[72] Simes RJ, Topol EJ, Holmes DR Jr, et al. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion: impor‐ tance of early and complete infarct artery reperfusion. GUSTO-I Investigators. Circu‐

256 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

lation 1995; 91:1923– 8.

The most important role of coronary angiography is to delineate coronary lesions that cause inducible ischaemia. It remains the primary tool influencing the decision to undertake revas‐ cularization and patient outcomes [1] [2-4]. However, there are inherent limitations to diag‐ nostic angiography. These pitfalls include difficulties delineating eccentric plaque (that can be underappreciated in the absence of multiple angiographic views), difficulty assessing le‐ sions of moderate severity, the assessment of overall plaque burden and the composition, appreciation of ostial lesions, culprit lesion assessment in acute infarct patients and side branch analysis in bifurcation lesions. Heavily calcified lesions can also produce hazy angio‐ graphic appearances which often leaves the operator at a loss to determine the actual true lumen path and in some circumstances even misdiagnose calcification as "pseudothrom‐ bus" [5]. This latter phenomenon significantly changes the approach to intervention. The ar‐ tery can be put at risk of perforation in the absence of adequate lesion preparation or wire induced dissection as calcified plaque is often undermined, complex and much more diffi‐ cult to wire than soft thrombus.

Furthermore, angiography is usually used in isolation to guide intervention and ensure an adequate final stent result. FFR, IVUS and OCT can all be used to assess final PCI results and stent performance over time.

To aid decision making processes, adjunctive tools are becoming essential in "getting it right" in the catheterization laboratory. In this chapter, the use of FFR, IVUS and OCT for assessing left main and non left-main coronary artery disease will be discussed.

© 2013 Incani et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **2. An overview of FFR**

Fractional Flow Reserve (FFR) is the ratio of two flows - maximal flow in the diseased vessel expressed as a ratio to maximal flow if the vessel was theoretically normal[6]. During the procedure, a 0.014 inch pressure sensor coronary guide wire is advanced beyond a coronary stenosis and under conditions of maximal hyperaemia, distal pressure recorded and divided by guiding catheter pressure. The procedure requires routine anticoagulation, a calibration process [zeroing and equalization of the aortic (guiding catheter pressure Pa) with the pres‐ sure wire (Pd) and attainment of maximal hyperaemia (this is usually achieved by intrave‐ nous or intracoronary adenosine)[6]. FFR is a robust technique and reproducible which is remarkable in that the microcirculation is able to vasodilate to the same degree each time and is independent of heart rate and blood pressure [7,8]. It takes into account length of le‐ sion, lesion severity, amount of myocardium supplied, viability and contribution of collater‐ al blood flow [3,9,10]. It is now considered the gold standard for invasive functional assessment of the physiological significance of coronary stenosis. |It has recently been given a Class Ia indication for guiding PCI in multivessel coronary disease by the European Soci‐ ety of Cardiology [6].

Catheters: In general, 5Fr or 6 Fr guiding catheters are used for performing FFR. This then allows the operator to immediately go on to perform an intervention based on the FFR result or indeed fix a wire induced dissection without needing to change catheters. The latter is a rare phenomenon in experienced hands and with modern steerable soft tip pressure wires. Larger French sizes are generally avoided on account of increased risk of catheter induced

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Given Pv is assumed to be negligible equal and at maximal hyperaemia R (resistance) is minimal then FFR = Pd/Pa

**8.** Cross stenosis with the pressure wire (N.B. the pressure sensor is at the junction of the

**9.** Run intravenous adenosine (our preferred method) to achieve maximal hyperaemia

ostial spasm and the possibility of reducing proximal coronary artery pressure.

Qs = flow in diseased artery and Qn = flow in artery if theoretically normal

Pd = pressure distal to stenosis; Pa = aortic or guiding catheter pressure

**2.2. Summary for the sequence of events for performing FFR**

**5.** Intracoronary GTN to overcome epicardial conduit resistance

**7.** Equalize pressure wire and guiding catheter transducers

radiolucent and radio-opaque segments of the wire)

**10.** Record FFR tracing with at least 2-3 min of adenosine

**11.** Remain vigilant for pressure signal drift and catheter damping

**12.** Pullback recording is reasonable across tandem stenoses or diffuse plaque

**2.** Guiding Catheter sitting at ostium of coronary artery without damping

**1.** Systemic Heparin to achieve ACT of at least 250 sec

Basic Formula for FFR:

Therefore: FFR = [Pd-Pv/R] / [Pa-Pv/R]

Pv = venous or right atrial pressure

**3.** Zero guide and pressure wire

**4.** Remove wire introducer

**6.** Flush with saline

FFR = Qs/Qn

R = resistance

#### **2.1. Practicalities of FFR**

Pressure Transducers: The current pressure transducers usually comprise a regular trans‐ ducer for aortic pressure (Pa) recorded through the guiding catheter and the second pres‐ sure (Pd beyond the stenosis) via a miniaturized sensor-tipped pressure wire that is connected to a small computerized interface. Of note, a new wireless system is also about to enter the commercial arena. Mean pressure recordings are essential as these form the nu‐ merator and denominator of the FFR formula, not peak systolic pressure. It is optional to re‐ cord Pv (central venous or right atrial pressure) via a central line if the operator wishes to correct FFR for right atrial pressure – a concept that has been reborn in the modern FFR era whereby filling pressures in cardiac failure patients may be significantly elevated and can affect FFR recordings.

Medications: As is usual in any case where coronary wires are placed down coronary arter‐ ies, systemic anticoagulation (unfractionated heparin, low molecular weight heparin or bi‐ valirudin) is essential to avoid wire induced coronary thrombus. At our institution, the usual practice is to administer heparin to achieve an ACT of at least 250 seconds. Intracoro‐ nary nitrate is then administered to overcome epicardial vessel vasospasm and for achieving hyperaemia, either intracoronary or intravenous adenosine. Our preference is for intrave‐ nous adenosine via a femoral venous sheath, although all that is required is to achieve hy‐ peraemia – the route of administration is not as important. Intracoronary adenosine can also be given, however, this is not suitable when there are side holes in the guiding catheter, when ostial disease exists and when the aim of the study is to achieve a "pull-back" over the course of a coronary artery. Alternative agents for achieving maximal hyperaemia include intracoronary papaverine, intracoronary ATP, intravenous dipyridamole and intravenous dobutamine, however these have not been as widely adopted.

Catheters: In general, 5Fr or 6 Fr guiding catheters are used for performing FFR. This then allows the operator to immediately go on to perform an intervention based on the FFR result or indeed fix a wire induced dissection without needing to change catheters. The latter is a rare phenomenon in experienced hands and with modern steerable soft tip pressure wires. Larger French sizes are generally avoided on account of increased risk of catheter induced ostial spasm and the possibility of reducing proximal coronary artery pressure.

Basic Formula for FFR:

#### FFR = Qs/Qn

**2. An overview of FFR**

ety of Cardiology [6].

**2.1. Practicalities of FFR**

affect FFR recordings.

Fractional Flow Reserve (FFR) is the ratio of two flows - maximal flow in the diseased vessel expressed as a ratio to maximal flow if the vessel was theoretically normal[6]. During the procedure, a 0.014 inch pressure sensor coronary guide wire is advanced beyond a coronary stenosis and under conditions of maximal hyperaemia, distal pressure recorded and divided by guiding catheter pressure. The procedure requires routine anticoagulation, a calibration process [zeroing and equalization of the aortic (guiding catheter pressure Pa) with the pres‐ sure wire (Pd) and attainment of maximal hyperaemia (this is usually achieved by intrave‐ nous or intracoronary adenosine)[6]. FFR is a robust technique and reproducible which is remarkable in that the microcirculation is able to vasodilate to the same degree each time and is independent of heart rate and blood pressure [7,8]. It takes into account length of le‐ sion, lesion severity, amount of myocardium supplied, viability and contribution of collater‐ al blood flow [3,9,10]. It is now considered the gold standard for invasive functional assessment of the physiological significance of coronary stenosis. |It has recently been given a Class Ia indication for guiding PCI in multivessel coronary disease by the European Soci‐

258 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

Pressure Transducers: The current pressure transducers usually comprise a regular trans‐ ducer for aortic pressure (Pa) recorded through the guiding catheter and the second pres‐ sure (Pd beyond the stenosis) via a miniaturized sensor-tipped pressure wire that is connected to a small computerized interface. Of note, a new wireless system is also about to enter the commercial arena. Mean pressure recordings are essential as these form the nu‐ merator and denominator of the FFR formula, not peak systolic pressure. It is optional to re‐ cord Pv (central venous or right atrial pressure) via a central line if the operator wishes to correct FFR for right atrial pressure – a concept that has been reborn in the modern FFR era whereby filling pressures in cardiac failure patients may be significantly elevated and can

Medications: As is usual in any case where coronary wires are placed down coronary arter‐ ies, systemic anticoagulation (unfractionated heparin, low molecular weight heparin or bi‐ valirudin) is essential to avoid wire induced coronary thrombus. At our institution, the usual practice is to administer heparin to achieve an ACT of at least 250 seconds. Intracoro‐ nary nitrate is then administered to overcome epicardial vessel vasospasm and for achieving hyperaemia, either intracoronary or intravenous adenosine. Our preference is for intrave‐ nous adenosine via a femoral venous sheath, although all that is required is to achieve hy‐ peraemia – the route of administration is not as important. Intracoronary adenosine can also be given, however, this is not suitable when there are side holes in the guiding catheter, when ostial disease exists and when the aim of the study is to achieve a "pull-back" over the course of a coronary artery. Alternative agents for achieving maximal hyperaemia include intracoronary papaverine, intracoronary ATP, intravenous dipyridamole and intravenous

dobutamine, however these have not been as widely adopted.

Qs = flow in diseased artery and Qn = flow in artery if theoretically normal

Therefore: FFR = [Pd-Pv/R] / [Pa-Pv/R]

Pd = pressure distal to stenosis; Pa = aortic or guiding catheter pressure

Pv = venous or right atrial pressure

R = resistance

Given Pv is assumed to be negligible equal and at maximal hyperaemia R (resistance) is minimal then FFR = Pd/Pa

#### **2.2. Summary for the sequence of events for performing FFR**

**c. Damping of pressure by the guiding catheter:** this is particularly true with diseased ostia and when using large guiding catheters. It creates a gradient between the guiding catheter and the proximal segment of the coronary artery and may only be unmasked during maximal hyperaemia. It is important to monitor the Pa waveform at baseline and during the FFR measurement and if indeed there is damping, the guiding catheter needs to be "backed out" over the wire to ensure the Pa measurement is valid. This usu‐ ally necessitates the use of intravenous adenosine to maintain maximal hyperaemia during the FFR recording. If guiding catheter damping is not appreciated, the obtained FFR value will be artificially higher and the true severity of the stenosis underestimat‐

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**d. Guiding Catheter with Side Holes:** it is technically obvious to avoid intracoronary ade‐ nosine in this setting however it is also important to always disengage the guide be‐ cause the side holes may actually confound true proximal coronary pressure measurement. Therefore, if side holes are used, intravenous adenosine and a guiding

**e. Signal Drift:** High fidelity equipment make problems of signal drift less likely. Howev‐ er the problem can still occur. This issue is detected when an apparent gradient appears between Pd and Pa without a change in waveform of the distal pressure. It should be checked for at the end of the FFR procedure by ensuring that equalization still holds true when the coronary wire is withdrawn back into the guiding catheter. This is an in‐ ternal check for the operator to ensure the final FFR reading is valid. In practical terms

**f. Maximal Hyperaemia:** It cannot be emphasized enough that there is no such thing as a resting FFR. It is only at maximal hyperaemia that resistance is minimal and that flow develops a linear relationship to pressure – a vital prerequisite for the FFR equation to hold true. Not achieving maximal hyperaemia will usually overestimate the FFR value and therefore underestimate the true severity of a coronary stenosis. At the usual dose of intravenous adenosine 140mcg/kg/min via a central sheath, all patients usually ach‐ ieve maximal hyperaemia within 2 minutes. Patients will often complain of chest tight‐ ness and dyspnoea and there will be a transient rise in blood pressure before the Pd value reduces and adopts an ischaemic waveform with diastolic blunting. At this stage, increasing the dose of adenosine will not alter the FFR value and the clinician will be comfortable that maximal hyperaemia is achieved. It is not unusual for PR prolongation or transient heart block to occur which can also be used as surrogate measures of maxi‐

Intravascular ultrasound is a catheter based pullback technique that provides invasive crosssectional tomographic imaging [13,14]. The ultrasound signal is produced by sending an electrical current through a crystal element on the transducer. Sound waves are reflected or

catheter sitting out of the ostium are imperative for an accurate FFR recording.

however, a pullback curve will also overcome this limitation.

ed.

mal hyperaemia [12].

**3. An overview of IVUS**

**Figure 1.** Typical Example of FFR Recording (n.b. mean Pd and Pa pressures and automatic FFR recording as well as transient bradycardia consistent with adenosine)

#### **2.3. Pitfalls in FFR**

Like most tools in coronary intervention, Fractional Flow Reserve is not immune to technical mistakes [11]. It is important to be aware of the following various pitfalls to ensure that the FFR measurement is both valid and reproducible.

## **3. An overview of IVUS**

**Figure 1.** Typical Example of FFR Recording (n.b. mean Pd and Pa pressures and automatic FFR recording as well as

260 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

Like most tools in coronary intervention, Fractional Flow Reserve is not immune to technical mistakes [11]. It is important to be aware of the following various pitfalls to ensure that the

**a. Use of a guide wire introducer:** when used through the Y connector, there is a subtle leak of aortic guiding catheter pressure. Although it tends to only be small (<10mmHg), when the FFR is near the ischemic zone, this small difference may have important im‐ plications. It is therefore recommended that when equalizing, measuring FFR and checking for drift at the end of the procedure, that the wire introducer be removed.

**b. Not clearing the catheter of contrast:** ensuring that the guiding catheter is cleared of contrast during equalization and FFR measurement is important to avoid subtle con‐ trast induced damping of pressure waveform. To overcome this, the guiding catheter should be flushed with saline at the time of equalization and FFR measurement. It is im‐ portant to note ST changes at this time as over-enthusiastic flushing of the guiding cath‐ eter can lead to ischaemia induced ventricular fibrillation. It is advisable to flush in stages giving the patient a break between 5-second flushes until the catheter is clear of

transient bradycardia consistent with adenosine)

contrast on fluoroscopy.

FFR measurement is both valid and reproducible.

**2.3. Pitfalls in FFR**

Intravascular ultrasound is a catheter based pullback technique that provides invasive crosssectional tomographic imaging [13,14]. The ultrasound signal is produced by sending an electrical current through a crystal element on the transducer. Sound waves are reflected or pass through structures depending on their acoustic impedance. The scanning process pro‐ vides both a qualitative and quantitative assessment of the artery. Vessel wall, atherosclerot‐ ic burden and plaque composition can all be assessed and with a well defined lumen-intima interface, measurements made of lesion severity such as minimum lumen area.

#### **3.1. IVUS assessment of wall layers**

The intima is a single layer of endothelial cells that is largely defined by its interface with blood in the lumen [15]. Saline or contrast flush can help delineate this interface in complex undermined plaque or when this interface may be ambiguous in cases such as lumen filling defects or intramural haematoma.

The media is composed of smooth muscle cells and does not reflect ultrasound and there‐ fore appears as a dark ring during the pullback [15]. It is often used to help size stents along with reference lumen dimensions.

The adventitia is a matrix of collagen and elastin and reflects ultrasound markedly to give a whitish appearance on the outer segments of the vessel wall [15].

#### **3.2. IVUS transducer type**

There are two main types of transducers commercially available - a rotational single trans‐ ducer and multiple stationary transducers in a phased array system [16]. The following table compares the current commercially available products.

**Figure 2.** Panel 1: Adventitia (A), Media (M), Intima (I) and Catheter (C), Panel 2: NURD (N), Panel 3: Wire Artifact, Pan‐

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Calcified Plaque has marked acoustic shadowing with signal drop out and appears white on IVUS [15]. If circumferential calcification exists, this may prompt the operator to perform ro‐ tablation to ensure full stent expansion. Eccentric masses of bulky calcified plaque should also alert the operator to the potential risk of vessel perforation during percutaneous coro‐ nary intervention (particularly if a cutting balloon is used or if aggressive postdilation is performed) or focal stent under expansion. Generally, when only part of the vessel perime‐ ter is rigid, aggressive postdilation will force stent expansion into the direction of least re‐

IVUS is also able to detect soft plaque, fibrous tissue and in-stent restenosis. Positive and

Definition of diagnostic IVUS parameters for describing parameters of lesion significance as

negative remodeling are also easily identified and generally best identified by IVUS.

el 4: Eccentric fibrous plaque (P)

sistance.

**3.3. Plaque morphology by IVUS**

per the "JACC IVUS Consensus Document" [17]:

**Table 1.**

The most commonly used device in our institution is the rotational system. There is a drive cable that rotates a single transducer element at the tip. The imaging system is located with‐ in a protective sheath that is very soft and creates a fluid interface for the imaging transduc‐ er. The two main artifacts that are encountered include wire artifact and occasionally NURD (Non-uniform Rotational Distortion) [16].

**Figure 2.** Panel 1: Adventitia (A), Media (M), Intima (I) and Catheter (C), Panel 2: NURD (N), Panel 3: Wire Artifact, Pan‐ el 4: Eccentric fibrous plaque (P)

#### **3.3. Plaque morphology by IVUS**

pass through structures depending on their acoustic impedance. The scanning process pro‐ vides both a qualitative and quantitative assessment of the artery. Vessel wall, atherosclerot‐ ic burden and plaque composition can all be assessed and with a well defined lumen-intima

The intima is a single layer of endothelial cells that is largely defined by its interface with blood in the lumen [15]. Saline or contrast flush can help delineate this interface in complex undermined plaque or when this interface may be ambiguous in cases such as lumen filling

The media is composed of smooth muscle cells and does not reflect ultrasound and there‐ fore appears as a dark ring during the pullback [15]. It is often used to help size stents along

The adventitia is a matrix of collagen and elastin and reflects ultrasound markedly to give a

There are two main types of transducers commercially available - a rotational single trans‐ ducer and multiple stationary transducers in a phased array system [16]. The following table

**Comparison Boston Scientific Volcano Volcano** Commercial Name iCross Eagle Eye Platinum Revolution Imaging Method IVUS IVUS IVUS Scanning Design Rotational Phased Array Rotational Frequency 40 MHz 20 MHz 45 MHz Overall Profile 3.2 Fr 3.5 Fr 3.2 Fr

Guide Catheter 6Fr 5Fr 6Fr Delivery Monorail Rapid Exchange Monorail

The most commonly used device in our institution is the rotational system. There is a drive cable that rotates a single transducer element at the tip. The imaging system is located with‐ in a protective sheath that is very soft and creates a fluid interface for the imaging transduc‐ er. The two main artifacts that are encountered include wire artifact and occasionally NURD

whitish appearance on the outer segments of the vessel wall [15].

Tip Entry Profile 0.022" 0.019"

(Non-uniform Rotational Distortion) [16].

compares the current commercially available products.

interface, measurements made of lesion severity such as minimum lumen area.

262 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

**3.1. IVUS assessment of wall layers**

defects or intramural haematoma.

with reference lumen dimensions.

**3.2. IVUS transducer type**

**Table 1.**

Calcified Plaque has marked acoustic shadowing with signal drop out and appears white on IVUS [15]. If circumferential calcification exists, this may prompt the operator to perform ro‐ tablation to ensure full stent expansion. Eccentric masses of bulky calcified plaque should also alert the operator to the potential risk of vessel perforation during percutaneous coro‐ nary intervention (particularly if a cutting balloon is used or if aggressive postdilation is performed) or focal stent under expansion. Generally, when only part of the vessel perime‐ ter is rigid, aggressive postdilation will force stent expansion into the direction of least re‐ sistance.

IVUS is also able to detect soft plaque, fibrous tissue and in-stent restenosis. Positive and negative remodeling are also easily identified and generally best identified by IVUS.

Definition of diagnostic IVUS parameters for describing parameters of lesion significance as per the "JACC IVUS Consensus Document" [17]:

**3.4. IVUS to guide intervention**

tional area whereby the use of IVUS improves outcomes [18].

OPTICUS [25] 550 6 mth angio;

**Table 3.** IVUS vs Angiographic Guidance of Bare Metal Stent Implantation

**4. Overview of optical coherence tomography**

pathology behind restenosis.

Despite the relatively attractive ability to size stents and ensure adequate apposition and full stent expansion, there is unfortunately a lack of evidence that IVUS improves the incidence of MACE in patients undergoing stenting although 6-month angiographic diameters may be improved (refer to table below). The exception to this however is in the left main interven‐

Improving the Utility of Coronary Angiography: The Use of Adjuvant Imaging and Physiological Assessment

**Study Number (N) End Point Result** Albiero et al [19] 312 6mth angio IVUS better Blasini et al [20] 212 6 mth angio IVUS better Choi et al [21] 278 Acute closure; 6 month angio IVUS better Gaster et al [22] 108 6 mth angio IVUS better AVID [23] 759 12 mth TLR IVUS better CRUISE [24] 499 9 mth TVR IVUS better

PRESTO [26] 9070 9 mth MACE NO DIFFERENCE

SIPS [28] 269 2 year TLR IVUS better TULIP [29] 144 12 mth MACE IVUS better

The use of IVUS in elucidating the mechanism of instent restenosis is also important particu‐ larly given that it may not be as benign as initially thought. Walters et al. have described that an acute coronary syndrome is a common presentation for in-stent restenosis [30]. An‐ giography alone tends to overestimate the degree of restenosis and usually offers little infor‐ mation regarding the mechanism such as stent undersizing, incomplete expansion, strut fracture and geographic miss. Now that we have arrived in the OCT era, we may gain fur‐ ther insights into neoatherosclerosis as apposed to proliferative fibrous neointima as the

OCT is an intravascular imaging modality akin to intravascular ultrasound (IVUS), howev‐ er, where IVUS uses sound, OCT uses light. The use of near infrared frequency (1300 nm) light waves has remarkably increased resolution. OCT, unlike IVUS, requires a bloodless field. This was originally achieved with proximal occlusion (i.e. time-domain OCT) but in its

RESIST [27] 155 18mth MACE NO SIGNIFICANT DIFFERENCE

12mth MACE

NO DIFFERENCE

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#### **Table 2.**

Reference segments can be proximal and distal to the tightest point of the lesion and are usually arbitrarily defined to be within 10 mm of the MLA at a point with the least disease and not involving any side-branches.

**Figure 3.** Panel 1: 180 degree arc of calcium (C), Panel 2: Near 360 degree ring of calcium (C) – this would warrant rotablator, Panel 3: Post Rota-PCI with full stent expansion (S), Panel 4: Plaque rupture (PR) – unstable plaque during ACS

#### **3.4. IVUS to guide intervention**

**Term Description** Lumen Cross-Sectional Area (CSA) The area defined by the luminal border

264 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

Minimum Lumen Diameter (MLD) The shortest diameter through the centre point of the

Maximum Lumen Diameter The maximum diameter through the centre point of the

Lumen Eccentricity (Maximum lumen – MLD)/Maximum Lumen Diameter Lumen Area Stenosis (Reference Lumen CSA – Minimum lumen CSA)/Reference

Lumen Diameter Stenosis (Reference Diameter – MLD)/Reference Diameter

Reference segments can be proximal and distal to the tightest point of the lesion and are usually arbitrarily defined to be within 10 mm of the MLA at a point with the least disease

**Figure 3.** Panel 1: 180 degree arc of calcium (C), Panel 2: Near 360 degree ring of calcium (C) – this would warrant rotablator,

Panel 3: Post Rota-PCI with full stent expansion (S), Panel 4: Plaque rupture (PR) – unstable plaque during ACS

**Table 2.**

and not involving any side-branches.

lumen

lumen

Lumen CSA

Despite the relatively attractive ability to size stents and ensure adequate apposition and full stent expansion, there is unfortunately a lack of evidence that IVUS improves the incidence of MACE in patients undergoing stenting although 6-month angiographic diameters may be improved (refer to table below). The exception to this however is in the left main interven‐ tional area whereby the use of IVUS improves outcomes [18].

**Table 3.** IVUS vs Angiographic Guidance of Bare Metal Stent Implantation

The use of IVUS in elucidating the mechanism of instent restenosis is also important particu‐ larly given that it may not be as benign as initially thought. Walters et al. have described that an acute coronary syndrome is a common presentation for in-stent restenosis [30]. An‐ giography alone tends to overestimate the degree of restenosis and usually offers little infor‐ mation regarding the mechanism such as stent undersizing, incomplete expansion, strut fracture and geographic miss. Now that we have arrived in the OCT era, we may gain fur‐ ther insights into neoatherosclerosis as apposed to proliferative fibrous neointima as the pathology behind restenosis.

## **4. Overview of optical coherence tomography**

OCT is an intravascular imaging modality akin to intravascular ultrasound (IVUS), howev‐ er, where IVUS uses sound, OCT uses light. The use of near infrared frequency (1300 nm) light waves has remarkably increased resolution. OCT, unlike IVUS, requires a bloodless field. This was originally achieved with proximal occlusion (i.e. time-domain OCT) but in its most recent iteration, has been achieved by contrast injection with Fourier Domain OCT. This has significantly improved the user-friendliness of OCT. The characteristics of IVUS, TD-OCT and FD-OCT are detailed below:

rich plaque, fibrous plaque, calcified nodules, macrophages, intimal disruption, red and white thrombus and thin capped fibroatheroma. OCT has revolutionized the assessment of stent performance with an unrivalled ability to detect malapposition, stent expansion, edge dissection, prolapse, filling defects, strut appearance and strut coverage. It can even discrim‐ inate between neointima and neo-atherosclerosis with regard to in-stent restenosis and de‐ tect neorevascularisation. OCT is in its infancy in its ability to define flow-limiting stenoses

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**Figure 4.** Panel 1: Blood swirl artifact ; Panel 2: Wire artifact (W) ; Panel 3: Stitch artifact from catheter movement (arrow) ; Panel 4: Spontaneous coronary dissection with visible false lumen (FL) ; Panel 5: Fibrous Plaque ; Panel 6:

on the basis of lesion parameters for severity (akin to IVUS measurements).

**Table 5.**

Proliferative neointima within a stent

#### **Table 4.**

#### **4.1. Procedural detail**

The currently available OCT catheter is a rapid exchange catheter compatible with a 6Fr guiding catheter. The OCT catheter has several markers and the position of the imaging op‐ tical lens is noted to be 25 mm from the tip of the catheter and 5 mm proximal to the proxi‐ mal marker. It appears as a radiolucent gap in the imaging catheter. It is thus important to note that a considerable length of catheter is needed to be placed beyond a stenosis and therefore a suitable landing zone is required that is of reasonable caliber and not excessively tortuous. A calibration process is performed prior to image acquisition – z offset or auto-cal‐ ibration whereby marker fiducials are placed equidistant around the border of the catheter on the computer interface. With an automated injection system, we advocate a contrast in‐ jection of 4mL/sec, 14mL volume for the left coronary system; 3mL/sec, 12 mL for the right coronary system. For manual injection, usually 10mL contrast at reasonably sustained injec‐ tion pressure will be sufficient to opacify the vessel. Ischemic electrocardiographic changes are not infrequent but almost always self-limiting; arrhythmia is rare and less frequent than with TD-OCT. REF Other complications such as those from guiding catheters and coronary wires are not attributable to OCT per se but are a part of the inherent risk of the procedure. The main advantages with the FD-OCT over TD-OCT are the faster pullback speed (20mm/ sec) and the avoidance of proximal vessel occlusion, with potentially clearer images and larger reference segment dimensions [31]. The safety and feasibility of FD-OCT has been widely reported [32-34]. Slowing the pullback speed to 10 mm/sec can enhance the imaging detail particularly if imaging for stent complications at the end of a PCI.

#### **4.2. Current uses of OCT**

Sine 1996, a lot of work has been performed evaluating the correlation of OCT with histopa‐ thology – an essential prerequisite to describing vessel pathology. Exquisite images and de‐ tailed analysis of plaque composition [35] can be achieved including clarification of lipid rich plaque, fibrous plaque, calcified nodules, macrophages, intimal disruption, red and white thrombus and thin capped fibroatheroma. OCT has revolutionized the assessment of stent performance with an unrivalled ability to detect malapposition, stent expansion, edge dissection, prolapse, filling defects, strut appearance and strut coverage. It can even discrim‐ inate between neointima and neo-atherosclerosis with regard to in-stent restenosis and de‐ tect neorevascularisation. OCT is in its infancy in its ability to define flow-limiting stenoses on the basis of lesion parameters for severity (akin to IVUS measurements).

**Table 5.**

most recent iteration, has been achieved by contrast injection with Fourier Domain OCT. This has significantly improved the user-friendliness of OCT. The characteristics of IVUS,

266 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

Axial resolution, micron 100 10-15 10-15

Frame rate, frames/sec 30 20 100 Maximum scan diameter, mm 10 6.8 9.7 Proximal occlusion No Yes No Pullback rate, mm/s 1 1-3 20

The currently available OCT catheter is a rapid exchange catheter compatible with a 6Fr guiding catheter. The OCT catheter has several markers and the position of the imaging op‐ tical lens is noted to be 25 mm from the tip of the catheter and 5 mm proximal to the proxi‐ mal marker. It appears as a radiolucent gap in the imaging catheter. It is thus important to note that a considerable length of catheter is needed to be placed beyond a stenosis and therefore a suitable landing zone is required that is of reasonable caliber and not excessively tortuous. A calibration process is performed prior to image acquisition – z offset or auto-cal‐ ibration whereby marker fiducials are placed equidistant around the border of the catheter on the computer interface. With an automated injection system, we advocate a contrast in‐ jection of 4mL/sec, 14mL volume for the left coronary system; 3mL/sec, 12 mL for the right coronary system. For manual injection, usually 10mL contrast at reasonably sustained injec‐ tion pressure will be sufficient to opacify the vessel. Ischemic electrocardiographic changes are not infrequent but almost always self-limiting; arrhythmia is rare and less frequent than with TD-OCT. REF Other complications such as those from guiding catheters and coronary wires are not attributable to OCT per se but are a part of the inherent risk of the procedure. The main advantages with the FD-OCT over TD-OCT are the faster pullback speed (20mm/ sec) and the avoidance of proximal vessel occlusion, with potentially clearer images and larger reference segment dimensions [31]. The safety and feasibility of FD-OCT has been widely reported [32-34]. Slowing the pullback speed to 10 mm/sec can enhance the imaging

detail particularly if imaging for stent complications at the end of a PCI.

Sine 1996, a lot of work has been performed evaluating the correlation of OCT with histopa‐ thology – an essential prerequisite to describing vessel pathology. Exquisite images and de‐ tailed analysis of plaque composition [35] can be achieved including clarification of lipid

Wavelength Ultrasound Near-infrared Near-infrared

**IVUS TD-OCT FD-OCT**

TD-OCT and FD-OCT are detailed below:

**Table 4.**

**4.1. Procedural detail**

**4.2. Current uses of OCT**

**Figure 4.** Panel 1: Blood swirl artifact ; Panel 2: Wire artifact (W) ; Panel 3: Stitch artifact from catheter movement (arrow) ; Panel 4: Spontaneous coronary dissection with visible false lumen (FL) ; Panel 5: Fibrous Plaque ; Panel 6: Proliferative neointima within a stent

**•** In the early phases of operator inexperience, there can be difficulty identifying calcium

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269

The presence of myocardial ischemia is an important determinant of adverse cardiac out‐ come [36,37]. Revascularization of stenotic coronary lesions, by eliminating myocardial is‐ chemia can improve patient symptoms, functional status and in patients with proven ischaemia, reduce death and major adverse cardiovascular events [38-40]. Importantly, for stenotic lesions that do not induce ischemia, medical therapy alone is likely to be equally ef‐ fective with less benefit for revascularization [2,3,40]. While most patients undergo non-in‐ vasive testing to detect the presence of myocardial ischemia prior to consideration of angiography many patients with high clinical likelihood of CAD are catheterized without functional testing. Additionally, noninvasive stress imaging studies may be non-diagnostic and are limited in their ability to accurately localize culprit lesions in patients with multives‐ sel CAD [41]. Ultimately where revascularization is considered, patients undergo coronary

Proving ischaemic burden in intermediate lesions requires invasive adjunctive tools – pres‐ sure derived measurements using FFR aim at functional evaluation whilst intravascular ul‐ trasound (IVUS) and OCT provide anatomical clarification of the vessel anatomy and lesion dimensions. Both intracoronary IVUS and OCT can be used to measure lesion and vessel pa‐ rameters such as minimum luminal area and diameter. Unlike IVUS, OCT has only just be‐ gun to be validated against FFR. Given FFR is now the gold standard of invasive physiological assessment of the stenosis functional significance, there are studies underway to validate lesion parameters for severity on OCT with the physiological information ob‐

Coronary angiography is a 2-dimensional lumenogram of a 3-dimensional vascular lumen. It reports stenosis severity as a ratio of the lesion minimal lumen diameter to the adjacent "normal" reference segment. But, coronary atherosclerosis is a diffuse process and the accu‐ racy of angiographic assessment is limited by the inability to identify both "diseased" and "normal" vessel segments. Histopathological studies have demonstrated that angiography fails to detect atheroma until the area stenosis approaches 40-50% as this is the approximate critical level at which further expansion of the external elastic membrane is not possible and so plaque begins to encroach upon the lumen. Furthermore, eccentric plaque produces an eccentric lumen that can give conflicting degrees of angiographic narrowing dependant on the viewing angulations. Despite improvements in quantitative coronary angiographic (QCA) techniques, coronary angiography frequently fails to identify the accurate hemody‐ namic significance of coronary stenoses, particularly those between 30% and 70% diameter stenosis [42-44]. The assessment and management of these "intermediate coronary lesions",

**5. Assessment of moderate coronary artery disease – Non Left Main**

and differentiating it from lipid rich plaque

**5.1. Coronary angiography and stenosis significance**

angiography.

tained by FFR.

**Figure 5.** Panel 1: Calcified Nodule (arrow); Panel 2: Red thrombus (arrow) ; Panel 3: Vasa Vasorum (arrow) ; Panel 4: Covered stent – uncovered 7 years post deployment; Panel 5: Lipid rich plaque that is catheter hugging ; Panel 6: dis‐ rupted intima with a small cavity

#### **4.3. Despite the overall attractiveness of OCT, some drawbacks include**

**•** In the early phases of operator inexperience, there can be difficulty identifying calcium and differentiating it from lipid rich plaque

## **5. Assessment of moderate coronary artery disease – Non Left Main**

The presence of myocardial ischemia is an important determinant of adverse cardiac out‐ come [36,37]. Revascularization of stenotic coronary lesions, by eliminating myocardial is‐ chemia can improve patient symptoms, functional status and in patients with proven ischaemia, reduce death and major adverse cardiovascular events [38-40]. Importantly, for stenotic lesions that do not induce ischemia, medical therapy alone is likely to be equally ef‐ fective with less benefit for revascularization [2,3,40]. While most patients undergo non-in‐ vasive testing to detect the presence of myocardial ischemia prior to consideration of angiography many patients with high clinical likelihood of CAD are catheterized without functional testing. Additionally, noninvasive stress imaging studies may be non-diagnostic and are limited in their ability to accurately localize culprit lesions in patients with multives‐ sel CAD [41]. Ultimately where revascularization is considered, patients undergo coronary angiography.

Proving ischaemic burden in intermediate lesions requires invasive adjunctive tools – pres‐ sure derived measurements using FFR aim at functional evaluation whilst intravascular ul‐ trasound (IVUS) and OCT provide anatomical clarification of the vessel anatomy and lesion dimensions. Both intracoronary IVUS and OCT can be used to measure lesion and vessel pa‐ rameters such as minimum luminal area and diameter. Unlike IVUS, OCT has only just be‐ gun to be validated against FFR. Given FFR is now the gold standard of invasive physiological assessment of the stenosis functional significance, there are studies underway to validate lesion parameters for severity on OCT with the physiological information ob‐ tained by FFR.

#### **5.1. Coronary angiography and stenosis significance**

**Figure 5.** Panel 1: Calcified Nodule (arrow); Panel 2: Red thrombus (arrow) ; Panel 3: Vasa Vasorum (arrow) ; Panel 4: Covered stent – uncovered 7 years post deployment; Panel 5: Lipid rich plaque that is catheter hugging ; Panel 6: dis‐

**•** Limited ability to image very large vessels given limited depth of penetration (imaging

**•** Blood pool artifact (this occurs when the lumen is not devoid of blood because of inade‐

**•** Stitch artifact (usually only subtle and not a major issue; this artifact relates mostly to catheter movement within the vessel and appears as an abrupt step in the vessel wall)

**•** If the catheter does not sit coaxially within the vessel then an oblique cut may be made

**•** Given the imaging catheter remains in the artery, there may be a tendency to straighten the vessel, cause vessel concertina and perhaps even distort stents of questionable longi‐

**•** Difficulty to image true aorto-ostial disease (IVUS is preferred in this scenario)

quate contrast injection – the erythrocytes cause a severe scatter of light)

**4.3. Despite the overall attractiveness of OCT, some drawbacks include**

268 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

rupted intima with a small cavity

**•** Need for extra contrast

>4.5 mm diameter vessels is difficult)

through the lumen and vessel wall

tudinal strength

Coronary angiography is a 2-dimensional lumenogram of a 3-dimensional vascular lumen. It reports stenosis severity as a ratio of the lesion minimal lumen diameter to the adjacent "normal" reference segment. But, coronary atherosclerosis is a diffuse process and the accu‐ racy of angiographic assessment is limited by the inability to identify both "diseased" and "normal" vessel segments. Histopathological studies have demonstrated that angiography fails to detect atheroma until the area stenosis approaches 40-50% as this is the approximate critical level at which further expansion of the external elastic membrane is not possible and so plaque begins to encroach upon the lumen. Furthermore, eccentric plaque produces an eccentric lumen that can give conflicting degrees of angiographic narrowing dependant on the viewing angulations. Despite improvements in quantitative coronary angiographic (QCA) techniques, coronary angiography frequently fails to identify the accurate hemody‐ namic significance of coronary stenoses, particularly those between 30% and 70% diameter stenosis [42-44]. The assessment and management of these "intermediate coronary lesions", then becomes a dilemma for the clinician. In this context, a more reliable technique at the time of angiography is vital to direct appropriate revascularization or medical therapy in a single setting. Fractional flow reserve (FFR) assessment and Intravascular ultrasound (IVUS) are two such techniques which are now part of standard clinical practice in guiding treat‐ ment of patients with intermediate coronary lesions [43,44] [45].

**5.3. Fractional flow reserve corrected for right atrial pressure and stenosis significance**

parameters for lesion severity.

cross-sectional area ≤3.0 - 4.0mm2

preference to FFR when:

**5.4. Intravascular ultrasound (IVUS) and stenosis significance**

gree of calcification and accurate vessel size are required.

rhythmia or severe asthma precluding the use of adenosine.

The original FFR calculation was derived from the following formula: FFR= (Pd-Pv)/(Pa-Pv) where Pd is distal mean pressure, Pa is aortic/guiding catheter mean pressure and Pv is cen‐ tral venous/RA (right atrial) pressure [48,49]. Effectively, this is an FFR corrected for right atrial pressure (FFRRA). FFRRA was used in some [49,50] but not all of the original validation studies to determine which FFR values best predicts an ischaemic burden [51-53]. In all re‐ cent studies validating IVUS with FFR and FFR with revascularisation/outcomes, FFR was never corrected for RA pressure. The simplified formula FFR = Pd/Pa was used largely based on the assumption that Pv was minimal and therefore did not greatly influence the final FFR result. Furthermore, previous data suggested that a correlation existed between FFR and positron emmission tomography (PET) derived myocardial blood flow indices even when RA pressure was ommitted [50]. However, this was a small series of low risk pa‐ tients with a mean RA pressure of 5 mmHg. This does not necessarily reflect the cohort of patients coming through a high volume tertiary hospital with congestive cardiac failure pa‐ tients in which filling pressure may not be insignificant. This lead Layland et al to compare FFRRA with FFR in assessing coronary stenoses in a real world cohort. They demonstrated that right atrial pressure does in fact influence the FFR and tends to shift it downward into the ischaemic threshold [54]. It is not known however, whether FFRRA (as opposed to FFR) can be used to guide intervention or whether it would better correlate with IVUS or OCT

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As previously described, intravascular ultrasound is a catheter-based technique that pro‐ vides high-resolution (up to 150microns) cross-sectional tomographic images of the coro‐ nary lumen and the coronary arterial wall that can be visualized in real time. It is currently the commonest intravascular imaging modality used as an adjunct to coronary angiography and PCI. Intravascular ultrasound is simple to perform, and its use is associated with very low complication rates [55]. IVUS does not provide direct hemodynamic data of a coronary lesion. However, several studies have demonstrated a strong correlation between IVUS le‐ sion parameter and ischemia by myocardial perfusion imaging [56], and FFR [57,58]. Param‐ eters that correlated with an FFR value ≤0.75 were area stenosis (>60-70%), minimal lumen

**1.** Precise information on extent of the atherosclerosis, plaque characteristics including de‐

**2.** FFR assessment is contraindicated; significant conducting system disease or bradyar‐

**3.** Situations where FFR values may be misleading; previous MI with significant scar, dif‐ fuse coronary disease, microvascular disease, significant left ventricular hypertrophy. The traditional cutoff of MLA <4 mm2 on IVUS has been questioned in recent studies, and it is now thought that an MLA of <2.4 mm2 may better predict a significant lesion [57-59]. Ulti‐

and minimal lumen diameter ≤1.8 mm. IVUS is used in

#### **5.2. Fractional flow reserve and stenosis significance**

Coronary pressure wire-derived FFR is now the technique of choice used in the cardiac cathe‐ terization laboratory to determine the functional significance of a coronary stenosis [45]. This method relies on the decrease in intra-arterial pressure induced by a stenosis to determine whether the lesion is producing physiologically significant ischemia. As described previously, Fractional flow reserve (FFR) is defined as the ratio of flow in the stenotic artery to the flow in the same artery in the theoretic absence of the stenosis [46]. Pressure is used as a surrogate of flow and FFR can be calculated by measuring the pressure difference across a stenosis under maxi‐ mal hyperemia induced usually by adenosine. The pressure distal to the stenosis is accurately measured by a 0.014-inch pressure sensor angioplasty guidewire passed distal to the stenosis. FFR in a normal coronary artery = 1.0. FFR values of <0.75 (normal 1.0) are associated with posi‐ tive functional stress tests in numerous comparative studies [sensitivity (88%), specificity (100%), positive predictive value (100%), and overall accuracy (93%)[45]. FFR values >0.80 are associated with negative ischemic results with a predictive accuracy of 95% [45]. Deferring re‐ vascularisation based on non-significant FFR values (>0.75) are associated with rates of death or myocardial infarction lower than that after routine stenting [3]. In patients with multivessel cor‐ onary artery disease FFR-guided PCI is associated with reduced major adverse cardiac events [40]. Furthermore, De Bruyne et al have recently demonstrated that managing patients medical‐ ly (deferring PCI) with lesions that have documented ischaemic burden (defined as FFR < 0.80) have an increased risk of urgent revascularisation [47].

**Table 6.**

#### **5.3. Fractional flow reserve corrected for right atrial pressure and stenosis significance**

then becomes a dilemma for the clinician. In this context, a more reliable technique at the time of angiography is vital to direct appropriate revascularization or medical therapy in a single setting. Fractional flow reserve (FFR) assessment and Intravascular ultrasound (IVUS) are two such techniques which are now part of standard clinical practice in guiding treat‐

270 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

Coronary pressure wire-derived FFR is now the technique of choice used in the cardiac cathe‐ terization laboratory to determine the functional significance of a coronary stenosis [45]. This method relies on the decrease in intra-arterial pressure induced by a stenosis to determine whether the lesion is producing physiologically significant ischemia. As described previously, Fractional flow reserve (FFR) is defined as the ratio of flow in the stenotic artery to the flow in the same artery in the theoretic absence of the stenosis [46]. Pressure is used as a surrogate of flow and FFR can be calculated by measuring the pressure difference across a stenosis under maxi‐ mal hyperemia induced usually by adenosine. The pressure distal to the stenosis is accurately measured by a 0.014-inch pressure sensor angioplasty guidewire passed distal to the stenosis. FFR in a normal coronary artery = 1.0. FFR values of <0.75 (normal 1.0) are associated with posi‐ tive functional stress tests in numerous comparative studies [sensitivity (88%), specificity (100%), positive predictive value (100%), and overall accuracy (93%)[45]. FFR values >0.80 are associated with negative ischemic results with a predictive accuracy of 95% [45]. Deferring re‐ vascularisation based on non-significant FFR values (>0.75) are associated with rates of death or myocardial infarction lower than that after routine stenting [3]. In patients with multivessel cor‐ onary artery disease FFR-guided PCI is associated with reduced major adverse cardiac events [40]. Furthermore, De Bruyne et al have recently demonstrated that managing patients medical‐ ly (deferring PCI) with lesions that have documented ischaemic burden (defined as FFR < 0.80)

ment of patients with intermediate coronary lesions [43,44] [45].

**5.2. Fractional flow reserve and stenosis significance**

have an increased risk of urgent revascularisation [47].

**Table 6.**

The original FFR calculation was derived from the following formula: FFR= (Pd-Pv)/(Pa-Pv) where Pd is distal mean pressure, Pa is aortic/guiding catheter mean pressure and Pv is cen‐ tral venous/RA (right atrial) pressure [48,49]. Effectively, this is an FFR corrected for right atrial pressure (FFRRA). FFRRA was used in some [49,50] but not all of the original validation studies to determine which FFR values best predicts an ischaemic burden [51-53]. In all re‐ cent studies validating IVUS with FFR and FFR with revascularisation/outcomes, FFR was never corrected for RA pressure. The simplified formula FFR = Pd/Pa was used largely based on the assumption that Pv was minimal and therefore did not greatly influence the final FFR result. Furthermore, previous data suggested that a correlation existed between FFR and positron emmission tomography (PET) derived myocardial blood flow indices even when RA pressure was ommitted [50]. However, this was a small series of low risk pa‐ tients with a mean RA pressure of 5 mmHg. This does not necessarily reflect the cohort of patients coming through a high volume tertiary hospital with congestive cardiac failure pa‐ tients in which filling pressure may not be insignificant. This lead Layland et al to compare FFRRA with FFR in assessing coronary stenoses in a real world cohort. They demonstrated that right atrial pressure does in fact influence the FFR and tends to shift it downward into the ischaemic threshold [54]. It is not known however, whether FFRRA (as opposed to FFR) can be used to guide intervention or whether it would better correlate with IVUS or OCT parameters for lesion severity.

#### **5.4. Intravascular ultrasound (IVUS) and stenosis significance**

As previously described, intravascular ultrasound is a catheter-based technique that pro‐ vides high-resolution (up to 150microns) cross-sectional tomographic images of the coro‐ nary lumen and the coronary arterial wall that can be visualized in real time. It is currently the commonest intravascular imaging modality used as an adjunct to coronary angiography and PCI. Intravascular ultrasound is simple to perform, and its use is associated with very low complication rates [55]. IVUS does not provide direct hemodynamic data of a coronary lesion. However, several studies have demonstrated a strong correlation between IVUS le‐ sion parameter and ischemia by myocardial perfusion imaging [56], and FFR [57,58]. Param‐ eters that correlated with an FFR value ≤0.75 were area stenosis (>60-70%), minimal lumen cross-sectional area ≤3.0 - 4.0mm2 and minimal lumen diameter ≤1.8 mm. IVUS is used in preference to FFR when:

The traditional cutoff of MLA <4 mm2 on IVUS has been questioned in recent studies, and it is now thought that an MLA of <2.4 mm2 may better predict a significant lesion [57-59]. Ulti‐ mately, it is still unclear which of the two MLA cuttoff's is more efficient in predicting sign‐ ficant stenoses, and future IVUS and OCT studies may also suffer from this "shifting goalpost" phenomenon. This reflects the need for more studies validating anatomical with physiological data.

OCT and IVUS were indeed much smaller than the traditional 4 mm2

requisite before OCT can be validly used to establish stenosis significance.

id. Specific in vivo validation data against FFR is required.

by a simple approach to the side-branch is usually all that is required.

vasculature pressures are high and thereby the FFR falsely elevated [6].

**6. Other uses for FFR**

struction post ACS is detrimental [69].

**7.1. Background**

**7. Assessment of the ambiguous left main**

not correct FFR for right atrial pressure nor did it include OCT values indexed to the size of the patient or reference vessel (in a bid to roughly adjust for mass of myocardium supplied) – two corrections that may improve the correlation between OCT and FFR and affect the anatomical parameter and its value that best predicts an FFR ≤0.80. Further studies are therefore a vital pre-

Improving the Utility of Coronary Angiography: The Use of Adjuvant Imaging and Physiological Assessment

In-vitro studies with a vascular phantom have shown that not only do OCT luminal meas‐ urements correlate strongly with IVUS but they are more accurate than IVUS [63]. Both in vitro and in vivo studies suggest, however, that OCT measurements tend to be smaller than IVUS measurements probably because of its better luminal definition [62,64]. Therefore, di‐ rect translation of IVUS parameters of stenosis significance to OCT is not appropriate or val‐

FFR can be used to guide PCI formally to ensure full stent expansion based on FFR >0.94 [65] and can also be used to evaluate side branch "pinching" post PCI. Koo et al demonstrated that when the side branch was <75% stenosed post PCI, the FFR was never in the ischaemic range and when it was >75% stenosed, it only fell into the ischaemic range approximately 1/3 of the time [66]. This emphasizes a common issue of over-interpreting the side branch appearance in PCI cases and vindicates bifurcation studies such as Nordic-Baltic Bifurcation Study III [67] where‐

The use of FFR in vein grafts or in cases of severe left ventricular hypertrophy has not yet been validated. Nor, is it a useful tool in the acute setting such as a STEMI when the micro‐

The pressure sensor wire also has a temperature sensing function that enables it to detect changes in temperature with saline flushes. Although beyond the scope of this chapter, it has allowed the FFR wire to also measure microcirculatory function (Index of Microcircula‐ tory Resistance or IMR). The basic physiology behind IMR relates to transit time and tem‐ perature change detected by the wire sensor after flushing 3mls of saline via the guiding catheter. Ultimately, transit time is inversely proportional to microcirculatory resistance [68]. Although IMR is still largely a research tool, it has been shown to correlate with peak CK enzyme rise post STEMI and therefore offers a proof of concept that microvascular ob‐

The accurate detection and description of disease of the left main coronary artery (LMCA) is of fundamental importance in the evaluation of patients in the catheterization laboratory.

. However, this study did

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273

In our catheterization laboratory about half of the stenosis assessments are done with IVUS. In some centers' it is the primary tool used [60]. There is a growing trend in our labarotory now for using OCT instead of IVUS for plaque characterisation and vessel dimensions.

#### **5.5. Optical coherence tomography and stenosis significance**

Optical coherence tomography (OCT) is a recently introduced medical imaging technology. It is an optical analogue of IVUS and measures the back-reflection of near-infrared light di‐ rected at tissues and generates images with a resolution close to 10micron; 10-15X greater than IVUS. With the current generation of FD-OCT imaging engines, it is also up to 20 times faster in imaging [35]. The safety of OCT imaging has been well described [61,62]. Given its significantly higher resolution, OCT has many advantages over IVUS both in atherosclerotic plaque assessment and in evaluating the acute and long-term effects of PCI [35]. It is likely to replace IVUS as the primary intravascular imaging modality.

#### **Table 7.**

With its better definition of the intimal-luminal interface and higher resolution compared to IVUS, OCT may improve accuracy and reduce observer variability in intravascular luminal cross-sectional measurements; in this context OCT may be particularly useful in assessing (in‐ termediate) coronary stenosis severity. However, unlike IVUS which has many studies validat‐ ing it against FFR albeit with differing MLA results, there has only been one such trial using OCT [59]. In this study, it was demonstrated that an MLA of 1.95 mm2 was most efficient at pre‐ dicting physiological significance. Gonzalo et al. [59] also demonstrated that OCT was more ef‐ ficient than IVUS in predicting stenosis severity and that the geometric cutoff values for both OCT and IVUS were indeed much smaller than the traditional 4 mm2 . However, this study did not correct FFR for right atrial pressure nor did it include OCT values indexed to the size of the patient or reference vessel (in a bid to roughly adjust for mass of myocardium supplied) – two corrections that may improve the correlation between OCT and FFR and affect the anatomical parameter and its value that best predicts an FFR ≤0.80. Further studies are therefore a vital prerequisite before OCT can be validly used to establish stenosis significance.

In-vitro studies with a vascular phantom have shown that not only do OCT luminal meas‐ urements correlate strongly with IVUS but they are more accurate than IVUS [63]. Both in vitro and in vivo studies suggest, however, that OCT measurements tend to be smaller than IVUS measurements probably because of its better luminal definition [62,64]. Therefore, di‐ rect translation of IVUS parameters of stenosis significance to OCT is not appropriate or val‐ id. Specific in vivo validation data against FFR is required.

## **6. Other uses for FFR**

mately, it is still unclear which of the two MLA cuttoff's is more efficient in predicting sign‐ ficant stenoses, and future IVUS and OCT studies may also suffer from this "shifting goalpost" phenomenon. This reflects the need for more studies validating anatomical with

272 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

In our catheterization laboratory about half of the stenosis assessments are done with IVUS. In some centers' it is the primary tool used [60]. There is a growing trend in our labarotory now for using OCT instead of IVUS for plaque characterisation and vessel dimensions.

Optical coherence tomography (OCT) is a recently introduced medical imaging technology. It is an optical analogue of IVUS and measures the back-reflection of near-infrared light di‐ rected at tissues and generates images with a resolution close to 10micron; 10-15X greater than IVUS. With the current generation of FD-OCT imaging engines, it is also up to 20 times faster in imaging [35]. The safety of OCT imaging has been well described [61,62]. Given its significantly higher resolution, OCT has many advantages over IVUS both in atherosclerotic plaque assessment and in evaluating the acute and long-term effects of PCI [35]. It is likely

With its better definition of the intimal-luminal interface and higher resolution compared to IVUS, OCT may improve accuracy and reduce observer variability in intravascular luminal cross-sectional measurements; in this context OCT may be particularly useful in assessing (in‐ termediate) coronary stenosis severity. However, unlike IVUS which has many studies validat‐ ing it against FFR albeit with differing MLA results, there has only been one such trial using

dicting physiological significance. Gonzalo et al. [59] also demonstrated that OCT was more ef‐ ficient than IVUS in predicting stenosis severity and that the geometric cutoff values for both

was most efficient at pre‐

OCT [59]. In this study, it was demonstrated that an MLA of 1.95 mm2

**5.5. Optical coherence tomography and stenosis significance**

to replace IVUS as the primary intravascular imaging modality.

physiological data.

**Table 7.**

FFR can be used to guide PCI formally to ensure full stent expansion based on FFR >0.94 [65] and can also be used to evaluate side branch "pinching" post PCI. Koo et al demonstrated that when the side branch was <75% stenosed post PCI, the FFR was never in the ischaemic range and when it was >75% stenosed, it only fell into the ischaemic range approximately 1/3 of the time [66]. This emphasizes a common issue of over-interpreting the side branch appearance in PCI cases and vindicates bifurcation studies such as Nordic-Baltic Bifurcation Study III [67] where‐ by a simple approach to the side-branch is usually all that is required.

The use of FFR in vein grafts or in cases of severe left ventricular hypertrophy has not yet been validated. Nor, is it a useful tool in the acute setting such as a STEMI when the micro‐ vasculature pressures are high and thereby the FFR falsely elevated [6].

The pressure sensor wire also has a temperature sensing function that enables it to detect changes in temperature with saline flushes. Although beyond the scope of this chapter, it has allowed the FFR wire to also measure microcirculatory function (Index of Microcircula‐ tory Resistance or IMR). The basic physiology behind IMR relates to transit time and tem‐ perature change detected by the wire sensor after flushing 3mls of saline via the guiding catheter. Ultimately, transit time is inversely proportional to microcirculatory resistance [68]. Although IMR is still largely a research tool, it has been shown to correlate with peak CK enzyme rise post STEMI and therefore offers a proof of concept that microvascular ob‐ struction post ACS is detrimental [69].

## **7. Assessment of the ambiguous left main**

### **7.1. Background**

The accurate detection and description of disease of the left main coronary artery (LMCA) is of fundamental importance in the evaluation of patients in the catheterization laboratory. Significant LMCA stenosis carries a poor prognosis without appropriate revascularization. [70-72] Therefore, the presence or absence of left main disease has a critical impact on thera‐ peutic decision making following angiographic evaluation.

adenosine infusion, care should be taken to ensure that the peripheral intravenous site is flushing normally and appropriately connected. Maximal hyperaemia will be achieved in most patients by two to three minutes, at which point the infusion can be ceased. An alterna‐ tive to the infusion of adenosine is intracoronary bolus injection, but this is potentially a less robust [85] method and can be practically difficult if guide catheter pressure damping man‐ dates catheter disengagement. A further potential confounder is the role of right atrial pres‐ sure in FFR assessment. Although FFR adjusted for right atrial pressure was tested by Layland et al in the non-left main subset, adjusting for assessment of left main has not been conducted although a similar phenomenon would be expected – that being as FFR ap‐ proaches the ischaemic zone, right atrial pressure becomes increasingly important.[54] This

Improving the Utility of Coronary Angiography: The Use of Adjuvant Imaging and Physiological Assessment

Intravascular ultrasound (IVUS) of the LMCA provides sonographically derived images of the LMCA lumen and vessel wall. As a result, IVUS provides real time anatomical and pathological information in 2 dimensions. IVUS parameters have been evaluated in multiple studies in the setting of LMCA disease. Initial work that correlated IVUS data with clinical outcomes demonstrated a relationship between IVUS derived minimal luminal diameter (MLD) and minimal lumen area (MLA) at a lesion site with major adverse cardiovascular events (MACE).[86] [87]These initial studies, however, did not mandate any specific cut off values for treatment decisions. A clinical outcome based study by Fassa et al subsequently demonstrated that deferral of revascularization is the appropriate strategy where the LMCA

Given the clinically validated findings for FFR, IVUS has also been investigated utilizing FFR as a gold standard comparator. In a cohort of 51 North American patients Jasti et al

<0.75. This study also correlated FFR measurements with clinical outcomes and confirmed the appropriateness of an FFR cut off of <0.75. [90]Kang et al performed a similar correlation

evaluation of clinical outcomes was not performed as was done in the study by Jasti et al. In addition, the applicability of the study by Kang et al to patients of European ethnicity is un‐ clear. Both studies also demonstrated that relative disease burden metrics such as plaque burden and area stenosis were insufficiently predictive of FFR measurements to be useful in

Based on the above data, a cut off of ≤5.9 mm<sup>2</sup> for MLA, if using IVUS alone, should be used in determining referral for LMCA revascularization following IVUS evaluation. Where there is uncertainty or ambiguity around measurements or their relevance in specific patients,

study in 55 South Korean patients. They found a MLA cut off of <4.1 mm2

strong consideration should be given to adjunctive FFR evaluation.

or an MLA ≤5.9 mm2

. [88]More recent work has revised this measurement down to ≥6 mm<sup>2</sup>

. [89]

correlated well

correlated strongly with a FFR

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275

correlated with a FFR of <0.8. However,

is an area that requires further investigation.

**7.3.

Angiographic assessment of the LMCA can be challenging. The anatomical plane of the LMCA, issues with vessel overlap, elliptical vessel configuration and plaque eccentricity all contribute to potential difficulty in accurately quantifying LMCA disease with conventional coronary angiography alone. In cases where LMCA disease severity is ambiguous, indeter‐ minate or equivocal, adjunctive intravascular imaging or physiological assessment is of key importance.[18]

Fractional flow reserve (FFR) offers a real time stress physiological assessment of coronary pressure dynamics. Intravascular ultrasound (IVUS) is able to define the anatomy of the LMCA. Both of these technologies allow for the potential to improve LMCA assessment and attendant clinical outcomes and are discussed further below. Optical coherence tomography (OCT) has a limited role in LMCA assessment, especially for ostial LMCA disease, largely due to the dependence on having a contrast filled lumen to allow satisfactory imaging reso‐ lution to occur. [73]

#### **7.2. Fractional flow reserve physiological assessment**

FFR has been evaluated in several studies in the setting of LMCA disease. A cut off value for the Pd/Pa (pressure distal/pressure aortic) ratio, following induction of hyperaemia, of <0.75 – 0.8 has been demonstrated to safely discriminate between patients who should be referred for revascularization, usually coronary artery bypass grafting, as opposed to ongoing medi‐ cal therapy and observation. [74-81] Patients with readings between 0.75 – 0.8 have physiol‐ ogy in a range that requires further study. In patients with intermediate readings of this kind the clinical context, as well consideration to additional evaluation with intravascular ultrasound become important.

The FFR technique involves the placement of a high fidelity pressure sensor beyond the left main plaque just as described in the "non left main" section previously. Consideration should be given to performing the procedure in both the left anterior descending and left circumflex artery to ensure concordance of results – this is particularly important if the cir‐ cumflex is dominant [18]. Once the wire is in position and the catheter flushed with 100 – 200 mcg of intracoronary nitroglycerine followed by saline, hyperaemia is induced with the use of adenosine, 140 - 180 mcg/kg/min via intravenous infusion (central or peripheral). Higher doses may be required if a systemic response is not demonstrated. Venous infusion is preferred, however, adenosine can also be delivered by intracoronary bolus and studies in the area suggest no major difference between the three administration methods, [82,83] al‐ though intracoronary bolus doses of up to 720 mcg on each injection may be required.[84]

There are several potential pitfalls to FFR evaluation of the left main. Of utmost importance is the particular issue of guiding catheter damping and potential obstructive interference with coronary flow. Disengagement of the guide catheter is required for accurate evaluation in order to not underestimate the significance of the FFR. If a peripheral line is used for the adenosine infusion, care should be taken to ensure that the peripheral intravenous site is flushing normally and appropriately connected. Maximal hyperaemia will be achieved in most patients by two to three minutes, at which point the infusion can be ceased. An alterna‐ tive to the infusion of adenosine is intracoronary bolus injection, but this is potentially a less robust [85] method and can be practically difficult if guide catheter pressure damping man‐ dates catheter disengagement. A further potential confounder is the role of right atrial pres‐ sure in FFR assessment. Although FFR adjusted for right atrial pressure was tested by Layland et al in the non-left main subset, adjusting for assessment of left main has not been conducted although a similar phenomenon would be expected – that being as FFR ap‐ proaches the ischaemic zone, right atrial pressure becomes increasingly important.[54] This is an area that requires further investigation.

#### **7.3. Intravascular ultrasound assessment**

Significant LMCA stenosis carries a poor prognosis without appropriate revascularization. [70-72] Therefore, the presence or absence of left main disease has a critical impact on thera‐

274 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

Angiographic assessment of the LMCA can be challenging. The anatomical plane of the LMCA, issues with vessel overlap, elliptical vessel configuration and plaque eccentricity all contribute to potential difficulty in accurately quantifying LMCA disease with conventional coronary angiography alone. In cases where LMCA disease severity is ambiguous, indeter‐ minate or equivocal, adjunctive intravascular imaging or physiological assessment is of key

Fractional flow reserve (FFR) offers a real time stress physiological assessment of coronary pressure dynamics. Intravascular ultrasound (IVUS) is able to define the anatomy of the LMCA. Both of these technologies allow for the potential to improve LMCA assessment and attendant clinical outcomes and are discussed further below. Optical coherence tomography (OCT) has a limited role in LMCA assessment, especially for ostial LMCA disease, largely due to the dependence on having a contrast filled lumen to allow satisfactory imaging reso‐

FFR has been evaluated in several studies in the setting of LMCA disease. A cut off value for the Pd/Pa (pressure distal/pressure aortic) ratio, following induction of hyperaemia, of <0.75 – 0.8 has been demonstrated to safely discriminate between patients who should be referred for revascularization, usually coronary artery bypass grafting, as opposed to ongoing medi‐ cal therapy and observation. [74-81] Patients with readings between 0.75 – 0.8 have physiol‐ ogy in a range that requires further study. In patients with intermediate readings of this kind the clinical context, as well consideration to additional evaluation with intravascular

The FFR technique involves the placement of a high fidelity pressure sensor beyond the left main plaque just as described in the "non left main" section previously. Consideration should be given to performing the procedure in both the left anterior descending and left circumflex artery to ensure concordance of results – this is particularly important if the cir‐ cumflex is dominant [18]. Once the wire is in position and the catheter flushed with 100 – 200 mcg of intracoronary nitroglycerine followed by saline, hyperaemia is induced with the use of adenosine, 140 - 180 mcg/kg/min via intravenous infusion (central or peripheral). Higher doses may be required if a systemic response is not demonstrated. Venous infusion is preferred, however, adenosine can also be delivered by intracoronary bolus and studies in the area suggest no major difference between the three administration methods, [82,83] al‐ though intracoronary bolus doses of up to 720 mcg on each injection may be required.[84]

There are several potential pitfalls to FFR evaluation of the left main. Of utmost importance is the particular issue of guiding catheter damping and potential obstructive interference with coronary flow. Disengagement of the guide catheter is required for accurate evaluation in order to not underestimate the significance of the FFR. If a peripheral line is used for the

peutic decision making following angiographic evaluation.

**7.2. Fractional flow reserve physiological assessment**

importance.[18]

lution to occur. [73]

ultrasound become important.

Intravascular ultrasound (IVUS) of the LMCA provides sonographically derived images of the LMCA lumen and vessel wall. As a result, IVUS provides real time anatomical and pathological information in 2 dimensions. IVUS parameters have been evaluated in multiple studies in the setting of LMCA disease. Initial work that correlated IVUS data with clinical outcomes demonstrated a relationship between IVUS derived minimal luminal diameter (MLD) and minimal lumen area (MLA) at a lesion site with major adverse cardiovascular events (MACE).[86] [87]These initial studies, however, did not mandate any specific cut off values for treatment decisions. A clinical outcome based study by Fassa et al subsequently demonstrated that deferral of revascularization is the appropriate strategy where the LMCA MLA is ≥7.5 mm<sup>2</sup> . [88]More recent work has revised this measurement down to ≥6 mm<sup>2</sup> . [89]

Given the clinically validated findings for FFR, IVUS has also been investigated utilizing FFR as a gold standard comparator. In a cohort of 51 North American patients Jasti et al demonstrated that an MLD ≤2.8 mm2 or an MLA ≤5.9 mm2 correlated strongly with a FFR <0.75. This study also correlated FFR measurements with clinical outcomes and confirmed the appropriateness of an FFR cut off of <0.75. [90]Kang et al performed a similar correlation study in 55 South Korean patients. They found a MLA cut off of <4.1 mm2 correlated well with a FFR <0.75 and a MLA cut off of <4.8 mm2 correlated with a FFR of <0.8. However, evaluation of clinical outcomes was not performed as was done in the study by Jasti et al. In addition, the applicability of the study by Kang et al to patients of European ethnicity is un‐ clear. Both studies also demonstrated that relative disease burden metrics such as plaque burden and area stenosis were insufficiently predictive of FFR measurements to be useful in clinical practice.

Based on the above data, a cut off of ≤5.9 mm<sup>2</sup> for MLA, if using IVUS alone, should be used in determining referral for LMCA revascularization following IVUS evaluation. Where there is uncertainty or ambiguity around measurements or their relevance in specific patients, strong consideration should be given to adjunctive FFR evaluation.

## **8. Case examples**

#### Case #1: FFR and IVUS of Left Main

A 48 year-old gentleman presents with ischaemic sounding chest pain, troponin 1.3 ng/L and subtle precordial ST depression on his ECG. He has a background history of smoking, dyslipidaemia and a strong family history of premature coronary disease.

A 65 year old female presented with a long history of exertional chest discomfort and dysp‐ noea. A stress echocardiogram demonstrated possible mild exercise induced basal inferior wall hypokinesia. She had a background history of severe uncontrolled hypertension. Her left coronary tree was unremarkable. A 50% mid RCA lesion was interrogated by OCT and

Improving the Utility of Coronary Angiography: The Use of Adjuvant Imaging and Physiological Assessment

mendation was for improved blood pressure control. This case highlights the importance of thorough assessment of moderate lesions despite a typical symptom profile of angina. This patient almost certainly had hypertensive heart disease as a cause of her shortness of breath

A 37 year-old female with a family history of coronary disease presents with chest pain, ele‐ vated biomarkers and ST praecordial T wave inversion on her 12 lead ECG a few months

Angiography revealed diffuse narrowing of distal left anterior descending artery (refer to

Case #3: Use of IVUS and OCT to diagnose spontaneous coronary dissection:

**Figure 7.** FFR of Left Main into LAD – dramatic drop in FFR to 0.71

on OCT and FFR > 0.80, the lesion was not stented. The recom‐

http://dx.doi.org/10.5772/54041

277

FFR – refer to figures 8 and 9.

Given an MLA > 1.95mm2

and chest discomfort.

postpartum.

figure 10).

Angiography revealed an ambiguous left main with a complex hazy calcified roof. There was an impression of severe ostial plaque with only a narrow jet of contrast effluxing back into the left coronary cusp.

**Figure 6.** Angiographic (A and B) views and IVUS of left main (panels C and D)

The patient clearly had a left main lesion with an MLD < 2.8 mm and MLA < 5.9 mm2 and an FFR <0.71 which was all consistent with a haemodynamically significant lesion. On the basis of physiological and anatomical confirmation of severity, the patient was sent for CABG and made an uneventful recovery. This case highlights the importance of careful inspection of the angiogram in multiple views, consideration of the pitfalls of angiography and the com‐ bined use of IVUS and FFR to assess ambiguous left main plaque.

Case #2: FFR and OCT of a moderate RCA lesion:

A 65 year old female presented with a long history of exertional chest discomfort and dysp‐ noea. A stress echocardiogram demonstrated possible mild exercise induced basal inferior wall hypokinesia. She had a background history of severe uncontrolled hypertension. Her left coronary tree was unremarkable. A 50% mid RCA lesion was interrogated by OCT and FFR – refer to figures 8 and 9.

Given an MLA > 1.95mm2 on OCT and FFR > 0.80, the lesion was not stented. The recom‐ mendation was for improved blood pressure control. This case highlights the importance of thorough assessment of moderate lesions despite a typical symptom profile of angina. This patient almost certainly had hypertensive heart disease as a cause of her shortness of breath and chest discomfort.

Case #3: Use of IVUS and OCT to diagnose spontaneous coronary dissection:

**8. Case examples**

into the left coronary cusp.

Case #1: FFR and IVUS of Left Main

A 48 year-old gentleman presents with ischaemic sounding chest pain, troponin 1.3 ng/L and subtle precordial ST depression on his ECG. He has a background history of smoking,

Angiography revealed an ambiguous left main with a complex hazy calcified roof. There was an impression of severe ostial plaque with only a narrow jet of contrast effluxing back

dyslipidaemia and a strong family history of premature coronary disease.

276 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

**Figure 6.** Angiographic (A and B) views and IVUS of left main (panels C and D)

bined use of IVUS and FFR to assess ambiguous left main plaque.

Case #2: FFR and OCT of a moderate RCA lesion:

The patient clearly had a left main lesion with an MLD < 2.8 mm and MLA < 5.9 mm2

FFR <0.71 which was all consistent with a haemodynamically significant lesion. On the basis of physiological and anatomical confirmation of severity, the patient was sent for CABG and made an uneventful recovery. This case highlights the importance of careful inspection of the angiogram in multiple views, consideration of the pitfalls of angiography and the com‐

and an

A 37 year-old female with a family history of coronary disease presents with chest pain, ele‐ vated biomarkers and ST praecordial T wave inversion on her 12 lead ECG a few months postpartum.

Angiography revealed diffuse narrowing of distal left anterior descending artery (refer to figure 10).

**Figure 7.** FFR of Left Main into LAD – dramatic drop in FFR to 0.71

**Figure 8.** Panel A: Moderate RCA lesion with yellow line through the tightest point, Panel B: Proximal Reference Di‐ mensions, Panel C: Distal Reference Dimensions, Panel D: MLA and MLD

**Figure 9.** FFR clearly not in the ischaemic zone

Improving the Utility of Coronary Angiography: The Use of Adjuvant Imaging and Physiological Assessment

http://dx.doi.org/10.5772/54041

279

Improving the Utility of Coronary Angiography: The Use of Adjuvant Imaging and Physiological Assessment http://dx.doi.org/10.5772/54041 279

**Figure 9.** FFR clearly not in the ischaemic zone

**Figure 8.** Panel A: Moderate RCA lesion with yellow line through the tightest point, Panel B: Proximal Reference Di‐

278 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

mensions, Panel C: Distal Reference Dimensions, Panel D: MLA and MLD

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[5] Duissaillant GRG, Mintz GSG, Pichard ADA, Kent KMK, Satler LFL, Popma JJJ, et al. Intravascular ultrasound identification of calcified intraluminal lesions misdiagnosed as thrombi by coronary angiography. Am. Heart J. 1996 Aug. 31;132(3):687–689.

[6] Pijls NHJ, Sels JWEM. Functional Measurement of Coronary Stenosis. JAC. Elsevier

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**Figure 10.** Angiogram, IVUS and OCT of the mid to distal LAD, Panel A: Arrow points to abrupt change in vessel cali‐ ber, Panel B: IVUS with intramural haematoma (arrow), Panel C: OCT with intramural haematoma (arrow)

IVUS and OCT both confirmed spontaneous coronary dissection as the cause of the angio‐ graphic appearance with clear evidence of intramural haematoma. The patient was man‐ aged conservatively and made an uneventful recovery.

## **9. Concluding statement**

This chapter has highlighted some of the most important points regarding FFR, OCT and IVUS. In essence, these modalities are complimentary and it is up to the experienced opera‐ tor to decide on when one modality may have a clear advantage over another (e.g. IVUS be‐ ing more appropriate than OCT for imaging true aorto-ostial disease). It is generally accepted that FFR is the most useful tool to help decide when to revascularise and IVUS/OCT to help decide on pathology, guide the intervention and optimise the PCI result.

## **Author details**

Alexander Incani1 , Anthony C. Camuglia1 , Karl K. Poon1 , O. Christopher Raffel1 and Darren L. Walters1

1 The Prince Charles Hospital, Rode Rd, Chermside, Brisbane, Queensland, Australia

2 University of Queensland, St Lucia, Brisbane, Queensland, Australia

## **References**

**Figure 10.** Angiogram, IVUS and OCT of the mid to distal LAD, Panel A: Arrow points to abrupt change in vessel cali‐

IVUS and OCT both confirmed spontaneous coronary dissection as the cause of the angio‐ graphic appearance with clear evidence of intramural haematoma. The patient was man‐

This chapter has highlighted some of the most important points regarding FFR, OCT and IVUS. In essence, these modalities are complimentary and it is up to the experienced opera‐ tor to decide on when one modality may have a clear advantage over another (e.g. IVUS be‐ ing more appropriate than OCT for imaging true aorto-ostial disease). It is generally accepted that FFR is the most useful tool to help decide when to revascularise and IVUS/OCT to help decide on pathology, guide the intervention and optimise the PCI result.

, Karl K. Poon1

1 The Prince Charles Hospital, Rode Rd, Chermside, Brisbane, Queensland, Australia

, O. Christopher Raffel1

and

ber, Panel B: IVUS with intramural haematoma (arrow), Panel C: OCT with intramural haematoma (arrow)

280 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

aged conservatively and made an uneventful recovery.

, Anthony C. Camuglia1

2 University of Queensland, St Lucia, Brisbane, Queensland, Australia

**9. Concluding statement**

**Author details**

Alexander Incani1

Darren L. Walters1

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5(4):402-8

204–211.

**Chapter 14**

**Coronary Angiography –**

Additional information is available at the end of the chapter

derstanding of the operative field prior to the procedure.

computed tomography, magnetic resonance and also echocardiography.

Maria Anna Staniszewska

http://dx.doi.org/10.5772/54034

attention has to be paid to CAD.

coronary angiography.

**1. Introduction**

**Technical Recommendations and Radiation Protection**

According to recent World Health Organization statistics for 2007, cardiovascular deaths ac‐ count for 33.7% of all deaths worldwide, whereas cancer represents 29.5%, other chronic dis‐ eases 26.5%, injury and communicable diseases 4.3%. [1]. Coronary artery disease (CAD) is the leading cause of cardiovascular death throughout the world. In the light of this, special

Imaging is an integral part of diagnostics and treatment of the disease, especially of surgical and transcatheter cardiological interventions. Pre-procedural imaging provides detailed un‐

Traditional two-dimensional (2D) imaging, i.e. standard echocardiography and convention‐ al angiography, relies on acquisition of a limited number of planes/projections, which can‐ not be changed during the review, while three-dimentional (3D) imaging allows fast acquisition of volumetric data sets and subsequent off-line reconstructions along unlimited 2D planes and 3D volumes. 3D imaging of the cardiovascular structures is pursued with

Cardiovascular surgery is a dynamically developing field and many procedures are per‐ formed under control of dedicated imaging systems but most of these procedures start from

Quantitative coronary angiography is the method for visualization of coronary vessels dur‐ ing exposure to x-rays, after their filling up with contrast agents. This allows to assess coro‐ nary artery stenoses for hybrid revascularization or quantifying stenoses in bypass grafts. Depending on a further proceeding expected for a patient two versions of the procedure are

and reproduction in any medium, provided the original work is properly cited.

© 2013 Staniszewska; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

possible: CCA – conventional coronary angiography and CTA- CT angiography.

## **Coronary Angiography – Technical Recommendations and Radiation Protection**

Maria Anna Staniszewska

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/54034

## **1. Introduction**

According to recent World Health Organization statistics for 2007, cardiovascular deaths ac‐ count for 33.7% of all deaths worldwide, whereas cancer represents 29.5%, other chronic dis‐ eases 26.5%, injury and communicable diseases 4.3%. [1]. Coronary artery disease (CAD) is the leading cause of cardiovascular death throughout the world. In the light of this, special attention has to be paid to CAD.

Imaging is an integral part of diagnostics and treatment of the disease, especially of surgical and transcatheter cardiological interventions. Pre-procedural imaging provides detailed un‐ derstanding of the operative field prior to the procedure.

Traditional two-dimensional (2D) imaging, i.e. standard echocardiography and convention‐ al angiography, relies on acquisition of a limited number of planes/projections, which can‐ not be changed during the review, while three-dimentional (3D) imaging allows fast acquisition of volumetric data sets and subsequent off-line reconstructions along unlimited 2D planes and 3D volumes. 3D imaging of the cardiovascular structures is pursued with computed tomography, magnetic resonance and also echocardiography.

Cardiovascular surgery is a dynamically developing field and many procedures are per‐ formed under control of dedicated imaging systems but most of these procedures start from coronary angiography.

Quantitative coronary angiography is the method for visualization of coronary vessels dur‐ ing exposure to x-rays, after their filling up with contrast agents. This allows to assess coro‐ nary artery stenoses for hybrid revascularization or quantifying stenoses in bypass grafts.

Depending on a further proceeding expected for a patient two versions of the procedure are possible: CCA – conventional coronary angiography and CTA- CT angiography.

© 2013 Staniszewska; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

CCA is performed under the control of x-ray unit with C-arm and is preferred if further car‐ diovascular surgery is planned for the patient.

**c.** The long periods of exposure can be recorded in so-called "cine-mode" (if x-ray system

Coronary Angiography – Technical Recommendations and Radiation Protection

http://dx.doi.org/10.5772/54034

293

The results of CCA procedure are analyzed by cardiologists during its performance and also

Cardiovascular surgery covers a wide array of procedures and methods, each with specific imaging requirements. Consequently, x-ray systems are offered by the vendors in many ver‐

Two types of construction are proposed generally: a fixed C-arm system and mobile C-arm. A fixed C-arm system can be floor-mounted or ceiling-mounted. The solution is chosen by the user in dependence on the space condition of operating room. Fixed C-arm systems are required for CCA and further surgery procedures such as: percutaneous coronary interven‐

A powerful mobile C-arm can be used for pacemakers or defibrillator implants and carotid artery stenting. However, fixed C-arm systems can offer added security and are preferred

Diagnostic procedures and a structural heart disease treatment in children using imaging system require a high temporal resolution, which is provided by dedicated fixed C-arm sys‐

**•** high frequency converter generator of minimum 80 kW (in possibly rectangular pulses),

**•** x-ray tube – image detector distance tracking (minimum focus skin distance 30 cm),

**•** display of fluoroscopy time, total dose-area product (fluoroscopy and radiographic) and

**•** image hold system (for example default storage of the last 20 sec. of fluoroscopy for refer‐

**•** generator should be controlled by microprocessor, power switch accurately controlled, with short switching time (about 1 ms); voltage should cover the range of (40-120) kV,

Despite of the general features, the system should fulfil the following requirements:

Any x-ray system used for CCA procedures should be equipped as follows:

**•** minimum two dose-rate modes (Low-Medium-High or Low- Standard),

is technically predicted to this mode of work).

**2.2. Technical requirements for x-ray systems with C-arm**

tions (PCI) and endovascular aortic repair (EVAR).

for complex cases and lengthier procedures.

**•** x-ray tube focuses not larger than 1.2/0.5mm,

**•** patient table made from low-attenuating materials,

**•** a high power tube with high heat dissipation,

**•** dose-area product meter with display visible for operator,

tems with very high frame rates.

estimated skin entrance dose,

ence or archiving).

retrospectively after that.

sions.

CTA is performed under the control of computerized tomography (CT scanner) and has on‐ ly diagnostic meaning.

This chapter is divided into three parts concerning both: the techniques of coronary angiog‐ raphy (CCA and CTA) and the new technical solutions in this field. Some details concerning the standards of CCA and CTA performance have already been published [2] and are used here with addition of new information.

## **2. CCA**

#### **2.1. Description of the procedure**

A patient lies in supine position on the table being a part of C-arm unit. X-ray tube moves rotationally in two perpendicular planes (horizontal and vertical) which makes any required type of projection possible. (The most common projections are: LAO, LAO/Cranial, LAO/ Caudal, RAO). The principal current-voltage parameters are chosen automatically.

Good practice rules require that the x-ray tube is kept under the table. This allows to avoid unnecessary irradiation of the staff and makes the doses to patient lower.

In order to visualize coronary vessels a contrast agent is administered intravenously: a thin catheter is previously introduced to the brachial artery or the femoral artery (there are two alternative access routes) and its movement is traced by fluoroscopy and observed on moni‐ tor by the operator.

(The physiological parameters of a patient are permanently monitored during the procedure.)

The operating team consists of 3 to 4 persons: usually they are an operator (with an assistant if necessary), a scrub nurse and an anaesthetic nurse. All the persons stay around the patient table and thus may be exposed to even high doses of radiation. (There are scattered x-rays mainly.) An especially exposed member of the team is the operator: the doses registered for such persons may achieve the highest level measured for occupational exposures [3,4].

Patient exposure results mainly from primary x-ray beam which covers a part of back sur‐ face (the area of left shoulder) by most time of the procedure. The remaining body of a pa‐ tient is exposed to rather scattered radiation.

Three types of images can be created during the procedure:

**c.** The long periods of exposure can be recorded in so-called "cine-mode" (if x-ray system is technically predicted to this mode of work).

The results of CCA procedure are analyzed by cardiologists during its performance and also retrospectively after that.

#### **2.2. Technical requirements for x-ray systems with C-arm**

CCA is performed under the control of x-ray unit with C-arm and is preferred if further car‐

292 What Should We Know About Prevented, Diagnostic, and Interventional Therapy in Coronary Artery Disease

CTA is performed under the control of computerized tomography (CT scanner) and has on‐

This chapter is divided into three parts concerning both: the techniques of coronary angiog‐ raphy (CCA and CTA) and the new technical solutions in this field. Some details concerning the standards of CCA and CTA performance have already been published [2] and are used

A patient lies in supine position on the table being a part of C-arm unit. X-ray tube moves rotationally in two perpendicular planes (horizontal and vertical) which makes any required type of projection possible. (The most common projections are: LAO, LAO/Cranial, LAO/

Good practice rules require that the x-ray tube is kept under the table. This allows to avoid

In order to visualize coronary vessels a contrast agent is administered intravenously: a thin catheter is previously introduced to the brachial artery or the femoral artery (there are two alternative access routes) and its movement is traced by fluoroscopy and observed on moni‐

(The physiological parameters of a patient are permanently monitored during the procedure.)

The operating team consists of 3 to 4 persons: usually they are an operator (with an assistant if necessary), a scrub nurse and an anaesthetic nurse. All the persons stay around the patient table and thus may be exposed to even high doses of radiation. (There are scattered x-rays mainly.) An especially exposed member of the team is the operator: the doses registered for such persons may achieve the highest level measured for occupational exposures [3,4].

Patient exposure results mainly from primary x-ray beam which covers a part of back sur‐ face (the area of left shoulder) by most time of the procedure. The remaining body of a pa‐

**a.** Real-time images (fluoroscopic images) observed by the operator (visible also on the

**b.** Radiographic images for saving some chosen moments of the procedure (so-called

Caudal, RAO). The principal current-voltage parameters are chosen automatically.

unnecessary irradiation of the staff and makes the doses to patient lower.

diovascular surgery is planned for the patient.

here with addition of new information.

**2.1. Description of the procedure**

ly diagnostic meaning.