Profiles in Coronary Artery Disease

Profiles in Coronary Artery Disease

Robert N. Piana

Aaron Kugelmass

Jeffrey J. Popma and Judith L. Meadows authored this chapter in the prior edition.

Atherosclerotic coronary artery disease (CAD) continues to be the most frequent cause of death in the United States and other developed nations.1, 2, 3 Besides mortality, coronary artery disease accounts for substantial morbidity and disability. Diagnostic and therapeutic procedures for coronary disease have evolved rapidly over the last 40 years, and in parallel with advancements in medical therapy, have resulted in a significant decrease in both morbidity and mortality.4 The medical and procedural progress in the treatment of CAD represents one of the major accomplishments of modern medicine.

Cardiologists play a crucial role in identifying clinical CAD and developing a cogent treatment plan for an individual patient. The cardiovascular physician is charged with applying evidence and guideline-based diagnostic and treatment regimens that are individualized around anatomic and clinical characteristics. Though technical in basis, these approaches must also consider patient and family preference, and thus incorporate cultural, emotional, and value-based considerations on a background of clinical science.

This chapter is designed to provide examples of patient-centered therapy of CAD based on individual clinical and angiographic profiles. These case-based examples have been selected to demonstrate the application of clinical evidence and guideline recommendations of percutaneous coronary intervention (PCI) in the contemporary management of CAD.5


In patients with symptoms of stable angina, it is critical to establish a diagnosis of coronary artery insufficiency. While this may be based solely on functional noninvasive testing, coronary angiography using cardiac catheterization6 and, in selected cases, coronary computed tomographic angiography (CTA)7 are indicated in patients with high-risk functional testing, or in whom diagnostic certainty is critical.6 The objective of therapy for stable CAD is to reduce not only mortality, but also prevent further progression, anginal pain, and disability.

For the majority of patients with clinically stable, symptomatic CAD, guideline-directed medical therapy (GDMT),8 including aspirin, beta blockade, hypertension control, and HMG-coA reductase inhibitors (statin) if tolerated, and lifestyle modification constitute the primary proven treatment modality at this time.9,10 In advanced CAD, significant left main CAD, and three-vessel CAD with diminished left ventricular systolic function, surgical revascularization with coronary artery bypass graft surgery (CABG) has demonstrated survival benefit over historic (limited) medical therapy.

The Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial randomized patients with stable coronary artery disease (single-vessel and low-risk multivessel) to GDMT versus GDMT and PCI.11 This trial demonstrated no significant reduction in cardiac mortality, myocardial infarction, need for revascularization, or long-term angina symptoms in those patients treated with PCI. These trial findings have remained controversial, but pending more contemporary trials that utilize advanced imaging techniques and drug-eluting stents (DESs), an initial therapeutic approach of guideline-directed medical therapy (GDMT) has been deemed appropriate.8,10 More recently, the Fractional Flow Reserve-Guided PCI versus Medical Therapy in Stable Coronary Disease (FAME 2) trial suggested that in patients with stable CAD, FFR-guided PCI of lesions (FFR < 0.80) in addition to optimal medical therapy can reduce the incidence of urgent revascularization.12 Whether this approach will be adopted in clinical guidelines or practice remains to be determined.

For those patients who continue to experience lifestyle limiting angina despite guideline-directed medical therapy, coronary revascularization is an option. For patients with single-vessel CAD, PCI is an option and class I indication8 when GDMT fails in relieving symptoms. For patients with
multivessel CAD, PCI and bypass surgery have been shown to have similar 5-year rates of myocardial infarction and death.13 However, the need for repeat revascularization is higher in patients undergoing PCI. Stratification of multivessel CAD patients for PCI on the basis of angiographic complexity can, however, select patients in whom this risk is minimal.14 In addition, a note of caution should be applied regarding the choice of revascularization for the subgroup of patients with diabetes mellitus. The Bypass Angioplasty Revascularization Investigation (BARI) trial suggested a survival benefit of CABG when compared to PCI in patients with multivessel disease and diabetes mellitus, thus raising an initial concern in this patient population.15 This concern has been confirmed by several subsequent clinical trials and registry analyses and by a meta-analysis summarizing 10 randomized clinical trials.16 More recently, in the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial, patients with diabetes mellitus and multivessel coronary artery disease were randomized to revascularization with CABG or with contemporary PCI utilizing drug-eluting stents.17 The primary outcome was a combined endpoint including death from any cause, nonfatal myocardial infarction, and nonfatal stroke at 5 years. At 5-year follow-up, the primary endpoint occurred more frequently in patients undergoing PCI when compared to patients undergoing CABG. The difference between PCI and CABG was driven by a higher rate of death from any cause and nonfatal myocardial infarction in the PCI group when compared to the CABG group.17 Thus, when considering revascularization for patients with multivessel CAD, the revascularization modality should be established on the basis of patient preference, clinical and angiographic characteristics that are determinant of acute and long-term success, and the presence of diabetes mellitus. As such, for patients with multivessel CAD requiring revascularization, collaborative, evidence-driven decision-making by cardiologists and cardiac surgeons, based on clinical and angiographic determinants of acute and long-term benefit, is essential.8

Invasive, as well as CT based, coronary angiography is effective in identifying fixed stenosis of coronary arteries. While important in establishing a diagnosis of CAD with attendant need for secondary prevention, it is the functional significance of individual coronary stenosis that is critical in developing a patient-centered therapeutic strategy. Physiologic stress testing, both exercise and pharmacologic, provides the physiologic basis for CAD treatment, especially revascularization. Similarly, fractional flow reserve (FFR) can provide critical functional information in the cardiac catheterization lab. This invasive technique (see Chapter 24) provides the opportunity to further assess the functional significance of specific coronary stenoses in order to direct therapy at the time of angiography. FFR has been shown to be similar to perfusion stress testing in predicting clinical events associated with a given stenosis. Conversely, FFR has been shown to be effective in identifying coronary stenoses that do not require revascularization in order to prevent CAD-related events.12,18,19 Like all procedures, FFR should be used judiciously. For those patients with a severe stenosis that corresponds to a territory of ischemia identified with functional testing, there is no need to perform FFR. However, in the case of intermediate stenoses, or stenoses that do not appear to be related to ischemia by functional testing, FFR should be performed in order to assess functional significance.


Indications for Angiography and Percutaneous Coronary Intervention

It has been estimated that annually 610,000 Americans will have a new myocardial infarction (MI) and 325,000 will have a recurrent MI.3 While the incidence of ST segment elevation myocardial infarction (STEMI) has been declining, the incidence of non-ST segment elevation myocardial infarction (NSTEMI) has increased.20 It has been suggested that the increase in the incidence of NSTEMI might be related to improved detection with the use of more sensitive biomarkers. Over the past six decades, the annual death rate for coronary artery disease has declined progressively,3,21 and it is today >50% lower than it was in 1950. This reduction is owing to a combination of factors including the institution of ICU care and EMS services, the decline in the rate of STEMI,3,20 improved primary and secondary prevention through GDMT20 and, more recently, by further evolution of reperfusion therapy for STEMI. Reperfusion therapy, by which coronary blood flow is reestablished through pharmacologic (thrombolytic) or mechanical (primary PCI) means, is the hallmark of therapy for STEMI. Primary PCI, when available in a timely fashion, is more effective than thrombolytic therapy for the treatment of STEMI (see Chapter 30), and it is associated with a significant reduction in mortality, reinfarction, and stroke. Despite these differences, the key to STEMI management depends on the timely establishment of reperfusion. Current ACC/AHA Guidelines place primary PCI as a Class I indication, when performed within 12 hours of symptom onset, when it can be performed in a timely fashion (goal within 90 minutes of medical contact), in patients ineligible for thrombolytic therapy, and in patients presenting with heart failure and/or cardiogenic shock.8,22 Thrombolytic therapy remains a viable and Class I indication for those patients who are unable to receive primary PCI within 120 minutes from first medical contact (FMC).22

Technical Considerations

Angiography and PCI should be performed expeditiously, with the goal to minimize the time to successful reperfusion. To this end, as described in Chapter 30, most operators routinely perform a diagnostic angiography of the “nonculprit” vessel initially, based upon ECG localization, and then perform angiography of the culprit vessel with a guide catheter. In vessels in which thrombotic obstruction persists, initial wiring attempts with a soft, hydrophobic wire are advisable, as most lesions are soft and easily crossed. Upon crossing the lesion, confirmation of intraluminal position, either based on angiography or in the event of persistent occlusion, by Dottering with a balloon to allow some distal flow, is advised. In patients with persistent obstruction, the balloon may be advanced distal to the obstruction and the wire removed, and careful, manual injection of contrast through the wire lumen can confirm intraluminal position. Thereafter balloon inflation of the thrombotic occlusion can proceed. In patients with large visible thrombi, or proximal occlusions, many operators will proceed initially with aspiration thrombectomy. The TAPAS trial demonstrated an acute improvement in coronary blood flow and a reduced incidence at 1 year of cardiac death and the composite of death and nonfatal reinfarction with aspiration thrombectomy.23 This approach carries a level IIa indication in current guidelines.22 Stent implantation can then follow. Both bare-metal and drug-eluting stents have been shown to be effective. Decisions about stent type remain operator dependent and should be based on vessel size and other angiographic factors, as well as clinical variables, including likelihood of patient compliance with dual antiplatelet therapy. In all cases, proper vessel sizing is critical in order to ensure adequate stent expansion and strut apposition, thereby reducing the risk of stent thrombosis.

STEMI often occurs in patients with multivessel CAD, with significant lesions in “non-culprit” vessels. Current guidelines argue against immediate treatment of “non culprit” lesions at the time of primary PCI8 (Class III indication). The guidelines are supported by several registry analyses and randomized clinical trials, as well as by a recent large meta-analysis showing that in the setting of primary PCI for acute myocardial infarction, staged PCI is associated with lower short- and long-term mortality when compared with simultaneous culprit vessel PCI and multivessel PCI.24


Indications for Angiography and Percutaneous Coronary Intervention

Coronary angiography, with an intent of revascularization (surgical or percutaneous), is a Class I recommendation for patients presenting with non-ST segment elevation acute coronary syndrome, unstable angina, or myocardial infarction. Patients with refractory ischemia—including angina, or hemodynamic or electrical instability—or more stable patients at higher risk for future clinical events should undergo early angiography, and if indicated PCI.8 Large randomized clinical trials utilizing a background of contemporary antithrombic therapy demonstrated that an initial strategy of angiography followed by appropriate revascularization reduced the incidence of death and recurrent myocardial infarction, as compared to a more conservative initial approach of medical therapy and noninvasive risk stratification.25, 26, 27 Early angiography and subsequent revascularization (6 to 24 hours), as compared to “cooling off,” with later angiography and revascularization, reduce clinical events (composite of death, myocardial infarction, or CVA in high-risk Acute Coronary Syndrome (ACS) patients).

In ACS patients undergoing coronary angiography, the determination of revascularization strategy (PCI versus CABG) should be similar to that for patients with stable CAD. The patient’s angiographic profile, likelihood of success, clinical variables, and patient preference should all be considered.


For patients with non-ST elevation ACS, appropriate medical management including aspirin, ADP receptor blockers, and anticoagulation with either unfractionated or low molecular weight heparin is mandatory (see Chapter 5). Additional
medical therapy including beta-blockers and blood pressure control in conjunction with aggressive lipid lowering therapy with statins is also indicated.28,29

Figure 41.3 ST segment elevation myocardial infarction. A. Angiography of the nonculprit RCA was performed first. B. Right anterior oblique view with cranial angulation demonstrating severe stenosis of the mid left anterior descending artery, with sluggish distal flow. The angiographic appearance is highly suggestive of intracoronary thrombus hallmarked by luminal irregularity and a filling defect. C. After crossing with a floppy wire, aspiration thrombectomy was performed (arrow points to marker tip of the thrombectomy catheter). D. Angiographic appearance of the culprit lesion following deployment of a 3.5 × 15 mm drug-eluting stent. Excellent distal flow was present.

Figure 41.4 Thrombus obtained via aspiration thrombectomy.

Approaches to PCI should be based on anatomic and clinical factors. Both bare-metal and drug-eluting stents can be utilized. As in the setting of STEMI, stent choice should be predicated on risk of restenosis, stent thrombosis, patient compliance, and other technical and clinical considerations. With fourth-generation drug-eluting stents being widely employed, stent delivery is rarely a consideration in determining if a bare or coated stent is to be employed. In patients with multivessel CAD undergoing PCI, multivessel intervention in a single setting is commonplace. That said, consideration of contrast burden and risk of contrast-induced nephropathy (CIN), radiation dose, initial lesion result, the extent of myocardium at risk, and other patient-specific factors should guide whether staging of secondary lesions should be considered.