Contrast injection Great care must be taken at all times to ensure that air is not injected into the coronary arterial tree. The injection syringe should be \201 lled with contrast from the reservoir and then the syringe held with the plunger elevated such that any air b ubbles rise to the top of the syringe. Contrast should then be injected at a continuous rat e, aiming to fully opacify the coronary vessel of interest. Care should be taken that the pressure trace prior to injection is nor- mal \200\224damping suggests an ostial lesions, excessively deep intubation, or selective intubation of a bran ch. JR 4 JL 4 AR II AL I MPR 1 PG Figure 14.3 Commonly used cardiac catheter shapes. JL, JR: Judkins left and right coronary catheters; AL, AR: Amplatz left and right; MP: multipurpose coronary access catheter; PG: p igtail catheter. CORONARY ANGIOGRAPHY 557 Box 14.2 Coronary angiography/left ventriculography Left coronary artery \200 The 50 left anterior oblique (LAO 50) is the best projection for cannulation of both the left and right coronary ostia. The JL4 catheter will almost invariably cannulate the left c oronary ostium without manipulation. In patients with large aortic roots (large, hypertensi ve patients), the JL5 (with a larger curve) may be needed, and conversely, a smaller root m ay need a smaller catheter curve, the JL3.5. Right coronary artery \200 The LAO 50 projection is best used for cannulation of the right coronary ostium. The JR4 ca theter is introduced to the aortic root, until it lies 1 \200\2232 cm above the aortic valv e. The catheter is then rotated ( \200\234torqued \200\235) in a clockwise direction such t hat the catheter tip rotates toward the right coronary ostium. It may be necessary to reduc e the torque to prevent the catheter from overshooting. There is often a noticeable lateral movement as the catheter enters the artery. Before contrast is injected, it must be ensure d that the pressure tracing transduced from the tip of the catheter is not damped, which ca n suggest that the catheter has selectively intubated the conus branch of the right coronar y artery, and injection of contrast into this vessel can induce ventricular arrhythmias. Left ventriculography \200 Position pigtail catheter a few centimeters above the aortic valve and pull wire back 5 \200\22310 cm to make catheter tip soft, and push gently (the catheter may cross at this po int). If catheter does not cross, apply torque as it is gently withdrawn. Once catheter has been placed in a stable (free of ectopy) position in mid-LV cavity, connect to manifold an d measure pressure. Disconnect manifold catheter connected to a power injector and expel al l air. Set injection rate: typically 36 mL of contrast at a rate of 12 mL/sec. Warn patient about hot \202 ush and the feeling of extra systoles. When the left ventriculogram has b een performed, the catheter is reconnected to the manifold to allow pressure recording as t he catheter is withdrawn across the aortic valve (the pullback pressure). \200 CHAPTER 14 Cardiac catheterization 558 Interpreting the coronary angiogram LCA angiographic views LCx OMB LAO Cranial LMCA D LAD LCx LAO Caudal LAD LMCA AP Caudal LCx LAD LCx AP Cranial LMCA S LAD LCx RAO Cranial S LAD RAO Caudal LAD LCx OMB Figure 14.4 This \201 gure was published in Libby P. Braunwald \200\231s Heart Disease, 8 th ed. Saunders. Copyright Elsevier 2001. INTERPRETING THE CORONARY ANGIOGRAM 559 RCA angiographic views RCA LAO Straight PLV AMB PDA LAO Cranial RCA PLV AMB PDA RAO Straight Conus branch RCA PDA Figure 14.5 AMB, acute marginal branch; LAO, left anterior oblique; PDA, posterior descendi ng coronary artery; PLV, posterior left ventricular branch; RCA, right coronary artery; RAO , right anterior oblique. This \201 gure was originally published in Libby P. Braunwald \200\231s Heart Disease, 8th ed. Saunders. Copyright Elsevier 2007. CHAPTER 14 Cardiac catheterization 560 Angiographic study of grafts It is important to study the surgical record to ascertain how many grafts were placed at the time of the operation. Sometimes, useful information (often from a surgeon \200\231s diagram) can be obtained as to the position in the ascending aorta that the grafts arise from. As a rule, leftward-facing grafts are best cannulated from the RAO 50 projection, and right ward-pointing grafts are best cannulated in the LAO 50 projection. It may be necessary to p erform an aortogram to visualize the position of grafts. Special catheters (e.g., the left coronary bypass cath- eter, or LCB) have been designed to aid cannulation of grafts. There is usually a predictable anatomy: Posterior descending artery (PDA) grafts originate from the right anterior aspect of the aorta and run vertically to the inferior surface of t he heart. Obtuse marginal branch (OM) grafts originate from the left anterior aspect of the aorta and arc toward the posterolateral surface of the heart. Left anterior descending art ery (LAD) and diagonal grafts originate from an intermediate position and run laterally tow ard the anterior interventricular groove. Common aortic positions for placement of saphenous vein graft (SVG) SVG-OVG SVG-LAD SVG-PDA LCA RCA Figure 14.6 Vein graft anatomy. This \201 gure was published in Braunwald E. Heart Diseas e: A Textbook of Cardiovascular Medicine, 5th ed. Copyright Elsevier 2001. COMPLICATIONS OF ANGIOGRAPHY 561 Complications of angiography Peripheral vascular complications Hematoma The incidence of he matoma formation is related to the following factors: \200 \200 \200 \200 Length of time sheath is left in place Gauge (size) of sheath Anticoagulation Risk factors, e.g., hypertension, obesity, and pre-existing peripheral vascular disease Technique of she ath removal Features suggesting that a hematoma may require further investigation are an overlying brui t, expanding mass, and a large, tense swelling. Pseudoaneurysm A pseudoaneurysm represents a rupture of the femoral arterial wall at the si te of puncture, with the formation of a false aneurysm involving the media and adventitia ( Fig. 14.7). They are best visualized on ultrasound examination (Fig. 14.8). Small pseudoaneurysms can often be managed conservatively; however, large pseudoaneurysms m ay require thrombin injection, compression, or surgical intervention. (a) Common femoral artery Pseudoaneurysm Tract Superficial femoral artery Femoral head Profunda femoral artery (b) (c) Pressure device Hematoma Pseudoaneurysm Figure 14.7 Anatomy of a pseudoaneurysm. (a) Bleeding along a small tract allows blood to c ollect within the extravascular tissues. Manual compression fails to obliterate the tract ( b) and allows the hematoma to persist. Failure of thrombosis of the hematoma produces an ex travascular collection with persistent connection and \202 ow from the main artery (c). T his can be visualized on ultrasound (see Fig. 14.8). CHAPTER 14 Cardiac catheterization 562 Hemorrhage If prolonged, then direct pressure (either manually or using a clamping device) may be needed. Limb ischemia This is rare and usually occurs in patients with pre-existing limb ischemia. If limb ischemia is suspected, urgent vascular surgical team review should be sought. Dissection Dissection can occur at the time of sheath insertion and/or catheter manipulatio n; this can be diagnosed by dampening in the pressure tracing. If this is noted, an iliac a ngiogram should be performed and pressure gradi- ent recorded. If signi \201 cant dissecti on is noted, a percutaneous intervention (i.e., iliac stent) should be pursued. Contrast reactions Mild contrast reactions such as rash, urticaria, blurred vision, and rig ors are relatively common. These symptoms may settle spontaneously but are often treated wi th a combination of IV diphenhydramine 25 mg and IV hydrocortisone 100 \200\223200 mg. Anap hylactic reactions are rare; these should be treated with diphenhydramine and hydrocortison e, but also plasma expanders and SQ adrenaline. Figure 14.8 Ultrasound of femoral pseudoaneurysm demonstrating \202 ow (arrow) in the ane urysm above the femoral artery. COMPLICATIONS OF ANGIOGRAPHY 563 Vasovagal reactions These are common both during angiography and at the time of sheath remo val. They are characterized by hypotension and bradycardia. They are treated with IV atropi ne and volume expanders. Arrhythmia Brief episodes of SVT are common and often transient. During catheter manipulati on (especially in the LV), runs of VT are common. VF may occur during coronary artery injec tion and should be treated with rapid de \201 brillation. CHAPTER 14 Cardiac catheterization 564 Right heart catheterization Indications for right heart catheterization \200 \200 \200 Evaluation of cardiac shunts Evaluation of valvular heart disease Dyspnea not explained by noninvasive investigation The acute settings in which right heart catheterization can be helpful (e.g., cardiogenic s hock) are discussed in Chapter 1. Access to the right heart is usually achieved via the right femoral vein (RFV). The RFV is located 0.5 cm to 1 cm medial to the femoral arterial pulsation (Fig. 14.1). An 18-gauge ne edle, attached to a syringe partially \201 lled with saline, can be used to locate the po sition of the vein, followed by the larger-bore needle. When venous blood is freely aspirated, a 0.035 \200\235 guide wire is passed into the vein, using a technique similar to femoral artery cannulation, and a hemostatic sheath introduce d. Right heart catheterization protocol \200 \200 A balloon-tipped catheter (Swan \200\223Ganz catheter) may be used. Ensure that the cathete r is \202 ushed and that the transducer is correctly zeroed. Advance catheter to the IVC, and with the balloon in \202 ated, advance further to the right atrium. Record the phasic and mean pressures. It is customary to then advance the catheter to the pulmonary artery w edge position. Advance into the RV. A combination of rotation of the catheter and gentle tr action will allow the catheter to \202 ick upward into the RVOT. It can then be advanced into the main PA and out to the periphery. Occasionally a guide wire is necessary to achiev e this. Advance the catheter to the pulmonary capillary wedge position and record phasic an d mean pressures. With a pigtail catheter in the LV, measure and record the LV pressures. R ecord simultanous PCWP and LV pressures, ensuring that the scale allows interpretation of t he end diastolic pressures accurately (to assess for MV gradient). Withdraw the wedge cathe ter slightly; the balloon may be de \202 ated, and record pulmonary artery phasic and mean pressure. Obtain oxygen saturations from the main PA (also RPA and LPA if a PDA is suspect ed). Withdraw the pulmonary catheter to the RV. Measure and record simultanous RV and LV pr essures. Withdraw the catheter to the RA and measure the pressures again. The LV catheter s hould be pulled back to the ascending aorta while the pressure is being monitored to record any pull-back gradient. Aortic saturations should be measured to allow calculation of card iac output (see Fig. 14.9) and to compare with saturations from the right side if a shunt i s suspected. For shunts a full saturation run should be performed (SVC, high to mid- and lo w RA, IVC, RV, MPA, RPA, LPA, etc.). \200 RIGHT HEART CATHETERIZATION 565 Pulmonary capillary wedge Right atrium Right ventricle Pulmonary artery 30 20 10 x v y a a c a v x y ) g H m m 0 ( Left atrium Left ventricle Aorta e r u s s e r P 150 100 a v c 50 x a y 0 Figure 14.9 Cardiac catheterization \200\224normal pressure waveforms. a contraction in atr ial systole c closure mitral valve x fall in left atrial pressure v ventricular systole and passive atrial \201 lling in diastole y fall in left atrial pressure following opening o f mitral valve and passive \201 lling of the left ventricle CHAPTER 14 Cardiac catheterization 566 Cardiac output and LV function Cardiac output is most often measured using the thermodiluti on method with a pulmonary catheter. Cardiac output can also be measured using the Fick principle, which assesses the difference between the pulmonary arterial and aortic O2 saturation. Oxygen consumption (mL/min) (Ao SaO2 \200\223 PA SaO2) x Hb x 1.34 Cardiac output (L/min) = Ao SaO2: systemic oxygen saturation; PA SaO2: pulmonary artery oxygen saturation; Hb: hemog lobin. Systemic and pulmonary vascular resistance Pulmonary vascular resistance (PVR) is an import ant prognostic factor in patients with valvular heart disease, heart failure, and cor pulmo nale or pulmonary hypertension. The measurement of PVR and SVR is especially important in p atients being assessed for cardiac transplantation. PVR and SVR are measured Woods units (mmHg/L/min) or dynes cm \200\2235, with 80 dynes cm \200\2235 = 1 wood unit. Mean aortic pressure \200\223 Mean right atrial pressure Systemic vascular resistance Cardiac output = Mean PA pressure \200\223 Mean left atrial pressure Pulmonary vascular resistance Cardiac output = CARDIAC CATHETERIZATION IN VALVE DISEASE 567 Cardiac catheterization in valve disease Valve stenosis Several parameters can be assessed during cardiac catheterization. Peak-to-peak gradient Aortic and LV pressures are recorded during withdrawal of the pigtail catheter across the aortic valve. The gradient is the difference between peak aortic and p eak LV pressure. Peak instantaneous gradient This is more accurately measured using a double-lumen pigtail c atheter where one lumen measures pressure in the LV while the other measures pressure in th e aortic root simultaneously. This is rarely done in practice. Alternatively, simultanous m easurements may be made from the side port of the arterial sheath (in the femoral artery) a nd the pigtail in the LV. However, this method can lead to erroneous gradient measurements if there is signi \201 cant peripheral vascular disease dampening the measured pressure in the femoral artery. Mean gradient The mean pressure gradient is measured using planimetry of the area between a ortic and LV pressure traces. This can be used to calculate valve area using the Gorlin equ ation, and a similar method can be used to assess the mitral valve area (see Fig. 14.10). Valve regurgitation The severity of aortic regurgitation can be estimated by performing an aortogram. In severe aortic regurgitation the LV is seen to opacify within one or two beats after contrast injection. Mitral regurgitation may be assessed by left ventriculography, with con- trast seen to opac ify the left atrium and pulmonary veins in severe regurgi- tation. In addition, mitral regu rgitation may be associated with a prominent V wave in the pulmonary capillary wedge tracin g. CHAPTER 14 Cardiac catheterization 568 50 40 30 g H m m LV 20 LV x y 10 0 Figure 14.10 Simultanous LV and PCWP tracing in mitral stenosis. The mean gradient across t he mitral valve is calculated as the area of the region colored in gray. This \201 gure w as published in Braunwald E. Heart Disease: A Textbook of Cardiovascular Medicine, 5th ed. Copyright Elsevier 2001. INTRAVASCULAR ULTRASOUND 569 Intravascular ultrasound Intravascular ultrasound (IVUS) is a technology that allows direct visualiza- tion of atherosclerotic plaque and the vessel lumen (Fig. 14.11). Ultrasound im ages are produced by passing an electrical current through a piezoelec- tric crystal that e xpands and contracts to produce sound waves when electrically stimulated. These sound waves are re \202 ected from tissues, and return to the transducer where they are detected and converted to an electrical impulse that can be presented graphically. A phased array of crystals (usually 64) is used, and these are sequentially activated to produce circumferential imaging. The equipment required to perform an IVUS examination involves a miniaturized ultrasound tr ansducer mounted on a catheter (usually 2.6 \200\2233.5 Fr gauge) and computer interface th at carries out image reconstruction. Examination technique \200 \200 Intracoronary nitroglycerin and IV heparin should be administered. The IVUS catheter should be carefully advanced distal to the area of interest. A motorized pullback device is then used to withdraw the IVUS catheter proximally at a \201 xed speed. Landmarks such as side branches can be useful, and positions may also be recorded angiographically. Advantages of ultrasound \200 Full circumference of vessel wall is seen, not just two surfaces as in angiography, and is thus the method of choice to determine vessel luminal area. IVUS is useful in imaging ambig uous lesions: \200 Intermediate lesions of unknown severity \200 Ostial stenosis \200 Left main stem disease \200 Bifurcation lesions It images the plaque, not just the lumen . It allows optimal results during angioplasty and stenting. \200 CHAPTER 14 Cardiac catheterization 570 Adventitia Media Intima Lumen IVUS Figure 14.11 Example of image obtained by IVUS. ANGIOPLASTY AND CORONARY STENTING 571 Angioplasty and coronary stenting Currently, coronary stents are implanted in >85% of revas cularization pro- cedures in the United States. AHA/ACC guidelines state that \200\234stents should be used routinely for people with eith er stable or unstable angina or with acute myocardial infarction undergoing percutaneous in tervention. \200\235 Angioplasty Before stents became widely used in the mid to late 1990s, balloon angioplasty alone was the most common percutaneous treatment for signi \201 cant coronary artery lesio ns (see Box 14.3). The two main designs of balloon catheters now commonly used are over-the -wire and rapid- exchange systems. Both types of catheter consist of three parts: 1. The sh aft: there are two main varieties: The hypotube, the advantage of which is a better balance between strength and \202 exibil ity The core wire design, which is superior in terms of \202 exibility 2. The lumen: coax ial design (a tube within a tube) is the most common. 3. The balloon: these are constructed from varying plastics (e.g., polyethylene, nylon), the mix of which affects the balloon \200\231s compliance. The design of the tip is important, as tapered tips are less traumati c when crossing index lesions. The balloon may also have a hydrophilic coating. \200\234Plain old balloon angioplasty \200\235 (POBA) remains indicated in the treatment o f some coronary artery lesions, particularly small vessels, vein grafts, and bifurcation si de branches, in which the bene \201 t of stenting has not been clearly demonstrated. It is also used for patients who need revasculariza- tion prior to noncardiac surgery, thus mini mizing the bleeding risk of dual antiplatelet agents required after stent placement. Coronary stenting Stents can be made of stainless steel, cobalt-based alloy, titanium, niti nol, or polymer. Most stents used today are stainless steel and balloon mounted. The primar y function of a stent is to act as a scaffold to maintain ves- sel patency (see Fig. 14.12) . Thus much of the success of stents is due primarily to their mechanical ability to produc e large, acute gains in lumen dimensions. Currently, there are two types of stents available for clinical practice: the bare metal st ent (BMS) and the drug-eluding stent (DES). With the BMS, there is an increased risk of in- stent restenosis (ISR) as a result of intimal hyperplasia after stent deployment. By contra st, use of the DES decreases signi \201 cantly the incidence of ISR because of the antipro liferative action of the agents that recover the stent. The delayed healing of the vessel wall has led to the occurrence of acute and late episodes of stent thrombosis, which requires the continuous long- term use of double antiplatelet a gents (1 \200\2232 years). In the case of BMS, 6 weeks of double antiplatelet therapy follo wed by continuous ASA use is the recommended approach. CHAPTER 14 Cardiac catheterization 572 Box 14.3 Angioplasty procedure \200 Cannulate artery with the chosen guiding catheter. Ideally, the guiding catheter should be coaxial with the coronary ostium (thus allowing maximum support and minimizing trauma to th e vessel). A steerable 0.014 \200\235 guide wire is introduced to the catheter via the hemo static valve. The tip of the guide wire may be preshaped; however, many operators prefer to take a straight guide wire and shape the tip by hand. Using \202 uoroscopy and contrast to delineate the coronary anatomy, the guide wire is advanced along the vessel, beyond the narrowing, and placed as distally as possible in the vessel. An appropriately sized balloon is then chosen; the guiding catheter can be used as a reference when sizing the vessel. Fo r calci \201 c lesions and in-stent restenosis, shorter balloons with higher rated burst p ressure may be better. The balloon is advanced along the guide wire to the correct position . In some situations, it may be dif \201 cult to pass the balloon to the desired position, thus deeper insertion of the guide catheter or a more supportive guide catheter may be nee ded. Radio-opaque markers are used to position the balloon accurately. In \202 ation shoul d be undertaken under X-ray screening to ensure that the balloon does not move. (a) (b) (c) (d) Fig 14.12 Coronary stenting: A guide wire is introduced across the stenotic segment of arte ry (a) and is used to position the stent (b). The stent is deployed by in \202 ating the b alloon (c). The balloon and guide wire are removed, leaving the stent in place (d). RESTENOSIS FOLLOWING PTCA 573 Restenosis following PTCA Pathophysiology The restenotic process consists of a series of co mplex events: \200 \200 Vessel injury leads to platelet activation and An lymphocyte migration to the site of injur y. Smooth muscle proliferation in \202 ammatory mediators. Finally, negative (inward) remo deling can occur, resulting in lumen compromise and restenosis. local thrombosis. in \202 ammatory reaction is invoked, with neutrophil, monocyte, and is driven by activated platelets and These processes occur at different rates and may occur to different degrees depending on th e nature of vessel injury and individual patient characteristics. The problem Large randomized trials have established that following percutaneous translumin al coronary angioplasty (PTCA), restenosis rates in the treated vessel are between 30% and 60% (following POBA) and 15% \200\22330% (follow- ing stent implantation). They are higher still in selected high-risk patients (e.g., diabetics). This relatively high incidence of angiographic restenosis, however, translates into revascu larization in about 10% of patients, in whom clinical restenosis is said to have occurred. Prevention of restenosis Mechanical Stent implantation Stent implantation reduces restenosi s rates by increasing the mean lumi- nal diameter after angioplasty and preventing elastic recoil and adventitial constriction. Optimization of stent deployment by IVUS guidance Using intravascular ultrasound to establi sh whether a stent has been ade- quately deployed improves the results of percutaneous inte rvention. Antithrombotic and antiplatelet treatment Early aggressive antithrombotic and antiplatelet therapy with heparin, aspi- rin, gpIIb/IIa antagonists, and clopidogrel reduces the inciden ce of acute stent thrombosis. CHAPTER 14 Cardiac catheterization 574 Drug-eluting stents Implantation of stents has to a great extent overcome the problem of el astic recoil and negative remodeling following PTCA. It is thus evident that neointimal pro liferation, resulting in stent restenosis, remains the major limiting factor for stenting p rocedures. Much research has focused on the role of antiproliferative agents in the reducti on of restenosis, and recently drug-eluting stents have emerged as the preeminent solution to this problem. Drug-eluting stents are coated stents, capable of releasing bioactive components into the l ocal tissue and bloodstream (see Box 14.4). The advent of stents as a platform for the deli very of drugs, with subsequent reduction in rates of stent restenosis, is radically changin g the treatment of patients with coronary artery disease. The number of CABG procedures performed worldwide is falling, with more patients who previo usly would only have been candidates for CABG being treated by percutaneous coronary interv ention (PCI). Increasingly, the favorable results obtained with DES mean that PCI is perfor med in complex cases such as LMCA stenosis, diffuse disease, and bifurcation anatomy. Several large RCTs, which have demonstrated both the safety and ef \201 - cacy of these st ents, have supported the introduction of DES into routine clinical practice. Sirolimus-eluting stents The drug sirolimus has potent antifungal, immunosuppressive, and a ntimi- totic properties. This agent was approved for rejection prophylaxis in renal transpl antation in 1999, with trials of a sirolimus-coated coronary stent following soon thereafte r. \200 The \201 rst human experience of a sirolimus-coated stent (45 patients) illustrated a vir tual absence of neoinitimal proliferation at follow-up. Box 14.4 Drug-eluting stents \200 Similarities between tumor growth and benign neointimal proliferation introduced the concep t that immunosuppressant and cytotoxic agents might be bene \201 cial for preventing in-st ent restenosis. Incorporation of these agents into stent coatings, using a number of techni ques, has now enabled delivery of the active agent directly to its site of action, while li miting systemic side effects. Crucially, the coatings allow sustained release of the agent such that the therapy is present at the time that the target mechanism is physiologically a ctive. The commonly used agents are sirolimus, which has a cytostatic action, and paclitaxe l, which is cytotoxic. Other agents include everolimus and zatorolimus. DRUG-ELUTING STENTS 575 The seminal RAVEL study enrolled 238 patients, randomly allocated to BX velocity stent, or sirolimus-eluting BX velocity stent (the Cipher \204 Stent). It reported 0% restenosis in the group treated with the DES. The large-scale SIRIUS study ( antirestenosis effects of Ci pher \204 stents. n = 1100) con \201 rmed the potent Paclitaxel eluting stents Paclitaxel has potent antitumor activity via its action as a micr otubule- stabilizing agent. Coronary stents eluting paclitaxel have been extensively invest igated. \200 TAXUS I studied 61 patients randomly assigned to paclitaxel-coated stent or bare metal sten t. This study both established the safety of the stent, but also showed a major adverse car diac events (MACE) rate in the DES arm of 3%, compared with 10% in the BMS arm at 1-year fo llow-up. TAXUS II compared slow- and moderate-release formulations of paclitaxel with bare metal stenting, and found signi \201 cantly lower MACE rates in both slow- and moderate-re lease DES (2.3%/4.7%) than those in BMS-treated control groups (20.2%). SIRIUS and TAXUS, and each of their subsequent follow-up studies and registries, have estab lished that Cipher \204 and Taxus \204 stents have similar, low rates of TLR (between 3% and 8%). Box 14.5 AHA/ACC/ESC recommends the use of a DES in PCI for patients with symptomatic CAD in whom th e target artery is <3 mm in caliber or the lesion is longer than 15 mm. In real-world pract ice this translates to coronary artery lesions in approximately 60% \200\22370% of patients under- going PCI. CHAPTER 14 Cardiac catheterization 576 Stent thrombosis It should be appreciated that documentation of ST by angiography under- es timates the real incidence of this event, since some of the patients with stent thrombosis develop MI or die without angiographic documentation of stent thrombosis. To address this issue, an Academic Research Consortium (ARC) com- posed of clinical investi gators, industry representatives, and regulatory authorities (including the FDA) has propos ed new de \201 nitions for ST in an attempt to establish uniformity and improve sensitivit y for the diagnosis of ST. There are three levels of evidence in de \201 ning ST: 1. De \201 nite stent thrombosis Angiographic con \201 rmation is based on TIMI (thrombol ysis in myocardial infarction) \202 ow: \200 TIMI \202 ow 0 with occlusion originating in the stent or in the segment 5 mm proximal or distal to the stent region with presence of thrombus TIMI \202 ow 1, 2, or 3 originating in the stent or the segment 5 mm proximal or distal to the stent region with presence of t hrombus AND at least one of the following criteria has been ful \201 lled within a 48-hours period : \200 \200 \200 New acute onset of ischemic symptoms at rest New ischemic electrocardiogram changes that su ggest acute ischemia Typical rise and fall in cardiac biomarkers as evidence for an acute M I Pathologic con \201 rmation \200 Con \201 rmation of recent ST either at autopsy or via examination of tissue retrieved aft er thrombectomy 2. Probable stent thrombosis Considered to have occurred after intracoronary stent implanta tion in the following cases: \200 \200 Any unexplained death within the \201 rst 30 days Irrespective of the time after the inde x procedure, any MI that is related to acute ischemia in the territory of the implanted ste nt without angiographic con \201 rmation of stent thrombosis and in the absence of any oth er obvious cause 3. Possible stent thrombosis \200 Any unexplained death from 30 days after intracoronary stenting until end of trial follow-u p Based on the timing after implantation of DES, ST could be \200 \200 \200 \200 Acute: 0 to 24 hours post \200\223stent implantation Subacute: 24 hours to 30 days post \200\223stent implantation Late: 30 days to 1 year post \200\223stent implantation Very lat e: >1 year post \200\223stent implantation STENT THROMBOSIS 577 Based on the design of the pivotal clinical trials that led to approval of DES, dual antipl atelet therapy was prescribed on an empirical basis for 2 \200\2233 months after implantati on of sirolimus-eluting stents and for 6 months after implantation of paclitaxel-eluting st ents, with lifelong aspirin. However, concerns about long-term safety were \201 rst made public in 2005 after several case reports were published that suggested that even late after DES placement, discontinuat ion of antiplatelet therapy may allow stent thrombosis. This appears to be due to failure o f DES to re-endothelialize. These concerns were con \201 rmed when 746 nonselected patients with 1133 stented lesions surviving 6 months without major events were fol- lowed for 1 year after the discontinuatio n of clopidogrel in the BASKET- LATE trial, which showed that documented late stent thrombo sis and related death/target vessel MI were twice as frequent after DES vs. BMS (2.6% vs. 1 .3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88% of the cases. Since then, multiple trials, registries, and meta-analyzes have studied the incidence of DE S ST with numbers that range from 0.4% to 2.9%. Based on these data, the FDA now recommends continuous use of dual antiplatelet therapy for 1 \200\2232 years if there are not major b leeding complications. CHAPTER 14 Cardiac catheterization 578 Physiological assessment of coronary \202 ow The shortcomings of coronary angiography in the physiological assessment of coronary stenosis are clear. Intravascular ultrasound can p rovide infor- mation on the size of the lumen and the composition of plaque, but again give s no information on the effect that an atheromatous plaque may have on coronary \202 ow. The knowledge as to whether a narrowing seen on angiography is the culprit causing hemodyna mic effects, and thus anginal symptoms, is valuable when guiding percutaneous intervention. The fractional \202 ow reserve (FFR) correlates distal coronary pressure to myocardial bl ood \202 ow during maximum hyperemia (induced by infusion of adenosine, or papaverine). F FR is de \201 ned as maximum myocardial blood \202 ow in the presence of a stenosis divi ded by the theoretical maximum \202 ow in the absence of a stenosis (see Fig. 14.13). Thus the information derived from FFR allows an \200\234on-the-spot \200\235 diag- nosis o f the extent to which a given stenosis contributes to myocardial ischemia (and angina), and can guide decisions regarding revascularization. At present, the best established indicati on for coronary FFR estimation is as a diagnostic tool to assess \200\234severe \200\235 c oronary stenosis, and for this it is extremely sensitive when used with a cutoff point of 0 .75. The technique has also been used to optimize the results of stent implantation. Two technologies are currently available that provide hemodynamic information derived from FFR calculations; these are pressure wires (which consist of a pressure transducer mounted on a 0.014 \200\235 guide wire), and Doppler \202 ow wires (which examine coronary \202 ow velocities using spectral analysis). Pressure wire, e.g., the PressureWire \204 (Radi Medical Systems, Volcano Medical Systems) \200 The pressure transducer is located at the transition between the radiopaque wire tip and th e nonradiopaque stem. The analyzer shows simultanous aortic and intracoronary pressure, as well as instantaneous FFR. Doppler wire, e.g., FlowWire \204 (Endosonics) \200 This obtains information on coronary \202 ow velocity in the central area of the arterial lumen. Combining \202 ow and ECG information, it calculates systolic and diastolic compo nents of \202 ow velocity at baseline. Following induction of hyperemia, the machine can calculate the coronary \202 ow velocity reserve. PHYSIOLOGICAL ASSESSMENT OF CORONARY FLOW 579 Q Pa 100 Pd 100 Pv 0 P Pd 100 Pv 0 Pa 100 Pd FFRmyo = = 0.70 Pa Figure 14.13 During maximal arteriolar vasodilatation, the resistance of the myocardium is minimal, and so maximum myocardial blood \202 ow is proportional to hyperemic perfusion p ressure. This equals Pd \210\222Pv. As there is no decline in pressure along a normal coron ary artery, and neglecting Pv, this implies that in a normal epicardial artery, perfusion p ressure at hyperemia equals Pa. In the presence of a stenosis, hyperemic perfusion pressure decreases to Pd (after the stenosis). Thus the maximum \202 ow in the presence of a sten osis as a ratio (fraction) of normal maximum \202 ow is represented by the ratio of perfu sion pressures: Pd/Pa. This fraction of normal maximum \202 ow, which is maintained despi te the stenosis, is called the fractional \202 ow reserve (FFR). Reproduced with permissi on from Pijls NH (2004). Heart 90(9):1085 \200\2231093. CHAPTER 14 Cardiac catheterization 580 Primary angioplasty for STEMI Pathophysiology In the context of cardiac chest pain, ST segm ent elevation on the 12 lead ECG usually signi \201 es complete occlusion of a proximal ep icardial coronary artery. This occurs as a result of rupture or erosion of a vulnerable ath ero- matous plaque, which leads to platelet activation and adhesion, formation of platelet- rich (white) thrombus, \201 brin deposition, and red cell entrap- ment (forming red throm bus). If untreated, myocardial necrosis commences within 30 minutes, affect- ing full myocardial thickness within 6 hours; 30% of patients die before reaching the hospital. Treatment Urgent restoration of coronary blood \202 ow (reperfusion) prevents further LV damage and improves prognosis (Box 14.6). The amount of myocar- dium that can be salvaged f alls exponentially with time, with the greatest bene \201 t within 3 hours following sympt om onset, and little bene \201 t after 12 hours. Primary angioplasty is the preferred reperfusion strategy, where angiography can be perform ed within 90 minutes of presentation. Patients can be transferred safely (by a trained ambulance crew with an ACLS trained escort ) from a community hospital to a cardiac center for primary angioplasty. Box 14.6 Options for reperfusion Primary angioplasty Immediate coronary arteriography, culprit vessel angioplasty, and stent implantation without antecedent \201 brinolysis achieves full arterial patency (TIMI gra de 3 \202 ow) in 90% \200\22395%, treating the occlusive thrombus and the culprit plaque. Intravenous \201 brinolysis Immediate administration of a \201 brinolytic agent (also c alled thrombolysis) without planned coronary arteriography achieves full arterial patency ( TIMI grade 3 \202 ow) in 50% \200\22360%. It is contraindicated in up to 30% of patients and does not treat the culprit plaque. Rescue angioplasty Urgent coronary arteriography, culprit vessel angioplasty, and stent imp lantation are performed when \201 brinolysis has failed to achieve reperfusion (persisten t ST-segment elevation 9 pain at 60 \200\22390 minutes). PRIMARY ANGIOPLASTY: PROCEDURE 581 Primary angioplasty: procedure Indications \200 \200 Cardiac chest pain <12 hours (e.g., see Fig. 14.14) ST Elevation (cid:116)1 mm in 2 contiguous leads and/or new LBBB Contraindications \200 \200 Suspected aortic dissection Major contraindication to anticoagulation therapy Relative contraindications \200 Active bleeding (antiplatelet therapy may have to be avoided but may compromise outcome. Th ese cases should be discussed directly with the operator). Pre-procedure (work quickly \200\224minutes matter) \200 \200 Consent Basic blood work including CBC, chemistries, type and cross, cardiac biomarkers Oxy gen if saturations <94% Aspirin 325 mg (chewed) Systemic anticoagulation (i.e., heparin, bi valirudin) Platelet glycoprotein gpIIb/IIIa receptor antagonist (abciximab) is indicated wh en heparin alone is used and as a bailout option in cases where bivalirudin is used and the re is a signi \201 cant thrombus burden, non-re \202 ow, and high risk of vessel closure. Access \200\224femoral or radial. The femoral region should always be prepared in case of need for transvenous pacing or intra-aortic balloon pump (IABP) insertion. Diagnostic angio gram should be performed to identify the culprit vessel. Angioplasty should then performed. \200 \200 \200 Additional considerations \200 Culprit-vessel PCI is a Class I indication. PCI to a non-infarct-related artery is Class II I and should be deferred for a later time (typically >24 hours). Procedural success is de \201 ned by TIMI grade 2 or 3 \202 ow with residual stenosis <30%. CHAPTER 14 Cardiac catheterization 582 (a) (b) stent LAD occluded Figure 14.14 Angiographic images from a 54-year-old male presenting with chest pain and ant erior ST elevation. (a) The left anterior descending (LAD) artery is occluded mid-vessel (a rrow). (b) The same artery now widely patent following primary angioplasty; a 3.5 x 24 mm b are metal stent has been implanted (arrow). The patient sustained minimal left ventricular damage and was discharged 48 hours later. INVASIVE ASSESSMENT OF VULNERABLE PLAQUE 583 Invasive assessment of vulnerable plaque It has become apparent from intravascular ultrasou