CHAPTER 63

Daniel M. Shivapour
Amar Krishnaswamy
Samir R. Kapadia

Percutaneous Coronary Intervention

I.Introduction

A.Coronary atherosclerosis may result in a flow-limiting stenosis that leads to myocardial ischemia and/or myocardial infarction (MI). Andreas Gruentzig first managed these lesions percutaneously on September 16, 1977, when he advanced a fixed-wire, distensible balloon across a stenosis in the mid–left anterior descending (LAD) artery and briefly inflated it to 6 atm (90 psi). This procedure was termed percutaneous transluminal coronary angioplasty (PTCA). With the advent of stents and other therapeutic coronary devices, these procedures are now more broadly termed percutaneous coronary intervention (PCI). It is estimated that more than 1 million PCI procedures are completed in the United States and approximately 2 million worldwide annually.

B.The field of interventional cardiology continues to evolve rapidly, as a result of many important advances in equipment, strategies, and adjunctive medication. These advances have been paralleled by a concomitant improvement in the safety and efficacy profile of PCI. The assimilation of a large body of basic and clinical research encompassing all areas of interventional cardiology continues to redefine the standard of care paradigm.

II.PCI Indications

A.Central tenet. Although there is no substitute for sound clinical judgment, PCI is generally reserved for patients in whom there is an objective demonstration of substantial myocardial ischemia or symptoms as well as angiographic demonstration of obstructive coronary disease. PCI may not be indicated for asymptomatic or mildly symptomatic patients who have only a small area of viable or jeopardized myocardium, have no objective evidence of myocardial ischemia, have other life-limiting disease processes, or have lesions that have a low likelihood of success (Tables 63.1 and 63.2).

TABLE 63.1 Standard PCI Evaluation

History

•Symptoms (angina, dyspnea, paroxysmal nocturnal dyspnea, syncope)

•Previous MI

•Previous cardiac interventions (PCI, CABG)

•Comorbidities (diabetes mellitus, hyperlipidemia, hypertension, etc.)

Medications (glucophage, statins, aspirin, thienopyridines, etc.)

Allergies (contrast dye, latex, etc.)

Physical examination (murmurs, jugular venous pressure, pulses, bruits, edema)

Laboratory data (creatinine, potassium, hemoglobin, platelets, INR)

Other tests (ECG, echocardiogram, stress tests)

Informed consent including risks, benefits, alternatives

CABG, coronary artery bypass grafting; ECG, electrocardiogram; INR, international normalized ratio; MI, myocardial infarction; PCI, percutaneous coronary intervention.

TABLE 63.2 Considerations for Every PCI

Review clinical and angiographic risk factors

Develop strategy and anticipate problems

Surgical backup

Access

Anticoagulation and antiplatelet therapy

Consider diagnostic adjuncts (e.g., PA line)

Consider therapeutic mechanical adjuncts (e.g., IABP)

Guidewire

Device (e.g., angioplasty, stent)

Closure of vascular access site

Post-PCI destination (telemetry ward, CICU)

CICU, cardiac intensive care unit; IABP, intra-aortic balloon pump; PA, pulmonary artery; PCI, percutaneous coronary intervention.

B.ST-segment elevation myocardial infarction (STEMI). Primary PCI should be the preferred treatment strategy for patients presenting with STEMI to a facility experienced with and capable of performing PCI. Randomized trials have demonstrated that clinical outcomes are improved when such patients are emergently transferred to centers able to perform primary PCI as opposed to therapy with thrombolytics—despite a significant delay (mean time of 44 minutes) in time to therapy because of transport. This seems especially true of patients presenting 3 to 12 hours after symptom onset, where the superiority of primary PCI becomes clearly evident. In those presenting within 3 hours of symptom onset, mortality data would suggest that either therapy is equally efficacious in appropriate candidates. For a more thorough discussion of the management of STEMI, please refer to Chapter 1.

C.Non–ST-segment elevation acute coronary syndrome (NSTEACS). Unstable angina and non–ST-segment elevation myocardial infarction (NSTEMI) are considered part of the spectrum of NSTEACS. Given that individual patients presenting with unstable angina/NSTEMI are at widely varying risk for subsequent morbidity and mortality, early and aggressive risk stratification including cardiac catheterization with subsequent percutaneous or surgical revascularization (rather than noninvasive stress testing) is recommended. This recommendation is supported by a number of clinical trials comparing an early invasive to delayed conservative strategy. For a more thorough discussion of the management of NSTEACS, please refer to Chapter 2.

D.Chronic stable angina. A significant proportion of all PCI procedures are performed in the elective setting for chronic stable angina. Whereas recent trials have questioned the mortality benefit of PCI or coronary artery bypass grafting (CABG) over optimal medical therapy in stable coronary artery disease (CAD), revascularization still remains the most rapidly effective treatment strategy for patients with angina. For a more thorough discussion of the management of stable CAD, please refer to Chapter 6.

III.Contraindications. The only absolute contraindication to PCI is significant active bleeding, given the absolute need for procedural anticoagulation and continued dual antiplatelet therapy (DAPT). Relative contraindications include a bleeding diathesis, unsuitable or high-risk coronary anatomy (e.g., chronic total occlusion in the absence of ischemia or diffuse distal disease), recurrent in-stent restenosis (ISR), and a short life expectancy because of a comorbid condition.

IV.Prognosis. A patient’s clinical status and coronary angiogram are powerful predictors of outcome. Certain clinical and angiographic variables have repeatedly been associated with adverse events (Table 63.3).

TABLE 63.3 Clinical and Angiographic Predictors of Adverse Outcomes
Clinical Predictors	Angiographic Predictors
•Older age	•Thrombus
•Unstable angina	•Bypass graft
•Acute MI	•Left main trunk
•Cardiogenic shock	•Lesion > 20 mm in length
•CHF	•Excessive tortuosity of proximal segment
•Left ventricular function	•Extremely angulated lesions > 90°
•Multivessel coronary disease	•Total occlusion >3 mo old and/or bridging collaterals
•Diabetes mellitus	•Inability to protect major side branches
•Renal impairment	•Degenerated vein grafts with friable lesions
•Peripheral vascular disease	•Unprotected left main trunk
•Small body size

CHF, congestive heart failure; MI, myocardial infarction.

V.Angiographic/procedural/clinical success. Angiographic success is defined as a residual stenosis <50% with PTCA or <20% with stenting with thrombolysis in myocardial infarction (TIMI) 3 flow and is achieved in 96% to 99% of patients. The definition of procedural success is angiographic success without major in-hospital complications (i.e., death, CABG, or MI). Clinical success is defined as procedural success with relief of the symptoms and signs of myocardial ischemia.

VI.Complications

A.The incidence of complications (death 0.5% to 1.4%, periprocedural MI, and emergency CABG surgery 0.2% to 0.3%) has consistently decreased over the past 20 years with the advent of stents, new and more effective antiplatelet therapies, improved equipment, and increasing reliance upon evidence-based strategies.

B.Abrupt closure is the most common cause of a major adverse cardiac event (MACE) and typically occurs within 6 hours of intervention. The most common cause of abrupt closure is suboptimal stent expansion or dissection followed by thrombus, spasm, and side branch occlusion. In the mid-1980s, the risk of abrupt closure approached 5%. The common use of periprocedural contemporary antithrombotic therapies and stent deployment has reduced this risk to <1% in modern practice. Risk factors for abrupt closure include presentation with acute MI, poor coronary flow postintervention (i.e., less than TIMI II), complex lesion morphology (i.e., class C lesions), and suboptimal result as judged by angiography or intravascular ultrasound (IVUS) imaging.

C.Atheroembolism and thromboembolism probably occur to varying degrees in all interventions, but are most frequently encountered in cases involving degenerated vein grafts, in patients presenting with acute coronary syndromes (ACSs), and in cases using directional/rotational atherectomy. Distal embolization can result in “no-reflow” (decreased coronary flow), abrupt closure, and periprocedural MI. Thromboembolism can be minimized by using aspiration catheters (e.g., Pronto, Export, Extract) or rheolytic thrombectomy (Possis AngioJet) to remove thrombus; however, the most effective measure is effective anticoagulant and antiplatelet therapy. The prevention of atheroembolus, most often encountered during vein graft intervention, is frequently addressed with the use of a filter device (e.g., FilterWire EZ) or proximal flow occlusion device (e.g., Proxis) to trap and remove the debris before it reaches the distal vascular bed. Intracoronary administration of vasodilators such as adenosine (36 to 72 µg repeatedly), nitroprusside (50 to 200 µg), and verapamil (200 µg) has been shown to prevent and manage no-reflow, but have no effect in preventing creatine kinase–muscle/brain (CK-MB) elevation.

D.Coronary perforation is typically identified using the Ellis classification: type I: extraluminal crater without extravasation; type II: pericardial or myocardial blush without contrast jet extravasation; type III: extravasation through frank (>1 mm) perforation; type III cavity spilling: perforation into an anatomic chamber, coronary sinus, and so on. Coronary perforation is estimated to occur in 0.1% to 1.14% of routine PCI cases, 0.25% to 0.70% of cases using directional atherectomy, up to 1.3% of cases using rotational atherectomy, and 1.9% to 2.0% following excimer laser angioplasty. Contrast extravasation is typically evident in the majority of cases at the time of PCI; however, up to 20% of cases can present several hours after the procedure and are frequently due to hydrophilic wire perforation of a small vessel. Treatment usually requires prolonged balloon inflation and reversal of anticoagulation. Transthoracic echocardiography should be immediately performed in the setting of clinical instability in order to evaluate for the presence of a pericardial effusion and/or tamponade, in which case urgent pericardiocentesis is required. Covered stents, coils, or surgical repair may be required for definitive management.

E.Vascular access site complications remain the most common complication of PCI and occur in up to 5% of patients. The most common are blood transfusion (3%), arteriovenous fistula (<2%), pseudoaneurysm (up to 5%), acute arterial occlusion (<1%), and infections (<0.1%). Shorter anticoagulation regimens, weight-adjusted heparin, use of bivalirudin, early sheath removal, vigilant monitoring of activated clotting times (ACTs), smaller sheaths, avoidance of routine venous sheath insertion, and widespread adoption of radial artery access have all contributed to a reduction in complications. Stopping heparin after PCI and substituting clopidogrel for warfarin has also resulted in a reduction of bleeding and coronary complications.

F.Contrast-induced nephropathy defined as increase in Cr >0.3 above baseline occurs in 3% to 7% of patients, and the risk increases 10-fold for patients with serum creatinine >2.0 mg/dL, especially in the presence of diabetes mellitus. Data regarding methods to prevent renal failure are not definitive, but the most proven benefit is seen with conservative contrast utilization. In addition, use of biplane imaging can significantly reduce the amount of contrast required. Numerous studies have provided mixed results on the benefits of saline infusion before catheterization, administration of N-acetylcysteine (NAC) 600 mg po or intravenous (IV) bid for 1 day before and after the day of catheterization, single bolus dose NAC prior to contrast load, using nonionic contrast dye, infusion of a sodium bicarbonate solution, and periprocedural IV administration of 5 to 10 g of ascorbic acid (vitamin C).

G.Contrast-mediated reactions can be serious. Anaphylactoid reactions occur in 1% to 2% of patients receiving iodinated contrast. These reactions can be severe in 0.10% to 0.23% of patients. The risk of a severe reaction can be effectively decreased by using nonionic contrast, preprocedural corticosteroids (i.e., prednisone 40 to 60 mg) given the evening before and the morning of the procedure, and the use of H₁ and H₂ blockers. If a patient presents for emergent PCI (i.e., STEMI) without having undergone preprocedural steroid preparation, the emergent administration of hydrocortisone 100 mg IV and diphenhydramine 25 to 50 mg IV is reasonable and is shown to be safe in small series. In patients undergoing an elective procedure, caution is prudent and a full premedication regimen is recommended.

H.Stent thrombosis (ST) is discussed later in Section XI.F.

VII.Experienced operators/centers

A.Procedural volume is an important predictor of PCI complications. Elective PCI should be performed in high-volume centers (>200 interventions per year, with an ideal minimum of >400 cases per year) by operators with an acceptable annual volume (>75 cases per year) at institutions with fully equipped interventional laboratories, experienced support staff, and an on-site cardiovascular surgical program. Primary PCI for STEMI should be performed in similarly experienced/skilled centers by operators who perform >75 elective cases per year and intervene on at least 11 cases of STEMI per year. Elective PCI should not be performed by low-volume operators (<75 cases per year) in low-volume centers (<200 cases per year), regardless of the availability of on-site cardiothoracic surgery, because of the increased risk of suboptimal outcomes. Referral to a larger regional center is recommended in this situation.

B.In cases of STEMI, there is an inverse relationship between the number of primary angioplasty procedures performed by an operator and in-hospital mortality. The data suggest that both door-to-balloon time and in-hospital mortality are significantly lower in institutions that perform a minimum of 36 primary angioplasty procedures per year.

VIII.Surgical backup. Emergency surgical intervention is a rare event and is required in 0.3% to 1.0% of cases of PCI, usually because of complications that cannot be addressed percutaneously or to provide urgent hemodynamic support. The most common reasons for emergency CABG surgery are dissection resulting in acute vessel closure, perforation, inability to retrieve a stent or other device, or aortic dissection. Emergency CABG after PCI has a mortality rate of 15% and periprocedural MI rate of 12%. The internal mammary artery may not be harvested, and surgery should not be delayed because of abciximab. Data from the Atlantic Cardiovascular Patient Outcomes Research Team and Primary Angioplasty in Acute Myocardial Infarction with No Surgery On-Site trials suggest that primary PCI for STEMI can be safely and effectively performed in centers that do not perform elective PCI and do not have on-site cardiac surgery capabilities if they implement a carefully developed and proven strategy capable of rapid and effective PCI (including an experienced operator with >75 total PCIs and at least 11 primary PCIs for STEMI per year) with a predetermined transfer plan to a nearby center with on-site surgical backup.

IX.Sheaths, guides, and wires

A.Typical guide access is radial access with 6F sheath. A modified Seldinger technique is used to obtain access over a soft wire using fluoroscopic guidance.

B.Another arterial access involves placing a 6F to 8F short sheath in the common femoral artery using the modified Seldinger technique (long sheaths, such as 23 or 35 cm, can be used if there is significant tortuosity and/or additional support is required). Using fluoroscopic guidance when entering the femoral artery above the inferior margin of the femoral head but below the pelvic rim increases the likelihood of entering the common femoral artery at a compressible site above the common femoral artery bifurcation and below the inferior epigastric artery. The superficial/profunda femoral artery bifurcation is best seen in the ipsilateral 30° to 40° projection. The brachial and radial arteries can accommodate up to 7F and 6F sheaths, respectively. Ulnar artery and digital arch patency should be confirmed via the Allen and/or Barbeau test in case the radial artery becomes occluded (approximately 3% to 5%). Radial access improves hemostasis and earlier ambulation but may have slightly increased radiation exposure. The choice of coronary equipment is no longer limited because of technologic advances in 6F to 7F compatible devices.

C.Larger guide size (7F or 8F) provides extra support and permits the use of larger rotational atherectomy burrs and use of simultaneous kissing stents. For straightforward lesions, a 6F system is typically adequate. The XB (extra backup) and Amplatz guiding catheters provide good support; the Amplatz guide is especially effective in cases of an acutely angled left circumflex artery, anomalous left circumflex artery originating from the right sinus, very anteriorly originating right coronary artery, or a tortuous/calcified right coronary artery. The Amplatz guide catheter is also the most likely catheter to traumatize the ostial/proximal coronary artery in inexperienced hands because of its tendency to deeply engage the vessel.

D.The coronary lesion is initially crossed with a 0.014-in. diameter coronary wire, which serves as a “rail” for devices such as balloons and stents. The choice of a wire depends on the wire tip’s stiffness, and support characteristics. Stiff tips are helpful to penetrate chronic total occlusions but increase the risk of vessel dissection or perforation. Hydrophilic wires are quite slippery and may be used to cross tortuous high-grade lesions, but can easily cause dissection or end-vessel perforation. Support wires also typically have stiffer tips and are primarily used as a supportive rail to deliver coronary equipment through tortuous vessels. Generally, most operators routinely use a “workhorse” wire (i.e., Runthrough, Prowater, or Balance MiddleWeight) and have “favorite” stiff (e.g., Miracle Bros series), hydrophilic (e.g., Whisper and Pilot series), and support (e.g., GrandSlam and Balance HeavyWeight) wires for use in appropriate situations. Both short (approximately 180 cm) and long (approximately 300 cm) wires are available. Most operators prefer the routine use of a rapid exchange (Rx) system, which uses a monorail that permits easy exchange over a short wire, although situations that require an over-the-wire system may be better served with the use of a longer wire to avoid dislodging the wire during equipment exchanges.

X.Diagnostic adjuncts

A.IVUS (anatomic)

1.An IVUS catheter generates a cross-sectional tomographic image of both the lumen and the vessel wall. This complementary imaging modality can be invaluable when repeated angiographic views fail to determine the mechanism and/or significance of a coronary lesion. IVUS has proven helpful in assessing adequacy of coronary stent deployment, mechanism of ISR (neointimal hyperplasia vs. inadequate stent expansion), a coronary lesion at a location difficult to image by angiography, a suboptimal angiographic result after PCI, coronary allograft vasculopathy after cardiac transplantation, coronary calcium when considering rotational atherectomy, and plaque location/circumferential distribution to guide directional coronary atherectomy. Further, IVUS can be indispensable in assessing the appropriate vessel size, especially during ACS when factors such as thrombus and vasoconstrictive substances can lead to significant stent undersizing.

2.IVUS provides anatomic, not physiologic, information. However, a lumen area <4.0 mm² in the proximal LAD, left circumflex, or right coronary artery or <6.0 to 7.0 mm² in the left main trunk suggests the presence of a hemodynamically significant lesion.

B.Optical coherence tomography (OCT). Similar to IVUS, OCT images are obtained by passing the catheter over a guidewire in the coronary artery. The catheter acquires images during an automated pullback over 5.6 cm and requires the clearance of blood in the vessel, thereby necessitating a 10 to 15 cc contrast injection with each acquisition. In comparison with IVUS, it provides much greater image resolution but a more shallow penetration. The superior image quality allows an evaluation of stent apposition, poststent dissection, and analysis of plaque characteristics and plaque rupture. Recently, investigators have used OCT to evaluate endothelial stent coverage, which in the future may allow a further tailoring of antiplatelet therapy at the patient-specific level. Currently, there is a paucity of clinical outcomes data using OCT, but interest in this imaging modality is gaining momentum, with supportive data likely to follow.

C.Coronary flow reserve (CFR) (physiologic)

1.A 0.014-in. wire capable of measuring coronary flow velocity permits assessment of epicardial and microvascular resistance. This information is helpful in determining whether a moderate-grade coronary stenosis (i.e., 30% to 70% stenosis) is hemodynamically significant. The ratio of hyperemic to basal flow is known as the CFR and is determined by giving an intracoronary vasodilator such as adenosine (36 to 64 µg). A normal CFR is 3 to 5. A CFR <2.0 is abnormal and is consistent with a flow-limiting epicardial stenosis or increased microvascular resistance.

2.The effect of the microvasculature can be eliminated by measuring the CFR in two vessels: the lesion-containing vessel and a normal-appearing vessel. This allows calculation of the relative coronary flow reserve velocity (rCFR = CFR_target/CFR_reference). A nonhemodynamically significant stenosis has an rCFR value of <0.8 and is similar in prognostic value to negative stress testing. Unlike fractional flow reserve (FFR), CFR depends on hemodynamic and microcirculatory changes. In general, FFR is the preferred diagnostic modality for assessing the hemodynamic significance of a coronary lesion.

D.FFR (physiologic). A 0.014-in. wire with a pressure transducer is placed distal to a coronary stenosis and the translesional gradient measured. This allows calculation of the FFR, which is the ratio of this distal coronary pressure to aortic pressure (Pd/Pa) during maximal hyperemia. A vasodilator such as adenosine (IV infusion 140 µg/kg/min or intracoronary 36 to 64 µg) is used. A coronary artery without flow-limiting coronary obstruction would have an FFR of 1.0. An FFR value of <0.75 to 0.80 is consistent with a hemodynamically significant obstruction with accuracy greater than 90% and positively correlates with myocardial ischemia on stress testing. Unlike CFR, the FFR reflects only the epicardial artery lesion. Prospective studies have demonstrated that an FFR-guided strategy to direct PCI of intermediate lesions results in less stents deployed, with a significant decrease in morbidity and mortality compared with an angiography-only strategy (8.4% vs. 23.9%, p = 0.02). The FAME 2 trial further demonstrated that, in patients with stable CAD and hemodynamically significant stenoses (FFR < 0.80), FFR-guided PCI in addition to best available medical therapy decreased the need for urgent intervention compared with those receiving best available medical therapy alone.

E.Instantaneous wave-free ratio (iFR; Volcano Corporation). Using wave-intensity analysis, a period of diastole in which equilibration occurs between pressure waves from the aorta and distal microcirculation was identified at approximately 75% into diastole (ending 5 ms before the R-wave). This wave-free period satisfied the requirements of FFR to have minimal and constant coronary resistance, and the Pd/Pa during this wave-free period was termed the “instantaneous wave-free pressure ratio,” or iFR. Using this proprietary pressure measurement modality, it was subsequently demonstrated that for iFR values lower than 0.86 or greater than 0.93, there was a strong correlation with hemodynamically significant and nonhemodynamically significant FFR values, respectively (using an FFR cut point of 0.80). For values falling within the “gray zone” between 0.86 and 0.93, performing confirmatory FFR or another modality to define lesion severity is recommended. One appealing measure of utilizing iFR is that it does not require a vasodilator or hyperemia to evaluate a lesion as it is a resting pressure-derived index of stenosis severity, therefore it has the potential to save time and reduce costs during the procedure.

F.Pulmonary artery catheter (physiologic). A balloon-tipped Swan–Ganz catheter advanced to the pulmonary arteries allows measurement of right and left heart filling pressures as well as the cardiac output. This information can be helpful in patients presenting with cardiogenic shock, during high-risk PCI in the setting of severe left ventricular (LV) dysfunction, when there is a question of pericardial tamponade or when the cause of hemodynamic deterioration is unclear.

XI.Therapeutic devices

A.Percutaneous transluminal coronary angioplasty. The coronary balloon remains the backbone of endovascular intervention, although it is almost never used as a stand-alone therapy. The initial gain in the coronary lumen achieved by balloon inflation results in localized dissection of the intima (and often the media) plus distension of the adventitia. The dissection is covered by platelet-rich thrombus and later by new intimal layers. As a result of these inevitable dissections, the abrupt closure rate is 4% to 7%, although the use of more potent contemporary antithrombotic therapies has reduced this rate. The 6-month angiographic restenosis rate of 30% to 40% is another downside to PTCA.

B.Bare-metal stents (BMS)

1.Present-day coronary stents are flexible, laser-cut and polished, balloon-mounted, and expandable, slotted tubes composed of either stainless steel or metal composites such as cobalt–chromium. They have proven effective in treating dissections and reducing the incidence of abrupt closure, emergency CABG (<1%), and restenosis. First implanted in 1986 and used for emergency treatment of coronary dissection after angioplasty, the early era of the intracoronary stent placement was plagued by high rates of subacute closure despite intensive anticoagulation regimens that often led to bleeding complications and prolonged hospitalization. Evolution of stent design, high-pressure implantation of stents, and advances in periprocedural antithrombotic regimens led to a rapid reduction in procedural complication rates and marked improvement in the ease of stent delivery.

2.Although subacute vessel closure may still occur in a small percentage of cases following stent implantation, by providing a scaffold and reducing elastic recoil, BMSs reduced the published rates of restenosis from >50% following PTCA alone to 20% to 30%. Restenosis risk is increased in patients with small reference vessel size, smaller postprocedural luminal diameter, or high degree of residual stenosis, long lesion length, diabetes, lesion location in the LAD artery, and presence of untreated edge dissection during the procedure.

C.Drug-eluting stents (DES). The Achilles heel of BMS has been ISR. Antiproliferative agents such as sirolimus, paclitaxel, zotarolimus, and everolimus arrest cell division during the mitotic growth phase. The use of polymers to coat these agents onto a stent’s surface and provide controlled, local drug delivery has dramatically reduced neointimal hyperplasia and thereby ISR. The “first-generation” DESs, introduced generally in 2003, were rapidly embraced and occupied almost 90% of the stent market by 2005. Although early studies raised concerns about higher rates of in-stent thrombosis in DES compared with BMS, subsequent large trials especially with second- and third-generation DES demonstrated similar ST rates for BMS and DES (see complete discussion below). In the current practice there is almost no advantage for BMS except some financial considerations. Even the difference in DAPT duration postprocedure between the two stents is disappearing (see below). There are a number of DESs available, with various studies supporting their clinical use. Whereas a thorough discussion of trial data is outside the scope of this chapter, a brief overview of the currently available DES is summarized below and in Table 63.4.

TABLE 63.4 Coronary Stents Approved in the United States
Name	Manufacturer	Stent Material	Drug	Notes/Comments
BMS
Integrity	Medtronic	Cobalt–chromium	N/A
Vision	Abbott Vascular	Cobalt–chromium	N/A
VeriFLEX	Boston Scientific	Stainless steel	N/A
REBEL	Boston Scientific	Platinum–chromium	N/A
Durable-Polymer DESs (currently in use)
Xience	Abbott Vascular	Cobalt–chromium	Everolimus	Pivotal trials: SPIRIT series
Promus	Boston Scientific	Platinum–chromium	Everolimus	Pivotal trials: PLATINUM series
Taxus Ion	Boston Scientific	Platinum–chromium	Paclitaxel	Pivotal trial: PERSEUS
Endeavor	Medtronic	Cobalt–chromium	Zotarolimus	Pivotal trials: ENDEAVOR series
Resolute	Medtronic	Cobalt–chromium	Zotarolimus	Pivotal trials: RESOLUTE series
Bioabsorbable Polymer DESs (currently in use)
SYNERGY	Boston Scientific	Platinum–chromium	Everolimus	First bioresorbable polymer DES to receive FDA approval (October 2015) Pivotal trials: EVOLVE series
Bioabsorbable Vascular Scaffolds
Absorb	Abbott Vascular	Biodegradable PLLA polymer	Everolimus	First bioresorbable scaffold to receive FDA approval (July 2016) Pivotal trials: ABSORB series
Previously Approved (“First-Generation”) DESs (no longer in use)
Cypher	Cordis/J&J	Stainless steel	Sirolimus	Discontinued in 2011 Pivotal trials: RAVEL, SIRIUS
Taxus	Boston Scientific	Stainless steel	Paclitaxel	Pivotal trials: TAXUS series

BMS, bare-metal stent; DES, drug-eluting stent; FDA, Food and Drug Administration; PLLA, poly-l-lactic acid.

1.Endeavor, Resolute, and Resolute Integrity (Medtronic) zotarolimus-eluting stents (ZES). The ZESs are considered second-generation DES. The Endeavor DES elutes zotarolimus from a cobalt–chromium Driver stent platform. The Resolute stent makes use of the Driver platform with a newly designed polymer that allows a delayed release of the drug for out to 3 months. The Resolute Integrity stent elutes zotarolimus from Medtronic’s Integrity stent platform.

2.Xience (Abbott Vascular, CA) and Promus (Boston Scientific, MA) everolimus-eluting stent (EES). Along with the ZES discussed above, the EESs are also considered “second-generation” DES.

D.Bioresorbable polymer DES

1.Synergy (Boston Scientific, MA). As long-term outcome data became available for first- and second-generation DES, there was an increasing focus on late adverse events and inherent limitations related to implanting permanent metallic scaffolds and polymers—specifically, incomplete endothelialization, persistent inflammatory reactions, loss of native vessel curvature and vasoregulation, and neoatherosclerosis. Approved by the Food and Drug Administration (FDA) in October 2015, the Synergy stent became the first bioresorbable polymer DES available in the United States. Whereas it also elutes everolimus from a platinum–chromium platform, the polymer which does so is absorbed over time, leaving the patient with what is then in effect a BMS (in contrast to the durable-polymer DES discussed above, in which the polymer remains permanently on the stent surface even after drug elution has completed).

E.Bioabsorbable vascular scaffolds (BVS; Abbott Vascular, CA). Bioabsorbable scaffolds were developed to incorporate the early benefits of DES—mechanical support to the artery to prevent elastic recoil and allow healing as well as controlled antiproliferative drug delivery to prevent ISR—while leaving no permanent metallic scaffold in the artery, which has been postulated to allow a return of normal vascular physiology and access to the vessel, should future surgical revascularization be required. The Absorb BVS (Abbott Vascular, CA) features a semicrystalline poly-l-lactic acid resorbable scaffold with an everolimus-coated poly-dl-lactide polymer that has a controlled drug release profile similar to the cobalt–chromium Xience EES. It was approved by the FDA in July 2016 and became the first BVS commercially available in the United States.

F.Stent thrombosis is defined as early (<30 days), late (30 days to 1 year), and very late (>1 year). It may be the result of stent-, procedure-, patient-, and antiplatelet therapy–related factors, and minimizing the risk of ST requires a conscious consideration of each of these issues. Compared with thrombosis of native coronary arteries, ST is associated with a higher thrombus burden and less frequent procedural success, all of which results in a much higher rate of death, recurrent MI, and recurrent ST.

1.Stent-related factors. Following BMS implantation, the vascular endothelium typically grows over the stent struts in 2 to 4 weeks, thereby eliminating contact between the stent and circulating platelets with a concomitant reduction in thrombotic risk. In contrast, reendothelialization following DES implantation is significantly retarded because of the antiproliferative effect of the coating polymer, thereby allowing for strut/platelet contact up to several years post-PCI (similar to the historical use of brachytherapy). In meta-analyses of large trials, the overall incidence of ST is similar in both BMSs and DESs (0.5% to 1.0% per year).

2.Procedure-related factors. Incomplete stent apposition to plaque/vessel wall, inadequate stent expansion (i.e., stent undersizing to the vessel), and stent-edge dissection all increase the risk of ST. Whereas angiography may indicate all of the above problems, stent sizing is routinely underestimated by the angiogram alone. Further interrogation of the vessel using IVUS or OCT (discussed in Sections X.A and X.B, respectively) may be necessary to optimize the chances of success and minimize the risk of ST. Additional risk factors for ST include long lesion length, small artery diameter, and complex lesion morphology (i.e., bifurcation stenting and chronic total occlusion).

3.Patient-related factors. Comorbid risk factors not only are important in assessing the relative benefit of DES but also increase the risk of ST. For instance, patients with diabetes, impaired LV function, and renal disease not only derive greater benefit from the antirestenotic properties of DES but also present a greater risk of ST. Premature cessation of DAPT (because of nonadherence, need for surgery, bleeding complications, or financial considerations) as well as poor clopidogrel response (seen in up to 15% of patients) also increase the risk of ST, especially in patients treated with DES.

4.Duration of antiplatelet therapy. In patients with ACS, the use of at least 12 months of DAPT is recommended for its established benefit in reducing MACE over aspirin alone. With respect to stent safety alone, however, use of 4 to 6 weeks of clopidogrel is sufficient to allow endothelialization of BMS. For DES, numerous authors have demonstrated that early cessation of DAPT is a significant predictor of ST. The optimal duration of DAPT after DES implantation is not known and likely depends on integrating multiple patient-specific ischemic and bleeding risks. The DAPT trial is the largest of the randomized trials that have compared longer to shorter duration DAPT after PCI. It randomly assigned 9,961 patients who had been successfully treated with 12 months of aspirin and either clopidogrel or prasugrel to continue receiving the same P2Y₁₂ receptor blocker or placebo for an additional 18 months (on the background of all patients continuing low-dose maintenance aspirin). The rates for both coprimary end points of ST and a composite of all-cause mortality, MI, or stroke were significantly lower with prolonged DAPT (0.4% vs. 1.4; hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.17 to 0.48 for ST, and 4.3% vs. 5.9%; HR 0.71, 95% CI 0.59 to 0.85 for the composite end point). The reduction in events with prolonged DAPT was mostly attributable to a lower rate of MI (2.1% vs. 4.1%; HR 0.47, p < 0.001); however, moderate and severe bleeding rates were significantly increased in patients treated with prolonged DAPT (2.5% vs. 1.6%, p = 0.001). Additional prespecified subanalyses suggested a greater benefit of prolonged DAPT in patients who received PCI for ACS (p-interaction = 0.03). Furthermore, the rate of MI not related to the stented site was also lower in patients treated with prolonged DAPT (1.8% vs. 2.9%; HR 0.59; p < 0.001), accounting for 55% of the total reduction in MI seen with prolonged DAPT. This suggests there may be a possible benefit from DAPT attributable to the prevention of adverse events from plaque rupture at sites remote from the stented index lesion. Of note, other smaller randomized trials, including PRODIGY, DES-LATE, and ARCTIC-Interruption did not show a decrease in ischemic events with prolonged DAPT. These and other trials have been studied together in several meta-analyses including up to 10 randomized control trials and representing over 30,000 patients, which have found a significantly lower rate of MI and ST with prolonged DAPT at the expense of significantly higher rates of bleeding. In a meta-analysis which included only studies comparing shorter duration (3 to 6 months) to 12 months of therapy (including the SECURITY, ITALIC, ISAR-SAFE, OPTIMIZE, EXCELLENT, RESET, and PRODIGY trials), there was no significant difference in the risk of all-cause death (HR 0.89, 95% CI 0.66 to 1.20) for 6 months of DAPT compared to 12 months or longer. However, each trial was noted to have one or more significant limitations, such as small sample size or enrollment of lower risk patients, and there was significant heterogeneity among the included trials. In summary, the optimal duration of DAPT must be tailored to the individual patient taking into account specific bleeding and ischemic risks, as well as cost. Our practice is to continue DAPT for at least 12 months following DES placement, and in patients who have tolerated this, continue either their current agent for up to 30 months, or for patients taking a third-generation P2Y₁₂ consider switching to clopidogrel for months 13 to 30 based on individualized bleeding risk. Several trials are underway to assess the safety and efficacy of discontinuing aspirin while continuing monotherapy P2Y₁₂ inhibition following stent implantation.

5.Although DESs have dramatically reduced the incidence of ISR and MACE, especially in patients with diabetes and complex coronary lesions, a mounting body of evidence suggests an increased risk of late and very late thrombosis following the discontinuation of antiplatelet therapies. Therefore, the decision to use BMS or DES in any given patient requires a thorough evaluation of factors that may predispose the patient to premature discontinuation of DAPT. In our catheterization laboratory, BMS use is very rare and generally reserved for patients who require revascularization before urgent noncardiac surgery and/or have malignancy or other significant bleeding issues which preclude DAPT continuation.

G.Covered stents. Covered stents use a material such as polytetrafluoroethylene (PTFE), which covers the stent struts and seals off the vessel wall from the stent lumen. The Jomed covered stent has PTFE sandwiched between two Jostents. This covered stent is approved for use after coronary perforation by the FDA, but requires reporting of their use in this situation as a sentinel event. FDA approval can also be obtained on a case-by-case basis in patients with coronary aneurysm.

H.Cutting balloon atherectomy

1.These balloons were initially developed to create a “controlled dissection.” A cutting balloon has three to four longitudinally mounted, razor-sharp atherotomes. These atherotomes cut into both plaque and vessel wall and allow vessel dilatation at a lower balloon pressure. Success in the treatment of balloon-resistant lesions led to FDA approval in 1995. Although randomized data have shown no difference between cutting balloon angioplasty and PTCA, many operators use this device in lesions with high elastic recoil (i.e., ostial or bifurcation lesions) before DES. The AngioSculpt device consists of a balloon surrounded by a nitinol cage that prevents balloon slippage and scores the plaque. An alternative to these specialized balloons is to place a second guidewire as a “buddy” in the coronary artery, which serves as a makeshift cutting device at the lesion during balloon inflation over the first wire.

2.Cutting balloons have also found a niche in the treatment of ISR. Regular balloons often slip when inflated across these rubbery lesions. The Restenosis Reduction by Cutting Balloon angioplasty Evaluation III trial randomized 521 patients to cutting balloon or PTCA before stenting (with angiographic or IVUS guidance) and demonstrated a significantly lower rate of angiographic restenosis in the cutting balloon before stenting group, primarily with IVUS guidance. The “buddy wire” technique may also be useful to increase friction and minimize balloon slippage in the treatment of ISR. It is important to use a second wire that does not have a hydrophilic coating in order to maximize effectiveness.

3.Care must be taken not to oversize cutting balloons, because perforation can occur. Placing these balloons through stent struts or down tortuous vessels can result in atherotome entrapment, as can a perforated balloon. These balloons should only be inflated to 6 to 10 atm in order to decrease the likelihood of balloon rupture.

I.Rotational atherectomy

1.Rotational atherectomy uses a 160,000 rpm, diamond-coated burr (i.e., drill bit) that is advanced over a 0.009-in. wire to the coronary lesion. The process generates microparticulate debris that embolize and may attenuate the coronary microcirculation, inducing transient myocardial stunning, periprocedural MI, and LV dysfunction in the region of the target vessel. Therefore, although limited clinical data suggest that rotational atherectomy can be safely performed in patients with depressed LV function in the hands of an experienced operator, it is not recommended.

2.Compared with plain balloon angioplasty, rotational atherectomy increases the chance of procedural success but has not been shown to reduce the risk of restenosis or MACEs in de novo or restenotic lesions. Although the use of rotational atherectomy has declined, it is recommended before stenting in patients with severely calcified lesions, undilatable lesions, chronic total occlusions, and bifurcation lesions to help ensure proper stent expansion and apposition in balloon-resistant lesions.

3.Familiarity with the device is essential. Sluggish coronary flow can occur, requiring a vasodilator such as verapamil, nitroprusside, or adenosine. Perforation occurs in approximately 1% of patients, typically when significant tortuosity forces the burr to the outside edge of a curve. Prophylactic pacing or aminophylline is frequently required if rotational atherectomy is performed in the vessel supplying the atrioventricular (AV) node. Rotational atherectomy is typically contraindicated in patients with thrombus, dissection, or severely reduced LV systolic dysfunction.

J.Orbital atherectomy

1.Orbital atherectomy, similar to rotational atherectomy, is a vessel preparation treatment to facilitate successful stent deployment for severely calcified lesions which utilizes a rotating burr to ablate plaque into particles small enough to be cleared by the reticuloendothelial system without the requirement for distal embolic protection devices. The device differs from rotational atherectomy in that the burr is flexible and the depth of plaque ablation can be changed by altering the speed of rotation. The Diamondback 360 Orbital Atherectomy System (Cardiovascular Systems, Inc.) employs a unique proprietary mechanism of differential sanding and centrifugal force and received FDA approval for coronary use in October 2013. The foundation for its use was established in the ORBIT II trial, in which 443 patients were treated with orbital atherectomy in an open-label registry. Following orbital atherectomy, successful stent delivery was possible in 98% of patients.

K.Excimer laser

1.The excimer (excited and dimer) laser catheter (excimer laser coronary atherectomy, ELCA) tip is brought into contact with the target lesion. It creates ultraviolet light (308 nm) at a rate of 25 to 40 pulses/s from a high-energy, metastable, dimeric molecule of xenon and chloride. This provides 45 mJ/mm², which can ablate 0.5 mm of tissue per second, and reduces the target tissue to gas and subcellular debris. The size of the lumen created is equivalent to that of the catheter (0.9 mm diameter).

2.The ELCA was approved by the FDA in 1992 for total occlusions, moderately calcified stenoses, balloon crossing/dilatation failures, ostial lesions, bypass grafts, and long diffuse disease. It is contraindicated in angulated lesions, coronary dissection, thrombotic lesions, and severely calcified lesions. However, long-term clinical data have failed to demonstrate a significant restenosis benefit, and routine use increases the complication rate in comparison with plain balloon angioplasty. Therefore, the American College of Cardiology (ACC)/American Heart Association (AHA) PCI guidelines do not recommend the use of ELCA as a primary strategy for revascularization, and its use in the present day is typically limited to cases of stent underexpansion and lesion modification in refractory ISR.

L.Thrombectomy

1.Aspiration thrombectomy. As intracoronary thrombus is frequently found in patients presenting with STEMI, the use of a catheter to aspirate thrombus from the infarct artery is intuitively attractive. However, although thrombus burden can be reduced by using manual aspiration thrombectomy, evidence from large-scale clinical trials does not demonstrate a significant benefit from its routine use. The three largest and most rigorously conducted randomized controlled trials (RCTs) to examine manual thrombectomy in STEMI are the TAPAS (n = 1,071), TASTE (n = 7,244), and TOTAL (n = 10,732) trials. Whereas the TAPAS trial and meta-analyses of early trials suggested increased perfusion and reduced clinical events (including all-cause mortality) among STEMI patients receiving aspiration thrombectomy, this finding was not replicated in the subsequent larger TASTE and TOTAL trials which both showed no significant difference for their primary end points. Furthermore, in the TOTAL trial, the key safety outcome of stroke occurred significantly more frequently at both 30 and 180 days in the patients who received thrombectomy (HR 2.0). In the 2015 ACC/AHA focused guideline update on the management of STEMI, aspiration thrombectomy was downgraded to a class IIb indication. Currently, the most widely used aspiration catheters include the Pronto LP, PriorityOne Export, and Extract (from smallest to largest lumen size; all these are compatible with a 6F system except the Extract which requires 7F).

2.Rheolytic thrombectomy. The Possis AngioJet is the dominant rheolytic thrombectomy device. The device is a 5F double-lumen, flexible catheter that contains a hypotube through which six high-speed saline jets create a low-pressure area at the tip (approximately −760 mm Hg), which serve to macerate and aspirate the thrombus back into the catheter lumen in accordance with the Venturi–Bernoulli principle. This catheter has proven to be successful in thrombotic vein grafts, for which it received FDA approval in 1998. Temporary prophylactic pacing is recommended when treating vessels supplying the inferior wall, because of potential temporary AV block. Temporary ST-segment elevation is frequent. Perforation can occur in vessels <2.0 mm in diameter because of the high-pressure saline injection. Although small studies using the AngioJet in the setting of ACS have been encouraging, prospective randomized data demonstrating a clinical benefit have been lacking. The AngioJet Rheolytic Thrombectomy in Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction trial randomized patients with acute MI to AngioJet thrombectomy followed by PCI or PCI alone and concluded that mortality rates (4.6% vs. 0.8%, p < 0.02), infarct size (12.5 ± 12.1% vs. 9.8 ± 10.9%, p = 0.02), and MACE rates (6.7% vs. 1.7%, p < 0.01) were considerably higher in those undergoing thrombectomy. Although not used in the routine care of patients, the AngioJet still holds a place in the interventional armamentarium for patients with overwhelming clot burden that is not adequately addressed by aggressive aspiration thrombectomy alone.

M.Filters. A collapsible microporous polyurethane net attached to a nitinol ring anchored distally to a 0.014-in. guidewire can be advanced across high-risk saphenous vein graft (SVG) or carotid stenoses and then deployed downstream of the lesion. When deployed, these porous devices appear as a windsock or umbrella and allow blood to flow through while filtering any debris larger than 80 to 100 µm. Advantages are ease of use and avoidance of prolonged ischemia. Potential disadvantages are incomplete sealing, passage of smaller particles through the filter pores, overloading of the device, and spillage during device retrieval. The FilterWire EX Randomized Evaluation trial prospectively randomized 650 patients undergoing PCI of diseased SVGs to either the EPI FilterWire EX or the PercuSurge GuardWire embolic protection device and revealed equal efficacy of both types of devices in regard to the primary end point of death, periprocedural MI, and target lesion revascularization (TLR) at 30 days. This trial led to FDA approval of the FilterWire EX for use in degenerated SVGs.

XII.SVG Interventions

A.Saphenous vein bypass grafts are frequently used in CABG surgery. However, 7% occlude the first week, 15% to 20% occlude the first year, and by the tenth year 50% of SVGs are occluded and 25% are severely degenerated. Redo CABG is high-risk surgery with high rates of morbidity and mortality that approach 7% to 10% nationally. At the Cleveland Clinic, the rate is 1.8%. A patient with a patent internal mammary artery graft to the LAD artery makes redo surgery less appealing. Patients with no prior arterial conduit, multiple failed SVGs, multivessel disease, and depressed LV systolic function are ideal candidates for redo surgery.

B.Early postoperative ischemia within the first 30 days usually reflects graft failure (often secondary to thrombosis) or incomplete revascularization, and urgent coronary angiography is indicated. Emergency PCI of the graft, even across suture lines, has been safely performed within days of surgery. Intracoronary thrombolysis should be used with caution. Mechanical thrombectomy is a safer choice. Given that SVG flow is pressure dependent, intra-aortic balloon pump use should be strongly considered in patients that present with hypotension or depressed LV function.

C.Recurrent ischemia 1 to 12 months after CABG surgery usually reflects perianastomotic graft stenosis. Distal anastomotic stenoses respond well to balloon inflation only. Mid-shaft vein graft stenoses are usually due to intimal hyperplasia.

D.Recurrent ischemia >1 year after CABG surgery usually reflects the development of atherosclerosis. SVGs have greater plaque burden than native coronary arteries, and aspirates are composed of atherosclerotic rather than thrombotic elements. This may explain the lack of benefit seen with glycoprotein IIb/IIIa inhibitors (GPIs). Unprotected PCI (i.e., no PercuSurge GuardWire or filter device) results in varying degrees of atheroembolization, with 15% of patients having a CK-MB more than five times normal. Therefore, use of distal protection devices during SVG interventions is strongly encouraged when technically feasible. The use of these devices is discussed above in Section XI. In situations of poor reflow after SVG PCI, copious administration of intracoronary adenosine and/or nitroprusside is recommended, with the goal of improving microvascular flow. It should also be noted that poor reflow may be seen due to a plaque-burdened filter, which should resolve with aspiration followed by filter retrieval.

XIII.Restenosis. Restenosis is the most commonly occurring late PTCA complication and typically occurs within 6 months primarily because of vessel contracture, elastic recoil, negative vessel remodeling, and neointimal hyperplasia. ISR is almost entirely due to neointimal hyperplasia. Not surprisingly, focal restenosis has a better outcome and response to treatment than does diffuse restenosis. The predictors of restenosis include diabetes, unstable angina, acute MI, prior restenosis, small vessel diameter, total occlusion, long lesion length, SVG, proximal LAD artery, higher percent stenosis after the procedure, and smaller minimal luminal diameter after the procedure. Strategies to decrease restenosis include maximizing stent expansion (i.e., bigger is better) and minimizing the distance of arterial injury.

Post-PTCA. Balloon angioplasty alone has a 6-month restenosis rate of 32% to 40%. For restenotic lesions managed with PTCA, the restenosis rate is comparable to de novo lesions. For a third episode of restenosis, PTCA has a restenosis rate approaching 50% (not 100%). With PTCA alone, late patency is 93% after three procedures. Only 1.6% of lesions require four or more procedures. Atheroablative approaches, such as excimer laser and rotational atherectomy, have not proven superior in managing restenosis. However, stents are superior to PTCA, with a 6-month TVR rate of 10% versus 32%.

In-stent restenosis. The risk of recurrent ISR after balloon angioplasty is 10% for focal ISR, 50% for diffuse restenosis, and 80% for total stent occlusion. Atheroablative approaches, such as use of the cutting balloon and rotational atherectomy, have not proven clinically superior to PTCA.

A.ISR occurs in 17% to 32% of patients treated with BMS depending upon such variables as vessel size, lesion length, diabetes mellitus, smaller postprocedure minimal luminal diameter, higher residual percent stenosis, and vessel location. In patients who cannot receive DES but for whom ISR is an issue, consideration may be given to a short course of oral sirolimus therapy. The Oral Rapamycin in ARgentina (studies I to III) investigators have found substantial reduction in TLR for BMS plus sirolimus (10 mg pre-PCI followed by 3 mg daily for 13 days) in comparison with BMS alone (8.3% vs. 38% at 1 year, p < 0.001) and equivalence in TLR compared with DES (8.2% vs. 7.0% at 18 months, p = 0.84).

B.The observed rate of ISR is significantly lower with DES. As discussed previously, 5-year follow-up from the SIRIUS trial of Cypher SES yielded a 9.1% rate of TLR, similar to the 9.6% TLR rate at 5 years in the TAXUS IV trial of PES. Follow-up data for the EES (Xience V or Promus) have been published up to 2 years in SPIRIT IV and show an ischemia-driven TLR rate of 4.5%. The Intracoronary Stenting or Angioplasty for Restenosis Reduction—Drug-Eluting Stents for In-Stent Restenosis trial compared SES and PES with balloon angioplasty in 300 patients with ISR following BMS and demonstrated a significant reduction in restenosis at 6-month follow-up in the DES groups as compared with angioplasty alone (8% vs. 33%). A comparison of EES and PES revealed a significant improvement in recurrent TLR with EES (1% vs. 11.5%, p = 0.0193) at 1 year, but similar rates of MI, death, and ST. Atheroablative approaches, such as use of the cutting balloon and rotational atherectomy, have not proven clinically superior to PTCA.

Brachytherapy. Brachytherapy damages chromosomes and prevents cell division, thereby inhibiting neointimal hyperplasia. Both β and γ brachytherapy catheter-based systems use closed-end lumen catheters that deliver the source and keep it out of contact with the blood, allowing reuse. Both γ (iridium 192) and β (phosphorus 32 and strontium 90) brachytherapy result in approximately 50% reduction in ISR compared with balloon angioplasty alone. It is important to ensure brachytherapy delivery to all balloon-injured segments in the target vessel, or else inadequate radiation to an injured segment can cause neointimal proliferation. Brachytherapy can only be used one or two times in each vessel, and long-term DAPT with aspirin and clopidogrel is essential, given the risk of late in-stent thrombosis. Ultimately, long-term data are disappointing with a high failure rate; brachytherapy has therefore fallen largely out of favor. However, it is seeing a small resurgence in its use at select centers for truly refractory ISR cases.

XIV.Pharmacologic adjunctive therapy

A.Antithrombins. Antithrombins prevent the generation of thrombin and/or inhibit the activity of thrombin. An antithrombin such as unfractionated heparin (UFH), bivalirudin (direct thrombin inhibitor [DTI]), or enoxaparin (low-molecular-weight heparin [LMWH]) should be used during all coronary interventions to prevent thrombus formation on the equipment. This principle applies even to patients with a high international normalized ratio (INR). Maintenance of appropriate levels of anticoagulation is imperative to safely navigate the path between thrombosis and bleeding complications. The following provides a brief overview of the anticoagulant agents used during PCI. For specific data regarding their use during ACS, please refer to Chapter 2.

B.Unfractionated heparin

1.UFH binds and induces a conformational change in antithrombin, converting it to a more efficient inhibitor of circulating thrombin (factor IIa), factor Xa, factor IXa, factor XIIa, and kallikrein. Initial dosing is weight-based and, at traditional dosing of 50 to 70 units/kg commonly used in PCI, it has a dose-dependent half-life of 30 to 60 minutes. No maintenance infusion is given. A distinct advantage of UFH is that its anticoagulant effect can be followed (and subsequent dosing titrated to achieve) by routine activated partial thromboplastin times or point-of-care ACTs in the catheterization laboratory, with common ACT targets ranging from 250 to 300 seconds for UFH monotherapy or 200 to 250 seconds when used with concurrent GPIs (or if being conservative in the setting of increased bleeding risk or other patient-specific factors). Of note, this ideal ACT range has not been rigorously reexamined with randomized control trials in the era of routine P2Y₁₂ receptor blocker use. Additional advantages of UFH include its widespread availability, low cost, rapid clearance after the infusion is discontinued, and the ability to reverse its anticoagulant effects with protamine in urgent situations. Potential disadvantages include the higher incidence of heparin-induced thrombocytopenia with UFH compared with other heparin preparations.

2.In uncomplicated PCI cases, prolonged postprocedural heparin infusions increase bleeding complications and do not lower the likelihood of abrupt vessel closure or the rate of restenosis. The sheath should be removed when the ACT is <180 seconds.

C.Low-molecular-weight heparin

1.LMWHs are a group of agents derived from UFH that act via antithrombin and preferentially inhibit factor Xa more than thrombin. Three LMWH agents have been approved by the FDA for clinical use: enoxaparin, dalteparin, and tinzaparin. Enoxaparin is the most rigorously studied of all the LMWH in the setting of ACS and is the agent typically used in the United States. Enoxaparin exhibits much less binding to plasma proteins and endothelial cells than UFH, giving it a more consistent and predictable factor Xa inhibition and subsequently anticoagulant effect. When given intravenously, enoxaparin has a time to peak effect of 5 to 10 minutes, compared with 3 to 5 hours when administered subcutaneously. Enoxaparin’s 5- to 7-hour half-life is dose-independent; however, dose adjustment is required in patients with renal insufficiency.

2.The majority of trials using LMWH in PCI have been in the setting of ACS; the evidence base supporting its use during routine elective PCI is much weaker. Multiple early trials demonstrated a reduction in death and MI among conservatively managed NSTEACS patients (not undergoing routine revascularization) treated with enoxaparin compared with UFH; however, in patients undergoing early invasive management LMWH was noninferior to UFH for composite ischemic end points. Of note, when reviewing the historical evidence base for LMWH use in PCI, it is important to recognize that very few utilized contemporary DAPT (aspirin plus oral P2Y₁₂ or GPI). Therefore, in contemporary practice with routine DAPT and the increasing utilization of radial artery access for PCI, LMWH use in the United States has been primarily limited to NSTEACS patients selected for conservative management.

3.If a hospitalized patient has been given subcutaneous enoxaparin, a reasonable strategy is as follows. If PCI is performed within 8 hours of subcutaneous enoxaparin administration, then no additional heparin is required. If PCI is performed within 8 to 12 hours, an additional IV dose of 0.3 mg/kg of enoxaparin should be administered. If PCI is performed >12 hours after enoxaparin injection, standard doses of UFH can be used.

4.When using LMWH, ACT measurement does not reflect the degree of anticoagulation and there is no rapid method for determining factor Xa activity. This inability to confirm adequate antithrombin activity and assess the level of anticoagulation with a bedside test makes some interventional cardiologists uncomfortable. Significant anti–factor Xa activity persists for about 12 hours. LMWH is only partially reversed with protamine.

5.Dosing LMWH in obese patients provides a much less reliable level of anticoagulation. Extreme caution should be exercised in patients with moderate-to-severe renal insufficiency (i.e., creatinine clearance < 30 mL/min), as the renal elimination of LMWH may result in unexpectedly high degrees of anticoagulation for a prolonged period. In these cases, most interventionalists will use an alternative antithrombotic agent.

D.Fondaparinux

1.Fondaparinux is a synthetic pentasaccharide that binds to antithrombin and induces a conformational change that increases its affinity for factor Xa. Fondaparinux has compared favorably with LMWH in both the NSTEMI and STEMI settings, in large part because of a significant decrease in bleeding complications. However, there is an increased risk of guide-catheter thrombosis during PCI (OASIS-8). Therefore, in contemporary practice, the use of fondaparinux is typically reserved for patients with a high risk of bleeding selected for a conservative management strategy, because it has not been shown to have added benefit over UFH or LMWH in patients undergoing PCI. Because of the unique concerns with catheter thrombosis and fondaparinux, it is not recommended for use as the sole anticoagulant agent during PCI and it is important that patients treated with fondaparinux who go on to have PCI performed do so with the addition of other antithrombotic therapy, such as UFH or bivalirudin.

E.Direct thrombin inhibitors (bivalirudin)

1.The initial DTI was isolated from leech saliva, although now these materials are synthesized using recombinant technology. These agents directly inhibit clot-bound thrombin without requiring an antithrombin cofactor. DTIs are better able to block both fluid-phase and clot-bound thrombin, which may be particularly important in a thrombus’ platelet-rich environment.

2.A hirudin analog, bivalirudin, is becoming increasingly more common in catheterization laboratories and is an important anticoagulant for patients undergoing PCI. Bivalirudin has several intrinsic advantages over UFH and LMWH in the setting of PCI: It has no known natural inhibitors (such as platelet factor 4), it has a more predictable bioavailability, it does not directly activate platelets, and (unlike UFH) it does not require periprocedural monitoring with ACT levels after it is administered.

3.Bivalirudin has been the focus of multiple randomized clinical trials over a 20-year period, comparing it with various anticoagulation regimens (most notably against UFH and against UFH + GPI) in nearly all PCI settings (elective PCI, NSTEACS, and STEMI). The REPLACE-2 trial compared bivalirudin with the combination of abciximab/UFH in a prospective, randomized, double-blind fashion and found it to be associated with fewer bleeding-associated complications and a statistically noninferior rate of MACEs. Bivalirudin has also shown similar salutary effects in patients with STEMI (HORIZONS-AMI) and NSTEACS (ACUITY). Although a higher incidence of acute ST was observed in patients with STEMI, which may (e.g., EUROMAX trial) or may not (e.g., MATRIX trial) be able to be reduced by prolonging the bivalirudin infusion after PCI, long-term mortality was similar or reduced by bivalirudin compared with heparin + GPI. For several years bivalirudin monotherapy had largely replaced the use of UFH + routine GPI in patients undergoing PCI. However, several concurrent advances in contemporary PCI such as radial artery access, newer thinner stent designs with second-generation antiproliferative drugs, and improved third-generation P2Y₁₂ antiplatelet agents have led to the reevaluation of bivalirudin against UFH-only regimens. In several of these recent trials (including NAPLES-III, MATRIX, and HEAT-PPCI), bivalirudin was not found to significantly reduce bleeding, and in one trial in a contemporary STEMI population (HEAT-PPCI), UFH alone reduced composite ischemic events compared with bivalirudin. Another such trial (BRIGHT), again in a contemporary STEMI population, however, found ischemic events and major bleeding reduced by bivalirudin compared with UFH. A high-quality meta-analysis examined 16 bivalirudin trials in nearly 34,000 patients to compare the relative safety and efficacy of bivalirudin to UFH in PCI, stratified according to the use of GPI. In their analyses, ischemic complications were slightly more frequent among patients receiving bivalirudin-based regimens compared with UFH-based regimens (risk ratio [RR] 1.09, 95% CI 1.01 to 1.17), regardless of the clinical indication for PCI or the GPI strategy used. The impact of bivalirudin on bleeding, however, was significantly impacted by the GPI strategy used. There was no significant difference found in bleeding in comparisons of bivalirudin monotherapy versus UFH monotherapy. Therefore, in the contemporary PCI era where GPIs are not routinely used, the role of bivalirudin over standard dose (70 U/kg) UFH monotherapy with third-generation DAPT is less clear.

4.Please refer to Chapter 2 for a more detailed discussion of bivalirudin use in STEMI.

5.Bivalirudin is given as a 1 mg/kg bolus followed by a 4-hour maintenance infusion of 2.5 mg/kg/h and by 0.2 mg/kg/h. A given bivalirudin dose provides a more predictable ACT than does UFH. The half-life is 25 minutes in patients with normal renal function, although in dialysis-dependent patients, the half-life may be as long as 3.5 hours. The maintenance infusion can be discontinued after completion of the coronary intervention. If a vascular closure device is not used, the sheath can typically be removed in 1 to 2 hours, given the drug’s short half-life. Unfortunately, the effects of bivalirudin cannot be reversed.

F.Warfarin. Routine warfarin is no longer recommended unless a patient has a mechanical prosthetic valve, atrial fibrillation, or intracardiac thrombus. DAPT has proven superior. An INR >1.6 is a strong relative contraindication to elective cardiac catheterization. If emergent cardiac catheterization is required due to ACS or MI, consider accessing the radial artery because hemostasis is rarely an issue with this approach.

G.Antiplatelet therapy

1.Platelets are essential in thrombus formation, and some form of antiplatelet therapy is typically given at the time of PCI.

2.Thromboxane A2 inhibitor (aspirin). Aspirin (acetylsalicylic acid [ASA]) is a cornerstone of effective antiplatelet therapy. Aspirin impairs platelet aggregation by irreversibly inhibiting platelet cyclooxygenase, thereby limiting thromboxane A₂ production. A loading dose of 325 mg of aspirin should ideally be given at least 2 hours before PCI and be continued indefinitely at 81 mg daily maintenance therapy following the procedure. Evidence from the CURRENT-OASIS 7 trial, which included a large subgroup of 17,263 patients undergoing PCI, has shown there is no benefit to a higher 325 mg daily maintenance dose, and it is associated with higher rates of bleeding complications. Secondary prevention trials have shown aspirin to reduce death, MI, and stroke by 27%. In PCI patients, aspirin reduces abrupt vessel closure.

3.Adenosine diphosphate receptor antagonists (ticlopidine, clopidogrel, prasugrel, ticagrelor, and cangrelor)

a.The addition of a second oral antiplatelet agent to aspirin (DAPT) marked a significant advance in contemporary pharmacotherapy for PCI. In the late 1990s, several landmark trials convincingly demonstrated that combined antiplatelet therapy (aspirin and thienopyridine), as compared with conventional anticoagulant therapy, after PCI reduced the incidence of both thrombotic and bleeding complications.

b.Thienopyridines such as clopidogrel and ticlopidine inhibit adenosine diphosphate–induced platelet aggregation by the P2Y₁₂ receptor. Clopidogrel is preferred to ticlopidine because of its better safety profile, although both require hepatic metabolism for activation.

c.Ticlopidine is poorly tolerated with prolonged use, resulting in 20% of patients discontinuing the drug because of nausea, diarrhea, and rash. Neutropenia and thrombotic thrombocytopenic purpura (TTP) occur in 1% to 3% and 0.03% of patients, respectively. The complete blood count should be serially examined in the first several months of use (q2wk × 3 months).

d.Clopidogrel is better tolerated than ticlopidine and has largely replaced it in clinical practice in the United States. The risk of TTP with clopidogrel is the same as in the general population (11 in 3 million), and neutropenia is not an issue, making blood count monitoring unnecessary.

e.The ACC/AHA guidelines recommend routine clopidogrel pretreatment with a dose of 600 mg, although this recommendation is made on the basis of studies that included patients with ACS. In patients undergoing elective PCI, a recent study revealed no difference in ischemic or bleeding complications between 300 and 600 mg loading doses. Similarly, in patients on chronic clopidogrel therapy undergoing elective PCI, the ARMYDA-4 RELOAD investigators found no benefit to an additional 600 mg “reloading” dose of clopidogrel; the group of patients with NSTEACS did have a reduction in MACE at 30 days, however.

f.For a discussion of clopidogrel duration after PCI, please refer to Section XI.F.4. For details of clopidogrel use after ACS, please refer to Chapter 2.

g.The issue of clopidogrel nonresponsiveness, defined as platelet inhibition <20%, is reported to be as high as 40% and is associated with worse clinical outcomes including ST, MI, and death. Mechanisms include genetic predisposition (i.e., CYP2C19 polymorphism that affects clopidogrel metabolism and thus activation) and drug–drug interactions. Unfortunately, recent studies (including OASIS-7 and GRAVITAS) have not shown a benefit to higher maintenance dose clopidogrel (150 vs. 75 mg daily), even in patients with established high platelet reactivity while on clopidogrel. Management of these patients is therefore difficult, and we typically change to a third-generation agent such as prasugrel or ticagrelor in cases of true clopidogrel nonresponse.

h.Prasugrel is a novel “third-generation” thienopyridine prodrug that requires conversion to an active metabolite with high affinity for the platelet P2Y₁₂ receptor site, resulting in a potent antiplatelet effect. The TRITON-TIMI 38 trial randomized 13,608 patients with moderate-to-high–risk ACS with scheduled PCI to either prasugrel or clopidogrel therapy and found a significant reduction in the primary efficacy end point of death from cardiovascular causes, nonfatal MI, or nonfatal stroke associated with prasugrel therapy. Prasugrel was also associated with a reduction in rates of MI, TVR, and ST. However, of some concern was a significant increase in major (HR 1.32, 95% CI 1.03 to 1.68, p = 0.03) and life-threatening (1.4% vs. 0.9%, p = 0.01) bleeding observed in the prasugrel group. An important subgroup of patients who had a net negative outcome was those with a prior history of stroke or transient ischemia attack, and prasugrel use in such patients is not recommended. Additional populations in which special caution is advised include patients over 75 years of age and patients weighing <60 kg because increased bleeding complications were noted in these groups. In an important distinction from the CURE trial, NSTEACS patients in TRITON-TIMI 38 only received the prasugrel loading dose after their coronary anatomy was angiographically defined and percutaneous revascularization planned.

i.Ticagrelor is a “third-generation” reversible P2Y₁₂ antagonist that is an active drug and does not require hepatic conversion to an active metabolite (unlike the thienopyridines). It exhibits the most rapid onset, greatest inhibition, and least individual variability of the oral P2Y₁₂ agents. The foundation of its use was established by the PLATO trial in which ticagrelor demonstrated a lower rate of composite cardiovascular events (death, MI, and stroke; 9.8% vs. 11.7%, p < 0.001) with fewer cases of in-stent thrombosis and without a significantly increased risk of major bleeding compared with clopidogrel. There was, however, a higher incidence of non-CABG major bleeding including intracranial hemorrhage in the ticagrelor group (4.5% vs. 3.8%, p = 0.03). It is important to recognize several key differences from the PLATO trial design and results when compared with the TRITON-TIMI 38 trial which established prasugrel use. First, in PLATO, ticagrelor was administered “upstream” at the time of randomization and prior to coronary angiography, which more closely fits contemporary patterns of ACS management. In addition, there was a significant benefit from ticagrelor not only among those patients who subsequently received revascularization with PCI, but also in those who were managed medically (“conservative management”) as well. In addition to its antiplatelet effects at the P2Y₁₂ receptor outlined above, recent studies have suggested possible “pleiotropic” effects of ticagrelor because of its biologic effects on adenosine. Patients with ACS were found to have significantly higher adenosine plasma concentrations 6 hours after ticagrelor loading compared with clopidogrel loading, and ticagrelor-treated patients (but not clopidogrel-treated patients) demonstrate reduced in vitro uptake of exogenous adenosine by erythrocytes. Whereas these early findings are still only hypothesis-generating, a number of reported clinical effects of ticagrelor (e.g., improved endothelial function) could be compatible with an adenosine-mediated effect and this warrants further dedicated investigation. Also in contrast to the other P2Y₁₂ agents discussed above, the use of ticagrelor is explicitly contraindicated in patients with severe hepatic dysfunction and another agent should be considered. Similar to clopidogrel and prasugrel, the use of ticagrelor in moderate liver dysfunction has not been well studied.

j.Cangrelor is an IV (nonthienopyridine) adenosine triphosphate analog which reversibly inhibits the P2Y₁₂ adenosine diphosphate receptor in a manner similar to ticagrelor. It was approved for use by the FDA in June 2015 as an adjunct to PCI in patients who have not been treated with a P2Y₁₂ agent and who are not being given a GPI. Major advantages of cangrelor when compared with other antiplatelet agents are its rapid onset of action and rapid return of platelet function after its discontinuation. Two trials (CHAMPION PLATFORM and CHAMPION PCI) evaluated its use in patients with ACS or stable angina requiring PCI and both failed to show clinical superiority compared to clopidogrel alone for a composite end point of death, MI, or ischemia-driven revascularization. A third trial (CHAMPION PHOENIX) studied patients undergoing urgent or elective PCI and found a composite primary efficacy end point (death, MI, ischemia-driven revascularization, or ST) occurred less often in the cangrelor group, without significant difference in the rate of severe or life-threatening bleeding at 48 hours. The most notable difference in the design of the CHAMPION PHOENIX trial compared with the earlier cangrelor trials was that it used a more sophisticated and detailed definition for PCI-related MI. In a pooled analysis of patient-level data from the three CHAMPION trials (comprised of 12% STEMI, 57% NSTEACS, 31% stable disease), cangrelor lowered the rate of the primary composite efficacy end point of death, MI, ischemia-driven revascularization, or ST at 48 hours compared with control (clopidogrel or placebo) (3.8% vs. 4.7%; OR 0.81; 95% CI 0.71 to 0.91). Mild, but not major, bleeding was increased with cangrelor (16.8% vs. 13.0%).

H.GP IIb/IIIa inhibitors (abciximab, eptifibatide, and tirofiban)

1.GPIs are IV medications that inhibit platelet aggregation and thrombus formation by preventing the binding of fibrinogen or circulating von Willebrand factor on the platelet surface. GP IIb/IIIa receptor inhibition prevents these receptors from binding to fibrin and forming the platelet–fibrin cross-linking that is required for thrombus formation. GP IIb/IIIa receptor occupancy >80% prevents the development of thrombus.

2.Abciximab is a human–murine chimeric antibody fragment that binds the GP IIb/IIIa receptor with high affinity, resulting in a slow dissociation rate (i.e., noncompetitive inhibition). Although abciximab remains detectable on platelets for the lifetime of the platelet, it is rapidly cleared from plasma, allowing platelet aggregation to return to normal in 12 to 36 hours. Rapid reversal of platelet inhibition in the event of bleeding requires discontinuation of the abciximab infusion, waiting 30 minutes for plasma clearance, and platelet infusion (12 units) so as to provide functional platelets. Profound thrombocytopenia occurs in 0.4% to 1.1% of patients. Platelet counts should be measured within the first 2 to 4 hours and the following day. Abciximab readministration has not been associated with hypersensitivity or anaphylaxis, although the risk of profound thrombocytopenia is somewhat higher (2.2%).

3.Eptifibatide is a cyclic heptapeptide and tirofiban is a tyrosine derivative nonpeptide mimetic. Both act as competitive inhibitors requiring high levels for adequate inhibition. Both have a short plasma half-life (2.0 to 2.5 hours), with platelet aggregation normalizing in 30 minutes to 4 hours. In the event of bleeding, the infusion should be stopped. Unlike abciximab, the effect cannot be reversed and platelets remain inhibited until plasma drug levels fall. Profound thrombocytopenia is rare (0.0% to 0.3%).

4.The use of GPI versus heparin alone during PCI prevents 65 adverse events per 1,000 treated patients and is arguably beneficial for all types of interventions. These benefits are particularly enhanced for unstable angina, diabetes mellitus, and bail-out stenting.

5.At proper doses, all three GPI agents are very potent inhibitors of platelet aggregation; however, their clinical use has been diminishing because much of their supporting evidence came prior to the contemporary era of routine oral DAPT. Trials reflecting routine use of clopidogrel early in the course of treatment or bivalirudin in PCI did not demonstrate an incremental benefit for ischemic outcomes with the routine addition of GPI. Therefore, current guidelines for management of patients with ACS call for dual, not triple antiplatelet therapy (ASA and usually oral P2Y₁₂ antagonists rather than GPI), with the addition of GPI reserved for selected patients who remain unstable, have a large thrombus burden on angiography, or have very high-risk clinical features.

For specific recommendations regarding the use of GPIs during ACS, please refer to Chapter 2.

I.Intracoronary vasodilators. PCI can result in no-reflow, which is defined as a reduction in coronary flow without an obstructive lesion. The most probable causes of no-reflow are microvascular spasm and distal embolization. Potent microvascular vasodilators, such as adenosine (36 to 72 µg), nicardipine (100 to 200 µg), nitroprusside (50 to 200 µg), or verapamil (200 µg), often restore normal flow. Nitroglycerin is a logical choice for relieving epicardial spasm but has no effect on the microvasculature. Immediately before SVG intervention, verapamil pretreatment has been shown to prevent no-reflow but has never been shown to reduce the risk of CK-MB elevation.

XV.Supportive adjunctive therapy

A.Please refer to the chapter on mechanical circulatory support devices.

XVI.Post-PCI Management

A.Access site care

1.The groin or arm access site should be examined for hematoma, pseudoaneurysm (systolic bruit), and arteriovenous fistulas (continuous murmur). A pulsatile mass also suggests a pseudoaneurysm. Ultrasound studies can confirm the diagnosis of pseudoaneurysm or arteriovenous fistula. Suprainguinal tenderness, back pain, lower quadrant abdominal pain, or hypotension should make one suspicious for retroperitoneal hemorrhage, which can be confirmed by computed tomography (CT). A hemoglobin level 1 day after PCI should be routine, and a decrease >2 g/dL is concerning. Distal pulses should be examined as well. Pulselessness, pain, pallor, paresthesias, and a cool extremity suggest an acute arterial occlusion.

2.Pseudoaneurysms <2 cm often close spontaneously; those 2 to 3 cm can often be closed by external, ultrasound-guided compression (90% success rate); and those >3 cm generally require surgical correction. Another frequently successful option is thrombin injection if the pseudoaneurysm has a thin neck.

3.Arteriovenous fistulas are typically small and inconsequential, rarely causing high-output failure. Indications for ultrasound-guided compression (success rate > 80%) or surgical closure include significant shunting, extremity swelling/tenderness, congestive heart failure (CHF), and deep venous thrombosis.

4.A retroperitoneal hemorrhage can be treated by supportive care (i.e., transfusions, close observation, and bed rest) in >80% of cases. Anticoagulation must be reversed, and frequent hemodynamic monitoring in an experienced intensive care unit is required. If required, transportation to CT scan should be deferred until the patient is hemodynamically stable. If the bleeding does not spontaneously stop, the patient may require vascular surgery consultation. Other options include balloon tamponade or coil embolization if a small side branch is the culprit.

5.Acute arterial occlusion may be due to dissection or thromboembolism. Both typically require angiography of the affected extremity with access from another extremity (e.g., with a cold right leg after right femoral artery access, left femoral access should be obtained and an angiogram of the right lower extremity can be performed by crossing over to the right common iliac artery). Dissection typically requires prolonged balloon inflation and possible stenting or surgery. Stenting at the common femoral artery is discouraged, because it is a flexion point and a frequent site of attaching bypass grafts. Thromboembolism can be treated with surgical (Fogarty catheter) or percutaneous mechanical thrombectomy (Possis AngioJet).

B.Monitoring for myocardial ischemia. A 12-lead electrocardiogram (ECG) should be obtained before and after PCI in order to have a baseline. The patient should be monitored on a cardiac ward that has continuous electrocardiographic monitoring and nurses familiar with routine post-PCI care. The CK and CK-MB levels should be measured 12 hours after the intervention. A procedural MI is presently defined as a CK-MB more than three times the normal (assuming a normal baseline CK-MB). Elevated CK, CK-MB, or electrocardiographic abnormalities occur in 5% to 30% of patients. Mechanisms include distal embolization, side branch occlusion, dissection, and spasm. Troponin levels are not routinely measured after PCI.

C.Monitoring for contrast-induced nephropathy. Nonsteroidal anti-inflammatory drugs, cyclosporine, and metformin should be withheld for 24 to 48 hours beforehand and for 48 hours afterward. Postprocedure saline hydration is continued at 75 to 150 mL/h for a total infusion of 1 to 2 L. Renal function (serum creatinine) should be monitored in patients with diabetes and renal dysfunction.

ACKNOWLEDGMENTS: The authors thank Drs. Matthew Casey Becker and Kent Dauterman for contributions to earlier editions of this chapter.

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