important answers to the question of PCI vs bypass surgery for left main coronary artery disease. Left main PCI exists along a spectrum of clinical scenarios (Fig 7). On one end lies the patient who undergoes a bailout PCI because the left main stem was injured or abruptly closed as a complication of a cardiac catheterization; such a patient is unlikely to survive while awaiting an operation and thus, PCI is appropriate (Fig 8). Similarly, there is the rare patient who presents with an acute MI and is found to have an occluded left main stem; PCI can more rapidly restore flow and is a better option than emergency bypass surgery in this setting. Patients who are deemed inoperable or very high risk for surgery because of comorbid conditions and those who are good surgical candidates but simply refuse an operation may also be considered for PCI. The final frontier and the most controversial group is the group of patients who are good operative candidates and willing to undergo surgery. Currently, surgery is considered the standard of care for this group. Many clinicians feel that PCI should not yet be offered to this group until the results of properly performed clinical trials comparing the outcomes of surgery vs PCI are available and show that PCI outcomes are at least equal to those with surgery. The assessment of patients for surgical candidacy is often a complex undertaking and is best achieved by using the Heart Team approach. In this manner, patients are seen by both a cardiac surgeon and an interventional cardiologist who together determine the best option for the patient with left main coronary artery disease. Tools to assess surgical risk are available online and include the euroSCORE and Society of Thoracic Surgeons (STS) score. By simply entering numerous clinical variables such as age, sex, left ventricular function, severity of the clinical syndrome, and Curr Probl Cardiol, March 2015

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FIG 7. The clinical spectrum of PCI for left main coronary artery disease.

coexisting conditions (Table 3), these tools provide an estimation of inhospital mortality as well as the likelihood of developing a serious morbidity such as stroke, prolonged mechanical ventilation, or need for dialysis. Using these tools, an estimated mortality of more than approximately 8%-10% is considered “high risk” and an estimated mortality of more than approximately 25% is generally considered prohibitive risk. Risk may be underestimated by these tools, however, as they do not include all of the conditions that affect outcomes with bypass surgery. Surgical judgment is clearly very important, and a surgeon may deem a patient inoperable or high risk even if the calculated score is low. Intangible or subjective factors affecting outcome include frailty, poor social support, dementia, cirrhosis of the liver, lack of suitable conduits for bypass, severe pulmonary hypertension, poor quality of surgical targets, the presence of a calcified (porcelain) aorta, or a “hostile” chest from prior chest irradiation or prior surgery. However, in the end, the value of an experienced surgeon's “eyeball” test regarding a patient's overall health status and surgical risk cannot be underestimated and often trumps a calculated score. David Shavelle: Despite the use of various objective scoring systems derived from hundreds of thousands of patients, an experienced surgeon who spends time evaluating the coronary angiogram, taking a detailed history and examining the patient may provide the most accurate assessment of operative risk.

Several additional aspects are important in deciding between surgery and left main PCI. Surgery is often favored if complete revascularization with PCI is unlikely. This is often owing to the presence of one or more 110


Curr Probl Cardiol, March 2015 FIG 8. The left panel shows an example of a severe ostial left main lesion discovered on catheterization in a patient with unstable angina. Shortly after the image was taken, the patient developed abrupt hemodynamic collapse and was found to have closure of the left main coronary artery. An intra-aortic balloon pump was inserted and the closed left main stem was emergently opened successfully and stented with the post PCI results shown on the right panel. 111

TABLE 3. Important variables used to determine surgical risk in the Society of Thoracic Surgeons (STS) calculator 1. Nature of surgical procedure Bypass, valve surgery, or ventricular assist device 2. Demographic variables Age, sex, race, and ethnicity 3. Risk factors Weight, height, diabetes, creatinine level, and dialysis Hypertension, infectious endocarditis, and chronic lung disease Immunosuppressive therapy, peripheral vascular, or cerebrovascular disease 4. Previous interventions Prior bypass surgery, valve surgery, or PCI 5. Preoperative status Prior, recent or remote myocardial infarction (MI), and time post-MI Symptoms on presentation: Stable angina, unstable angina, NSTEMI, or STEMI Congestive heart failure and NYHA class Cardiogenic shock Resuscitation Arrhythmia (atrial fibrillation and atrial flutter) Inotropes 6. Hemodynamics and cardiac catheterization results Number of diseased coronary vessels Left main coronary artery disease Ejection fraction Presence of mild, moderate, or severe valvular disease (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, and tricuspid regurgitation) 7. Operative status First surgery vs first, second, or third reoperation Status of procedure (elective, urgent emergent, or salvage) Intra-aortic balloon pump NSTEMI, non-STEMI; NYHA, New York Heart Association.

chronic total occlusions. Similarly, the inability to comply with or tolerate prolonged dual antiplatelet therapy (DAPT) because of a bleeding problem or the imminent need for an important invasive procedure would likely contraindicate a PCI approach.

PCI vs Surgery for Left Main Coronary Artery Disease There are a few small, randomized controlled trials comparing PCI with surgery for left main stem disease (Table 4).13,46-48 The results of additional, large-scale trials are anxiously awaited. A meta-analysis of some of the smaller trials found no overall difference in the rate of major adverse cardiac and cerebrovascular events (MACCE), death, or MI 112


between PCI and surgery but a lower rate of stroke with PCI and a lower rate of repeat revascularization with surgery.49 Upon subgroup analysis, it became clear that the most important determinant of outcome regarding the difference between surgery and PCI related to the extent of disease. Patients with isolated left main coronary artery disease did very well with PCI (1 year MACCE of 5.8% compared with 8.6% for surgery, P ¼ 0.53), whereas those with left main coronary artery and 3-vessel disease had much better outcomes with surgery (1 year MACCE of 17.9% for PCI compared with 10.4% with surgery, P ¼ 0.03).49 This observation is important and clearly the extent of disease must be well defined in any study of left main PCI vs surgery. The Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) trial is the largest, single published study to date comparing the outcome of PCI vs coronary artery bypass graft surgery (CABG) in patients with 3-vessel coronary disease and left main coronary artery disease.13 One of the major contributions of the SYNTAX trial was the creation of the SYNTAX score. This score is an effort to quantify the extent and complexity of coronary disease and takes into account variables such as vessel dominance, the number and location of lesions within the arterial tree, and the presence of unfavorable characteristics such as chronic total occlusion, bifurcation disease, calcification, vessel tortuosity, and long lesion length (Table 5). The higher the score, the greater is the extent and the complexity of disease. The SYNTAX trial stratified the entire randomized population (ie, both patients with 3-vessel and patients with left main coronary artery disease) by tercile of SYNTAX score and found that the patients in the lowest tercile (score: 0-22) fared just as well with PCI as surgery, whereas those in the highest tercile (score Z33) clearly did better with surgery.13 When the SYNTAX score was subsequently applied to a registry of 819 patients undergoing left main PCI or surgery in 2 Italian centers, the investigators found that the outcomes of patients with SYNTAX score Z 34 was better with surgery as compared with TABLE 4. Randomized studies of PCI vs surgery for left main coronary artery disease Study (references)

n (PCI)

n (CABG)

Outcome

46

52 357 300 100

53 348 300 101

EF improved in PCI group at 1 y MACCE at 1 y was similar PCI was noninferior to CABG at 1 y PCI was inferior to CABG at 1 y

LEMANS SYNTAX13 PRECOMBAT47 Boudriot et al48 EF, ejection fraction.


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PCI but patients with SYNTAX score o34 had similar outcomes with surgery or PCI.50

David Shavelle: The syntax score provides an objective measure of the extent and the severity of coronary artery disease; a higher syntax score indicates more extensive and complex disease.

The SYNTAX study included a subset of 705 patients with left main stem disease; 5-year outcomes have been recently published.51,52 For the overall group with left main coronary artery disease, there was no significant difference in the rate of MACCE, MI, or death at 5 years in patients treated with PCI compared with those treated with surgery.52 The rate of stroke was lower in patients treated with PCI (1.5% vs 4.3%, P ¼ 0.03), and the rate of repeat revascularization was lower in patients treated with surgery (15.5% vs 26.7%, P o 0.001). When the left main cohort was divided into 2 groups based on the SYNTAX score, striking differences between the treatment strategies became apparent. For the high SYNTAX score group (Z33), the rate of MACCE was significantly greater in the PCI group compared with surgery (46.5% vs 29.7%, P ¼ 0.003). Although not statistically powered for mortality, the rate of death trended alarmingly higher in the PCI group (20.9% vs 14.1% for surgery, P ¼ 0.11). By contrast, for patients with scores o33, there was no difference in MACCE (31.3% for PCI vs 32.1% for CABG, P ¼ 0.74). Interestingly, in this group with low or intermediate scores, there was actually a lower mortality rate with PCI (7.9% vs 15.1% for CABG, P ¼ 0.02). TABLE 5. Components of the SYNTAX score 1. 2. 3. 4.

Vessel dominance Number of lesions Lesion location in the coronary tree Each lesion assessed for presence of: Total coronary occlusion and features predicting successful PCI Bifurcation involvement and medina classification Trifurcation involvement Aorto-ostial disease Severe tortuosity Lesion length 420 mm Heavy calcification Thrombus Diffuse and distal disease

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These data provide solid evidence that patients with left main coronary artery disease and high SYNTAX scores (433) do better with surgery. The group with low or intermediate SYNTAX scores, however, remain in question, and the data so far provide equipoise for further randomized trials in this subgroup. None of the studies to date were powered to define the optimal strategy for left main coronary artery disease in terms of hard end points such as death in the low and intermediate SYNTAX score groups. The Evaluation of XIENCE Everolimus Eluting Stent System Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial was designed to randomize 2600 patients with left main coronary artery disease and SYNTAX scores o33 to bypass surgery or PCI using a second-generation drug-eluting stent. The primary end point of the study is the rate of death, MI, or stroke at 3 years, and the study was powered for sequential noninferiority and superiority testing. Unfortunately, because of financial reasons, the sponsor (Abbott Medical) decided to withdraw funding after the study enrolled 1800 patients. Nevertheless, this will be the largest randomized trial involving patients with left main coronary artery disease, and the results will likely be the basis for guideline recommendations in the future. David Shavelle: The results of the recently completed Evaluation of XIENCE Everolimus Eluting Stent System Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial will provide additional information as to which patients will benefit from surgery or PCI for left main disease.

Based on the data available so far, several societal documents have addressed the question of PCI vs surgery for left main coronary artery disease. The most recent PCI guidelines53 recommend a Heart Team approach in decision making for patients with left main coronary artery disease and suggest that decision making is based upon an estimation of surgical risk using the STS score as well as a calculation of a SYNTAX score. The guidelines strongly recommend bypass surgery to improve survival in patients with Z50% stenosis of the left main coronary artery (Class I recommendation). PCI is considered reasonable (Class IIa recommendation) as an alternative to surgery in patients with left main stenosis at high operative risk (STS estimated mortality 45%) with a good predicted outcome with PCI. These include patients with a low SYNTAX score (o22) and ostial or midtrunk disease (ie, nonbifurcation disease). The guidelines also consider PCI reasonable (Class IIa recommendation) in the setting of unstable angina Curr Probl Cardiol, March 2015

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or non-STEMI in patients not eligible for surgery and for patients with STEMI and a left main culprit in whom PCI can be performed more rapidly and safely than surgery. There is less support (Class IIb recommendation) for PCI in patients with left main coronary artery disease who have a lower level of estimated surgical risk (severe chronic obstructive pulmonary disease, prior stroke or cardiac surgery, or STS risk of operative mortality 42%) and more complex extent of coronary disease (bifurcation left main or SYNTAX score o33 or both). The guidelines have assigned a Class III indication (potentially harmful) for PCI in stable patients with significant left main coronary artery disease who have unfavorable PCI anatomy (SYNTAX score Z33) and who are candidates for CABG. Appropriate use criteria have been created for coronary revascularization procedures.54 Three specific subsets of left main coronary artery disease are specifically addressed: isolated left main coronary artery disease, left main coronary artery disease with low associated disease burden (1- or 2-vessel disease or low SYNTAX score) and left main coronary artery disease with high associated disease burden (3-vessel disease, presence of chronic total occlusion, or high SYNTAX score). Coronary bypass surgery is considered “appropriate” for all 3 subsets. PCI is considered inappropriate for the subset with left main coronary artery disease and high associated disease burden; the other subsets are considered “uncertain.” These guidelines will likely evolve as additional data become available from ongoing clinical trials and with the refinement of techniques and development of new approaches to treat this challenging subset.

Technical Aspects of PCI for Left Main Coronary Artery Disease The interventionalist planning a left main PCI will face numerous, specific technical challenges. Operators must be proficient in managing aorto-ostial disease and have an understanding and mastery of the numerous bifurcation techniques currently in use. Because of the large amount of myocardium supplied by the left main stem and the potential for hemodynamic collapse during the procedure, it is important to have access to temporary support devices such as IMPELLA or TANDEM heart. The operator must also make important decisions regarding stent choice, and adjunctive pharmacology and must be highly proficient in the use of IVUS to guide the intervention. David Shavelle: In addition to the technical aspects of PCI for left main lesions, pre-PCI medications including aspirin, adenosine diphosphate antagonists (clopidogrel), and statins are essential. High-dose statin therapy (atorvastatin 116


or rosuvastain) reduces PCI-related myonecrosis and should be considered in all patients before PCI.

Management of the Ostium and Bifurcation Ostial involvement is common in left main coronary artery disease; this offers challenges in terms of guide catheter selection and adequacy of guide catheter backup. Delineating the true aorto-ostium by angiography can be very tricky and creates difficulties with optimal stent placement and adequate coverage of the ostium. Ideally, the stent is inserted to allow a millimeter or so to hang out into the aorta, thus ensuring coverage of the ostium. In general, the left anterior oblique projection with cranial angulation can be useful to outline the aorto-ostium and help ensure coverage, but this view will foreshorten the left main segment, so it cannot be used to determine stent coverage distally. Often, there is calcium that can help the operator position stents accurately. The aorto-ostium may be very rigid and has the tendency to recoil. If densely calcified, rotational atherectomy can help accomplish balloon and stent expansion and limit recoil. Sometimes, in aorto-ostial disease, a stent may be positioned properly and fully expands, yet still recoils. This likely reflects the need for greater radial strength at the ostium, as the recoil is likely coming from the aortic wall. It can often be treated by placing an additional stent within the first stent to provide additional radial strength. In most cases of ostial disease, IVUS proves very helpful to ensure coverage and proper stent expansion. Distal bifurcation left main lesions are much more challenging and, unfortunately, a common occurrence. At least 50% of left main coronary artery disease involves the distal bifurcation. The outcomes for PCI are clearly worse for distal left main lesions as compared with lesions involving the ostium or midshaft. The DELTA Registry observed a 3year rate of freedom from target vessel revascularization of 89% for distal bifurcation PCI compared with 96% for ostial or midshaft lesions.55 Bifurcations are difficult to treat at any location in the coronary tree, and this is especially true for the left main, where the “side branch” is actually an entire epicardial coronary artery. There are multiple variations of bifurcation disease depending on whether the disease is restricted to the segment proximal to the bifurcation or whether it involves one or both of the side branches. The size of the side branch and the bifurcation angle are important determinants of outcome and may limit the available strategies that can be used. The Medina Classification system is useful to define the variations of bifurcation disease; a true bifurcation lesion is defined as Medina 1/1/1 and means that the disease involves the vessel before the bifurcation, distal to the bifurcation, and at the Curr Probl Cardiol, March 2015

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origin of the side branch.56 Numerous techniques for bifurcation PCI have been proposed and are beyond the scope of this publication. Considerable debate exists regarding the optimal method. In general, the operator has a choice between a single stent strategy (where only the main vessel is stented and the side branch may or may not be ballooned but is provisionally stented, only if the angiographic result is unsatisfactory) and a more complex strategy (where 2 stents are planned and deployed in one of several different ways to treat both the main branch and the side branch). The NORDIC bifurcation trial and others like it have suggested that the “simple,” or 1-stent strategy, is better than the more complex, 2-stenting strategy for non–left main lesions.57 There are several studies that have looked at bifurcation stent strategy specifically for left main coronary artery disease. Similar to bifurcations elsewhere, a 1-stent strategy seems to be better than more complex techniques.58-60 If 2 stents are needed, the “culotte” method has better outcomes than a “T stent” strategy,61 and the more complex “double kissing crush” method has better outcomes than the “culotte” method.62 Clearly more work is needed to define the optimal management of left main bifurcation disease; the large-scale EXCEL trial will hopefully shed additional light on this complex problem. David Shavelle: A number of advanced interventional techniques are available to treat distal (bifurcation) lesions of the left main. The lack of randomized data in this area makes it difficult to advocate one strategy over another.

Need for Hemodynamic Support Most cases of left main stem PCI do not require support. In a large registry of 5627 left main PCI procedures in the United States, the rate of intra-aortic balloon pump (IABP) use during PCI was 6.4%.63 Another registry of 1612 patients found that those with more complex lesions involving the distal left main stem were more likely to need IABP support than those with ostial or midshaft lesions (9.0% vs 3.1%).55 Nevertheless, support is sometimes necessary during the PCI procedure. Patients more likely to need support include those with severe left ventricular dysfunction, occlusion of the right coronary artery, a left dominant circulation, and patients in whom the PCI procedure is likely to be complex and difficult, thus increasing the ischemic time. For example, it may prove difficult to pass stents or balloons in rigid lesions and prolonged efforts may result in prolonged ischemia, which may not be tolerated. In general, careful attention to the patient's baseline hemodynamic status before and during the procedure is necessary. Patients with tenuous hemodynamics or those in whom even brief balloon inflations result in 118


hemodynamic compromise (Fig 9) may benefit from support. An IABP may be adequate, but some patients, particularly those with very poor left ventricular function, may require the greater levels of support provided by percutaneous left ventricular assist devices such as the IMPELLA or TANDEM heart devices. David Shavelle: Although most left main lesions can be percutaneously treated without the use of a left ventricular support device, the operator should be prepared to rapidly insert one in the setting of hemodynamic compromise, slow or no reflow, or other procedural complications. Patients with decompensated heart failure with a significantly elevated left ventricular diastolic pressure may benefit from the placement of a left ventricular support device before PCI; this allows hemodynamic stabilization before transient ischemia that frequently occurs during balloon inflation or stent placement.

Stent Choice and Adjunctive Pharmacology The superior outcomes of drug-eluting stents have been established for lesions at other locations in the coronary tree and are preferred over baremetal stents. Specifically for unprotected left main lesions, a large metaanalysis has confirmed that drug-eluting stents are better than bare-metal stents in terms of mortality, and myocardial and target vessel revascularization,64 and thus, drug-eluting stents should be the stent of choice for left main PCI. There was no difference between sirolimus or paclitaxel stents for left main PCI in a randomized trial.65 The second-generation stents appear to

FIG 9. An example of the abrupt cardiovascular collapse that may occur with PCI of the left main coronary artery. Shortly after balloon inflation, the pressure is noted to drop. The balloon is rapidly deflated but pressure recovery is slow. (Color version of figure is available online.)


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perform at least as well as sirolimus in a large, nonrandomized study.66 The second-generation stents have been used in the pending large-scale trials of left main PCI vs surgery, and the results of these trials are anxiously awaited. Adjunctive pharmacology for left main PCI is similar to that used for routine PCI procedures. DAPT should be initiated before the procedure. Similar to PCI of other arterial segments, antithrombin therapy with either unfractionated heparin or bivalirudin is necessary during the procedure. The glycoprotein IIb/IIIa inhibitors are not routinely used, unless there is a large thrombus burden or the development of an angiographic complication such as no reflow or abrupt closure from thrombus. Following the PCI, DAPT should be continued uninterrupted for a minimum of 12 months after PCI with drug-eluting stents. Whether DAPT should be continued longer than 12 months is unknown at present and is the topic of ongoing studies.

Procedural Role of IVUS IVUS plays a very important role in performing an optimal PCI procedure for left main stem disease. As described earlier, preprocedural IVUS is an essential tool for determining the significance of moderately narrowed or angiographically ambiguous left main lesions. In addition to determining the MLA, IVUS can provide insight on the presence of calcification that may require rotational atherectomy and can offer precise measurements of vessel diameter to guide in the selection of stent diameter or postdilatation strategy. Importantly, IVUS offers an assessment of disease involvement of the side branches (ie, ostial LAD and LCX) in cases of distal bifurcation disease. Poststent deployment, IVUS is necessary to ensure that there is adequate stent apposition and expansion and that the ostium is completely covered in the event of ostial left main involvement. A study found that, compared with those treated without IVUS, the use of routine IVUS for left main PCI was associated with a greater rate of freedom from major adverse cardiac events at 3 years (88.7% vs 83.6%, P ¼ 0.04) and a lower rate of stent thrombosis.67 Most experts in the field advocate the routine use of IVUS in the performance of left main PCI. David Shavelle: Many interventional cardiologists feel that IVUS should be used in all cases of left main PCI. Stent underexpansion is a common cause of stent thrombosis that can be minimized or eliminated with the routine use of IVUS following stent placement.

The optimal strategy for follow-up of a patient after PCI for left main coronary artery disease has not been defined. DAPT is continued for a year. 120


Currently, there is no evidence that prolonging the duration of DAPT is necessary. During the balloon and early bare-metal stent eras, routine coronary angiography was recommended 2-6 months following left main intervention to look for asymptomatic restenosis. However, angiography is not predictive of subsequent stent thrombosis, and large cohorts of left main PCI found no evidence to support this practice. Thus, the current guidelines specifically do not recommend routine coronary angiography during follow-up.53 Similarly, there is little evidence to recommend routine stress testing. Careful clinical follow-up at regular intervals and further workup based on the presence of recurrent symptoms is most prudent.

David Shavelle: Dr Ragosta has presented an extensive, yet concise review on the prevalence, diagnosis, and management of patients with left main coronary artery disease. Although revascularization for left main coronary artery disease has traditionally been achieved with coronary artery bypass surgery, recently clinical trials including Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) suggest that PCI may be acceptable in patients with favorable anatomy. The recently completed Evaluation of XIENCE Everolimus Eluting Stent System Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial will provide additional useful information in this area. This edition of current problems in cardiology provides an excellent resource for general cardiologists, interventional cardiologists, and cardiovascular surgeons. Dr Ragosta should be commended for this excellent contribution to the medical literature.

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Left main coronary artery disease: importance, diagnosis, assessment and management. Foreword.

Importance of identifying left main coronary artery narrowing in subsets of patients with coronary artery disease.

Coronary artery bypass surgery for left main coronary artery disease.

Left main coronary artery disease. Risks of angiography, importance of coexisting disease of other coronary arteries and effects of revascularization.

Left Main Coronary Artery Aneurysm.

Coronary anomalies: left main coronary artery aneurysm.

Interventional Management of Unprotected Left Main Coronary Artery Disease: Patient Selection and Technique Optimization.

Optimal revascularization for left main coronary artery disease-coronary artery bypass grafting versus percutaneous coronary intervention.

Isolated left main coronary artery disease: a diagnostic dilemma.

Appraisal of treatment for left main coronary artery disease.

Double left anterior descending coronary artery originating from left main coronary stem and right coronary artery.

Left Main Coronary Artery Hypoplasia in Elderly.

Saccular aneurysm of left main coronary artery.

Adolescent with occluded left main coronary artery.

Acute left main coronary artery occlusion.

Spasm of left main coronary artery.

Spontaneous left main coronary artery dissection.

Anomalous left main coronary artery originating from the pulmonary artery.

The impact of downstream coronary stenosis on fractional flow reserve assessment of intermediate left main coronary artery disease: human validation.

Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in Patients with Diabetic Nephropathy and Left Main Coronary Artery Disease.

Chronic kidney disease in patients with significant left main coronary artery disease qualified for coronary artery bypass graft operation.

Left Main Coronary Artery Occlusion and the Collateral-Dependent Heart.

Left main coronary artery disease progression after percutaneous transluminal coronary angioplasty.

Coronary artery disease: Similar 5-year outcomes with CABG surgery or PCI for left main disease.