Coronary Angiography, Intravascular Imaging, and Physiologic Testing
CORONARY ANGIOGRAPHY, INTRAVASCULAR
IMAGING, AND PHYSIOLOGIC TESTING
ACCSAP
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Table of Contents
Coronary Angiography, Intravascular Imaging, and Physiologic Testing ........................................................1
Coronary Angiography, Intravascular Imaging, and Physiologic Testing ........................................................... 2
Introduction ....................................................................................................................................................... 3
Indications for Coronary Arteriography ............................................................................................................. 4
Contraindications for Coronary Arteriography .................................................................................................. 5
Requirements for Catheterization Laboratories ................................................................................................ 7
Concomitant Pharmacotherapy ......................................................................................................................... 8
Contrast Agents................................................................................................................................................ 10
Vascular Access ................................................................................................................................................ 11
Catheter Selection............................................................................................................................................ 14
Normal and Variant Coronary Anatomy .......................................................................................................... 18
Intracoronary Imaging...................................................................................................................................... 41
Coronary Physiology ........................................................................................................................................ 50
References ....................................................................................................................................................... 65
Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Coronary Angiography, Intravascular Imaging,
and Physiologic Testing
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Coronary Angiography, Intravascular Imaging, and
Physiologic Testing
Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Authors
David F. Kong, MD, AM, FACC
Disclosures
Consultant Fees/Honoraria: AllMed Healthcare Management, Chiesi USA, The Medicines Company;
Research/Research Grants: IBM, Medtronic, OrbusNeich, Philips, Terumo.
William F. Fearon, MD, FACC
Disclosures
Consultant Fees/Honoraria: HeartFlow; Research/Research Grants: Abbott Vascular, Edwards LifeSciences,
Medtronic.
Learner Objectives
Upon completion of this module, the reader will be able to:
1. Review the indications and contraindications for coronary arteriography in patients with suspected
coronary artery disease (CAD).
2. Review optimal arterial access technique for both femoral and radial access.
3. Describe normal and variant coronary anatomy and review appropriate catheters and imaging
techniques for optimal angiography and stenosis evaluation.
4. Discuss the complications associated with coronary angiography.
5. Formulate a basic working knowledge of coronary anatomy and its variants in patients undergoing
cardiac catheterization.
6. Review techniques to examine intracoronary anatomy.
7. Describe intravascular ultrasound (IVUS) structure and image interpretation.
8. Utilize IVUS in assessing lesion morphology, determining stenosis severity, and optimizing
percutaneous coronary intervention (PCI) results and outcomes.
9. Review newer intravascular imaging technologies, including optical coherence tomography (OCT).
10. Explain the importance of assessing coronary physiology to guide revascularization decisions in the
catheterization laboratory.
11. Differentiate between fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs), and
know the advantages and disadvantages of each.
12. Describe the emerging importance of assessing the coronary microvasculature in both stable and
unstable patients with CAD.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Introduction
Introduction
Despite the proliferation of cardiac imaging technologies in the 21st century, the coronary arteriogram
remains the hallmark technique of the cardiac catheterization laboratory and the de facto gold standard
method for defining coronary anatomy. Although highly informative and exceptionally useful, the potential
perils of selective coronary arterial injection were recognized even by the pioneers of the 1950s. Cournand
experienced a 100% fatality rate in his early attempts to selectively image canine coronaries, leading to the
hypothesis that asymmetrical hypoxia from unilateral coronary injection would precipitate fatal ventricular
arrhythmias. The serendipitous power injection of a 30 cc contrast bolus into a right coronary artery (RCA)
by Sones in 1958 induced asystole that responded to repeated deep coughs. Yet the detailed images that
resulted encouraged Sones, Judkins, and Amplatz to continue their innovative work, introducing and
popularizing intentional selective injection, preformed catheters, and femoral access.
In the contemporary era, techniques for arteriography have come full circle, with renewed interest in upper
extremity vascular access, power injection, and heparin anticoagulation. The specter of complications,
although reduced considerably over the prior 6 decades, remains ever-present and mandates careful
attention to patient selection and meticulous technique from new generations of vigilant operators.
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Indications for Coronary Arteriography
Indications for Coronary Arteriography
Coronary arteriography continues to be
Key Points
the practical reference standard for
assessment of CAD and the most
• Coronary arteriography provides the most
common method for identifying
specific information about the presence or absence
subsequent treatment strategies,
of coronary artery narrowing and continues to
including medical therapy, PCI, or
guide decisions regarding medical therapy and
revascularization in patients with coronary artery
surgical revascularization. Coronary
disease.
arteriography provides the most specific
information about the presence or
• Coronary arteriography is regarded as
absence of coronary artery narrowing
appropriate in symptomatic patients with a high
and continues to guide decisions
pretest probability of disease, with suspected
regarding medical therapy and
acute coronary syndrome, or with intermediate- or
revascularization in patients with CAD.
high-risk findings on noninvasive diagnostic
testing.
An analysis of patients without known
heart disease enrolled in the National
Cardiovascular Data Registry CathPCI
Registry between 2004-2008 revealed that only 38% of patients undergoing elective angiography had
obstructive coronary disease.
Efforts to encourage rational, evidence-based use of angiographic technologies led to a technical panel
review of 166 indications for cardiac catheterization, which are reflected in a consensus document of
Appropriate Use Criteria. Most of these indications include performance of coronary angiography, either as
the principal procedure for the detection of CAD or as a discretionary procedure in combination with
hemodynamic measurements, as part of the evaluation of valvular heart disease, pulmonary hypertension,
cardiomyopathy, or other conditions. The consensus Appropriate Use Criteria are also freely available as a
calculator application (scaiaucapp.org/auc_welcome). The Society for Cardiovascular Angiography and
Interventions (SCAI) expert consensus statement for best practices in the cardiac catheterization laboratory
was updated in 2016.1 This document updates the preprocedure checklist to include inquiries for prior stress
testing and assessments of left ventricular function; an additional assessment for multiple allergies;
computation of risk scores for bleeding, contrast-induced nephropathy, and mortality; estimated glomerular
filtration rate; preferred vascular access; and candidacy for same-day discharge.
In general, coronary arteriography is regarded as appropriate in symptomatic patients with a high pretest
probability of disease, with suspected acute coronary syndrome (ACS), or with intermediate- or high-risk
findings on noninvasive diagnostic testing. Coronary arteriography should not be performed routinely as an
initial evaluation for asymptomatic, low-risk patients; as part of a preoperative evaluation before noncardiac
surgery in patients with good exercise capacity; or prior to low-risk noncardiac surgery.
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Contraindications for Coronary Arteriography
Contraindications for Coronary Arteriography
Coronary arteriography is performed in
Key Points
a wide variety of clinical settings,
ranging from elective stable outpatients
• Major complications are uncommon (<1%) after
to emergencies with cardiogenic shock.
coronary arteriography but include death (0.10The notion that no contraindications
0.14%), myocardial infarction (0.06-0.07%), and
exist is overly simple. Like any
stroke (0.07-0.14%).
procedure, the decision to perform
• The most frequent complication of
angiography is couched in estimates of
catheterization is related to the vascular access
benefit versus risk. Major complications
site. These complications occur in 1-3% of patients
are uncommon (<1%) after coronary
and include local bleeding and hematoma, femoral
arteriography, but include death (0.10arterial pseudoaneurysm, retroperitoneal bleeding,
0.14%), myocardial infarction (MI; 0.06femoral arteriovenous fistula, the need for blood
0.07%), and stroke (0.07-0.14%). Accesstransfusion or required surgical repair, and
prolonged discomfort and length of stay.
site related pseudoaneurysms,
hematomas, and bleeding events are
the most common procedural
complications (1-3%). For elective procedures, efforts to attenuate modifiable risks are prudent. In
emergency circumstances, a greater amount of procedural risk may be tolerable if deferral of angiographic
evaluation has mortal implications.
The 2012 American College of Cardiology Foundation/Society for Cardiovascular Angiography and
Interventions Expert Consensus Document on Cardiac Catheterization Laboratory Standards Update
addresses best practices for mitigating risk by adequate patient preparation before cardiac catheterization.
Patients with chronic renal insufficiency should be hydrated with either intravenous saline or sodium
bicarbonate at 1-1.5 mL/kg/min for 3-12 hours preprocedure and 6-12 hours postprocedure. Acetylcysteine
is no longer recommended. The dose of contrast media should be minimized; biplane or rotational
angiographic techniques are often helpful if available. Patients taking warfarin ordinarily should have an
international normalized ratio of ≤1.8 for femoral access or <2.2 for radial access. Vitamin K reversal is
discouraged. Novel anticoagulants (such as dabigatran, rivaroxaban, or apixaban) should be stopped 24-48
hours before catheterization, depending on the agent and renal function.
Patients with a strong atopic history or prior contrast allergy should be considered for premedication with
steroids or H1 and H2 histamine blockers. Shellfish allergies are no longer considered important for contrast
reactions, with rates of reaction in patients with seafood allergies being similar to patients with other food
allergies or asthma. Women of childbearing age should have a normal urine or serum beta-human chorionic
gonadotropin test within 2 weeks of the procedure. To avoid iatrogenic lactic acidosis, patients with
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diabetes mellitus taking metformin should discontinue the drug at the time of contrast exposure, with
resumption 48 hours afterward if renal function remains normal.
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Requirements for Catheterization Laboratories
Requirements for Catheterization Laboratories
The risk of diagnostic catheterization is sufficiently low that many patients can be accommodated in most
facilities with suitable staff and equipment. Previous restrictions on the types of patients who may safely
undergo catheterization on an outpatient basis have been liberalized. Therapeutic procedures, including PCI,
require additional levels of expertise. Although the overall numbers of coronary interventions have been
declining, the diversity of facilities that offer therapeutic catheterization has broadened. Elective and
primary PCI are permissible in sites without cardiovascular surgery. Adherence to national guidelines for
operator and facility qualifications is essential for optimal clinical outcomes. Patients with pulmonary edema
due to ischemia, patients with complex congenital heart disease, and pediatric patients should be treated
only in facilities with onsite cardiovascular surgery and expertise to manage potential complications from
these conditions. All catheterization laboratories should have a quality-assurance and quality-improvement
program in place to assure clinical proficiency of operators, maintenance of equipment, radiation safety, and
peer review.
Additional standards for catheterization laboratory governance recommend that all cardiac catheterization
laboratories should have a clinician director and a nonclinician manager working in collaboration with
hospital administrators and other team members. The SCAI best-practice document1 also provides
recommendations on maintaining appropriate industry relationships as a foundation for policies determined
by the hospital or catheterization laboratory director.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Concomitant Pharmacotherapy
Concomitant Pharmacotherapy
Heparin and Nonheparin Anticoagulants
The deposition of thrombus on intra-arterial catheters was observed in >50% of diagnostic catheterizations
before systemic heparinization was empirically adopted by Wallace in 1972. Currently, unfractionated
heparin remains the mainstay for diagnostic coronary arteriography due to its low cost and wide availability.
The anticoagulant effect of unfractionated heparin can be reversed with protamine, 1 mg/100 U of heparin.
Protamine reversal may cause anaphylaxis or shock in ≤2% of patients and may promote thrombotic
complications. Catheterization also may be performed in the setting of low molecular weight heparin and
direct thrombin inhibitors. For patients with heparin-induced thrombocytopenia or who are at high risk for
bleeding events, diagnostic coronary arteriography may be performed from the femoral approach without
systemic anticoagulation.
Antithrombin therapy is generally required for angiography from the radial approach, although the
compressibility of the vessel and the use of mechanical devices to assist with establishing postprocedure
hemostasis from the radial approach reduce the risk for access-site bleeding. Direct thrombin inhibitors,
such as bivalirudin, lepirudin, desirudin, and argatroban, have been used as antithrombotic agents in the
setting of coronary arteriography, although their use has been generally reserved for PCI. Fondaparinux as a
sole anticoagulant during angiography and percutaneous intervention is not recommended due to catheterrelated thrombus formation.
Antiplatelet Agents
Adjunctive antiplatelet therapy is common prior to coronary arteriography, particularly in the setting of ACS.
Aspirin and oral P2Y12 inhibitors such as clopidogrel, prasugrel, and ticagrelor are frequently administered
as part of initial ACS management and do not interfere with angiography. The use of upstream glycoprotein
IIb/IIIa inhibitors prior to angiography has been de-emphasized. Cangrelor, a short-acting parenteral P2Y12
inhibitor, is indicated in antiplatelet-naive patients with anticipated PCI. Parenteral antiplatelet agents may
increase bleeding risk for patients undergoing invasive procedures but do not need to be suspended prior to
angiography. Adjunctive antiplatelet therapy remains frequently administered for ACS, and it is not
uncommon for patients to switch among the different available agents for a variety of reasons. A 2017
international expert consensus document now provides guidance and dosing recommendations for
switching among the current P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor, cangrelor).
The different pharmacokinetics of the various concomitant antithrombin agents often determine the timing
of vascular sheath removal in patients undergoing femoral access. Measurement of the activated clotting
time is useful in situations in which the degree of anticoagulation is uncertain. Radial sheath removal is
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
facilitated by a variety of bracelets that help immobilize the arteriotomy site while providing compression
for hemostasis.
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Contrast Agents
Contrast Agents
Dose Effects
The mechanism by which contrast produces renal injury remains poorly understood. Vasoconstriction within
the kidney may induce medullary ischemia and tubular damage. Exposure of the proximal tubule cells to
hyperosmolar contrast media may directly cause tubular injury. High-osmolar ionic contrast agents (e.g.,
diatrizoate) are five to seven times more hyperosmolar than blood, with osmolalities >1500 mOsm/kg. Lowosmolar contrast agents (e.g., iohexol, iopamidol, ioxaglate) have osmolalities of 600-900 mOsm/kg and are
still two to three times more hyperosmolar than blood. Iso-osmolar contrast agents (e.g., iodixanol) have
osmolalities equivalent to blood (290 mOsm/kg).
Nonionic, low-osmolar contrast agents (e.g., iohexol, iopamidol, ioversol) are recommended for the majority
of cases. Iso-osmolar contrast agents (e.g., iodixanol) may be considered in the setting of chronic renal
insufficiency, but accumulating data suggest that this approach may have negligible benefit.1
A contrast volume/creatinine clearance ratio of >3.7 has been suggested as a ceiling for contrast use to
reduce nephrotoxicity risk.1 Diabetes mellitus and heart failure also may impair nitric oxide generation,
which may increase susceptibility to contrast-induced kidney injury. A risk score weighting eight risk factors
(hypotension, intra-aortic balloon pump use, congestive heart failure, age >75 years, anemia, diabetes
mellitus, baseline creatinine, and contrast volume) has been validated for predicting the development of
contrast nephropathy. It is advisable to limit contrast volume and use iso-osmolar contrast agents in
patients with poor left ventricular function to reduce the potential for adverse hemodynamic effects.
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Vascular Access
Vascular Access
Vascular Access
Methods for obtaining vascular access have evolved considerably over time. The original methods for direct
access to the arterial system using surgical cutdown techniques are now generally reserved for largediameter access for endovascular and structural interventions and no longer used for routine diagnostic
angiography. A modified Seldinger technique with single-vessel wall entry using an 18 gauge thin wall needle
and a spring-tip guidewire is suitable for the femoral and brachial approach. Femoral, brachial, and radial
access can be obtained using smaller versions of the guidewire-through-needle set, usually employing a 21
gauge needle followed by a 0.018 inch guidewire. Radial access kits using a needle-through-cannula system
are available, with the principal Cournand-like technique passing the needle-through-cannula system
through both arterial walls, removing the needle, and advancing a 0.018 inch guidewire through the cannula
as the cannula is withdrawn back into the lumen of the radial artery.
Transradial
Transradial
Initially described in 1948, transradial access has gained popularity over the prior 20 years, particularly for
diagnostic angiographic procedures. It offers a reduction in access-site bleeding risks, eliminates the
potential for retroperitoneal complications, allows near-immediate postprocedure ambulation, and requires
minimal bedrest or immobilization. Radial access is particularly attractive in patients with morbid obesity or
patients with coagulopathy, where hemostasis may be problematic. Candidates for radial access should have
an intact palmar arch. Tests to ensure adequate arterial supply to the hand in the event of radial artery
compromise, such as the Barbeau or the Allen, should be performed before attempting radial access.
Contralateral or alternative access sites should be considered in patients with breast cancer, mastectomy,
longstanding hypertension, small frames, advanced age, contraindications to vasodilators, or arteriovenous
dialysis fistulas, or in patients who rely on the upper extremity for weight-bearing and locomotion. The left
radial artery is preferred for patients with left internal mammary aortocoronary bypass grafts. Uncommonly,
the ulnar artery can be accessed using similar techniques to the radial approach. A common approach is to
use 5 French (F) diagnostic catheters through a 6F short (10-11 cm) sheath. Larger sheath diameters are
possible but increase the risk of radial artery spasm and late radial artery occlusion.
Although radial access is often regarded as a safer alternative to femoral access due to a reduction in accesssite bleeding, complications of transradial access exist. The most common challenge for angiographers is
spasm of the radial artery, which can be managed by use of intra-arterial vasodilator agents (e.g., verapamil,
nitrates), by sedation, and by minimizing catheter manipulation and catheter exchanges. The radial artery
supplies many small perforators into the forearm and excessive traction on the radial artery may avulse
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these branches, causing forearm hematomas. Early recognition and tamponade (often using a
sphygmomanometer cuff to apply direct pressure to the forearm) can avert compartment syndrome. Radial
arterial thrombosis occurred with rates of ≤10% in early reports, but this has been reduced markedly by
careful attention to compression for hemostasis and decreasing the time occlusive pressure is maintained.
Neointimal hyperplasia after traumatic manipulation of the radial artery may produce arterial stenosis,
making subsequent access attempts more difficult.
The popularity of transradial catheterization techniques continues to increase. The European Society of
Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines now prefer radial
access for any PCI regardless of clinical presentation, unless there are overriding procedural considerations.2
For management of radial arterial access sites, a “patent hemostasis” technique is now recommended,1
performed by placing a pulse oximeter on the corresponding index finger and compressing the ulnar artery
while lowering the hemostatic wristband compression pressure to the point where the plethysmographic
waveform returns without pulsatile bleeding at the radial access site.
Transfemoral
Transfemoral
Transfemoral access still remains a standard technique in the United States due to the large number of
operators who have been introduced to transfemoral technique as the mainstay of their training.
Transfemoral approaches offer the ability to upsize to large-bore arterial access (≥7F), better catheter
support for PCI, the ability to use long sheaths to overcome tortuosity and aneurysms, nearly unlimited
catheter exchanges, and straightforward access to the arch vessels and the contralateral leg. Transfemoral
access-site complications can be minimized by careful evaluation of landmarks, which may include
fluoroscopy of the femoral head to identify bony landmarks. Care should be taken to position the
arteriotomy inferior to the inguinal ligament and superior to the bifurcation of the superficial femoral artery
and the profunda femoris.
The exact location of this bifurcation varies somewhat among patients. Hemostasis at femoral access sites
frequently can be achieved with manual compression alone, but requires 2-4 hours of bedrest to avoid
rebleeding. Vascular closure devices have been shown to shorten the time to hemostasis and time to
ambulation, although in large series there remains insufficient evidence to show they reduce bleeding
complications over manual compression alone.1 Transfemoral complications occur in 1-3% of patients and
include local bleeding and hematoma, femoral arterial pseudoaneurysm, retroperitoneal bleeding, femoral
arteriovenous fistula, the need for blood transfusion or required surgical repair, and prolonged discomfort
and length of stay.
For transfemoral access, there is an increasing emphasis for use of ultrasound as an adjunctive technique to
surface landmarks and fluoroscopy to optimize the location of the arteriotomy. Ultrasound imaging
facilitates identification of the common femoral artery, the origin of inferior epigastric artery, and origin of
the superficial femoral artery and profunda femoris. This technique becomes increasingly important when
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
the access initially used for diagnostic angiography may later be upsized to accommodate large-bore access
for structural intervention or mechanical circulatory support.
Brachial
Brachial
Brachial access is becoming increasingly uncommon with the escalating use of the radial artery as an upper
extremity access technique. The brachial artery offers the shortest route to the coronary ostia and therefore
becomes attractive when catheter manipulation is expected to be difficult, when ≥7F access is anticipated,
or in very tall patients. The location of the access site should be chosen carefully to avoid median or ulnar
nerve injury. Because the brachial artery is a terminal artery, thrombosis or dissection can threaten the
upper extremity distal to the arteriotomy site. The thrombosis rate for brachial access is higher than for
radial. Care should be taken during sheath removal to allow back-bleeding from both the proximal and the
distal vessel before initiating compression for hemostasis. Manual compression of the brachial artery is
generally required. Immobilization of the elbow is often more challenging than immobilization of the wrist,
particularly because the brachial site offers fewer structural supports for hemostasis than femoral or radial
sites. Hematomas at the brachial level carry an additional risk for compartment syndrome within the medial
brachial fascial compartment. Arm boards should be padded to reduce the risk of ulnar nerve injury. Motor
and sensory symptoms may be delayed, even ≤2 weeks after the procedure.
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Catheter Selection
Catheter Selection
Selective coronary intubation using
Key Point
woven polyester (Sones) catheters
required considerable manipulation,
• Coronary diagnostic catheters are shaped to
increasing the risk for catheter kinking,
selectively engage coronary and bypass graft ostia
inadvertent embolization, and arterial
and are designed to allow advancement and
spasm near the access site. The advent
directional control without kinking.
of polyurethane, nylon, and
thermoplastic catheters has reduced the
effort required to obtain selective access to the coronary and bypass graft ostia. Diagnostic catheters are
manufactured using several layers of material to transmit axial and rotational forces at the hub near the
operator while remaining relatively soft and minimally traumatic at the tip within the patient.
Coronary diagnostic catheters are shaped to selectively engage coronary and bypass graft ostia and are
designed to allow advancement and directional control without kinking. During catheter manipulation, axial
movement improves torque transmission and further reduces the risk for kinking. Each catheter shape is
available in a variety of diameters (measured in French or millimeters circumference) and curve sizes
designed to function in narrower or wider aortas.
The shapes pioneered by Judkins remain the most common for operators using both upper extremity and
lower extremity approaches (Figure 1). The JL4 and JR4 catheters fit the majority of patents from the
femoral and left upper extremity approaches. The right upper extremity requires the catheters to bend in a
direction mirror-image to the usual bend of the aortic arch, and the JL3.5 and JR5 curves provide
approximately equivalent tip positions. The Judkins catheters rely on additional curvature in the ascending
aorta to produce spring tension to drive the tip of the catheter toward the coronary ostium. The Amplatz
catheters, which are relatively straight in the ascending aorta, offer improved directional control in
situations in which tortuosity or unfavorable curvature creates unfavorable flexion and bias in the Judkins
catheters (Figure 2).
For any given ostial target, catheter selection depends on the horizontal distance from the principal axis of
the catheter in the aorta (reach) and whether the catheter at that distance needs to point superiorly, level,
or inferiorly (Figure 1). For any given aortic width, selecting a larger curve number (e.g., JL4 to JL5 or JL6) will
cause the tip of the catheter to point inferiorly, whereas selecting a smaller curve number (e.g., JL4 to JL 3.5
or JL 3) will cause the catheter tip to point superiorly. Thus, just as golf clubs can be arranged in terms of
increasing degrees of loft, catheters can be grouped into families describing their overall degrees of
curvature.
Specialty catheters for radial access include Tiger, Jacky, Kimny, and Ikari patterns, which are often designed
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
to engage both left and right coronary ostia. The use of a single catheter may reduce the need for catheter
exchanges and further reduce the incidence of spasm from the radial approach.
The injection of contrast is facilitated by the use of multiple stopcock manifolds, which facilitate switching to
pressure monitoring, saline flush, and management of waste fluids. Control syringes increase the ability to
manually push contrast solutions against the hydraulic resistance of the catheters. This becomes particularly
challenging when using 4F equipment. Alternatively, power injectors that precisely deliver small contrast
injections are now commercially available, with the additional ability to perform ventriculography or other
large volume injections by changing the injector settings. Beyond convenience to the operator, these
injection systems also may improve the efficiency of contrast use.
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Figure 1
Selection of a catheter curve depends on the width of the aortic root, access approach, and direction that the
tip must point at the ostial target. The top row shows catheters for the right coronary artery arranged with
those that point inferiorly (right) to those that point superiorly (left). This is similar to the faces of various golf
clubs (middle row), which span a range of lofts that produce low trajectories (right) to high trajectories (left).
Similarly, catheters for the left coronary (bottom row) can be arranged from inferior-pointing (right) to
superior-pointing (left).
3W = 3 Wood; I = iron; IM = internal mammary; JL = Judkins left; JR = Judkins right; MP = multipurpose; PW =
pitching wedge; RCB = right coronary bypass.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 2
The Amplatz family of catheters is particularly suited for wide aortas and provide good torque control from
the right upper extremity.
AL = Amplatz left; AR = Amplatz right; MOD = modified.
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Normal and Variant Coronary Anatomy
Normal and Variant Coronary Anatomy
Normal and Variant Coronary Anatomy
Coronary anatomy varies, and several nomenclatures have been used to describe the anatomy and extent of
disease. Among invasive angiographers, the most commonly used is that described in CASS (Coronary Artery
Surgery Study), modified by the BARI (Bypass Angioplasty Revascularization Investigation) Study Group
(Tables 1a, b, c, d, e, f; Figure 3). Other coronary segmentation systems include the Systematized
Nomenclature of Medicine—Clinical Terms, maintained by the National Library of Medicine, as well as
classification schemes endorsed by the Clinical Data Interchange Standards Consortium. These schemes
acknowledge three major coronary arteries: the left anterior descending (LAD), the circumflex, and the RCA,
with right-dominant, balanced, or left-dominant circulations. The left main coronary arises from the left
coronary sinus of Valsalva and divides into the LAD and left circumflex (LCX) coronary arteries. A ramus
intermedius branch may originate from the juncture of the LAD and the LCX; however, for purposes of
taxonomy, it is frequently considered part of the circumflex system. Branches of the LAD that supply the
anterolateral wall are called diagonal branches and are numbered from proximally to distally. Branches of
the LAD that supply the interventricular septum are likewise numbered proximal to distal. Branches of the
LCX are called marginals and are numbered from proximal to distal.
In most patients, the RCA, arising from the right sinus of Valsalva, supplies an atrial branch, a right
ventricular branch, an acute marginal branch, a posterior descending artery (PDA), and a series of
posterolateral branches. In three dimensions, the coronary anatomy can be considered to be a system of
one complete ring and one half ring. The half ring is formed by the LAD and the PDA. Orthogonal to this lies
a complete ring centered in the atrioventricular groove formed by the circumflex and the body of the RCA.
The angiographic rationale for coronary dominance is described by whether the PDA and the posterolateral
branches receive their supply from the RCA or the LCX. In 89.1% of patients, the PDA and the posterolateral
branches arise from the RCA (right dominant). In 8.4% of patients, the RCA is tiny and the PDA and the
posterolateral branches are supplied from the LCX (left dominant). In codominant anatomy (2.5%), the RCA
supplies the PDA and the posterolateral branches arise from the LCX. Note that the territory supplied by the
PDA and the posterolateral branches remains the same; the key difference in the dominance pattern is how
these branches connect to either the RCA or the LCX.
Although descriptions of ventricular arterial supply are abundant, the arterial supply to the atria have
received little attention in the literature. The atrial circulation has considerably more anatomic variation
than the ventricular circulation. Prominent atrial branches were originally described by Kugel and sometimes
carry his name eponymously. Although poorly defined, the so-called Kugel’s artery generally connects an
anterior coronary artery located around the aortic root (left main artery, circumflex artery, or RCA) to a
posterior arterial branch (RCA or circumflex artery) in the atrioventricular groove. Similarly, a right conus
branch collateral to an atrial branch arising from the LAD is often called Vieussens’ ring, based on his original
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
reports in 1706. The atrial branches have little clinical utility aside from being a potential collateral supply in
the setting of chronic coronary occlusions.
Variations in coronary anatomy are uncommon but important to angiographers. Anomalous coronary
arteries that arise from the opposite sinus of Valsalva are particularly concerning for their association with
sudden death, including anomalous left main coronary artery arising from the right sinus (Figures 4a, b) and
anomalous RCA arising from the left sinus (Figure 5). The course that an anomalous coronary takes to reach
its distal myocardial bed is variable, often including intramyocardial and intraseptal septal courses. These
also include wrap-around courses in the atrioventricular groove and retroaortic courses. The interarterial
course between the aorta and pulmonary artery has particularly high risk. Although several angiographic
characteristics to identify the coronary course have been described, the current preferred method is to use
sectional imaging (particularly computed tomography) for definitive ascertainment of variant coronary
supply.
Even in the absence of variant anatomy, there may be intramyocardial coronary segments (myocardial
bridging). The functional contribution of these segments to ischemia and variant angina remains
controversial. Administration of nitroglycerin or other vasodilators can help distinguish between
intracoronary spasm and fixed coronary obstructions (Figure 6). Occasionally, anomalies of coronary
drainage are observed. Fistulous connections may exist between the epicardial circulation and the rightsided circulation, particularly the right ventricle (Figure 7). Coronary aneurysms and ectatic dilation of
arterial segments are typically incidental findings but also can be associated with inflammatory or
connective tissue disorders, such as Kawasaki disease (Figure 8).
In patients who have undergone surgical revascularization, adequate images of each bypass graft also must
be obtained, normally in at least two orthogonal views. The proximal origin and distal insertion of each graft
should be visualized, in addition to the complete course of the graft. Grafts that are bound to the chest wall
by scar tissue may need to be evaluated during inspiration and expiration to evaluate for kinking that
persists into diastole. Patients with previous coronary stents should have the stented coronary regions
evaluated in orthogonal angiographic views. A few seconds of cineradiography prior to the injection of
contrast may facilitate delineation of the stented segments.
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Table 1a
Table 1a
BARI = Bypass Angioplasty Revascularization Investigation (BARI) Study Group; CDISC = Clinical Data
Interchange Standards Consortium; PERFUSE = core laboratory for the Thrombolysis In Myocardial Infarction
(TIMI) Study Group; SNOMED = Systematized Nomenclature of Medicine.
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Table 1b
Table 1b
BARI = Bypass Angioplasty Revascularization Investigation (BARI) Study Group; CDISC = Clinical Data
Interchange Standards Consortium; PERFUSE = core laboratory for the Thrombolysis In Myocardial Infarction
(TIMI) Study Group; SNOMED = Systematized Nomenclature of Medicine.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Table 1c
Table 1c
BARI = Bypass Angioplasty Revascularization Investigation (BARI) Study Group; CDISC = Clinical Data
Interchange Standards Consortium; PERFUSE = core laboratory for the Thrombolysis In Myocardial Infarction
(TIMI) Study Group; SNOMED = Systematized Nomenclature of Medicine.
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Table 1d
Table 1d
BARI = Bypass Angioplasty Revascularization Investigation (BARI) Study Group; CDISC = Clinical Data
Interchange Standards Consortium; PERFUSE = core laboratory for the Thrombolysis In Myocardial Infarction
(TIMI) Study Group; SNOMED = Systematized Nomenclature of Medicine.
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Table 1e
Table 1e
BARI = Bypass Angioplasty Revascularization Investigation (BARI) Study Group; CDISC = Clinical Data
Interchange Standards Consortium; PERFUSE = core laboratory for the Thrombolysis In Myocardial Infarction
(TIMI) Study Group; SNOMED = Systematized Nomenclature of Medicine.
Copyright © 2019 American College of Cardiology
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Table 1f
Table 1f
BARI = Bypass Angioplasty Revascularization Investigation (BARI) Study Group; CDISC = Clinical Data
Interchange Standards Consortium; PERFUSE = core laboratory for the Thrombolysis In Myocardial Infarction
(TIMI) Study Group; SNOMED = Systematized Nomenclature of Medicine.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 3
Figure 3
Segment definitions are described in Table 1.
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 4a
Figure 4a
The pigtail in the pulmonary artery provides a reference to evaluate for intra-arterial course. This emphasizes
the difficulty of ascertaining vascular relationships using a projection technology (compared with computed
tomography).
LAD = left anterior descending; LCX = left circumflex.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 4b
Figure 4b
The proximal RCA can be seen in the RAO view.
RAO = right anterior oblique; RCA = right coronary artery.
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 5
Figure 5
The Judkins left catheter is engaged in the left coronary anatomy. The origin of the right coronary artery is
observed originating from a separate ostium anterior to the left coronary ostium.
RCA = right coronary artery.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 6
Figure 6
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 7
Figure 7
Note the location of the Swan-Ganz catheter.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 8
Figure 8
Evaluation of Coronary Stenosis
Evaluation of Coronary Stenosis
Coronary stenosis typically is described by the degree of reduction in the observed vessel diameter using an
adjoining (and presumably normal) arterial segment as a reference. A 50% reduction in diameter is
equivalent to a 75% reduction in cross-sectional area and is the threshold for significant flow limitation. The
visually estimated ratio of normal to stenosis artery diameter is widely used in clinical practice but is subject
to the technical limitations of angiography, including foreshortening and lesion eccentricity. As a result, the
variability for interpretation of coronary stenosis may range 40-80% between observers.
Coronary dissection is characterized by a radiolucent intimal flap, often accompanied by delayed contrast
clearance from the false lumen (Figures 9a, b). The intimal flaps may have a spiral appearance in the setting
of extensive dissection. Intracoronary thrombus has a variety of appearances, depending on the age and
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
composition of the clot (Figure 10). Thrombotic filling defects range from hazy segments to discrete filling
defects and may be partially or fully occlusive of the vessel lumen.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 9a
Figure 9a
Haze is noted in proximal LAD in the LAO cranial view (left), with resolution of the dissection after
percutaneous coronary intervention and stenting (RAO cranial view, right).
LAD = left anterior descending; LAO = left anterior oblique; RAO = right anterior oblique.
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 9b
Figure 9b
Dissection of obtuse marginal branch after motor vehicle accident (left); a follow-up angiogram 6 months
later shows healing of the dissection.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 10
Figure 10
Angiographic Projections
Angiographic Projections
Due to the orientation of the heart
within the chest cavity, the coronary
circulation is best visualized using
angulated right anterior oblique and left
anterior oblique projections with cranial
or caudal angulation. Sufficient images
should be obtained to examine each
coronary segment in two nearorthogonal views. The sequence in
Copyright © 2019 American College of Cardiology
Key Point
• Due to the orientation of the heart within the
chest cavity, the coronary circulation is best
visualized using angulated right anterior oblique
and left anterior oblique projections with cranial or
caudal angulation.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
which the images are obtained varies among operators and institutions; examples of typical imaging
sequences for the left and right coronary circulation are provided in Figures 11a, b, and c.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 11a
Figure 11a
LAD = left anterior descending coronary artery; LAO = left anterior oblique; LCX = left circumflex coronary
artery; LPDA = left posterior descending coronary artery; LPL = left posterolateral branch; RAO = right
anterior oblique.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 11b
Figure 11b
LAD = left anterior descending coronary artery; LAO = left anterior oblique; LCX = left circumflex coronary
artery; PD = posterior descending coronary artery; PL = posterolateral branch; RAO = right anterior oblique;
RCA = right coronary artery.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 11c
Figure 11c
LAO = left anterior oblique; RAO = right anterior oblique.
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Intracoronary Imaging
Intracoronary Imaging
Intracoronary Imaging
Conventional angiographic coronary imaging techniques are limited by attenuation and interference from
the chest wall and loss of spatial resolution caused by the movement of the epicardial circulation during the
cardiac cycle. Ultrasound evaluation of the coronaries from the transthoracic or transesophageal approach is
limited to the very proximal portions of the left main coronary trunk and RCA; the ultrasound frequencies
required to image these structures several centimeters from the transducer with sufficient temporal
resolution cannot spatially resolve the more distal portions of the coronary tree. By moving the transducer
inside the coronary, the distance to the imaging target is reduced to millimeters. The transducer moves with
the cardiac cycle, synchronizing its relative position to the coronary segment of interest. Current
intracoronary imaging techniques allow for cross-sectional assessments of coronary anatomy, with
longitudinal assessments available through reconstruction. These features have made intracoronary imaging
techniques valuable for research and clinical practice.
Intravascular Ultrasound
Intravascular Ultrasound
IVUS is a safe and accurate method of
Key Points
characterizing vessel wall composition.
Current IVUS transducers fall into two
• Intravascular ultrasound is a safe and accurate
broad groups: rotational and solid state.
method of characterizing vessel wall composition.
In rotational IVUS, a single ultrasound
transmitter and detector pair are
• Other functional modalities, rather than
intravascular ultrasound, should be primarily used
mounted on a rotating shaft. The beam
to determine the physiologic significance of
(oriented orthogonal to the shaft)
atherosclerotic lesions.
traverses the cross-section of the
coronary with every rotation of the
• Intravascular ultrasound is useful in optimizing
shaft. In solid-state IVUS, a phased array
percutaneous coronary intervention results,
of stationary transmitter/detectors is
particularly in complex lesions.
oriented circumferentially around the
• Intravascular ultrasound is able to define the
catheter. Rotational systems generally
mechanism of vessel wall changes contributing to
offer greater spatial resolution because
lumen renarrowing after percutaneous coronary
of a higher ultrasound frequency (40-45
intervention.
MHz) compared with solid-state systems
(20 MHz), but they are susceptible to
nonuniform rotational distortion
artifacts if the shaft rotation speed is not constant during acquisition.
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In the early 1990s, the pioneers of PCI recognized that adjunctive IVUS evaluation of the coronary could
improve estimates of stenosis, plaque morphology, and adequacy of an interventional result. The
recognition of subtle dissections and verification of stent apposition became routine practice until the late
1990s when (as stent delivery systems became more reliable) routine high-pressure deployments to 16-17
atmospheres were thought to produce adequate stent apposition. The use of IVUS declined in the United
States; however, it remained a fundamental part of interventional practice in Asia. Concerns over late stent
thrombosis and acquired stent malapposition have led to a renewed interest in intravascular imaging
techniques in an attempt to reduce the rate of thrombotic complications.
Similar to angiography, intravascular imaging is still an anatomic assessment, with functional estimates of
flow limitation inferred indirectly from the anatomic measurements. IVUS generally reveals more plaque
than angiography, with minimal luminal areas generally correlating with FFR. Although minimum nominal
diameters for the left main coronary trunk have been recognized in the current PCI guidelines, evidence for
nominal luminal diameters of cross-sectional areas is limited for the more distal portions of the coronary
tree. Consequently, other functional modalities, rather than IVUS, should be primarily used to determine the
physiologic significance of atherosclerotic lesions.
The primary strength of intracoronary imaging is for measurement of vessel and lesion dimensions, both
directly in terms of diameter and cross-sectional area and indirect estimates of plaque volume (relying on
motorized pullback to estimate the longitudinal axis). The internal elastic lamina is readily identified by IVUS,
facilitating discrimination between the nominal arterial dimensions, pathologic plaque, and vessel lumen
(Figure 12). The ability to assess the entire cross-section of a coronary artery makes intracoronary imaging
preferable to angiography (or lumenography) for estimating vessel dimensions and late loss in clinical trials.
Likewise, stent material is highly echo reflective, making IVUS a useful technique for assessing apposition of
stent struts. In cases of coronary dissection, IVUS can identify the length and morphology of intimal tears
and hematomas, as well as confirm the presence of true and false lumina (Figure 13). Some IVUS systems
provide colorized highlighting of regions with flow coregistered with gray-scale IVUS, facilitating assessment
of true and false lumina and malapposition (Figure 14). Therefore, IVUS is useful for optimizing PCI results,
particularly in complex lesions.
Calcification is readily distinguished by IVUS, with its substantial density creating prominent echo reflections
with shadowing beyond the luminal boundary of the calcium. IVUS detects calcium twice as frequently as
coronary angiography and correlates well with calcium scores from computed tomography. The extent of
calcification can be described in degrees of arc and depth of calcification. Beyond calcium, IVUS has been
used to assess for intraluminal thrombus and plaque rupture, which have relatively low echo reflections. The
improved density resolution over angiography has led to development of techniques to further define
plaque composition and potential for rupture (Figure 15).
IVUS catheters emit ultrasound waves, which are either absorbed by tissue (and converted to heat) or
scattered, with a signal that propagates in multiple directions. In conventional signal processing, the
Copyright © 2019 American College of Cardiology
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
brightness of the pixel on the image is proportional to the amplitude of the reflected signal. Alternatively,
the signal can be processed using different mathematical models (e.g., autoregression, fast Fourier
transformation, wavelet analysis) to assess the radiofrequency components of the backscattered ultrasound
signal.
The PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree ) trial
sought to evaluate the utility of these IVUS techniques to detect lesion-related factors that might predispose
to future adverse cardiac events in 697 patients with angiographically complete revascularization by PCI.
Within 3 years, 11.6% of patients had unanticipated major adverse cardiovascular events (MACE) associated
with untreated coronary segments. Small luminal area, large plaque burden, and presence of a thin-cap
fibroatheroma were significant predictors of subsequent events. By characterizing vessel wall composition,
IVUS is able to define the mechanism of vessel wall changes contributing to lumen compromise after PCI and
delineate subsequent risk for adverse cardiovascular events. However, these lesion characteristics were not
sufficient to determine which atheromas would undergo intermediate-term progression. The ability of
backscatter processing to visualize the thin fibrous caps characteristic of vulnerable atheromas is limited by
the spatial resolution of the ultrasound technique (approximately 150 mc).
Five meta-analyses of the published IVUS versus angiographic-guided DES studies, as well as propensityscore-matching substudies and subanalyses of high-risk lesions and unstable patient subsets, showed that
IVUS guidance reduced overall MACE, including early and late ST and MI and mortality during follow-up of
≥1 year. After the publication of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With
TAXUS and Cardiac Surgery), EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for
Effectiveness of Left Main Revascularization), and NOBLE (Nordic–Baltic–British Left Main Revascularisation
Study) trials, interest in left main coronary revascularization has been increasing. IVUS remains essential for
identifying the extent of left main calcification, accurately identifying vessel dimensions, and optimizing
stent delivery. It is now standard care for treatment of left main coronary disease. The 2017 multisociety
Appropriate Use Criteria for Coronary Revascularization in Patients With Stable Ischemic Heart Disease
include IVUS assessments for determining hemodynamically significant left main disease.3 For left main
coronary artery stenoses, a minimum lumen diameter of <2.8 mm or a minimum lumen area of <6 mm 2
suggests a physiologically significant lesion. It has been suggested that a minimum lumen area >7.5 mm2
suggests revascularization may be safely deferred. A minimum lumen area between 6-7.5 mm2 requires
further physiologic assessment, such as measurement of FFR.
Radiofrequency-IVUS technologies have been developed to improve the ability of IVUS to assess tissue
composition, but the impact of these techniques on clinical outcomes remains to be demonstrated.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 12
Figure 12
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 13
Figure 13
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 14
Figure 14
The stent struts at 8 o’clock are not fully apposed, with the space between the malapposed struts and the
coronary wall further visualized with color flow imaging.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Figure 15
Figure 15
The postprocessing algorithm codes different densities to indicate lipid-rich plaque, fibrofatty plaque, and
calcification.
Optical Coherence Tomography
Optical Coherence Tomography
A method that offers improved
Key Point
resolution over IVUS is OCT, which uses
near-infrared light as a stimulus to
• Optical coherence tomography is a newer
produce backscatter, rather than
intravascular imaging technique that has a 10-fold
ultrasound. At approximately 15 mc, the
higher resolution than intravascular ultrasound.
OCT axial resolution is 10-fold greater
than IVUS, but tissue penetration is
limited to 1-3 mm for OCT compared with the 4-8 mm for ultrasound. Early time domain implementations of
optical coherence tomography (TD-OCT) divided light from a broadband 1300 nm source into a sample beam
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
focused on the coronary wall and a reference beam sent to a moving reference mirror. The back-reflected
light from the two beams recombined at a single detector to form an interference pattern. The
interferometric intensity at the detector is processed as a function of the distance to the moving reference
mirror to create an image.
The image acquisition rate and sensitivity in TD-OCT is limited by the mechanical speed of the reference
mirror. Current Fourier domain systems use a fixed mirror with a tunable laser light source to rapidly detect
backscatter signals, enabling motorized pullback speeds of ≤20 mm/sec. The infrared light is absorbed by
erythrocytes; therefore, a blood-free environment is required to reduce artifacts during OCT image
acquisition. Older TD-OCT systems required occlusion of the artery with a low-pressure balloon and
instillation of a flush solution in a manner similar to angioscopy. With their faster acquisition times, current
Fourier domain systems simply require a simultaneous injection of contrast or saline at approximately 4
mL/sec during acquisition to displace blood. Higher-viscosity solutions displace blood better than lower
viscosity solutions, with a tradeoff of higher injection pressures. If not properly recognized, residual blood
artifact can mimic thrombus or dissection.
As a backscatter technique offering increased spatial resolution, OCT provides improved detection of vessel
wall components compared with IVUS, but it has less penetration depth. Unlike ultrasound, light penetrates
calcium, producing sharp borders with little shadowing. OCT also allows measurement of tissue coverage
over stent struts, which may augment mechanistic studies evaluating novel intracoronary device designs,
such as bioabsorbable platforms. OCT used in in vivo studies has revealed important differences in
neointimal formation and composition after stent placement. The effects of intracoronary devices on tissue
characteristics and vascular biology are readily detected by continuing improvements in OCT resolution,
which is now approaching 1 mc in investigational systems. The OCT techniques have facilitated numerous
inroads in research studies, but the adoption of OCT technology for clinical practice remains limited because
of limited evidence linking this new wealth of high-resolution data to procedural and longer-term outcomes.
Randomized trials of OCT and IVUS have demonstrated that both guidance systems produce similar clinical
results. Compared with angiography-guided PCI, OCT guidance generally leads to a greater detection of
stent underexpansion, stent malapposition, and edge dissection, prompting a greater use of postdilation
and a lower residual stenosis. The optimal patient population that may clinically benefit from the tissue
characterization abilities of OCT remains to be defined.
Closer integration of intravascular imaging with angiography provides a useful clinical tool by identifying the
position of cross-sectional images obtained by IVUS or OCT along an angiographic roadmap. Coregistered
intravascular and angiographic images may facilitate procedural planning, real-time decision making, and
interventional device sizing, particularly in patients with complex or diffuse disease.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Angioscopy
Angioscopy
Coronary angioscopy relies on fiber optic bundles coupled with a xenon lamp light source, a charge-coupled
device color camera, and systems for recording the image. Unlike IVUS and OCT, angioscopy provides a
forward-looking optical view of the region distal to the catheter tip, as opposed to imaging the area
perpendicular to the catheter. Visualization of the coronary wall requires displacement of blood, which is
accomplished by flushing with saline or 3% dextran solution, sometimes augmented by deployment of a
low-pressure occlusion balloon proximal to the area of interest during visualization (20-30 seconds). The
fiber optic bundles are relatively large, limiting the area of examination to the proximal coronary arteries.
Atherosclerotic plaques are either white or yellow protrusions in the vessel lumen. Yellow lesions tend to be
lipid-rich and are associated with thin-cap fibroatheroma. White regions indicate fibrous lesions or thick
fibrous caps. The relationship between the color of the plaque and the histologic composition of the lesion
remains to be defined. Although popular in the 1990s, clinical applications of angioscopy are sparse because
of the wider availability of other intracoronary imaging techniques. Angioscopes remain available in Japan,
but they are no longer commercially available in the United States because of limited demand.
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Coronary Physiology
Coronary Physiology
Coronary Physiology
Traditionally, invasive coronary
angiography has been the reference
standard for diagnosing CAD. However,
it is now well known that there is a poor
correlation between the angiographic
severity of a coronary stenosis and its
functional significance. Moreover,
adjunctive coronary wire-based
methods for assessing the physiologic
significance of coronary artery stenosis,
and in particular measuring the FFR, has
been shown to better identify lesions
responsible for ischemia and symptoms
and to improve outcomes when guiding PCI.
Key Points
• There is a poor correlation between a
physiologically significant stenosis and
angiographic percent diameter stenosis.
• Intracoronary pressure measurements such as
measurement of fractional flow reserve during
drug-induced hyperemia provide a means to
determine the functional/hemodynamic
significance of a coronary stenosis.
Coronary Flow Reserve
Coronary Flow Reserve
Coronary flow reserve (CFR), defined as the ratio between the resting coronary flow velocity measured with
a Doppler wire and the hyperemic flow velocity after administration of a vasodilator such as adenosine, was
the first index introduced for assessing the hemodynamic significance of a coronary stenosis. However, CFR
is limited by the fact that it interrogates the entire coronary circulation, both the epicardial vessel and the
microvasculature. In patients with microvascular dysfunction, CFR may be abnormal despite a physiologically
normal epicardial vessel. In addition, because resting coronary flow is part of the equation for calculating
CFR, changes in heart rate and blood pressure (which can have significant effects on resting flow) affect the
reproducibility of CFR. Finally, although a CFR value <2 is clearly abnormal, there is no clear cutoff value for a
normal CFR. All these features and the technical challenges associated with obtaining adequate Doppler
velocity wire signals limited the role of measuring CFR in the catheterization laboratory and prompted the
development of FFR.
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
Fractional Flow Reserve
Fractional Flow Reserve
FFR is defined as the ratio of the
Key Points
maximum myocardial blood flow in the
presence of an epicardial stenosis
• Stenting of coronary lesions that are not
compared with the maximum flow in
significant by fractional flow reserve (>0.8) can be
the hypothetical absence of the
safely deferred and treated with maximal medical
stenosis. Its derivation and case
therapy.
examples are shown in Figure 16 and
• A strategy of multivessel stenting that
Figures 17a, and b. This ratio is a
incorporates fractional flow reserve results in
reflection of the fraction of normal flow
superior outcomes, fewer stents per patient, and
reaching the region of myocardium
less cost compared with angiographically driven
subtended by the vessel being
percutaneous coronary intervention.
interrogated. FFR has a number of
unique features (Table 2). Because FFR
• In patients with stable coronary artery disease
and at least one lesion with a fractional flow
is measured during maximal hyperemia,
reserve ≤0.8, an up-front strategy of percutaneous
the effects of resting hemodynamics are
coronary intervention results in a lower rate of
eliminated. Therefore, changes in heart
death, myocardial infarction (MI), and urgent
rate, blood pressure, and left ventricular
revascularization compared with best medical
contractility do not affect FFR. FFR has a
therapy and a lower rate of spontaneous MI alone.
clearly defined normal value of 1 in
every patient and every vessel. The
ischemic threshold is narrow, with a cutoff value of 0.75 and a gray zone extending to 0.8. If a vessel has an
FFR value >0.8, it is very unlikely that it is responsible for myocardial ischemia.
FFR is an index that specifically interrogates the epicardial vessel and its contribution to myocardial
ischemia, independent of the microvasculature (Figure 18). For example, in a narrowed vessel supplying
previously infarcted myocardium, the FFR value across the stenosis may be higher than expected because of
the decrease in maximum achievable flow down the vessel. However, FFR remains reliable in the setting of
chronic MI and still informs the operator regarding the expected gain in epicardial coronary flow should the
stenosis be relieved. In the setting of acute ST-segment elevation myocardial infarction (STEMI), in which
case the myocardium subtended by the culprit vessel may have a component of reversible damage, the
acute FFR measurement may not be accurate because, with time, the microvascular dysfunction may
improve and a greater peak flow with a lower FFR may be achieved. For this reason, measuring FFR in the
culprit vessel of a patient with acute STEMI is not recommended. In a patient with a very large infarction,
this microvascular stunning may extend to nonculprit territories. However the impact on the accuracy of
measuring FFR in a nonculprit vessel at the time of STEMI is small; additionally, large, multicenter
randomized studies demonstrate the utility of FFR guidance in this setting.
A potential disadvantage of FFR is that it requires administration of a hyperemic agent to minimize
microvascular resistance and maximize myocardial flow. Some of these agents can add cost, time, and side
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Coronary Angiography, Intravascular Imaging, and Physiologic Testing
effects to the procedure, as outlined in Table 3.
FFR was first validated in an animal model and subsequently against a composite of three different
noninvasive stress-testing modalities using a noninvasive reference standard. Subsequently, over the prior
25 years, numerous different investigators have further validated FFR against a variety of comparators and
in a variety of patient populations. Multiple clinical outcome studies, including a multicenter, randomized
trial called DEFER (Deferral Versus Performance of PTCA in Patients Without Documented Ischemia), have
demonstrated the safety of deferring revascularization in patients with lesions with FFR values in the
nonischemic range.4 The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation)
study was the first large, multicenter, randomized trial demonstrating the benefit of routine FFR assessment
to guide PCI in patients with multivessel CAD when compared with angiography-guided PCI.5 The study
found that the FFR-guided strategy resulted in significantly fewer stents placed and lower procedural costs.
The primary endpoint of the FAME trial was the 1-year rate of death, MI, or repeat revascularization, which
occurred in 18.3% of patients who received angiography-guided PCI compared with 13.2% of patients who
received FFR-guided PCI, p < 0.02 (Figure 19). These benefits have been demonstrated now at 2- and 5-year
follow-up. Data such as these led the ESC to give FFR its highest recommendation, class Ia, in favor of FFRguided PCI when objective evidence of ischemia is lacking. Older guidelines from the American cardiology
societies give FFR a class IIa recommendation for assessing the need for PCI of an intermediate lesion.
Although the FAME trial successfully demonstrated that decisions regarding patients who received PCI with
multivessel coronary disease should be based on FFR guidance and not the angiogram alone, one criticism of
FAME was the lack of a medical therapy arm in the randomization scheme, particularly in the stable patients
with CAD. The FAME 2 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 2) trial was
designed to address this concern by comparing PCI of lesions with an abnormal FFR to best medical therapy
in patients with stable single or multivessel coronary disease.6 The complete 2-year follow-up of the FAME 2
trial demonstrated a significant reduction in the primary endpoint of the composite of death, MI, or urgent
revascularization in patients treated with PCI compared with those treated with medical therapy alone (8.1%
vs. 19.5%, p < 0.001). This difference was driven primarily by a lower rate of urgent revascularization in the
patients who received PCI, as there was no significant difference in the rate of death or MI between the two
groups.
At 5 years, the composite of death, MI, and urgent revascularization continued to be significantly lower after
FFR-guided PCI compared with medical therapy alone, despite the fact that 51% of the medical-therapyalone group had crossed over to PCI. Importantly, however, the hard endpoint MI was lower in the PCI
group compared with the medical therapy group (8.1% vs. 12%, p = 0.049), as was the rate of spontaneous
MI (6.5% vs. 10.2%, p = 0.04) (Figure 20). These data suggest that up-front PCI in patients with stable CAD
and at least one stenosis with an FFR ≤0.8 have improved long-term outcomes compared with initial medical
therapy, including a reduced rate of spontaneous MI.
Cost-effectiveness analyses from both FAME and FAME 2 have found that FFR-guided PCI is cost-effective in
comparison with angiography-guided PCI and with medical therapy alone. FFR has been validated further in
a variety of patient populations and lesion subsets, including for assessing intermediate left main disease,
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serial lesions, bifurcation disease, diffuse disease, patients with ACS, nonculprit vessels of patients with
STEMI, and culprit vessels after remote MI. Multiple large registries have also demonstrated improved
outcomes when FFR is used to guide PCI and have shown improved decision making when FFR is employed
routinely during diagnostic angiography. A large meta-analysis of >9,000 patients confirmed that FFR
demonstrates a continuous and independent relationship with clinical outcomes (Figure 21).
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Figure 16
Figure 16
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Figure 17a
Figure 17a
FFR = fractional flow reserve; RCA = right coronary artery.
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Figure 17b
Figure 17b
FFR = fractional flow reserve; LAD = left anterior descending artery.
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Table 2
Table 2
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Figure 18
Figure 18
FFR = fractional flow reserve; LAD = left anterior descending artery.
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Table 3
Table 3
FFR = fractional flow reserve; IC = intracoronary; IV = intravenous; kg = kilogram; mcg = microgram; mg =
milligram; min = minute; VT = ventricular tachycardia.
Reproduced with permission from Fearon WF. Invasive coronary physiology for assessing intermediate
lesions. Circ Cardiovasc Interv 2015;8:e001942.
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Figure 19
Figure 19
FAME = Fractional Flow Reserve Versus Angiography for Multivessel Evaluation; FFR = fractional flow
reserve; MACE = major adverse cardiovascular event; MI = myocardial infarction.
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Figure 20
Figure 20
CI = confidence interval; FAME = Fractional Flow Reserve Versus Angiography for Multivessel Evaluation; HR
= hazard ratio; MT = medical therapy; PCI = percutaneous coronary intervention.
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Figure 21
Figure 21
CABG = coronary artery bypass graft; FFR = fractional flow reserve; MACE = major adverse cardiovascular
event; MI = myocardial infarction; PCI = percutaneous coronary intervention.
Nonhyperemic Pressure Ratios
Nonhyperemic Pressure Ratios
As the enthusiasm for measuring FFR has increased based on the previously mentioned data, operators have
sought methods for streamlining its measurement. One possible technique is to avoid the need for
administration of a hyperemic agent by measuring an NHPR, such as resting Pd/Pa (Pd = distal coronary
pressure with pressure wire; Pa = aortic pressure with guiding catheter) during the entire cardiac cycle, or
the instantaneous wave-free ratio (iFR) evaluating Pd/Pa just during the wave-free period in diastole when
myocardial resistance is presumed to be at its lowest level. Studies have found the diagnostic accuracy of
both of these indices to be in the 80% range when compared with FFR. However, they do avoid the need for
a hyperemic agent, potentially shortening procedure time and limiting side effects.
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Two large, multicenter, randomized clinical trials were recently published that compared iFR-guided
assessment with FFR-guided assessment in patients with both stable CAD and ACS, not including STEMI.7,8
Both studies found that iFR was noninferior to FFR, with similar rates of death, MI, or revascularization at 1
year. Based on these results and because iFR is a proprietary index limited to use by one pressure wire
vendor, a number of other pressure wire vendors have introduced their own NHPRs. Studies have shown
that resting Pd/Pa correlates extremely well with iFR and that other NHPRs are indistinguishable from iFR,
demonstrating that there is nothing specific about measuring the ratio during the wave-free period of
diastole.
Another method for assessing the physiologic significance of a coronary stenosis without having to
administer a hyperemic agent is to measure contrast fractional flow reserve (cFFR). Contrast media injection
induces vasodilation that results in 60% of the hyperemia achieved with adenosine. A large multicenter
study comparing cFFR with resting Pd/Pa and iFR found that cFFR had a superior diagnostic accuracy
compared with FFR than did the NHPRs.
Index of Microcirculatory Resistance
Index of Microcirculatory Resistance
Appreciation of the prognostic importance of microvascular function has grown as our techniques for
evaluating the microcirculation have improved. A number of noninvasive methods such as positron emission
tomography and cardiac magnetic resonance allow interrogation of the microvascular function.
Microvascular dysfunction results in adverse outcomes in stable patients with chest pain and nonobstructive
epicardial CAD, as well as in unstable patients presenting with acute MI. Earlier identification of these
patients may allow more efficient and effective therapy, as well as improve outcomes.
However, patients commonly present to the catheterization laboratory without having had a noninvasive
evaluation. Determining microvascular resistance, such as by measuring the index of microcirculatory
resistance (IMR), allows a readily available, quantitative, and reproducible method that is specific for the
microvasculature and independent of epicardial disease (Figure 18). Measuring IMR in patients with chest
pain and nonobstructive CAD can be helpful in determining the cause of the chest pain and in guiding
medical therapy. In patients with STEMI, an elevated IMR measured at the time of primary PCI is an
independent predictor of late mortality. These and other studies highlight the next frontier in coronary
physiology—obtaining a better understanding of the determinants of microvascular dysfunction and of the
therapeutic options for improving microvascular function and outcomes.
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Figure 18
Figure 18
FFR = fractional flow reserve; LAD = left anterior descending artery.
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References
References
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